The American Journal of Surgical Pathology

About the journal

Publisher: Wolters Kluwer Health, Inc
Published: 1977 to the present, United States
Language: English
ISSN: 0147-5185 (print), 1532-0979 (electronic)
Its record in the NLM Catalog

2020s

Ki-67 Proliferation Index Is Associated With Tumor Grade and Survival in Pleural Epithelioid Mesotheliomas. B. Galeano, C.J. Smith, E.S. Yi, et al. 2024;48(5):615-622. PubMed · Publisher · Free full text

Abstract

Pleural epithelioid mesothelioma (PEM) is divided into low and high grades based on nuclear atypia, mitoses, and necrosis in the tumor. Assessing mitoses and nuclear atypia tend to be labor-intensive with limited reproducibility. Ki-67 proliferation index was shown to be a prognostic factor in PEM, but its performance has not been directly correlated with tumor grade or mitotic score. This study evaluated the potential of Ki-67 index as a surrogate of tumor grade. We also compared the predictability of mitoses and Ki-67 index for overall survival (OS). Ninety-six PEM samples from 85 patients were identified from the surgical pathology file during 2000-2021 at our institution, and all glass slides were reviewed by 2 pulmonary pathologists to confirm the diagnosis and assign the tumor grade. Digital image analysis (DIA) was done for Ki-67 index. The agreement on tumor grading between 2 reviewers was moderate (kappa value = 0.47). The correlation between mitotic count (average count by 2 reviewers) and Ki-67 index was 0.65. The areas under the curve for predicting tumor grade by mitotic score and Ki-67 index were 0.84 and 0.74 (reviewer 1) and 0.85 and 0.81 (reviewer 2), respectively. High Ki-67 index and mitoses were significantly associated with poor OS ( P =0.03 and 0.0005, using 30% and 10/2 mm 2 as cutoffs, respectively). In conclusion, Ki-67 index by DIA was associated with tumor grade as well as mitotic count, and its predictability for OS was comparable to that of mitotic score, thus being a potential surrogate for tumor grade.

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Prevalence of S-methyl-5'-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer: A Tissue Microarray Study on 13,067 Tumors From 149 Different Tumor Types. N. Gorbokon, N. Wößner, M. Lennartz, et al. 2024;48(10):1245-1258. PubMed · Publisher · Free full text

Abstract

Loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression is a common event in cancer leading to a critical vulnerability of cancer cells towards anti-cancer drugs. Homozygous MTAP deletions result in a complete expression loss that can be detected by immunohistochemistry (IHC). In this study, a tissue microarray containing 17,078 samples from 149 different tumor entities was analyzed by IHC, and complete MTAP loss was validated by fluorescence in situ hybridization. MTAP loss was observed in 83 of 149 tumor categories, including neuroendocrine neoplasms (up to 80%), Hodgkin lymphoma (50.0%), mesothelioma (32.0% to 36.8%), gastro-intestinal adenocarcinoma (4.0% to 40.5%), urothelial neoplasms (10.5% to 36.7%), squamous cell carcinomas (up to 38%), and various types of sarcomas (up to 20%) and non-Hodgkin lymphomas (up to 14%). Homozygous MTAP deletion was found in 90% to 100% of cases with MTAP expression loss in most tumor categories. However, neuroendocrine tumors, Hodgkin lymphomas, and other lymphomas lacked MTAP deletions. MTAP deficiency was significantly linked to unfavorable tumor phenotype in selected tumor entities and the presence of PD-L1 expression on tumor cells, absence of PD-L1 expression on immune cells, and a low density of CD8 + lymphocytes. In summary, MTAP deficiency can occur in various tumor entities and is linked to unfavorable tumor phenotype and noninflamed tumor microenvironment, but is not always related to deletions. MTAP IHC is of considerable diagnostic value for the detection of neoplastic transformation in multiple different applications.

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature: A Molecular and Clinicopathologic Study of 3 Cases. J.K. Dermawan, L. Villafania, T. Bale, et al. 2023;47(2):270-277. PubMed · Publisher · Free full text

Abstract

TRAF7 somatic mutations are rare and have been reported in meningiomas, intraneural perineuriomas, and mesotheliomas. Triggered by an index case of an unclassified low-grade mesenchymal tumor with TRAF7 mutation as the only genetic alteration, we searched our files and identified 2 additional cases with similar features. The tumors arose in 2 females and 1 male, aged 63 to 75 years old (median: 67 y). They were infiltrative deep soft tissue masses involving the shoulder, chest wall, and thigh, measuring 7.0 to 9.1 cm in greatest dimensions. One tumor was locally aggressive, and 2 were associated with lung and bone metastases. The tumors displayed alternating fibrous and myxoid stroma with mild to moderate cellularity and consisted of uniform spindle cells with open chromatin, inconspicuous nucleoli and scant cytoplasm. Significant mitotic activity or necrosis were not present. However, the metastatic tumor of 1 case showed an epithelioid morphology and brisk mitotic activity. Immunohistochemically, the tumors showed nonspecific and focal smooth muscle actin or CD34 expression. By DNA sequencing, all 3 cases harbored TRAF7 missense mutations involving the C-terminal WD40 domains as the only somatic mutations, showed nonrecurrent focal copy number alterations, and were negative for gene fusions by targeted RNA sequencing. On methylation profiling, the tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes and were distinct from morphologic mimics. On follow-up (5 to 36 mo), 2 patients died of disease following aggressive chemotherapeutic regimens. We describe a novel TRAF7- mutated mesenchymal tumor characterized by aggressive clinical behavior despite the histologic appearance of a low-grade fibromyxoid spindle cell tumor.

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Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases. A. Malpica, E.D. Euscher, M.L. Marques-Piubelli, et al. 2022;46(10):1352-1363. PubMed · Publisher

Abstract

Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Malignant Mesothelioma of the Peritoneum in Women: A Clinicopathologic Study of 164 Cases. A. Malpica, E.D. Euscher, M.L. Marques-Piubelli, et al. 2021;45(1):45-58. PubMed · Publisher

Abstract

Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.
Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters. T. Mujahed, H.D. Tazelaar, W.R. Sukov, et al. 2021;45(2):255-262. Case report PubMed · Publisher

Abstract

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases. P. Argani, D.W.Q. Lian, A. Agaimy, et al. 2021;45(5):653-661. PubMed · Publisher · Free full text

Abstract

Pediatric mesotheliomas are rare and their pathogenesis remains undefined. In this study, we report 5 cases of malignant mesothelioma in children, characterized by fusions involving the anaplastic lymphoma kinase (ALK) gene. Four cases occurred in females involving the abdominal cavity and were characterized by a pure epithelioid morphology. The fifth arose in the tunica vaginalis of a 15-year-old male and displayed a biphasic epithelioid-sarcomatoid phenotype. All cases demonstrated the classic morphologic and immunohistochemical features of malignant mesothelioma, including tubulopapillary architecture and cuboidal epithelioid cells with eosinophilic cytoplasm and uniform nuclei with vesicular chromatin. Immunohistochemically, all cases showed labeling for ALK, cytokeratins, WT1, and calretinin, while lacking expression of adenocarcinoma immunomarkers. Four cases demonstrated weak-moderate labeling for PAX8 protein, which resulted in diagnostic challenges with primary peritoneal serous carcinoma. The ALK genetic abnormalities were investigated by a combination of molecular methods. Archer FusionPlex was performed in 2 cases, showing fusions between ALK with either STRN or TPM1 genes, resulting in a transcript that retained the ALK kinase domain. One case was further studied by DNA targeted sequencing, but no additional genetic alterations were observed. In 1 case, cytogenetic analysis showed the presence of a t(2;15)(p23;q22) and fluorescence in situ hybridization confirmed the ALK gene break-apart. In the remaining 2 cases, ALK gene rearrangements were demonstrated by fluorescence in situ hybridization. Unlike adult mesotheliomas, which are tightly linked to asbestos exposure, often show loss of BAP1 expression and have complex karyotypes, ALK-rearranged mesothelioma appears to be similar to other fusion-positive mesotheliomas, such as those harboring EWSR1/FUS-ATF1 fusions, sharing significant morphologic overlap, occurring in young patients and displaying a simple, translocation-driven genetic profile.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
HEG1 Is a Highly Specific and Sensitive Marker of Epithelioid Malignant Mesothelioma. J.R. Naso, S. Tsuji, A. Churg. 2020;44(8):1143-1148. PubMed · Publisher

Abstract

Malignant mesothelioma can be difficult to distinguish from other malignancies, particularly non-small cell lung carcinomas (NSCLCs), without immunohistochemistry. However, conventional markers of mesothelial lineage all have variable degrees of cross-reactivity with other neoplasms, including NSCLCs, necessitating the use of multiple mesothelioma and carcinoma markers in every case for accurate diagnosis. A recently described monoclonal HEG homolog 1 (HEG1) antibody was proposed to be a specific marker for mesothelioma. Here we performed a large scale assessment of the SKM9-2 HEG1 antibody using tissue microarrays containing 69 epithelioid mesotheliomas, 32 sarcomatoid mesotheliomas, 167 NSCLCs, and 17 ovarian high-grade serous carcinomas. Strong membrane staining, usually diffuse, for HEG1 was seen in 65/69 (94%) epithelioid mesotheliomas, 0/60 pulmonary squamous cell carcinomas, 0/73 pulmonary adenocarcinomas, and 0/13 pulmonary large cell carcinomas. HEG1 showed staining in 14/32 (44%) sarcomatoid mesotheliomas compared with 0/21 sarcomatoid pulmonary carcinomas. Three of 17 (18%) high-grade serous carcinomas demonstrated membrane staining. Ten B3 thymoma whole sections were negative. On the microarrays, the conventional mesothelial markers calretinin, WT1, D2-40, and CK5/6 had sensitivities for epithelioid mesothelioma of 94%, 90%, 96%, and 91%, respectively. We conclude that HEG1 SKM9-2 antibody offers sensitivity comparable to conventional markers for epithelioid mesotheliomas, but provides considerably better specificity, such that the diagnosis of epithelioid mesothelioma versus NSCLC potentially could be confirmed with a combination of HEG1 and a suitable broad spectrum carcinoma marker such as claudin-4. HEG1 is specific but insensitive for separating sarcomatoid mesotheliomas from sarcomatoid lung carcinomas.
Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases. E.N. Pavlisko, B. Liu, C. Green, et al. 2020;44(3):293-304. PubMed · Publisher

Abstract

We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.
Molecular Analysis of a Patient With Neurofibromatosis 2 (NF2) and Peritoneal Malignant Mesothelioma. C. Glass, L.M. Sholl, J.R. Landgraf, et al. 2020;44(2):288-292. Case report PubMed · Publisher

Abstract

Neurofibromatosis type 2 (NF2), an inherited disorder associated with multiple inherited schwannomas, meningiomas and ependymomas is caused by an autosomal dominant, likely loss of function germline mutation of the NF2 gene. Interestingly, biallelic NF2 gene inactivation is one of the most common mutations associated with the development of malignant mesothelioma (MM), a highly fatal malignancy that arises in the pleura and less frequently in the pericardium, peritoneum, and tunica vaginalis. It has been proposed that NF2 patients could potentially be at increased risk of developing MM. However, patients with inherited NF2 rarely develop MM. To date, only 2 cases describing patients diagnosed with both have been reported in the literature. Here, we describe the third case and for the first time, also provide molecular evidence that a "second hit" involving a somatic mutation is likely required to trigger the development of MM in this rare cohort. In our patient diagnosed with NF2 at age 25 who developed an aggressive peritoneal MM 15 years later, we identified a germline NF2 mutation and somatic mutations including BAP1. Of clinical relevance, our case supports a germline NF2 mutation may not necessarily be more susceptible to develop mesothelioma without a "second hit" mutation.

2010s

Molecular and Ultrastructural Features of Diffuse Intrapulmonary Malignant Mesothelioma. B.T. Larsen, M.L. Smith, A.C. Roden, et al. 2019;43(1):147-150. Letter PubMed · Publisher

Summary

This letter asked whether diffuse intrapulmonary malignant mesothelioma (DIMM) is truly mesothelial. DIMM is a rare variant with mostly intrapulmonary growth and minimal pleural involvement that can mimic interstitial lung disease, and its classification had rested only on morphology and immunophenotype. The authors studied 4 cases from their consultation practice at Mayo Clinic Arizona, seen from 2010 to 2017, that had tissue blocks available. Three came from their earlier series and 1 was newly reported. All patients were men (mean age 63 years, range 55 to 70). The new patient, a 70-year-old man, had a recurrent unilateral pleural effusion and nonspecific pulmonary infiltrates. No asbestos exposure was reported, but small bilateral calcified pleural plaques were present. The authors performed BAP1 immunohistochemistry, CDKN2A (p16) fluorescence in situ hybridization (FISH) and transmission electron microscopy. BAP1 expression was lost in tumor cells in all 4 cases, including the sarcomatoid component in the 2 biphasic cases, and was retained in non-neoplastic lung. FISH showed heterozygous CDKN2A loss in 1 case and a normal pattern in 3. In every case, electron microscopy showed long, sinuous, smooth microvilli (length-to-width ratios averaging 10 to 15:1), desmosomes and tonofilaments, which are features of mesothelial differentiation. The authors concluded that these findings support classifying DIMM as a variant of mesothelioma and that immunohistochemistry is usually sufficient for diagnosis. They stated that the value of molecular testing for prognosis and treatment remains unknown.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
SMARCA4 Loss Is Very Rare in Thoracic Mesothelioma. M.S. Ahadi, A.J. Gill. 2019;43(8):1154-1155. Letter · Comment PubMed · Publisher

Summary

This letter to the editor responded to a study by Perret et al that reported loss of SMARCA4 in 4 of 31 (13%) epithelioid mesotheliomas. The authors had not previously seen SMARCA4 loss in mesothelioma, so they examined how often it occurred in their own single-institution series. They performed immunohistochemistry for SMARCA4 and SMARCA2 on a tissue microarray containing two 1 mm cores from all available mesotheliomas encountered at their institution from 1992 to 2016. They repeated negative, weak or equivocal stains on whole slides. Of 296 assessable mesotheliomas, 179 (60.5%) were epithelioid, 63 (21.3%) sarcomatoid and 54 (18.2%) biphasic. Complete loss of SMARCA4 was found in only 2 tumours, both epithelioid. This was 0.7% of all cases and 1.1% of epithelioid cases. No case showed loss of SMARCA2. The two patients, a 77-year-old woman and a 76-year-old man, had pleurally based lesions and a history of asbestos exposure. They died 9 and 4 months after diagnosis. Both tumours showed only focal weak staining for the mesothelial markers WT1 and calretinin, and one showed focal weak TTF1 and BerEP4. The authors therefore could not fully exclude poorly differentiated carcinoma. They concluded that SMARCA4 loss is very rare in mesothelioma. They suggested that the higher rate reported by Perret et al might reflect small sample size and selection bias. They also suggested that, if confirmed, SMARCA4 status may help distinguish mesothelioma from SMARCA4-deficient thoracic sarcoma and lung adenocarcinoma.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma. R. Pillappa, J.J. Maleszewski, W.R. Sukov, et al. 2018;42(2):256-263. PubMed · Publisher

Abstract

Distinguishing reactive mesothelial proliferation from malignant mesothelioma (MM) can be difficult, particularly on small biopsies. In this scenario, a diagnosis of atypical mesothelial proliferation might be rendered. However, the distinction between a reactive process and MM is important for prognosis and treatment. Recently, loss of BRCA1-associated protein 1 (BAP1) expression and/or homozygous deletion of CDKN2A were identified in some MM, but not in reactive mesothelial proliferations. We studied 34 cases of atypical mesothelial proliferation from our institutional files (1993 to 2016) for BAP1 expression, deletion of CDKN2A, and clinical outcome. Fifteen of 34 patients (44%) were subsequently diagnosed with MM. BAP1 expression was lost in 6 of these 15 (40%) patients. Ten of 15 (67%) patients died of disease within a median time of 18.2 months. BAP1 expression was also lost in 1 case of probable MM. In this case atypical mesothelial proliferation was identified in the pleura during a lobectomy procedure for lung adenocarcinoma. Follow-up of 57.0 months was remarkable for visceral and parietal pleural thickening with continued unilateral effusion identified on imaging studies but no subsequent definitive diagnosis of MM. CDKN2A studies by fluorescence in situ hybridization (performed in 31 cases) found no homozygous deletion of that gene in any case. In conclusion, loss of BAP1 expression in atypical mesothelial proliferation helps to predict MM and is a useful adjunct test in these cases. Homozygous deletion of CDKN2A in mesothelial cell proliferations did not prove to be useful to predict MM in cases of atypical mesothelial proliferation.
A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions. P. Desmeules, P. Joubert, L. Zhang, et al. 2017;41(7):980-988. PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality. As both index cases occurred as intra-abdominal tumors in young adults, we searched our files for pleural and peritoneal MM occurring in adults younger than age of 40. All cases were tested by fluorescence in situ hybridization using custom bacterial artificial chromosomes probes for EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was performed. A total of 25 MM from patients aged 40 or less were screened, either from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40 y). Two additional ATF1-rearranged tumors were identified at pleural and peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100. BAP1 expression was retained in the 3 fusion-positive cases with available material, and in 80% (12/15) of the fusion-negative cases. Our results expand the spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a subgroup of conventional epithelioid MM. Other features of this unique MM subset include young age at presentation, lack of asbestos exposure and retained BAP1 expression.
Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features. N. Makise, A. Yoshida, M. Komiyama, et al. 2017;41(11):1523-1531. PubMed · Publisher

Abstract

Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelioid morphology in DDLPS has only rarely been documented. Here, we report 6 cases of DDLPS with striking epithelioid/epithelial features. The patients were 5 men and 1 woman with a median age of 61 years. All tumors were located in the internal trunk. During follow-up of 1 to 41 months, local recurrence, distant metastases, and tumor-related death occurred in 4, 2, and 4 patients, respectively. Beside well-differentiated liposarcoma component and conventional high-grade spindle cell morphology, all tumors focally exhibited growth comprising small or large epithelioid cells in diffuse or sheet-like proliferation. Rhabdoid cells were present in 2 cases. All 5 tumors tested harbored MDM2 amplification. Cytokeratin and/or epithelial membrane antigen were at least focally positive in all 5 tumors tested. One case contained a small focus of novel heterologous epithelial differentiation with acinar structures, wherein cytokeratin, MOC31, and claudin-4 were diffusely expressed and H3K27me3 expression was lost. DDLPS with epithelioid/epithelial features may lead to misdiagnosis of carcinoma or mesothelioma, and their diagnosis should be based on correlation with clinicopathologic and molecular findings. The epithelioid morphology in DDLPS may suggest an aggressive behavior based on this small series. In addition, we document 2 cases of MDM2-amplified undifferentiated neoplasm with epithelioid features in the internal trunk that lacked association with well-differentiated liposarcoma histology and showed rapid clinical course. Whether these latter tumors belong to DDLPS with epithelioid features requires further study.
GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma From Sarcomatoid Carcinoma of the Lung. K.B. Berg, A. Churg. 2017;41(9):1221-1225. PubMed · Publisher

Abstract

The separation of sarcomatoid and desmoplastic malignant mesotheliomas from sarcomatoid carcinomas of the lung metastatic to the pleura may be difficult, since both types of tumor can be morphologically similar and are frequently positive only for pan-keratin. GATA binding protein 3 (GATA3) is most commonly used as an immunohistochemical marker of breast and urothelial carcinoma, but is also known to stain other types of tumors including some mesotheliomas. In this study we asked whether GATA3 stains could be used to distinguish sarcomatoid/desmoplastic malignant mesotheliomas (N=19) from sarcomatoid carcinomas of the lung (N=13). Tumor staining was scored for diffuseness and intensity, with a maximum possible score of 6. All 19 sarcomatoid/desmoplastic malignant mesotheliomas examined showed strong diffuse staining for GATA3 (no case scored <3, mean score±SD for all 19 cases 5.4±0.9), whereas only 2 of 13 sarcomatoid carcinomas of the lung stained positively for GATA3 and the staining was weak and patchy (score 2 for each case, mean±SD for all 13 cases 0.4±0.8). There was no correlation between the intensity and diffuseness of GATA-3 staining and staining for traditional mesothelioma markers. Overall, any positive staining for GATA3 was 100% sensitive and 85% specific for sarcomatoid/desmoplastic mesothelioma. We conclude that strong diffuse staining for GATA3 favors a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma over metastatic sarcomatoid carcinoma of the lung; conversely, complete absence of GATA-3 staining is evidence against a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma.
Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma. M. Kuraoka, V.J. Amatya, K. Kushitani, et al. 2017;41(8):1045-1052. PubMed · Publisher

Abstract

As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional "positive" markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.
PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma. D.B. Chapel, A.N. Husain, T. Krausz, et al. 2017;41(12):1675-1682. Case report PubMed · Publisher

Abstract

Distinguishing malignant peritoneal mesothelioma (MPM) from serous carcinoma involving the peritoneum remains a diagnostic challenge, particularly in small biopsy and cytology specimens. In this distinction, PAX8 expression has been regarded as a specific marker of serous carcinoma. In addition, BAP1 loss is reportedly specific to MPM, in the distinction from both benign mesothelial lesions and ovarian serous tumors (OSTs). Using immunohistochemistry, we examined PAX8 and BAP1 expression in 27 MPMs, 25 cases of benign mesothelium, and 45 OSTs. Five MPMs were PAX8 (5/27, 18%), while 8 cases of benign mesothelium expressed PAX8 (8/25, 32%). PAX8 expression in mesothelium was significantly more common in women than in men (P=0.01). Sixteen MPMs exhibited BAP1 loss (16/25, 64%), while BAP1 was retained in all benign mesothelium and all OSTs. All cases of PAX8 mesothelium were negative for expression of estrogen receptor. These data show that PAX8 is expressed in both benign and malignant mesothelium, and that BAP1 loss is highly specific for MPM, in the differential with both benign mesothelial proliferations and OTSs. These results also have implications for primary diagnosis and for pathologic staging of OST. Caution should be applied when PAX8 expression is used to distinguish mesothelial and serous proliferations, and BAP1 loss may be confirmatory in cases where mesothelioma is favored.
A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype. K. Valente, A.U. Blackham, E. Levine, et al. 2016;40(9):1243-8. PubMed · Publisher · Free full text

Abstract

Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype.
BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas. H.C. Hwang, S. Pyott, S. Rodriguez, et al. 2016;40(5):714-8. PubMed · Publisher

Abstract

The separation of sarcomatous and desmoplastic mesotheliomas from benign organizing pleuritis can be morphologically very difficult. Deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) testing appears to be a reliable marker of malignancy in mesothelial proliferations, and more recently it has been reported that, in this setting, loss of BAP1 by immunohistochemistry is only seen in malignant mesotheliomas. To determine how useful these tests are with sarcomatous and desmoplastic mesotheliomas, we examined 20 such tumors. Loss of BAP1 was seen in 3/20 (15%) and deletion of p16 by FISH was seen in 16/20 (80%) cases. Loss of one or the other marker was observed in 17/20 (85%). We also examined 13 sarcomatoid carcinomas, an important differential diagnosis of sarcomatoid mesotheliomas, and found that BAP1 was never lost, but p16 was deleted in 3/11 (27%). We conclude that: (1) BAP1 immunohistochemistry is relatively insensitive in the context of sarcomatous and desmoplastic mesotheliomas, but as a matter of time and cost efficiency may nonetheless be a useful first approach to the problem; (2) deletion of p16 by FISH is considerably more sensitive, but there remain a proportion of cases in which p16 is not deleted; (3) a small improvement in sensitivity can be achieved by using both markers; (4) in the context of a spindle cell malignant tumor in the pleura or peritoneum, which morphologically might be a metastatic sarcomatoid carcinoma or a mesothelioma, the finding of BAP1 loss favors mesothelioma, but p16 FISH cannot be used to separate sarcomatous mesotheliomas from sarcomatoid carcinomas.
Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens. H.C. Hwang, B.S. Sheffield, S. Rodriguez, et al. 2016;40(1):120-6. PubMed · Publisher

Abstract

The diagnosis of malignant mesothelioma in effusion cytology specimens is controversial. BAP1 immunohistochemistry and p16 fluorescence in situ hybridization (FISH) have recently been reported as reliable markers of malignancy in biopsies of mesothelioma. To determine whether these markers, singly or in combination, might also be useful in effusion cytology specimens, we examined 15 biopsies of epithelial mesotheliomas and 3 benign mesothelial reactions and corresponding effusion cytology paraffin-embedded cell blocks. Four cytology specimens were too scanty for p16 FISH analysis but were interpretable for BAP1 immunohistochemistry. Overall, loss of BAP1 and/or deletion of p16 was seen in 11/11 (100%) of matched cytology and tissue biopsy specimens. BAP1 loss alone was seen in 10/15 (67%) biopsies and 10/15 (67%) cytology specimens. Homozygous deletion of p16 by FISH was found in 12/15 (80%) biopsy specimens and 8/11 (73%) evaluable cytology specimens. Seven of 15 (47%) biopsies and 5/11 (42%) cytology specimens showed loss of both markers. All mesothelioma biopsy/cytology pairs showed exactly the same pattern of BAP1 or p16 retention or loss in the biopsy and cytology specimens. The 2 peritoneal mesothelioma cases demonstrated loss of BAP1 but not p16. None of the benign mesothelial reactions or corresponding cytology specimens showed loss of either marker. We conclude that both BAP1 immunohistochemistry and p16 FISH analysis provide reliable markers of mesothelial malignancy in effusion cytology specimens, especially where the atypical mesothelial proliferation is well sampled. BAP1 is easier to interpret with scanty specimens. On the basis of small numbers of cases, use of both markers appears to increase sensitivity.
BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations. B.S. Sheffield, H.C. Hwang, A.F. Lee, et al. 2015;39(7):977-82. PubMed · Publisher

Abstract

A variety of immunohistochemical (IHC) stains have been proposed to mark either benign or malignant mesothelial proliferations. Loss of the p16 tumor suppressor (CDKN2A), through homozygous deletions of 9p21, is a good marker of mesotheliomas but lacks sensitivity. Recent reports indicate that some mesotheliomas are associated with loss of BRCA-associated protein 1 (BAP1) expression. Here we investigate BAP1 and p16 as potential markers of malignancy and compare test characteristics with previously proposed markers using a well-characterized tissue microarray. BAP1 protein expression was interrogated by IHC. The p16 locus was examined by fluorescence in situ hybridization (FISH) directed toward chromosome 9p21. Loss of BAP1 was identified in 7/26 mesotheliomas and 0/49 benign proliferations. Loss of p16 was identified in 14/27 mesotheliomas and 0/40 benign proliferations, yielding 100% specificity and positive predictive value for each marker. Together, BAP1 IHC and p16 FISH were 58% sensitive for detecting malignancy. Various combinations of p53, EMA, IMP3, and GLUT1 showed reasonably high specificity (96% to 98%) but poor to extremely poor sensitivity. Combined BAP1 IHC/p16 FISH testing is a highly specific method of diagnosing malignant mesotheliomas when the question is whether a mesothelial proliferation is benign or malignant and is particularly useful when tissue invasion by mesothelial cells cannot be demonstrated. However, combined BAP1/p16 FISH testing is not highly sensitive, and negative results do not rule out a mesothelioma. The test characteristics of previously proposed markers EMA, p53, GLUT1, IMP3 suggest that, even in combination, these markers are not useful tools in this clinical setting.
Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal high-grade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia. J.T. Rabban, P. Vohra, C.J. Zaloudek. 2015;39(1):35-51. PubMed · Publisher

Abstract

Mucosal alterations of the fallopian tube are generally thought to represent alterations of the native tubal mucosal epithelium, whether benign or malignant. The current paradigm implicating the fallopian tube fimbriae as the origin of most pelvic high-grade serous carcinomas (HGSCs) is based on the premise that HGSC growing within the tubal mucosa originated there. This has fueled proposals to redefine classification rules for assigning the primary site of origin on the basis of the presence or absence of HGSC in the tubal mucosa. The corollary is that it is unlikely for metastatic carcinoma to grow within fallopian tube mucosa. Evidence to support or refute this corollary is minimal, in part because the fallopian tubes historically have been ignored. This study reports the pattern and topography of 100 nongynecologic cancers that metastasized to the fallopian tubes. Most tumors were adenocarcinoma (87%), and the remainder included lymphomas, neuroendocrine tumors, and mesotheliomas. The most common primary origins of tumor were the colon (35%) and breast (15%). Gross evidence of a tubal nodule or mass was only seen in 35% of cases. Ovarian metastases were present in 95% of cases, although 23% did not exhibit gross evidence of metastasis. Tumor involved the fimbriae in 49% of cases, including 10% of cases in which the tumor was restricted to the fimbriae without involving the nonfimbriated portion of the tube. The anatomic distribution of metastases included the tubal mucosa (29%), submucosa (43%), muscularis (54%), serosa (76%), lymphovascular spaces (38%), intraluminal space (16%), and mesonephric remnants (39%). The most common architectural pattern of mucosal growth was a flat layer (22/29 cases), followed by varying degrees of stratification, tufting, and papillary growth. High-grade atypia was present in 18/29 cases of mucosal growth, resulting in patterns that resembled primary tubal HGSC. Accompanying growth in the tubal submucosa frequently produced a pseudoinvasive pattern mimicking invasive tubal HGSC. Immunohistochemical expression of p53 by 8/18 high-grade mucosal metastases further contributed to the resemblance to primary tubal HGSC. Bland cytology was present in 11/29 cases of mucosal growth, some of which also exhibited mucinous features, resulting in patterns that resembled either tubal mucinous metaplasia or nonmucinous tubal hyperplasia. Although uncommon, it is possible for metastases of nongynecologic cancers to grow within the mucosa of the fallopian tube and create a potential diagnostic pitfall. Intramucosal growth of a tumor in the fallopian tube is not pathognomonic of a primary tubal origin of the tumor. These findings may carry implications for proposed criteria using the status of the fallopian tube mucosa to assign primary origin of a gynecologic cancer.
Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases. M. Miettinen, Z. Wang, J. Lasota, et al. 2015;39(10):1305-12. PubMed · Publisher · Free full text

Abstract

Brachyury is a transcription factor of the T-box family typically expressed in notochord and chordoma. Some studies report brachyury as highly specific for chordoma, whereas others have concluded that brachyury is expressed in many types of common carcinomas by reverse transcription polymerase chain reaction and immunohistochemistry and could be involved in the epithelial-mesenchymal transition and metastatic process. In this study, we immunohistochemically evaluated 5229 different tumors for nuclear brachyury expression using a new rabbit monoclonal antibody and automated immunostaining (Leica Bond Max). Only nuclear labeling was scored, and antibody dilution of 1:2000 was used. In normal tissues, only rare cells in seminiferous tubules were labeled; all other organs were negative. All chordomas (75/76), except a sarcomatous one, were positive, whereas chondrosarcomas were negative. Among epithelial tumors, positivity was often detected in embryonal carcinoma (74%) and seminoma (45%). Pulmonary small cell carcinoma was often positive (41%), whereas pulmonary and pancreatic adenocarcinomas only rarely showed nuclear brachyury positivity (3% to 4%). Common carcinomas such as ductal carcinomas of the breast or adenocarcinomas of the prostate only exceptionally showed nuclear positivity (<1%). No colorectal, hepatocellular, renal cell, squamous cell, thyroid or urothelial carcinoma, or mesothelioma showed nuclear brachyury positivity. Among mesenchymal and neuroectodermal tumors, only isolated cases of melanoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and follicular lymphoma showed nuclear expression. However, as shown previously with lung carcinoma, experiments with lower antibody dilutions (1:200 to 1:500) showed weak cytoplasmic and nuclear labeling in breast cancers. In addition to chordoma, we show here for the first time that nuclear brachyury expression is prevalent in embryonal carcinoma, seminoma, and small cell carcinoma of the lung but very rare in common carcinomas, sarcomas, and melanoma. With these reservations, we have demonstrated the presence of nuclear brachyury immunoreactivity to be a sensitive and fairly specific marker for chordoma.
Sarcomatoid Peritoneal Mesothelioma: Clinicopathologic Correlation of 13 Cases. E.N. Pavlisko, V.L. Roggli. 2015;39(11):1568-75. PubMed · Publisher

Abstract

Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.
Florid mesothelial hyperplasia of the tunica vaginalis mimicking malignant mesothelioma: a clinicopathologic study of 12 cases. S. Lee, P.B. Illei, J.S. Han, et al. 2014;38(1):54-9. PubMed · Publisher

Abstract

The tunica vaginalis is an embryologically derived mesothelium-lined outpouching of the peritoneal cavity, which may develop neoplastic mesothelial proliferations similar to, although much less commonly than, pleural or peritoneal surfaces. We herein report our experience with 12 cases of florid paratesticular mesothelial hyperplasia, highlighting the spectrum of morphologic changes seen and the utility of fluorescence in situ hybridization analysis of homozygous deletion of 9p21 as an adjunct diagnostic tool. All cases were referred because of concern regarding the nature of the mesothelial proliferation. The median age of patients at presentation was 44.5 years (range, 16 to 71 y). Ten of 12 patients clinically presented with hydroceles (2 of which were complicated by infection or hemorrhage), 1 with "paraepididymal cyst" and 1 patient with an epididymal cyst. In contrast to the normal tunica consisting of a thin fibrous wall lined by a monolayer of flattened bland mesothelium and no significant inflammation, all of our cases were characterized by background changes of fibroblastic organization and stromal chronic inflammation. In all cases, the mesothelial proliferation within the fibrous and inflamed stroma was sparse and consisted of linear arrays of widely spaced horizontally orientated simple nonbranching elongated tubules and small solid nests and cords that were well spaced apart. There was an abrupt linear demarcation of tubules at the deep aspect of the fibrous tissue, with no evidence of definite invasion into the submesothelial tissue. Fluorescence in situ hybridization for 9p21 was negative in all 5 cases in which tissue was available for analysis. Nine patients with extended follow-up were alive (median 8 y; range, 1 to 13 y). In summary, the proliferative changes seen in reactive mesothelial hyperplasia associated with hydroceles may be florid and mimic malignant mesothelioma. In particular, the entrapment of isolated mesothelial clusters within deep fibrous tissue may be the cause of significant diagnostic difficulty. There are, however, morphologic clues such as linear arraying of widely spaced architecturally simple cell clusters that may aid in the correct identification of the benignity of these proliferations.
GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. M. Miettinen, P.A. McCue, M. Sarlomo-Rikala, et al. 2014;38(1):13-22. PubMed · Publisher · Free full text

Abstract

GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tumors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was <10%. Chromophobe renal cell carcinoma was a unique renal tumor with frequent positivity (51%), whereas oncocytomas were positive in 17% of cases but other types only rarely. Among mesenchymal and neuroectodermal tumors, paragangliomas were usually positive, which sets these tumors apart from epithelial neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas.
p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma. H. Hwang, C. Tse, S. Rodriguez, et al. 2014;38(5):681-8. PubMed · Publisher

Abstract

An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal mesotheliomas that had both an invasive component and a separate surface mesothelial proliferation. In 5/11 pleural samples and 1/7 peritoneal samples, the invasive mesotheliomas showed homozygous deletion of p16 (all cases in excess of 90% of cells deleted); the surface proliferation in all 6 cases with deletion in the invasive tumor was also p16 deleted. Conversely, the 12 tumors that did not show p16 deletion in the invasive compartment also did not have deletion in the surface component. We conclude that (1) surface mesothelial proliferations near invasive mesotheliomas show the same pattern of p16 by FISH as the underlying tumor and may represent in situ disease or growth of the underlying mesothelioma along the serosal surface; (2) p16 deletion in mesothelial surface proliferations is strongly associated with p16 deletion in underlying mesotheliomas, and biopsies consisting of pure surface mesothelial proliferations that are p16 deleted allow a diagnosis of mesothelioma without an additional biopsy if there is clinical (thoracosopic/laparoscopic) or radiologic evidence of diffuse pleural or peritoneal tumor; (3) however, the absence of p16 deletion in surface proliferations does not rule out underlying invasive mesothelioma.
Well-differentiated papillary mesothelioma with invasive foci. A. Churg, T. Allen, A.C. Borczuk, et al. 2014;38(7):990-8. PubMed · Publisher

Abstract

Well-differentiated papillary mesotheliomas (WDPMs) are usually encountered as incidental findings in the peritoneal cavity in women. Most WDPMs are benign, and the histologic features that indicate a more aggressive course are controversial. We report 20 cases of WDPM, which contained invasive foci. Thirteen cases arose in the peritoneal cavity, 1 in a hernia sac, 3 in the pleural cavity, and 3 in hydroceles. The female:male ratio was 16:4, and age range was 7 to 74 years. Tumor was multifocal in 15 cases. Some tumors showed back-to-back papillae, a pattern mimicking invasion but discernible on pan-keratin stain as compressive crowding. True invasive patterns ranged from simple bland-appearing glands invading the stalks of the papillae to solid foci of invasive tumor of higher cytologic grade than the original WDPM. All 5 tested cases were negative for p16 deletion by fluorescence in situ hybridization, but 2/3 had abnormal karyotypes. Recurrences were seen in 8 patients, and in 4 multiple recurrences were documented. Of 16 patients with follow-up, 14 are alive from periods of 6 months to 6 years (average 3.5 y), and 2 have known recurrent disease. One patient died of disseminated tumor at 8 years but without histologic confirmation of the nature of the tumor. We conclude that WDPM with invasive foci in the papillae appear to be prone to multifocality and recurrence, but that they rarely give rise to life-threatening disease. We suggest that these lesions be called WDPM with invasive foci to alert clinicians to the possibility of recurrence.
Diffuse intrapulmonary malignant mesothelioma masquerading as interstitial lung disease: a distinctive variant of mesothelioma. B.T. Larsen, J.R. Klein, H. Hornychová, et al. 2013;37(10):1555-64. Case report PubMed · Publisher

Abstract

Malignant mesothelioma typically encases lungs as a thick rind, while relatively sparing lung parenchyma. We describe an unusual presentation of mesothelioma characterized by diffuse intrapulmonary growth, with absent or inconspicuous pleural involvement, clinically simulating interstitial lung disease (ILD). We identified 5 patients (median age 56 y, all men) with diffuse intrapulmonary malignant mesothelioma in our pathology consultation practice from 2009 to 2012. Clinical history, imaging, and pathology materials were reviewed. Symptoms included chronic dyspnea (4 cases), cough (3), and acute dyspnea with bilateral pneumothorax (1). Chest imaging showed irregular opacities (5), reticulation (4), pleural effusions (2), and subpleural nodular densities (1), without radiologic evidence of pleural disease or masses. A clinicoradiologic diagnosis of ILD was made in all cases, and wedge biopsies were performed. Histologic evaluation revealed a neoplastic proliferation of bland epithelioid or spindled cells, showing various growth patterns simulating silicotic nodules, desquamative interstitial pneumonia, organizing pneumonia, and Langerhans cell histiocytosis. Some areas mimicked adenocarcinoma, with lepidic, acinar, micropapillary, and solid patterns. Initial diagnoses by referring pathologists included reactive changes (1), hypersensitivity pneumonitis versus drug reaction (1), desquamative interstitial pneumonia versus neoplasm (1), and mesothelioma (2). Microscopic pleural involvement was identified in 4 cases. Immunohistochemistry confirmed the characteristic immunophenotype of mesothelioma in all cases. Median survival of 3 patients treated with chemotherapy was 28 months. Two patients received no therapy and survived 3 and 4 weeks, respectively. "Diffuse intrapulmonary malignant mesothelioma" is a rare variant with a distinctive presentation that clinically mimics ILD. Recognition is essential to avoid misdiagnosis.
IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations. A.F. Lee, A.M. Gown, A. Churg. 2013;37(3):421-6. PubMed · Publisher

Abstract

Distinguishing malignant mesotheliomas from benign mesothelial proliferations on hematoxylin and eosin-stained sections can be extremely challenging. Various immunohistochemical stains have been suggested to help in making this distinction, but all are controversial. Recently, IMP3 (insulin-like growth factor II mRNA binding protein 3) and GLUT-1 (glucose transporter protein 1) have been proposed as immunohistochemical markers that are positive in mesotheliomas but not in benign proliferations. We evaluated the performance of these markers on a tissue microarray containing 30 malignant mesotheliomas and 48 benign thoracic or abdominal mesothelial proliferations. IMP3 was positive in 53% of malignant and 27% of benign cases (P=0.03), whereas GLUT-1 was positive in 60% of malignant and 13% of benign cases (P=0.0003). Forty-three percent of malignant cases, but only 4% of benign cases, were positive for both IMP3 and GLUT-1 (P=0.00003). We conclude that, statistically, both IMP3 and GLUT-1 are more frequently positive in malignant compared with benign mesothelial processes; however, the frequency of positive staining in benign cases is too high to allow their diagnostic use as single stains. The combination of both markers may be of greater diagnostic value, but this hypothesis should be confirmed in further studies.
Immunoreactivity for calretinin and keratins in desmoid fibromatosis and other myofibroblastic tumors: a diagnostic pitfall. S. Barak, Z. Wang, M. Miettinen. 2012;36(9):1404-9. PubMed · Publisher · Free full text

Abstract

Calretinin is an intracellular calcium-binding EF-hand protein of the calmodulin superfamily. It plays a role in diverse cellular functions, including message targeting and intracellular calcium signaling. It is expressed in the mesothelium, mast cells, some neural cells, and fat cells, among others. Because of its relative specificity for mesothelial neoplasms, calretinin is widely used as one of the primary immunohistochemical markers for malignant mesothelioma and in differentiating it from adenocarcinoma. On the basis of our sporadic observation on calretinin immunoreactivity in desmoid fibromatosis, we systematically evaluated calretinin, keratin cocktail (AE1/AE3), and WT1 immunoreactivity in 268 fibroblastic/myofibroblastic neoplasms. Calretinin was observed in 75% (44/58) of desmoid fibromatosis, 50% (21/42) of proliferative fasciitis, 23% (8/35) of nodular fasciitis, 33% (13/40) of benign fibrous histiocytoma, 35% (22/62) of malignant fibrous histiocytoma, and 13% (4/31) of solitary fibrous tumors but not in normal connective tissue fibroblasts at various sites. Keratin AE1/AE3 immunoreactivity was also commonly (6/13) present in the large ganglion-like cells of proliferative fasciitis and sometimes in nodular fasciitis (3/35), solitary fibrous tumor (3/27), and malignant fibrous histiocytoma (9/62). Nuclear immunoreactivity for WT1 or keratin 5 positivity was not detected in myofibroblastic tumors. On the basis of these observations, it can be concluded that calretinin and focal keratin immunoreactivity is fairly common in benign and malignant fibroblastic and myofibroblastic lesions. Calretinin-positive and keratin-positive spindle cells in desmoid and nodular fasciitis or calretinin-positive ganglion-like cells in proliferative fasciitis should not be confused with elements of epithelioid or sarcomatoid mesothelioma. These diagnostic pitfalls can be avoided with careful observation of morphology, quantitative differences in keratin expression, and use of additional immunohistochemical markers such keratin 5 and WT1 to verify true epithelial and mesothelial differentiation typical of mesothelioma.
Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice. T. Mohammad, J. Garratt, E. Torlakovic, et al. 2012;36(10):1503-8. PubMed · Publisher

Abstract

Most reports on antibodies that claimed to separate mesothelioma from pulmonary adenocarcinoma originated from academic centers or specialized immunohistochemistry laboratories, but little is known about how such stains perform in general practice laboratories. The Canadian Immunohistochemistry Quality Control program circulates tissue array slides to laboratories across Canada; these are stained and then interpreted by the local laboratory and by a set of experienced reviewers. For Canadian Immunohistochemistry Quality Control run 16, tissue array slides from 16 pulmonary adenocarcinomas and 6 mesotheliomas were stained in 36 different laboratories for CEA, CD15, CK5/6, and calretinin. A total of 736 results (cores) were interpretable. If 3 of 4 staining results concordant with the diagnosis was accepted as definitive, 166/192 (86.4%) mesothelioma cores and 461/544 (84.7%) adenocarcinoma cores were correctly diagnosed. However, if 4 of 4 concordant markers were required, then 93/192 (48.4%) mesothelioma cores and 265/544 (48.7%) adenocarcinoma cores were correctly diagnosed. Only 3/192 (1.6%) mesothelioma cores were incorrectly classified as carcinomas and 8/544 (1.5%) of adenocarcinoma cores incorrectly classified as mesotheliomas on the basis of the immunoprofile (ie, 3 of 4 or 4 of 4 marker results were discordant with the diagnosis). We conclude that, in a study based on results from nonspecialized laboratories, the combination of CEA, CD15, calretinin, and CK5/6, used as a panel, has a very low false-positive rate when separating pulmonary adenocarcinomas from mesotheliomas; however, single negative or incorrect results are common, therefore the panel is only useful diagnostically if 3 of 4 correct results are deemed acceptable for diagnosis.
Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. M. Miettinen, M.S. Rikala, J. Rys, et al. 2012;36(4):629-39. PubMed · Publisher · Free full text

Abstract

Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non-neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant epithelioid mesothelioma. Expression in biphasic synovial sarcoma epithelium, chordoma, and some carcinomas has to be considered in differential diagnosis. Information on VEGFR2 tissue expression may be useful in development of targeted oncologic therapy through VEGFR2-specific tyrosine kinase inhibitors.
Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases. A. Malpica, S. Sant'Ambrogio, M.T. Deavers, et al. 2012;36(1):117-27. PubMed · Publisher

Abstract

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial tumor that occurs in the peritoneum of women over a wide age range. Although considered a tumor of uncertain malignant potential, information about its biological behavior is still limited. In this study, we present the clinicopathologic features of 26 cases of WDPM of the female peritoneum seen in our institution over a 20-year period (1990 to 2010). Clinical information and pathology material were reviewed in all cases. Patients ranged in age from 23 to 75 years (median, 47 y; mean, 48.6 y). There was no history of asbestos exposure in any of our cases. Ten patients had undergone surgery previously, and 6 had a history of endometriosis. In 24 patients, the WDPM was an incidental finding during surgery for a benign or malignant lesion. Only 2 patients presented with symptoms: 1 with an acute abdomen and the other with chronic pelvic pain. The former had developed a small hemoperitoneum because of bleeding of 1 of the lesions of WDPM, whereas the latter had a 2-cm WDPM involving the distal fallopian tube. The lesions were single or multiple (13 cases each) and ranged in size from 0.1 cm to 2 cm. The following sites were involved: abdominal or pelvic peritoneum not otherwise specified (10 cases), omentum (7 cases), cul-de-sac (6 cases), colonic serosa (4 cases), small bowel mesentery (2 cases), uterine serosa (2 cases), stomach serosa (1 case), large bowel mesentery (1 case), fallopian tube (1 case), ovary (1 case), and inguinal hernia (1 case). In all cases the lesions were excised. Microscopically, all of our cases had the typical features described for WDPM (ie, a papillary architecture that may be accompanied by glandular/tubular patterns, nests of cells and individual cells, bland mesothelial cells, absent or rare mitotic figures). The initial diagnosis in our cases was variable, including WDPM, mesothelial hyperplasia, malignant mesothelioma, serous tumor of low malignant potential of the peritoneum, papillary endosalpingiosis, and chronic xanthogranulomatous salpingiosis. Follow-up was obtained for 25 patients, and it ranged from 4 to 192 months (mean, 47.5 mo; median, 32 mo); 22 patients are alive with no evidence of WDPM after a follow-up that ranged from 5 to 144 months. One of these patients experienced recurrence of WDPM 46.5 months after initial diagnosis. In this patient, WDPM was an incidental finding during a total abdominal hysterectomy and bilateral salpingo-oophorectomy for serous cystadenofibroma. The recurrence was also an incidental finding during a colectomy for colonic adenocarcinoma. This patient is alive with no other recurrences 73 months after initial diagnosis and 36 months after diagnosis of the recurrence. Three patients died of other causes: pancreatic cancer at 4 months and 12 months and leukemia at 192 months. Recognition of the histologic features of WDPM and proper clinical correlation allow for the correct diagnosis of this entity. If necessary, immunohistochemical studies such as calretinin and keratin 5/6 facilitate the recognition of the mesothelial nature of this neoplasm. Although no patient died of disease in this series, follow-up of patients with this diagnosis is warranted on the basis of possible recurrences or misdiagnosis of an undersampled malignant mesothelioma.
ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma. M. Miettinen, Z.F. Wang, A. Paetau, et al. 2011;35(3):432-41. PubMed · Publisher · Free full text

Abstract

ERG, an ETS family transcription factor, is known to be expressed in endothelial cells, and oncogenic ERG gene fusions occur in subsets of prostatic carcinoma, acute myeloid leukemia, and Ewing sarcoma. In this study, we immunohistochemically investigated nuclear ERG expression using a new monoclonal antibody, CPDR ERG-MAb, that is highly specific for detecting ERG protein and ERG-expressing prostate carcinomas. A broad range of vascular endothelial (n = 250), other mesenchymal (n = 973), and epithelial tumors (n = 657) was examined to determine the use of ERG immunohistochemistry in surgical pathology. Only immunostains with ERG-positive normal endothelia (internal control) were considered valid, and only nuclear staining was considered to be positive. In adult tissues, ERG was restricted to endothelial cells and to a subset of bone marrow precursors, but early fetal mesenchyme and subpopulations of fetal cartilage were also positive. In vascular tumors, ERG was expressed in endothelia of all hemangiomas and lymphangiomas, and typically extensively expressed in 96 of 100 angiosarcomas, 42 of 43 epithelioid hemangioendotheliomas, and all 26 Kaposi sarcomas. Among nonvascular mesenchymal tumors, only blastic extramedullary myeloid tumors (7 of 10) and rare Ewing sarcomas (2 of 29) were positive. Among epithelial tumors, 30 of 66 prostatic adenocarcinomas showed focal-to-extensive ERG positivity, with no immunoreactivity in the normal prostate. Other carcinomas and epithelial tumors (n = 643) were ERG negative, with the exception of 1 of 42 large cell undifferentiated pulmonary carcinomas and 1 of 27 mesotheliomas, each of which showed focal nuclear ERG positivity. On the basis of the above observations, ERG is a highly specific new marker for benign and malignant vascular tumors. Among epithelial tumors, ERG shows a great promise as a marker to identify prostatic carcinoma in both primary and metastatic settings.
Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation. M. Shi, A.E. Fraire, P. Chu, et al. 2011;35(6):878-82. PubMed · Publisher

Abstract

The distinction of malignant mesothelioma from reactive mesothelial proliferation remains to be a major challenge for surgical pathologists. In this study, we investigated whether insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), an oncofetal protein, can be used as a biomarker to distinguish between malignant and reactive mesothelial cells. A total of 109 cases (mesothelioma, n=45; reactive mesothelial proliferation, n=64) were examined by immunohistochemistry for IMP3 expression. IMP3 showed strong cytoplasmic staining in 33 of 45 (73%) mesothelioma cases. In contrast, the expression of IMP3 was undetectable in all (64 cases) benign reactive mesothelial proliferations. Among the IMP3-positive mesotheliomas, 27 (82%) exhibited diffuse IMP3 expression. The vast majority of IMP3-positive subtypes of mesotheliomas showed IMP3 expression in >50% of malignant cells, as this diffuse staining pattern occurred in 17 (81%) cases of epithelial, 4 (100%) cases of sarcomatoid, and 6 (75%) cases of mixed types of mesothelioma. In addition, 2 cases, which were initially diagnosed as atypical mesothelial proliferations and later confirmed to be mesotheliomas, showed diffuse IMP3 expression. Our findings suggest that IMP3 is a new positive biomarker for malignant mesothelioma. IMP3 immunohistochemical staining can be used as an adjunct tool in the distinction of malignant mesothelioma from reactive mesothelial proliferations.
PAX8 and PAX2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract. G.X. Tong, L. Memeo, C. Colarossi, et al. 2011;35(10):1473-83. Case report PubMed · Publisher

Abstract

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.
The fake fat phenomenon in organizing pleuritis: a source of confusion with desmoplastic malignant mesotheliomas. A. Churg, P. Cagle, T.V. Colby, et al. 2011;35(12):1823-9. PubMed · Publisher

Abstract

We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.
PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma. A.R. Laury, J.L. Hornick, R. Perets, et al. 2010;34(5):627-35. PubMed · Publisher

Abstract

Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker for mesothelioma.

2000s

Tenascin-X is a novel diagnostic marker of malignant mesothelioma. Y. Yuan, D.A. Nymoen, H.T. Stavnes, et al. 2009;33(11):1673-82. PubMed · Publisher · Free full text

Abstract

Tenascin XB (TNXB) was previously identified as a gene that is more highly expressed in malignant mesothelioma compared with ovarian/peritoneal serous carcinoma based on gene expression array analysis. The objective of this study was to validate this finding at the mRNA and protein levels. Effusions (n = 91; 71 ovarian carcinomas, 10 breast carcinomas, and 10 malignant mesotheliomas) were assayed for TNXB mRNA expression using quantitative polymerase chain reaction. Tenascin-X protein expression was studied in 183 effusions (137 carcinomas of different origin, 37 mesotheliomas, and 9 reactive effusions) and 178 solid lesions (122 ovarian/peritoneal carcinomas and 56 mesotheliomas) using immunohistochemistry. Quantitative polymerase chain reaction analysis showed significantly higher TNXB mRNA level in mesotheliomas compared with ovarian and breast carcinomas (P < 0.001). By immunohistochemistry, tenascin-X protein expression was significantly higher in malignant mesothelioma compared with metastatic carcinoma in effusions (34 of 37 vs. 31 of 137 positive cases; sensitivity = 92% and specificity = 77%; P < 0.001). Reactive mesothelial cells had focal or no tenascin-X expression. Tenascin-X protein was detected in 41 of 56 mesothelioma biopsy specimens and was uniformly absent from all 122 ovarian carcinomas (sensitivity = 73% and specificity = 100%; P < 0.001). Our data suggest that tenascin-X may be a new diagnostic marker of malignant mesothelioma in the differential diagnosis of cancers involving the serosal cavities, particularly in the differential diagnosis between this tumor and ovarian/peritoneal serous carcinoma.
Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases. J. Fukuoka, T.J. Franks, T.V. Colby, et al. 2005;29(7):948-54. Review PubMed · Publisher

Abstract

Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance. We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure; another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine user, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders. It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD). Patients are mostly older women, with mild symptoms and CT findings. Survival appears to be favorable.
Well-differentiated papillary mesothelioma of the pleura: a series of 24 cases. F. Galateau-Sallé, J.M. Vignaud, L. Burke, et al. 2004;28(4):534-40. PubMed · Publisher

Abstract

Well-differentiated papillary mesothelioma (WDPM) of the pleura represents a distinct mesothelial tumor presenting with unilateral pleural effusion and superficial spreading of stout papillary formations with myxoid cores, lined by bland, flattened, or epithelioid cells, without or with limited invasion of the submesothelial layer. The majority of cases have been reported in the peritoneum in women of reproductive age with no history of asbestos exposure and also in the tunica vaginalis of men. We report 24 cases of pleural WDPM and compared their histologic, epidemiologic, and clinical features with those of classic mesothelioma. Men and women were equally affected, with a mean age of 60 years. Half of the patients had a history of occupational asbestos exposure. In 11 patients with a minimal follow-up period of 24 months, the survival ranged from 36 to 180 months with an average of 74 months as compared with 9.89 months for 1248 paired patients with diffuse malignant mesothelioma. Ten-year survival was 30.8%. We conclude that WDPM is a rare and unusual mesothelial tumor, characterized by a lack of deep invasion and associated with an indolent clinical course and long survival. For these reasons, WDPM is best considered as a specific clinico-pathologic entity distinct from conventional diffuse malignant mesothelioma.
Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura. M. Miettinen, M. Sarlomo-Rikala. 2003;27(2):150-8. PubMed · Publisher

Abstract

Several immunohistochemical markers, among them calretinin, thrombomodulin (CD141), keratin 5, and mesothelin, have been documented or suggested as useful markers for positive identification of mesothelioma and to differentiate it from pulmonary adenocarcinoma; numerous studies have documented their variable specificity. However, expression of these markers in other types of lung carcinomas has not been systematically explored, although these tumors can enter in the differential diagnosis of mesothelioma. In this study we immunohistochemically evaluated 596 lung carcinomas of different types for the four above-mentioned mesothelioma markers, all of which reacted with a great majority of epithelioid mesotheliomas studied for comparison. Calretinin expression was common in giant cell carcinomas (67%), small cell carcinomas (49%), and large cell carcinomas (38%), whereas it was rare in usual adenocarcinomas but slightly more common in those with neuroendocrine differentiation (11% and 17%, respectively). Thrombomodulin was present in all keratinizing squamous carcinomas and the great majority (87%) of nonkeratinizing tumors in a membrane-staining pattern. It was moderately common in small cell (27%) and large cell carcinomas (25%) but relatively rare in adenocarcinomas (13%). Keratin 5 was expressed in all keratinizing and the great majority (87%) of nonkeratinizing squamous carcinomas, and a majority of large cell carcinomas (56%) and some small cell carcinomas (27%). It was rare in acinar adenocarcinomas (12%) and absent in those with neuroendocrine differentiation. Mesothelin was present in more than half (53%) of adenocarcinomas and a minority (13%) of large cell carcinomas but was absent in small cell carcinomas. In squamous carcinomas it was more often seen in nonkeratinizing versus keratinizing tumors (31% vs 16%). These results show that each of these "mesothelioma" markers reacts with different subsets of pulmonary carcinomas with a variable frequency; this should be considered when using these markers in the differential diagnosis of thoracic tumors.
'Black Spots' and hyaline pleural plaques on the parietal pleura of 150 urban necropsy cases. K. Mitchev, P. Dumortier, P. De Vuyst. 2002;26(9):1198-206. PubMed · Publisher

Abstract

The absence of any direct connection between the lung and the parietal pleura raises questions about the mechanisms of pleural migration and retention of inhaled particles. It has been suggested that specific areas of parietal pleura absorb and retain inorganic particles from the pleural space, including carbon pigments and asbestos fibers, and could be starting points for pathologic changes induced by mineral fibers. These particle-collecting structures have been called "black spots." To study their distribution, macroscopic appearance, and possible relationship with pleural plaques, the parietal pleura of 150 consecutive necropsies of urban dwellers (mean age 67.7 +/- 12.9 years) were examined. The size and intensity of spots were scored and recorded on a computer scheme together with information of the presence of pleural plaques. Black spots were observed in 92.7% of the cases. They were mainly located in the lower costal and diaphragmatic zones and could correspond to the anatomic distribution of structures involved in pleural cavity clearance. Scores correlated with sex and age. There was no relationship between the predominant locations of black spots and hyaline pleural plaques.
Benign cystic mesothelioma of the liver. P. Flemming, T. Becker, J. Klempnauer, et al. 2002;26(11):1523-7. Case report PubMed · Publisher
The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity. W. Liu, W. Fackler, T.W. Rice, et al. 2002;26(6):784-8. PubMed · Publisher

Abstract

Pseudoachalasia is an esophageal motor disorder usually associated with malignancy that has clinical, radiographic, and manometric findings that are often indistinguishable from primary achalasia. There are few reports examining the histologic features of the associated neoplasms and their relationship with the esophageal myenteric plexus. We studied the clinical and pathologic features of 13 cases of pseudoachalasia seen at our institution between 1979 and 1999. Detailed clinical and radiographic data were obtained from medical records. In all cases available histologic material was reviewed to confirm the presence and type of associated neoplasm. When possible, the relationship of the neoplasm to the esophageal myenteric plexus was examined. In selected cases immunohistochemical stains were performed to further evaluate this relationship. All patients had clinical, radiographic, and manometric features similar to primary achalasia. The cohort included seven men and six women, age range 24-79 years (median 61 years). Associated neoplasms included esophageal adenocarcinoma arising in Barrett's esophagus (n = 1), adenocarcinoma of the esophagogastric junction (n = 7), metastatic renal cell carcinoma to the esophagogastric junction (n = 1), breast adenocarcinoma (n = 1), pulmonary small cell carcinoma (n = 1), pleural malignant mesothelioma (n = 1), and mediastinal fibrosis (n = 1). The mechanism of pseudoachalasia was consistent with neoplastic infiltration of the esophageal myenteric plexus in 11 cases. Neoplastic cells surrounded myenteric ganglion cells, which appeared normal in number and morphology. In the patient with pulmonary small cell carcinoma, there was no evidence of neoplastic infiltration of the esophagogastric junction, and anti-ANNA-1 antibody was detected, suggesting a paraneoplastic syndrome. Tissue obtained at the time of esophagomyotomy revealed lymphocytic myenteric inflammation and marked depletion of ganglion cells identical to that seen in primary achalasia. The mechanism pseudoachalasia in the patient with breast adenocarcinoma is uncertain, as there was no evidence of direct involvement of the esophagogastric junction. In summary, we describe 13 cases of pseudoachalasia resulting in a clinical syndrome indistinguishable from primary achalasia. The most common mechanism is direct involvement of the esophageal myenteric plexus by neoplastic cells. Rarely, a distant neoplasm may cause this syndrome as a paraneoplastic process.
Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma. M. Miettinen, J. Limon, A. Niezabitowski, et al. 2001;25(5):610-7. PubMed · Publisher

Abstract

Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression. In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells. The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells. The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful.
Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis. R. Carella, G. Deleonardi, A. D'Errico, et al. 2001;25(1):43-50. PubMed · Publisher

Abstract

Immunohistochemistry provides an important indicator for differential diagnosis between pleural malignant mesothelioma and lung adenocarcinoma, which have complex therapeutic and medicolegal implications. To pinpoint a reliable, restricted panel of markers, the authors evaluated the efficacy of select commercial antibodies in a series of patients with confirmed clinicopathologic diagnosis of mesothelioma or lung adenocarcinoma with the aid of multiple logistic classification tables. Specimens of 46 mesotheliomas and 20 lung adenocarcinomas were examined with calretinin, thrombomodulin, cytokeratins (CKs) 5/6, and high-molecular weight CKs (indicators of mesothelioma), alongside MOC 31, Ber-EP4, and carcinoembryonic antigen (CEA; indicators of lung adenocarcinoma). Of the mesotheliomas, 40 of 46 (87%) were positive with calretinin, 29 of 46 (63%) with thrombomodulin, 40 of 46 (87%) with CKs 5/6, and 41 of 46 (89%) with high-weight CKs; five of 46 mesotheliomas (11%) were focally reactive with MOC 31, four of 46 (9%) with Ber-EP4, and two of 46 (4%) with CEA. Of the lung adenocarcinomas, 18 of 20 (90%) were positive with MOC 31, 20 of 20 (100%) with Ber-EP4, and 17 of 20 (85%) with CEA; and two of 20 (10%) were focally reactive with calretinin, one of 20 (5%) with thrombomodulin, none of 20 (0%) with CKs 5/6, and five of 20 (25%) with high-weight CKs. Multiple logistic modeling indicated two batteries of three antibodies permitting more than 98% overall accuracy: Ber-EP4 plus CKs 5/6 plus calretinin, and Ber-EP4 plus CKs 5/6 plus CEA.
Serous borderline tumor of the paratestis: a report of seven cases. R.F. McClure, G.L. Keeney, T.J. Sebo, et al. 2001;25(3):373-8. PubMed · Publisher

Abstract

We report the clinical, morphologic, immunophenotypic, and ploidy findings of seven cases of serous borderline tumor of the paratestis. Mean patient age was 56 years (range, 14-77 years), and the clinical presentation was that of a testicular mass. Tumors ranged in size from 1 to 6 cm (mean, 3.5 cm). Six tumors arose from the tunica albuginea, and two of these tumors were intratesticular. One tumor arose from the tunica vaginalis. Serous borderline tumor of the paratestis is histologically identical to its ovarian counterpart. The tumors were cystic with numerous intracystic blunt papillae lined by stratified epithelial cells with minimal to mild cytologic atypia. Psammoma bodies were present in two cases. In all cases, the neoplastic cells stained strongly and diffusely for cytokeratin 7, estrogen receptor, and CD15, and six of seven cases were positive for progesterone receptor and MOC-31. The cells did not stain for cytokeratin 20, carcinoembryonic antigen, calretinin, and HER2/neu. Proliferative activity, as assessed by MIB-1 staining, ranged from 1.3% to 10% (mean, 5.5%). Five of six tumors were diploid, and one was tetraploid. Patients were treated by radical orchiectomy and followed up from 4 months to 18 years (mean, 48 months; median, 8.5 months). No recurrences or metastases occurred. Serous borderline tumor of the paratestis is morphologically and immunophenotypically identical to ovarian serous borderline tumor. To date, no serous borderline tumor of the paratestis reported in the literature or in our series has recurred or metastasized after resection.
Well-differentiated papillary mesothelioma. K.J. Butnor, T.A. Sporn, S.P. Hammar, et al. 2001;25(10):1304-9. PubMed · Publisher

Abstract

Well-differentiated papillary mesothelioma is an unusual variant of epithelial mesothelioma considered to be of low malignant potential. The majority of previously reported cases developed in the peritoneum of young women without a history of asbestos exposure. The authors report 14 cases of well-differentiated papillary mesothelioma, seven of which originated in the pleura, six in the peritoneum, and one in the tunica vaginalis. Eleven of the patients were male and three were female, with an average age at presentation of 58 years (range 32-82 years). Six of the patients had a quantifiable history of asbestos exposure. Of the nine cases with complete follow-up, six had clinically indolent disease, one showed resolution after adjuvant chemotherapy, one pursued an aggressive course, and one died of other causes. These findings indicate that well-differentiated papillary mesothelioma is a rare variant of mesothelioma with a variable clinical prognosis that is etiologically related to asbestos exposure in some cases.
Deciduoid or pseudodecidual mesothelioma. A. Talerman. 2000;24(8):1179. Comment · Letter PubMed · Publisher

Summary

In this letter to the editor, the author responded to a recent paper by Shanks et al. showing that malignant mesotheliomas with "deciduoid" morphology were not confined to young females or to the peritoneal cavity. The author noted that earlier reported cases, and unreported cases he had seen, occurred in children and young adult females. In contrast, the cases of Shanks et al. were all in older subjects, were equally divided between males and females, and in one case arose in the pleura rather than the peritoneum. He recalled that the original case with this morphology was a peritoneal malignant mesothelioma in a 13-year-old girl. It had been submitted to him with a diagnosis of deciduosis and had posed serious diagnostic problems for reputable pathologists. Nascimento et al. later coined the term deciduoid mesothelioma for three cases in young women. Since then the author had seen in consultation a number of similar cases in young females, including cases submitted as hepatoid and other types of yolk sac tumor. He agreed that this morphology tended to be more frequent in peritoneal mesotheliomas of young women. Because he had been asked whether the tumor was related to deciduosis, he proposed the term "pseudodecidual" as more correct. He suggested studying large series of peritoneal and pleural mesotheliomas to determine how frequent this variant is and whether it is more common in young females.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Epithelial mesothelioma with deciduoid features: report of four cases. N.G. Ordóñez. 2000;24(6):816-23. Case report PubMed · Publisher

Abstract

Deciduoid mesothelioma is the designation given to an unusual morphologic variant of epithelial mesothelioma that closely simulates exuberant ectopic decidual reaction. Because all four previously reported cases involved the peritoneum and occurred in young women without a history of asbestos exposure, it was suggested that deciduoid mesothelioma was a subtype of epithelial mesothelioma characterized by its unique morphology, that it affects a distinct patient population, and that it is unrelated etiologically to asbestos. The author reports four cases of mesothelioma with deciduoid features, all of which originated in the pleura. Three of the patients were men and one was a woman. Their ages ranged from 46 to 78 years (mean age, 67 yrs). Two of the patients had a history of asbestos exposure. These findings indicate that this morphologic variant of mesothelioma is not limited to a specific patient population nor is it restricted to the peritoneum.
Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females. J.H. Shanks, M. Harris, S.S. Banerjee, et al. 2000;24(2):285-94. Case report PubMed · Publisher

Abstract

Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.

1990s

Malignant mesotheliomas presenting as ovarian masses. A report of nine cases, including two primary ovarian mesotheliomas. P.B. Clement, R.H. Young, R.E. Scully. 1996;20(9):1067-80. PubMed · Publisher

Abstract

Nine cases of malignant mesothelioma (MM) presenting as ovarian masses occurred in female patients aged 16 to 63 (median, 52) years. In most of the cases, the referring pathologist initially misdiagnosed the neoplasm or was uncertain about its nature. In two cases, the tumors were confined to one or both ovaries, representing primary ovarian MMs; only one similar case has been previously reported. In the other cases, widespread peritoneal tumor precluded definite conclusions about the primary or secondary nature of the ovarian involvement. That at least some of the latter were also primary ovarian MMs is suggested by a degree of ovarian enlargement, the striking parenchymal replacement, or both, which are not usually seen in cases of secondary ovarian involvement by peritoneal MMs. The clinical presentation was usually that of abdominal or pelvic pain or abdominal swelling, an adnexal mass on pelvic examination or at laparotomy, or combinations thereof. One tumor was an autopsy finding. There was no history of asbestos exposure in any patient. Eight patients underwent bilateral oophorectomy, usually with hysterectomy and biopsies of extraovarian tumor. Four patients were given chemotherapy and one, radiation therapy. Follow-up in five cases revealed that three patients had died of tumor at postoperative intervals of 8 to 44 months, one was alive with persistent tumor at 18 months, and one was alive with no clinical evidence of tumor at 11 years. The ovaries were replaced by tumors 3 to 15 cm in maximum diameter; seven were bilateral. The neoplastic tissue was typically solid, but small cysts were present in two cases, and one tumor was a unilocular cyst with a solid mural nodule. On microscopic examination, tumor involved both the serosa and the parenchyma of the ovary in seven cases, the serosa only in one case, and the parenchyma only in one case. Seven tumors were exclusively epithelial, with papillary, tubular-glandular, and solid patterns, and two were biphasic. The cells in the epithelial mesotheliomas usually exhibited moderate atypicality and a low mitotic rate. The stroma was typically hyalinized, and in three of the cases with a papillary pattern papillae with hyalinized cores were a striking finding. Psammoma bodies were present in three cases. Histochemical and immunohistochemical stains confirmed the mesothelial nature of the tumor cells. Because of the wide variety of microscopic patterns in MMs, the differential diagnosis of ovarian MM includes a variety of primary and metastatic ovarian tumors as well as other peritoneal mesothelial lesions.
Malignant mesothelioma of the tunica vaginalis. A clinicopathologic analysis of 11 cases with review of the literature. M.A. Jones, R.H. Young, R.E. Scully. 1995;19(7):815-25. Review PubMed · Publisher

Abstract

Eleven malignant mesotheliomas of the testicular tunica vaginalis occurred in patients aged 12 to 76 (mean, 54.1) years. Hydrocele, with or without an associated mass, or appreciation of a paratesticular mass accounted for the clinical presentation. One patient had a history of asbestos exposure. Grossly, the tumors typically presented as multiple nodules studding a hydrocele sac, frequently associated with a mass infiltrating the spermatic cord or adjacent testis. Microscopically, five tumors were epithelial and six biphasic, with the typical architectural and cytologic features of mesothelioma. Mixtures of papillary, tubular, and solid patterns predominated in the epithelial areas; interlacing fascicles of spindle cells with scanty stroma characterized the sarcomatous components. All eight of the tumors that were stained for keratin (AE1/AE3) were positive, four of five for epithelial membrane antigen, and four of five for vimentin. Seven of seven tumors were carcinoembryonic antigen negative and five of five B72.3, Leu-M1, and Ber-Ep4 negative. Follow-up ranging from 1 to 15 (mean, 4.3) years was available for seven patients. Three died of disease after 4, 4, and 3 years, and three are alive with disease 2, 2, and 15 years after diagnosis. Two of the latter three patients had extensive local recurrences, one 15 years after the diagnosis of a well-differentiated papillary mesothelioma, the other 2 years following treatment with hydrocelectomy only. One patient who has been followed for only 1 year has no evidence of disease. This series emphasizes a number of important features of testicular mesothelioma; (a) a wide age range with occasional occurrence at a young age, (b) a wide morphologic spectrum with regard to degree of differentiation, and (c) an aggressive natural history with a potential for late recurrence or metastasis of even well-differentiated tumors, suggesting the need for initial aggressive surgical treatment.
Deciduoid peritoneal mesothelioma. An unusual phenotype affecting young females. A.G. Nascimento, G.L. Keeney, C.D. Fletcher. 1994;18(5):439-45. Case report PubMed

Abstract

Two cases of malignant peritoneal mesothelioma are reported. These tumors affected young women and displayed an unusual histopathologic pattern that closely simulated exuberant, ectopic decidual reaction or at least a malignant counterpart thereof. The importance of the differential diagnosis from decidual reaction is emphasized because decidua-like mesothelioma appears to be a highly malignant neoplasm. The cause of this lesion is unknown; and, considering the young age of the patients and the failure to demonstrate hormone receptors in the neoplastic cells, it is unlikely that asbestos exposure or hormonal imbalance played any role in the development of the disease.
Localized malignant mesothelioma. A clinicopathologic and flow cytometric study. T.B. Crotty, J.L. Myers, A.L. Katzenstein, et al. 1994;18(4):357-63. Case report · Review PubMed

Abstract

Six examples of malignant mesothelioma appearing as a localized pleural mass are described. There were four women and two men, ranging in age from 42 to 76 years. A history of asbestos exposure was obtained from three patients. The tumors ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile with broad-based pleural attachments. Histologically, three tumors were purely epithelioid and three were biphasic. Immunohistochemical stains in all six cases were positive for cytokeratin and negative for carcinoembryonic antigen. Five were also positive for epithelial membrane antigen. Five were negative for Leu-M1, while one showed focal staining in a peripheral membrane pattern. Electron microscopy in two purely epithelioid tumors showed long, thin microvilli, well-developed desmosomes, and numerous tonofilaments. Flow cytometry showed an aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry in five cases identified a DNA aneuploid cell population in four tumors and a diploid population in one. Three patients showed signs of local recurrences 4, 7, and 18 months after excision and died of their disease 12, 10, and 24 months after diagnosis, respectively. Three patients are well with no evidence of disease 8, 24, and 96 months after diagnosis. These findings indicate that malignant mesotheliomas of the pleura may rarely appear as a localized mass. The biologic behavior of such tumors is difficult to predict, but some patients survive disease-free for a long time after surgical excision.
A novel biotinylated probe specific for hyaluronate. Its diagnostic value in diffuse malignant mesothelioma. N. Azumi, C.B. Underhill, E. Kagan, et al. 1992;16(2):116-21. PubMed · Publisher

Abstract

Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predominantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderate or greater in 26 mesotheliomas (79%), thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an important adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma.
Solitary fibrous tumor of the upper respiratory tract. A report of six cases. G.B. Witkin, J. Rosai. 1991;15(9):842-8. Case report PubMed · Publisher

Abstract

We report six cases of a neoplasm that arose in the upper respiratory tract and had a histological appearance indistinguishable from that of solitary fibrous tumor of the pleura (SFT, so-called fibrous mesothelioma). The patients were adults who presented with nasal obstruction. The lesions lacked the characteristic features of other recognized neoplasms that occur in this region. The tumor cells were immunoreactive for vimentin but not for keratin. The occurrence of SFT in this location further supports the argument that SFT is a tumor of mesenchymal and not mesothelial origin. None of the tumors in this series had the histologic features of malignancy described for SFT in other locations, and there was no aggressive behavior in limited follow-up. Until more cases of SFT in unusual locations have been studied, we recommend that the same criteria used for assessing aggressiveness in SFT of the pleura be applied to them.
The significance of epithelial differentiation in mixed mesodermal tumors of the uterus. A clinicopathologic and immunohistochemical study. P. Bitterman, B. Chun, R.J. Kurman. 1990;14(4):317-28. PubMed · Publisher

Abstract

Mixed mesodermal tumors and carcinosarcomas of the uterus are classified as sarcomas. However, in other sites, malignant biphasic tumors may be classified as carcinomas, mesotheliomas, or sarcomas. In order to clarify their behavior and patterns of differentiation, we performed a clinicopathologic and immunohistochemical study of 22 cases aimed at analyzing the pattern of spread and histologic appearance of the metastasis, as well as the distribution of intermediate filaments in the primary tumor and the metastasis. Four monoclonal antibodies (Mabs) were used to detect epithelial lineage, three that recognize keratin (AE1/AE3, CAM5.2, MAK6) and one that recognizes epithelial membrane antigen (EMA). A Mab against vimentin was also used. Metastases involved the omentum, pelvic peritoneum, ovaries, fallopian tubes, pelvic or para-aortic lymph nodes, liver parenchyma, and tonsil. These metastases were composed of carcinoma only. Lymphatic/vascular invasion was identified in 11 cases; it consisted exclusively of carcinoma. In all 12 cases evaluated immunohistochemically, keratin and EMA were identified in the majority of the cells in the epithelial component and in a more focal distribution in the spindle cell component in 11 (92%). Vimentin was detected in the majority of spindle cells in nine cases (75%) and in a more focal distribution in the epithelial component in six cases (50%). In the spindle cell component, keratin and EMA were present in widely scattered individual spindle-shaped and rounded cells, within solid clusters of rounded cells, and in nests of cells with small lumens. The distribution of keratin, EMA, and vimentin in the metastases (carcinoma in all instances) was similar to the epithelial component in the primary tumor. Our findings indicate that the epithelial component of these tumors invades lymphatic/vascular spaces and metastasizes, whereas the spindle cell component has limited metastatic potential, if any. Since the behavior of these neoplasms is dictated by the epithelial element, we believe that mixed mesodermal tumors of the uterus should be classified as carcinomas rather than sarcomas.

1980s

A biphasic tumor of the mediastinum with features of synovial sarcoma. A report of four cases. G.B. Witkin, M. Miettinen, J. Rosai. 1989;13(6):490-9. PubMed · Publisher

Abstract

Four cases of a biphasic mediastinal tumor histologically identical to synovial sarcoma of soft tissue were observed. The tumors presented as solitary mediastinal masses. Although the tumors were frequently adherent to adjacent pleura or pericardium, none appeared to be arising from a mesothelial surface. All cases were composed of an intimate admixture of keratin-positive epithelial cells and vimentin-positive spindle cells with areas of transition, hyalinization, and calcification. Follow-up was available on three patients, who died of their disease 10 months, 14 months, and 4 years after diagnosis, respectively. Although synovial sarcoma usually occurs in deep soft tissues near joints in the extremities, it has been reported in locations removed from synovial, tendon sheath, and bursal structures. This report adds a previously unrecognized location for synovial sarcoma, the mediastinum. Occurrence in this location further supports an origin from pluripotential mesenchyme as opposed to synovium. The differential diagnosis includes mesothelioma, thymoma, germ cell tumors, malignant peripheral nerve sheath tumor with glandular differentiation, and metastatic carcinoma.
Peritoneal malignant mesothelioma versus serous papillary adenocarcinoma. A histochemical and immunohistochemical comparison. D.J. Bollinger, M.R. Wick, L.P. Dehner, et al. 1989;13(8):659-70. PubMed · Publisher

Abstract

In order to evaluate adjunctive histologic methods for separating mesothelioma (MM) and serous adenocarcinoma (SC), we studied 28 and 46 respective cases histochemically and immunohistochemically. Ten serous adenocarcinomas arose primarily in extraovarian sites within the abdomen. Diagnoses in each case were established retrospectively by a combination of electron microscopy and clinicopathologic correlation. A panel of antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), B72.3, placental alkaline phosphatase (PLAP), S-100 protein, carcinoembryonic antigen (CEA), Leu M1, CA-125, and amylase (AM) was applied to paraffin sections of each case. Serous carcinoma was reactive for neutral mucins whereas mesothelioma was not; however, only 50% of adenocarcinoma cases stained in this manner. Peritoneal mesothelioma showed reactivity for CK (28 of 28 cases), EMA (24 of 28 cases), AM (five of 28 cases), CA-125 (four of 28 cases), and S-100 protein (three of 28 cases), but lacked B72.3, PLAP, and CEA. Three mesotheliomas expressed Leu M1, but in an extremely focal distribution. Serous carcinoma reacted for CK (46 of 46 cases), EMA (46 of 46 cases), CA-125 (42 of 46 cases), S-100 protein (40 of 46 cases), Leu M1 (34 of 46 cases; with diffuse staining), B72.3 (33 of 46 cases), PLAP (29 of 46 cases), AM (15 of 46 cases), and CEA (six of 46 cases). Two profiles (S-100 + B72.3; S-100 + PLAP) were seen in 41 of 46 serous adenocarcinoma cases but were absent in all mesotheliomas. Hence, these combinations of determinants are effective in separating such neoplasms diagnostically. Moreover, diffuse reactivity for Leu M1, B72.3, PLAP, or CEA in papillary peritoneal neoplasms appears to exclude the possibility of mesothelioma; however, focal Leu M1 reactivity may indeed be seen in mesothelioma. Although CA-125 is a sensitive marker for serous carcinoma, it is not effective in distinguishing it from mesothelioma.
Sarcomatous tumor of the chest wall with osteochondroid differentiation. Evidence of mesothelial origin. A. Andrion, G. Mazzucco, P. Bernardi, et al. 1989;13(8):707-12. Case report PubMed · Publisher

Abstract

We describe a case of sarcomatous tumor of the chest wall with differentiation toward bone and cartilage that was observed in an asbestos-exposed worker. Although the mesothelial nature of the tumor was at first considered, it was not proven. Later, the tumor was shown to be a mesothelioma using a panel of pertinent antibodies that included a recently described anti-mesothelial cell marker. In addition, asbestos bodies were found in association with the sarcoma cells. Our findings indicate that whenever physicians encounter any type of primary sarcomatoid tumor involving serous membranes, the possibility of malignant mesothelioma should be regarded a priori.
Solitary fibrous tumor of the mediastinum. A report of 14 cases. G.B. Witkin, J. Rosai. 1989;13(7):547-57. PubMed · Publisher

Abstract

Fourteen cases of a mediastinal neoplasm identical to solitary fibrous tumor (so-called fibrous mesothelioma) of the pleura were observed. The lesions presented with cough, chest pain, dyspnea, or as asymptomatic masses detected radiographically. Two patients had associated hypoglycemia. Eleven of the tumors were in the antero-superior mediastinum. One arose on a pedicle from the thymus, and another had entrapped thymic elements. Tumor cells were variably immunoreactive for vimentin and actin, but not for keratin, and lacked ultrastructural evidence of mesothelial or epithelial differentiation. Eight cases had highly cellular mitotically active regions of which six of seven with follow-up behaved aggressively; the exception was the pedunculated tumor. A 13-cm, histologically bland tumor has recurred twice. Aggressive behavior was more common than reported for solitary fibrous tumor of the pleura, but the same criteria (size, cellularity, mitotic activity, presence of pedicle) were of prognostic significance. The occurrence of solitary fibrous tumor in the mediastinum with the suggestion of thymic origin for some cases, combined with the immunohistochemical and ultrastructural findings, support a mesenchymal origin for this tumor. The differential diagnosis includes spindle cell thymoma, hemangiopericytoma, and peripheral nerve tumors.
Observations on bronchiolo-alveolar carcinomas with special emphasis on localized lesions. A clinicopathological, ultrastructural, and immunohistochemical study of 11 cases. C.A. Axiotis, T.A. Jennings. 1988;12(12):918-31. PubMed · Publisher

Abstract

Pathological and clinical features in early localized mucinous and nonmucinous bronchiolo-alveolar carcinomas (BAC) have not been adequately compared. In an attempt to characterize such lesions, we studied the clinicopathological, ultrastructural, and immunohistochemical features of three mucinous and eight nonmucinous BAC (four Clara cell, four Type II pneumocyte) along with one sheep pulmonary carcinoma (SPC). Tumor border, associated fibroplasia, tumor cell incohesion, lymphocytic infiltrate, T-lymphocytes, Langerhans cells (LC), and Leu-M1 and OC 125 immunoreactivity were evaluated. Localized tumors of both types had a similarly favorable prognosis, even when the tumor size was greater than 3 cm or showed more complex histology. Type II pneumocyte carcinomas with tumor cell disassociation and desquamation or a pseudomesotheliomatous phenotype did poorly. Clara cell and type II carcinomas elicited an LC and T-lymphocyte immune response. LC and T-lymphocytes were absent in mucinous BAC and SPC. All of the three mucinous and three of the seven nonmucinous BAC were Leu-M1 negative, indicating that Leu-M1 may not distinguish between BAC and mesothelioma, especially in a small biopsy specimen. Tumors with absent or slight Leu-M1 immunoreactivity had a favorable outcome irrespective of cell type and presence or absence of LC. Inasmuch as OC 125 was negative in all cases of BAC, OC 125 may be a useful adjunct in the immunodiagnosis of mesothelioma. Our investigation supports the view that two different groups of tumors are assembled under the single nosologic entity of BAC: one, mucinous, which grows along an unaltered pulmonary alveolar framework and elicits a B-lymphocytic response, and the other, nonmucinous, which induces desmoplasia and elicits an LC and T-lymphocytic response. Only mucinous BAC represent a biologic entity distinct from conventional pulmonary adenocarcinomas.
Rete testis adenocarcinoma. I.S. Schwartz. 1988;12(12):967. Case report · Letter PubMed · Publisher
Unusual intestinal talcosis. P.A. Anani, C. Ribaux, D. Gardiol. 1987;11(11):890-4. Case report PubMed · Publisher

Abstract

A case of intestinal talcosis in a 46-year-old man is reported. At the age of 27, the patient was treated for pulmonary tuberculosis with tablets containing talc (183 g talc per 2,670 g total drug intake) over a period of 28 months. Eighteen years later, the patient was hospitalized for abdominal pain that remained refractory to antacids; he subsequently underwent a right hemicolectomy. Light-microscopic examination revealed a prominent fibrosis of the intestinal wall in which birefringent particles were demonstrated by polarized light. Using energy-dispersive spectroscopy, an analysis of these particles showed that they were predominantly composed of silicon and magnesium as well as small amounts of phosphorus, sulphur, calcium, and iron--the spectrum typically associated with talc. We believe that the source of this talc is the tablets ingested by the patient during prior antituberculosis therapy.
Leu-M1 antigen in human neoplasms. An immunohistologic study of 400 cases. K. Sheibani, H. Battifora, J.S. Burke, et al. 1986;10(4):227-36. PubMed · Publisher

Abstract

Several studies have shown that the Leu-M1 antigen, a monocyte/granulocyte-related marker, is consistently expressed by the neoplastic cells of patients with Hodgkin's disease (HD). It has been suggested that reactivity of Reed-Sternberg cells with Leu-M1 can be used in support of a morphologic interpretation of HD, and that it is helpful in the differential diagnosis of HD from morphologically similar lesions. To evaluate the significance of the Leu-M1 positivity of Reed-Sternberg cells in the diagnosis of HD, we investigated the distribution of Leu-M1 antigen in a series of patients with HD, non-Hodgkin's lymphomas, and nonhematopoietic neoplasms. We were able to demonstrate the presence of Leu-M1 antigen not only in the majority of patients with HD, but also in 12 of 18 (67%) peripheral T-cell lymphomas, as well as in a variety of nonhematopoietic neoplasms, which included 113 of 199 carcinomas, most of them (58%) adenocarcinomas. Only one of 34 sarcomas showed a focal positive reaction. Leu-M1-related antigen was not detected in any of 18 mesotheliomas, 15 germ cell tumors, 13 melanomas, three schwannomas, or three astrocytomas. Our study indicates that Leu-M1 positivity has no value in supporting the diagnosis of HD in situations where the histologic diagnosis of HD is doubtful. However, since anti-Leu-M1 reacted positively in the majority of adenocarcinomas but was absent in mesotheliomas, melanomas, and most sarcomas, this antigen could serve as a new marker that may be helpful in situations in which carcinoma is a part of the differential diagnosis.
Reactive and neoplastic serosal tissue. A light-microscopic, ultrastructural, and immunocytochemical study. J.W. Bolen, S.P. Hammar, M.A. McNutt. 1986;10(1):34-47. PubMed · Publisher

Abstract

Normal and reactive non-neoplastic serosal tissues and a spectrum of serosal neoplasms were studied using light-microscopic, ultrastructural, immunocytochemical, gel electrophoretic, and immunoblot techniques. Normal surface mesothelium expressed both low- and high-molecular-weight cytokeratins, whereas the scattered submesothelial cells were decorated only with antibodies to vimentin. Reactive non-neoplastic subserosal cells, however, coexpressed both low-molecular-weight cytokeratin and vimentin and demonstrated the ability for surface differentiation during which higher-molecular-weight cytokeratins were acquired and vimentin was lost. The authors suggest the term "multipotential subserosal cells," recognizing the unique intermediate filament expression of reactive subserosal cells and the ability for surface differentiation. The intermediate filament expression of the sarcomatoid/desmoplastic mesotheliomas resembled the MSC, whereas epithelial mesotheliomas resembled surface mesothelium. These findings have potential usefulness for diagnostic pathology.
Immunohistochemical staining for vimentin and keratin in malignant mesothelioma. A. Churg. 1985;9(5):360-5. PubMed · Publisher

Abstract

Because tissue culture studies have suggested that mesothelial cells might produce large amounts of vimentin, I stained eight mesotheliomas (two fixed in alcohol) for vimentin using the Gown and Vogel monoclonal antibody 43 beta E8. The two tumors that had alcohol fixed blocks were strongly positive for vimentin, whereas one of the tumors fixed only in formalin showed moderately strong staining and two others showed very weak focal positivity; the remaining tumors were negative. In the mesotheliomas that did stain, both epithelial and spindled elements gave a positive reaction. Three alcohol-fixed lung cancers and two blocks of alcohol-fixed pleura failed to stain for vimentin. By contrast, all mesotheliomas and carcinomas, whether alcohol or formalin fixed, as well as sections of pleura, were strongly positive when stained with anticytokeratin antibody 35 beta H11. I conclude that the combination of staining for vimentin and keratin might be a useful diagnostic finding in malignant mesothelioma, but that specially fixed material is required for reliable vimentin staining.
Malignant mesothelioma and CEA staining. K. Mukai. 1985;9(2):159-60. Letter PubMed · Publisher
Ferruginous bodies and the histologic evaluation of dust exposure. E. Crouch, A. Churg. 1984;8(2):109-16. PubMed · Publisher

Abstract

Ferruginous bodies are frequently observed in histologic sections of lung from individuals with occupational or environmental exposure to asbestos and other mineral dusts. Analysis of large numbers of such ferruginous bodies has demonstrated that the types with asbestos cores can be differentiated by light microscopy from several chemically and morphologically distinct classes of nonasbestos ferruginous bodies, including those formed on sheet silicates (talc and mica), carbon, rutile, and fly ash. Light-microscopic screening of lung tissue sections for ferruginous bodies is a reliable, convenient, and economical method for documenting exposure to a variety of mineral dusts and can assist in determining the etiology of pneumoconiotic lesions. Because tissue sections are relatively insensitive detectors of particles, the finding of ferruginous bodies in section implies heavy dust exposure.
So-called sclerosing hemangioma of the lung. Evidence for mesothelial origin. A.L. Katzenstein, D.L. Weise, K. Fulling, et al. 1983;7(1):3-14. PubMed · Publisher
Papillary peritoneal tumors in women. A. Foyle, M. Al-Jabi, W.T. McCaughey. 1981;5(3):241-9. PubMed · Publisher

Abstract

Twenty-five peritoneal tumors in women are described. All were partly or entirely of papillary or tubulopapillary structure and multifocal. Eight were unusually well-differentiated mesotheliomas. This appearance was associated with indolent behavior. In 10 cases the growth closely resembled serous papillary carcinoma, including the frequent presence of psammoma bodies, but the ovaries were free of primary tumor. The latter group of tumors progress rapidly and are thought to be derived from extraovarian mesothelium with müllerian potential. Four further cases showed some resemblance to ovarian papillary carcinoma. Only three tumors in the entire series (12%) closely resembled papillary or tubulopapillary diffuse malignant mesothelioma of the type that occurs in the pleural cavities in both sexes. The histopathologic spectrum of papillary tumors of peritoneum in women is extensive, and mesothelial tumors of the type known to be associated with asbestos are rare.

1970s

Solitary (localized) pleural mesothelioma. A light- and electron-microscopic study. T. Kawai, K. Yakumaru, A. Mikata, et al. 1978;2(4):365-75. PubMed · Publisher

Abstract

Six solitary (localized) pleural mesotheliomas were studied by light and electron microscopy. All the lesions were benign and were composed mainly of fibrous tissue of variable cellularity with or without cystic spaces lined by round cells. The lining cells of the cysts and the adjoining round plump cells were interpreted as true neoplastic cells of the fibroblast type. Results of light- and electron-microscopic study of human mesothelial cells and fetal mesothelial cells of rats were compared. The cytoplasmic organelles of the tumor cells were generally scanty, though rough endoplasmic reticulum, sparse mitochondria, intracellular bundles of fibrils, and numerous polysomes were seen. Some tumor cells had junctional apparatus and basement membrane and showed interdigitation of the plasma membrane. These cells lined the cystic spaces irregularly and also proliferated into the surrounding fibrous tissue, where they assumed a spindle shape and resembled fibroblasts. Ultrastructurally, the tumor cells were similar to mesothelial and stromal cells of fetal rat pleura. We speculated that the solitary (localized) mesotheliomas were probably derived from coelomic epithelium and that tumor cells remained undifferentiated or revealed minimal differentiation toward mesothelial cells.

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