Pathology, Research and Practice

Our medical research library holds 48 studies published in Pathology, Research and Practice (1980–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 45 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 1 study PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Gustav Fischer Verlag
• Published: 1978 to the present, Germany
• Language: English, German, French
• ISSN: 0344-0338 (print), 1618-0631 (electronic)
• Continues: Beiträge Zur Pathologie
• Its record in the NLM Catalog

2020s

• Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series. G. Broggi, M. Massimino, M. Failla, et al. 2024;259:155350. PubMed · Publisher

  Abstract

  Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.

  Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.

• Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma. A. Salman, S.S. Abdel Mageed, D. Fathi, et al. 2023;252:154947. Review PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/β-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.

  Copyright © 2023 Elsevier GmbH. All rights reserved.

• The role of miRNAs in laryngeal cancer pathogenesis and therapeutic resistance - A focus on signaling pathways interplay. M. Hegazy, M.A. Elkady, A.M. Yehia, et al. 2023;246:154510. Review PubMed · Publisher

  Abstract

  Laryngeal cancer (LC)is the malignancy of the larynx (voice box). The majority of LC are squamous cell carcinomas. Many risk factors were reported to be associated with LC as tobacco use, obesity, alcohol intake, human papillomavirus (HPV) infection, and asbestos exposure. Besides, epigenetics as non-coding nucleic acids also have a great role in LC. miRNAs are short nucleic acid molecules that can modulate multiple cellular processes by regulating the expression of their genes. Therefore, LC progression, apoptosis evasions, initiation, EMT, and angiogenesis are associated with dysregulated miRNA expressions. miRNAs also could have some vital signaling pathways such as mTOR/P-gp, Wnt/-catenin signaling, JAK/STAT, KRAS, and EGF. Besides, miRNAs also have a role in the modulation of LC response to different therapeutic modalities. In this review, we have provided a comprehensive and updated overview highlighting the microRNAs biogenesis, general biological functions, regulatory mechanisms, and signaling dysfunction in LC carcinogenesis, in addition to their clinical potential for LC diagnosis, prognosis, and chemotherapeutics response implications.

  Copyright © 2023 Elsevier GmbH. All rights reserved.

• Incidental mesonephric remnant hyperplasia of the jejunal mesentery: A diagnostic challenge. J.F. Val-Bernal, M.M. Mayorga, A.K. Calapaquí-Terán, et al. 2021;220:153388. Case report PubMed · Publisher

  Abstract

  Mesonephric remnants are embryonic vestiges of the mesonephric (Wolffian) ducts which regress during normal development. These remnants have been uncommonly reported in the female and male reproductive tract as a spectrum of morphologic lesions that can be misdiagnosed as carcinoma. One case of mesonephric remnant hyperplasia of the jejunal mesentery incidentally found in a 47-year-old man is herein reported. This is the first description of mesonephric hyperplasia arisen in the mesentery. The presence of ducts, tubules, and cysts lined by bland, epithelial, cuboidal cells with scant cytoplasm, and diffuse pseudoinfiltrative growth pattern can raise the possibility of neoplasia. Immunohistochemically, mesonephric epithelia have a characteristic staining. CD10 highlights the apical-luminal aspect of the cells. Besides, intense reactivity is showed for high-molecular-weight cytokeratin (CK), CK7, bcl2, and vimentin. The main differential diagnosis includes mesothelial hyperplasia, epithelial mesothelioma, well-differentiated neuroendocrine tumor, and infiltration due to acinar adenocarcinoma of the prostate. However, a detailed microscopic study with the aid of immunohistochemistry helps separate mesonephric remnants from malignant processes. The mesonephric hyperplasia of the mesentery we have reported adds to the spectrum of mesonephric remnants a new location. Familiarity with this lesion is indispensable to avoid overdiagnosis.

  Copyright © 2021 Elsevier GmbH. All rights reserved.

• Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value. M.L. Balancin, W.R. Teodoro, C.M. Baldavira, et al. 2020;216(12):153277. PubMed · Publisher

  Abstract

  Previous studies have reported a close relationship between type V collagen (Col V) and tumor invasion and motility in both breast cancer (BC) and lung cancer (LC). The present work aims to determine whether the extracellular-matrix (ECM)-defined microenvironment influences patient clinical outcome and investigate to which extent histological patterns of Col V expression in malignant cells have a prognostic effect in patients. To that end, we examined the expression of Col V in the tissues of 174 primary tumors (MM, N = 82; LC, N = 41; and BC, N = 46) by immunohistochemistry. We found: (1) diffuse strong green birefringence in membrane and cytoplasm individualizing malignant cells in MM; (2) a focal and weak birefringence mainly in cytoplasmic membrane involving groups of malignant cells in LC and BC; (3) higher average H-score of Col V in MM than in LC and BC samples; (4) a direct correlation between Col V histologic pattern and TNM stage IV, status and median overall survival; (5) patients with LC in TNM stage I, and Col V ≤ 41.7 IOD/mm2 had a low risk of death and a median survival time more than 20 months; (6) patients with MM in TNM stage IV and Col V > 41.7 IOD/mm2 presented a high risk of death and a median survival time of just 20 months. These findings suggest that high levels of Col V individualizing malignant cells, as observed in MM, and low levels grouping malignant cells, as observed in LC and BC, confers different immune-privileged tissue microenvironment for tumor invasion with impact on prognosis of the patients.

  Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.

• Malignant peritoneal mesothelioma presenting as a splenic mass. M. Podberezin, M.J. Fitzpatrick, L.P. Hariri, et al. 2020;216(12):153273. Case report · Letter PubMed · Publisher

• Primary pulmonary meningiomas: report of two cases and review of the literature. D. Han, H. Deng, Y. Liu. 2020;216(12):153232. Case report · Review PubMed · Publisher

  Abstract

  Background: Meningiomas rarely occur outside the skull, and primary pulmonary meningiomas (PPMs) are more rare. Only a few cases have been reported in the literature. The clinicopathological characteristics are not clear and it is easy to be misdiagnosed, so it is very important to master its diagnosis and differential diagnosis.

  Methods: We report two women with primary pulmonary meningioma. At the time of physical examination, the small solitary pulmonary nodules were detected on chest radiograph, and wedge resection was performed by Video-assisted Thoracoscope Surgery(VATS), and histologic evaluation showed that the lesions were benign PPMs. The clinicopathological features, immunophenotype and differential diagnosis of PPMs were analyzed, with a review of the cases published in the literature.

  Results: The study group comprised of 40 patients, 14 males and 26 females. The median age was 56.5 years (range 18-108). Thirty patients who underwent routine screening studies were asymptomatic but had a pulmonary nodule detected on chest X-ray. Nine patients had respiratory symptoms. Only 1 patient had non-specific symptoms. Most of the PPMs were benign, only 3 cases were malignant. Benign PPMs ranged from 0.6 cm to 6 cm in diameter (median 2 cm). The 3 malignant PPMs were 5 cm, 6.5 cm and 15 cm in diameter. The prognosis of benign PPM resection is good, with almost no recurrence or metastasis. But the two of three malignant PPMs relapsed.

  Conclusions: PPM is very rare. It needs to be diagnosed by combining histology and immunohistochemistry. Diseases that need to be identified include spindle cell mesothelioma, spindle cell thymoma, spindle cell carcinoma, metastatic tumor, etc.

  Copyright © 2020 Elsevier GmbH. All rights reserved.

• Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1. M. Zaleski, N. Kalhor, J. Fujimoto, et al. 2020;216(12):153267. PubMed · Publisher

  Abstract

  Fifty-three cases of sarcomatoid pleural mesothelioma were evaluated for CDKN2A (p16) homozygous deletion and correlated with BRCA-associated protein-1 (BAP1) expression by immunohistochemistry. The patients are 45 men and 8 women between the ages of 37 and 79 years (average age: 58 years), who presented with symptoms of chest pain, cough, and weight loss. Diagnostic imaging showed the presence of diffuse pleural thickening with encasement of the lung parenchyma in all the cases. All patients were surgically treated with extrapleural pneumonectomy. Loss of BAP1 reactivity was seen in 49 tumors and p16 homozygous deletion was seen in 41 tumors, while in 16 patients either BAP1 or p16 were noncontributory to the diagnosis of mesothelioma. However, we were able to detect a better survival rate in those patients in whom BAP1 was lost and p16 showed homozygous deletion. Our findings showed that even though the use of BAP1 and p16 are important tools in the diagnosis of mesothelioma, a proportion of cases still remains negative with approximately 30 % of the cases in which the concordance of BAP1 loss and p16 homozygous deletion will not be present. We consider that the final diagnosis of mesothelioma is best accomplished by a global interpretation of clinical, radiographic, and pathological features including immunohistochemistry and molecular studies.

  Copyright © 2020. Published by Elsevier GmbH.

2010s

• Signet ring cell mesothelioma; A diagnostic challenge. H. Wang, C. Herath. 2019;215(7):152462. Review PubMed · Publisher

  Abstract

  Signet ring cell mesothelioma is a rare variant of epithelioid mesothelioma with limited cases published. It has a male predilection and most commonly occurs on pleura; it can also arise in the peritoneal cavity. The signet ring cell morphology can pose a challenge leading to a potential diagnostic error. A variety of benign and malignant diseases, including reactive histiocytic hyperplasia, adenocarcinoma, melanoma, and lymphoma with signet ring cell morphology should be considered in the differential diagnosis. In signet ring cell mesothelioma work up, mucin stains are of limited value. Even though immunohistochemistry is routinely used in mesothelioma diagnosis, there is no sole specific mesothelial marker. Hence, a panel of mesothelial and epithelial markers are used; these should be interpreted with caution especially in this variant. Electron microscopy and genetic testing can be very helpful in distinguishing signet ring cell mesothelioma from its mimickers.

  Copyright © 2019 Elsevier GmbH. All rights reserved.

• The importance of FISH signal cut-off values for 9p21 deletion in malignant pleural mesothelioma: Is it underestimated?. G. Kulduk, Ö. Ekinci, G. Toker, et al. 2019;215(6):152377. PubMed · Publisher

  Abstract

  Malignant mesothelioma (MM) is an aggressive cancer with a poor prognosis. The most common genetic alteration in MM is the deletion of the INK4a/ARF locus, which encodes the p16 protein and is located on the short arm of chromosome 9 (9p21). Recently, it has been shown that homozygous deletion of 9p21 has both diagnostic and prognostic significance in MM. It is a known fact that, to interpret fluorescence in situ hybridization (FISH) signals, a cut-off value for each probe should be determined for a correct diagnosis. To our knowledge, there is no consensus or confirmed protocol for cut-off values to evaluate FISH signals in MMs. Therefore, the aim of our research was to address 9p21 deletion status and p16 expression profiles of MM by determining our own cut-off values and the effectiveness of using p16 negativity and 9p21 deletion as markers for differentiating MMs from benign mesothelial proliferations in 114 cases. We established a cut-off value for the detection of 9p21 deletion by using 13 benign reactive cases (6 reactive mesothelial hyperplasias and 7 chronic fibrinous pleuritis cases) and found between 0-7%. According to our calculations, homozygous deletion was defined by loss of both p16 gene signals in at least 13.3% of the nuclei that showed at least 1 signal for the CEP 9 probe. Our FISH results showed homozygous 9p21 deletion in 82 of the 114 cases of MM (71.9%), and p16 expression was negative in 75 of the 114 cases (65.8%). The correlation between loss of p16 protein expression and 9p21 deletion was statistically significant. Among the p16-negative cases, 86.7% also had the 9p21 deletion. The combined examination of the 9p21 deletion and loss of p16 expression is helpful for diagnostic purposes, but because the FISH method is an expensive technique and loss of p16 expression is not specific for mesotheliomas, p16 negativity can guide practitioners to eliminate cases that require further investigation by FISH. The variability in the significance of 9p21 homozygous deletion results from inconsistencies among different institutes, suggesting that each institute should establish its own cut-off value using reactive mesothelial proliferations. Alternatively, global studies are needed to assess cut-off values.

  Copyright © 2019 Elsevier GmbH. All rights reserved.

• Clear cell colorectal carcinoma: Time to clarify diagnosis. A. Remo, F. Grillo, L. Mastracci, et al. 2017;213(5):447-452. Case report · Review PubMed · Publisher

  Abstract

  Primary clear cell colorectal carcinoma (CCC) is a very rare entity accounting for only 35 cases reported in the Literature. CCC is neither classified as a distinct entity nor is it defined as a CRC variant because its ontogeny remains unclear. Most of the reported CCC were found in the distal colon in patients with a mean age of 56 years. Histologically, clear cell change is the main morphologic feature and may present in a "pure" form, composed exclusively of clear cells, or in a "composite" form, admixed with other morphologically different components. It is possible to distinguish two biologically different types of CCC, with different clinical-pathologic features, therapeutic management and diagnostic criteria: a) Intestinal CCC consisting of an aggressive neoplasm, affecting mainly adult men, characterized by an intestinal-type immunoprofile (CK20+, CK7-, CEA+, CDX-2+) and b) Müllerian CCC consisting of an indolent carcinoma of the sigmoid-rectum, affecting young women, characterized by a different (CK7+, CK20-, CEA-, CA125 +) immunoprofile. Considerable diagnostic difficulties can arise in distinguishing CCC and primary or secondary clear cell neoplasms, such as metastases from renal carcinoma, lower urinary tract, female genital tract, adrenal gland, mesothelioma, melanoma and primary intestinal PEComa. In this paper we review the Literature with two additional cases in order to define the diagnostic criteria of CCC.

  Copyright © 2017 Elsevier GmbH. All rights reserved.

• Clinical and pathological characteristic of metastatic malignant mesothelioma initially diagnosed by lymph node biopsy. X.L. Zhu, L.M. Gao, F. Li, et al. 2017;213(6):598-605. PubMed · Publisher

  Abstract

  Background: It is a great challenge for pathologists to initially diagnose metastatic malignant mesothelioma (MM) by the lymph node biopsy without any history of primary MM. Because the onset of MM is hidden and the metastatic MM in lymph node is relatively uncommon. Besides, morphologic and immuohistochemistry features of MM are similar to other tumors.

  Methods: In order to improve the initial diagnostic accuracy of metastatic MM from LN biopsy and to reduce or avoid the possibility of missed diagnosis or misdiagnosis, we had collected the clinical and pathological data of the metastatic MM cases in our department, and summarized the characteristics of morphological, immunohistochemical and fluorescence in situ hybridization (FISH) results.

  Results: Seven patients (4 males and 3 females) with 21-73 year-old had been included in our study. Six cases showed serous cavity effusion, serosal thickening and systemic multiple lymph node enlargement. The "moderate, nice" tumor cells were arranged in variable patterns. Mitosis was hardly to be found and necrosis was absent. Four immunohistochemical staining panels and FISH detection had been used for diagnosis and differential diagnosis of MM. All cases expressed broad-spectrum epithelial markers and at least 2 mesothelial-cell-origin markers. None were positive for specific-tissue-origin markers, and all cases were diagnosed of malignancy according to immunohistochemical markers and detection of pl6 gene deletion.

  Conclusion: It is necessary for us to keep our awareness of metastatic MM in lymph node. Correct diagnosis of MM metastasis by lymph node biopsy were based on detailed understanding of the clinical manifestation and the image data, careful observation of morphologic characteristics, and properly using immunohistochemical markers or FISH detection if necessary for diagnosis and differential diagnosis.

  Copyright © 2017 Elsevier GmbH. All rights reserved.

• Malignant peritoneal mesothelioma, clear cell variant, in a female and its differentiation from clear cell carcinoma. H. Hayashi, T. Kawata, I. Shimokawa. 2017;213(5):580-584. Case report PubMed · Publisher

  Abstract

  Epithelial type malignant mesothelioma with a clear cell morphology is rare, and no case arising in the peritoneum of a female patient has been reported. Here we report a case of clear cell mesothelioma that developed in the peritoneum of a 61-year-old female. The patient died from massive ascites and respiratory failure 11days after her hospital admission. The autopsy demonstrated marked thickening of the omentum and a yellowish-whitish tumor diffusely covering the abdominal organs. The predominantly solid tumor was characterized microscopically by the growth of atypical cells with an abundant clear cytoplasm. The immunohistochemical study suggested mesothelioma rather than carcinoma. Electron microscopy showed the long and slender villi of the tumor cells, confirming the diagnosis. Primary clear cell carcinoma of the peritoneum, like clear cell mesothelioma, is rare and was also a diagnostic consideration in this patient. The differentiation between these two tumors is discussed herein.

  Copyright © 2017 Elsevier GmbH. All rights reserved.

• Pathology reporting of malignant pleural mesothelioma first diagnosis: A population-based approach. V. Ascoli, G. Minelli, I. Cozzi, et al. 2016;212(10):886-892. PubMed · Publisher

  Abstract

  Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive (1990-2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p<0.000; Kruskal-Wallis test). Our findings show that although guidelines are designed to improve actual reporting practices, there is ample room for improvement in their application to standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to be implemented to better utilize pathology information.

  Copyright © 2016 Elsevier GmbH. All rights reserved.

• Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case. Y. Tsukamoto, T. Otsuki, H. Hao, et al. 2015;211(12):1014-9. Case report PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.

  Copyright © 2015 Elsevier GmbH. All rights reserved.

• Use of automated image analysis in evaluation of Mesothelioma Tissue Microarray (TMA) from National Mesothelioma Virtual Bank. W. Amin, M. Srinivasan, S.Y. Song, et al. 2014;210(2):79-82. PubMed · Publisher

  Abstract

  The National Mesothelioma Virtual Bank (NMVB) was established to provide annotated biospecimens to the mesothelioma research community. The resource provides tissue microarrays (TMA) to evaluate the biomarkers along with a variety of other resected mesothelioma specimens. In this manuscript, we describe the immunohistochemical evaluation of the mesothelioma TMA with three key antibodies that are used in making the diagnosis of mesothelioma, and compared the immunohistochemical assessment between manual scoring and image analysis. The TMA was assessed for the immunohistochemical expression of calretinin (N=39), cytokeratin (CK) 5/6 (N=33), and D2-40 (N=37). Immunohistochemistry was evaluated by semi-quantitative (manual) scoring using light microscope (MS) and by automated image analysis (AS). Calretinin staining was seen in both cytoplasmic and nuclear locations. CK5/6 stain was localized to the cytoplasm. D2-40 stain showed only membranous expression in our cases. • Based on the pathologist’s scores, calretinin was positive in 31 of the 39 cases (80%), CK 5/6 in 15 of the 33 cases (46%) and D2-40 in 18 of the 37 cases (49%). • The percent-positive agreement between manual scores and image analysis was 90% (35/39), 94% (31/33), and 95% (35/37) for calretinin, CK 5/6, and D2-40, respectively. There was a substantial agree-ment between manual and automated scores for calretinin (kappa = 0.614) and an almost perfect agreement for CK5/6 (kappa = 0.879) and D2-40 (kappa = 0.892). Our study confirms that the immunohistochemical staining pattern of mesotheliomas in the NMVB UPMC TMA is similar to other studies. Our findings also show that automated image analysis provides similar results to manual scoring by pathologists, and provides a reproducible, objective, and accurate platform for immunohistochemical assessment of biomarker expression.

  Copyright © 2013 Elsevier GmbH. All rights reserved.

• Well-differentiated papillary mesothelioma manifesting in a hernia sac. J.F. Val-Bernal, M. Mayorga, D. Val, et al. 2014;210(9):609-12. Case report PubMed · Publisher

  Abstract

  Well-differentiated papillary mesothelioma (WDPM) is a tumor of uncertain malignant potential that usually occurs as a multifocal lesion of the female peritoneum, and is incidentally found at the time of surgery. We present here a multifocal case that had arisen from the lining of a hernia sac. To our knowledge, only four cases of this event have been previously described. A review of the five cases reported, including our case, revealed that the mean age of the patients was 56.6±8.35 years. There was predominance in men (4:1). In four cases, the lesion was incidental. Most tumors were found in inguinal hernias. Four cases presented with gross abnormalities in the hernia sac. All the five patients were alive with no evidence of WDPM after a mean follow-up of 38.6 months. Extensive sampling of this rare lesion helps to rule out an epithelial malignant mesothelioma and prevents overtreatment.

  Copyright © 2014 Elsevier GmbH. All rights reserved.

• Malignant mesothelioma of the peritoneum invading the liver and mimicking metastatic carcinoma: a case report. S. Nagata, M. Tomoeda, C. Kubo, et al. 2011;207(6):395-8. Case report PubMed · Publisher

  Abstract

  We present a case of malignant mesothelioma of the peritoneum with massive direct invasion to the liver in a 58-year-old Japanese woman. She had no history of asbestos exposure or other malignancies. Abdominal computed tomography revealed one 8-cm intrahepatic mass adjacent to the abdominal wall with peritoneal thickening, multiple smaller nodules in the peritoneal cavity, and intra-abdominal lymphadenopathy. Liver biopsy showed a small cluster of atypical cells similar to epithelial neoplasm, which formed a tubulopapillary structure. The tumor cells were positive for calretinin with strong nuclear and cytoplasmic expression together with podoplanin (D2-40) and some cytokeratins, but were negative for hepatocyte paraffin 1 and other adenocarcinoma markers. We confirmed a diffuse peritoneal mesothelioma with direct invasion to the liver. Liver masses with other peritoneal nodules are mostly encountered as metastatic diseases. However, the possibility of mesothelioma should be considered, even in women without an apparent history of asbestos exposure.

  Copyright © 2011 Elsevier GmbH. All rights reserved.

• Nodular hemangiomatosis of pleura and peritoneum. S. Ribback, A. Thiele, C. Rosenberg, et al. 2011;207(11):718-21. Case report PubMed · Publisher

  Abstract

  Multiple, simultaneously occurring hemangiomas in one or more organs are known as hemangiomatosis syndromes in the context of phacomatosis manifesting in childhood. Nevertheless, hemangiomas of the serous membranes are extremely rare and often present as solitary lesions. We report the case of an elderly patient who suffered from diffuse hemangiomatosis of the visceral peritoneum and pleura and deceased due to acute respiratory distress syndrome following persistent and unmanageable pulmonary hemorrhage. We present an unusual case of a disseminated but histologically benign appearing hemangiomatosis of the serous membranes.

  Copyright © 2011 Elsevier GmbH. All rights reserved.

• Primary pleural epithelioid angiosarcoma. A case report and review of the literature. E. Dainese, B. Pozzi, M. Milani, et al. 2010;206(6):415-9. Case report · Review PubMed · Publisher

  Abstract

  Malignant vascular tumors are uncommon sarcomas that arise from endothelial cells of small blood vessels and may affect every organ. Pleural localization is very exceptional, and only 48 cases have been reported in the English literature to date. Even if etiological factors implicated in the development of vascular sarcomas are still unclear, the strongest association with the disease was a history of chronic tuberculous pyothorax, observed only in Japanese patients, while prior radiotherapy and occupational exposure to asbestos have been reported in few Western cases. The mean age at diagnosis was 58 years, and the male to female ratio was 6:1. The overall prognosis was poor, and most of the patients died of disease soon after diagnosis. Histological features and clinical presentation often cause several problems in the differential diagnosis, particularly with mesothelioma and metastasis from poorly differentiated carcinomas. Immunohistochemistry plays an important role in identifying these rare entities, confirming the endothelial origin of the neoplasm with the expression of at least one of the vascular markers CD31, CD34, or factor VIII-related antigen. We report herein a further case of a 62-year-old man who presented with progressive dyspnea and bilateral massive hemothorax. The overall pathological and immunohistochemical features of the pleural specimens supported the diagnosis of epithelioid angiosarcoma.

  2009 Elsevier GmbH. All rights reserved.

• Survey of British pathologists' performance of mesothelioma post-mortems. R. Goldstein, P.S. Hasleton. 2010;206(3):174-9. PubMed · Publisher

  Abstract

  We analyzed the practice of mesothelioma post-mortems in the United Kingdom (UK). Between 2003 and 2004, a questionnaire was sent to all UK Consultant Histopathologists, and 12% were recruited. In general post-mortems, the Coroner approved 60% of requests for organ retention, and Pathologists failed to make such a request in 5.9% of cases. In asbestos cases, the lungs were not fixed for sampling in 54.8% of cases, owing to the Coroners' refusal in 46.4% and the pathologists' failure to make a request in 8.4% of cases. In epithelioid mesothelioma, mesothelial and epithelial stains were considered to be of similar importance, and calretinin was the most popular individual stain. In sarcomatoid mesothelioma, mesothelial stains were chosen by 45.9% of pathologists, cytokeratin by 18.7% and epithelial stains by 18.5%. Calretinin was the most popular stain. Accurate mesothelioma diagnosis is impeded by the lack of tissue being made available by the Coroner and failure of some pathologists to make requests. Pathologists use appropriate immunohistochemical testing in epithelioid mesothelioma. In sarcomatoid mesothelioma, epithelioid stains were popular but have limited use. The Coroner should approve more requests for organ retention, and information should be disseminated to pathologists regarding best practice in mesothelioma.

  Copyright 2009 Elsevier GmbH. All rights reserved.

2000s

• Epithelioid and sarcomatoid malignant pleural mesothelioma in endoscopic gastric biopsies: a diagnostic pitfall. A. Agaimy, P.H. Wünsch. 2006;202(8):617-22. Case report PubMed · Publisher

  Abstract

  Pleural malignant mesothelioma (MM) usually presents with chest pain, pleural effusion, or cough in middle-aged and elderly individuals with a history of asbestos exposure, but may rarely present at unusual metastatic sites. The luminal gastrointestinal (GI) tract is only rarely involved in patients with wide-spread disease at autopsy. Encountering MM in endoscopic GI biopsies is an exceptionally rare event in surgical pathology practice and may therefore pose great diagnostic challenges if not considered, in particular if the clinical history is not informative or the GI symptoms are the presenting signs of the disease. To our knowledge, only three cases of epithelioid mesothelioma (EM) involving the luminal GI tract (intestine) have been reported so far, but no case of sarcomatoid MM (SM) involving the GI mucosa has been described. We herein present the first two cases of MM (one each of EM and SM) of the pleura, presenting in endoscopic gastric biopsies as small polypoid lesions and poorly healing ulcers 30 and 35 months after the initial diagnosis of pleural MM, respectively. The major differential diagnoses encompass primary or metastatic adenocarcinoma in case one and cytokeratin-positive (KIT negative!) GI stromal tumors (GISTs) and sarcomatoid carcinoma in case two, as well as other rare entities.

• Localized fibrous tumors (LFTs) of the pleura: clinical data, asbestos burden, and syntactic structure analysis applied to newly defined angiogenic/growth-regulatory effectors. K. Kayser, J. Trott, G. Böhm, et al. 2005;201(12):791-801. PubMed · Publisher

  Abstract

  This study was performed to add clinical data, to introduce new markers, and to perform syntactic structural analysis on localized fibrous tumors (LFTs) of the pleura. The material comprised clinical data and processed sections obtained from 36 patients. The results achieved from quantitative imaging techniques and syntactic structure analysis were correlated with clinical data, including patients' habits (smoking), asbestos exposure, survival, and tumor recurrence. The disease caused increasing chest pain and dyspnea in 47% of patients. Exposure to asbestos was noted in 13 out of 36 patients, whereas smoking posed no major risk factor. Two patients developed a recurrent tumor after 8 and 42 months, respectively; none of the other patients died of this tumor disease within the follow-up period of maximal 212 months. The cases were clearly discriminated from mesotheliomas by the marker profile. Frequent expression of accessible ligands for endogenous lectins galectins-1 and -3, the expression of the angiogenic macrophage migration inhibitory factor (MIF), and the dense vascularization intimate a functional relationship. The proliferation index (Nv) was computed to be 1.6% in line with the balance of galectin expression. Abnormal p53 was expressed in only 19.4% of the cases. The diagnosis of LFT can be aided by quantitative assessment of vimentin, CD34, MIF, vascularization, and proliferation. Considering the galectin network, differential expression was noted with preference to effectors limiting growth and aggressiveness.

• Pseudomesotheliomatous adenocarcinoma of the lung with rhabdoid features. J.H. Attems, F. Lintner. 2001;197(12):841-6. Case report PubMed · Publisher

  Abstract

  Pseudomesotheliomatous adenocarcinoma of the lung is a rare entity, clinically and pathologically mimicking diffuse malignant pleural mesothelioma. We report a case of pseudomesotheliomatous adenocarcinoma consisting of two distinct histopathologic components with marked differences in morphological appearance and immunohistochemical staining pattern: a small subpleural nodule consisting of adenocarcinoma and undifferentiated carcinoma with rhabdoid features, the latter extending to the visceral pleura in a diffuse mesothelioma-like growth pattern. The adenocarcinomatous component showed strong reactivity with various epithelial markers, but no reactivity with vimentin. The undifferentiated component showed strong reactivity for vimentin, but no reactivity for epithelial markers. Both components showed no reactivity with CEA, Ber Ep4, MOC-31, B72.3, cytokeratin 5/6, calretinin and thrombomodulin. Metastatic lesions in the duodenum and the periumbilical skin consisted entirely of undifferentiated carcinoma with rhabdoid features. Fluorescence in situ hybridisation (FISH) was performed for chromosomes 4, 7, 20, and 22. FISH results showed polysomy 7 in both components. The diagnosis of pseudomesotheliomatous adenocarcinoma in this case was based on the finding of the subpleural nodule. We conclude that in cases of undifferentiated malignant pleural tumors with cells of rhabdoid phenotype, the possibility of peripheral pulmonary adenocarcinoma dedifferentiating into a more aggressive phenotype should be considered.

• Papillary serous carcinoma of the tunica vaginalis testis. P. Becerra, M.A. Isaac, B. Márquez, et al. 2000;196(11):781-782; discussion 780. Case report PubMed · Publisher

  Abstract

  This is a case report of a testicular papillary serous carcinoma of ovarian type (PSCOT) diagnosed in a 50-year-old man. The tumor presented in the form of multiple papillary exophytic excrescencies on the visceral tunica vaginalis testis lining the inner surface of a hydrocele sac. The tumor was histologically a papillary serous carcinoma with numerous psammoma bodies, indistinguishable from similar tumors arising on the surface of the ovary. Following the tumor's surgical removal, the patient was treated with the same drugs used to treat ovarian serous carcinomas, and he is alive two years after the initial diagnosis. PSCOT must be distinguished from mesothelioma of the tunica vaginalis testis, a tumor with a most unfavorable prognosis. As shown here, immunohistochemical findings can be useful for formulating the correct diagnosis of PSCOT.

1990s

• The value of anti-calretinin antibody in the differential diagnosis of normal and reactive mesothelia versus metastatic tumors in effusion cytology. H. Nagel, B. Hemmerlein, I. Ruschenburg, et al. 1998;194(11):759-64. PubMed · Publisher

  Abstract

  In effusion cytology the distinction of reactive mesothelia from metastatic carcinoma cells may be a diagnostic challenge. Immunocytochemistry using antibodies suitable to detect epithelial cells must be considered carefully due to limited sensitivity and specificity of these antibodies. Efficient results in histological differential diagnosis of malignant mesothelioma versus lung-adenocarcinoma applying a novel antiserum against the calcium binding protein calretinin inspirated us to investigate the value of anti-calretinin antibody in effusion cytology combined with an epithelial marker. Cytoslides prepared by cytocentrifugation from 42 malignant and 65 reactive effusion specimens were immunostained using antibodies against calretinin and the epithelial marker Ber-EP4. Positive immunoreaction for calretinin in normal and reactive mesothelial cells was noted in 93% of the cases, whereas immunoreaction for calretinin was completely negative in the metastatic cells in 95% of the malignant effusions. Metastatic carcinoma cells were detected with anti-Ber-EP4 in 83% of malignant effusions. Non-specific positive reactions for Ber-EP4 in single mesothelial cells were observed in 16% of all cases and, moreover, frequently with macrophages or neutrophilic granulocytes. Our results demonstrate high sensitivity and specificity of anti-calretinin antibody for mesothelial cells in effusion specimens. They support its application to improve the diagnostic reliability of epithelial markers, especially because anti-calretinin antibody could be helpful in the assessment of false positive and false negative reactions of epithelial markers.

• Lipoblastic differentiation in a primary localized fibrous mesothelioma of the peritoneum. A. Donna, P.G. Betta, M. Ribotta. 1996;192(12):1252-6; discussion 1257-8. Case report PubMed · Publisher

  Abstract

  Lipoblastic differentiation in fibrous mesotheliomas is an extremely rare occurrence. We present the histological and immunohistochemical features of a case of localized peritoneal mesothelioma with lipoblastic differentiation in an 80-year old man and discuss the differential diagnosis with liposarcoma.

• Stereological evaluation of malignant mesothelioma versus benign pleural hyperplasia. J. Bogers, W. Jacobs, K. Segers, et al. 1996;192(1):10-4. PubMed · Publisher

  Abstract

  The differential diagnosis between malignant mesothelioma and benign pleural hyperplasia constitutes a well-known problem. In the present study we examined unbiased stereological techniques to assess the mean nuclear volume (MNV) using the point-sampled intercepts (PSI) in 37 cases of malignant mesothelioma and in 28 cases of benign pleural hyperplasia. Neither the use of different fixatives nor the histological type of malignant mesothelioma produced any significant difference on the measured nuclear volume. The differences observed between the MNV data obtained from benign pleural hyperplasia and those from any of the three types of malignant mesothelioma were found to be highly significant. All lesions with an MNV larger than 250 microns3 were found in our study to correspond to the malignant mesothelioma type, while an MNV that was smaller than 200 microns3 could only be detected in benign specimens. These observations lead us to propose the MNV measurement using PSI as an additional tool to enhance the differential diagnosis of malignant mesothelioma versus benign pleural hyperplasia.

• The calcium binding protein calretinin is a selective marker for malignant pleural mesotheliomas of the epithelial type. V. Gotzos, P. Vogt, M.R. Celio. 1996;192(2):137-47. PubMed · Publisher

  Abstract

  In a series of 23 cases of mesothelioma of either the epithelial, sarcomatoid or the mixed type, the expression of three calcium-binding proteins (calretinin, parvalbumin and calbindin-D28k) was studied using immunohistochemical techniques on paraffin sections. The results show that calretinin is expressed in mesotheliomas of the epithelial type (papillary, adenomatous or solid) and by the epithelial component of the mixed tumours. The immunohistochemical reaction is specific and reproducible. The tissues of the pulmonary parenchyma and of the pleura are negative for calretinin except for the rare fibroblasts and some skeletal muscle fibres situated in the interstices of, or near the epithelial tumour mass. The sarcomatoid mesotheliomas and the sarcomatoid component of the mixed tumours do not express calretinin. Parvalbumin and calbindin-D28k are expressed neither in mesotheliomas nor in normal lung tissue. Primary adenocarcinomas of the lung are negative for all three calcium binding proteins cited. Thus, calretinin seems to represent a selective marker for mesotheliomas of the epithelial type and allows their differentiation from metastases of lung adenocarcinomas.

• Multiple skeletal muscle metastases from malignant pleural mesothelioma. W. Grellner, M. Staak. 1995;191(5):456-60; discussion 461-2. Case report PubMed · Publisher

  Abstract

  A 54-year-old male patient (occupational asbestos exposure over 27 years) died 2 years and 4 months after the diagnosis of malignant pleural mesothelioma of the right side, despite twice undergoing pleurectomy and radiotherapy. The autopsy revealed a locally advanced pleural mesothelioma of both sides involving the pericardium, heart, right diaphragm, liver and peritoneum. Disseminated metastases in numerous lymph nodes and a hematogenous metastatic spread into both lungs, the thyroid gland, peritoneum and skeletal musculature were found. The left temporal muscle and proximal limb skeletal muscles of the right upper arm and both thighs exhibited multiple metastases measuring up to 7 cm in diameter. Microscopically, a biphasic type of mesothelioma was detected. To our knowledge this is the first extensive case report on muscle metastases in malignant mesothelioma. Reviewing the literature, it is thought that in the presented case the long survival time of the patient and his protracted preterminal immobility could have contributed to the unusual formation of multiple skeletal muscle metastases.

• A new case of malignant mesothelioma of the tunica vaginalis testis. Immunohistochemistry in comparison with an adenomatoid tumor of the testis. H. Moch, H. Ohnacker, R. Epper, et al. 1994;190(4):400-4; discussion 404-8. Case report · Review PubMed · Publisher

  Abstract

  Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor with 41 previously reported cases. The histological and immunohistological features of a new case in an 80-year-old patient are described and compared with an adenomatoid tumor of the tunica vaginalis testis, which is considered to be the benign variant of malignant mesothelioma. Both tumors revealed strong cytoplasmic staining for a panepithelial antibody (Lu-5) and membranous staining for BMA-120 (a mesothelial/endothelial cell marker) but yielded negative staining results with the endothelial cell markers QBend-10 (CD 34), Factor VIII-related antigen (vWF) and UEA-1. There was also negative staining for CEA, Ber-EP4, HEA-125 and Blood group related antigens A, B, H. An identical staining pattern was evident in normal and reactive mesothelial cells. Our data support a mesothelial rather than an endothelial derivation of the adenomatoid tumor studied.

• Malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease. A. Andrion, E. Feyles, G. Zai, et al. 1994;190(6):615-22; discussion 623-6. Case report PubMed · Publisher

  Abstract

  A case of malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease (MID) is presented. The patient had mesenteric and omental lesions characterized at biopsy by extensive fibrosis of fat tissue with mild to moderate inflammation. One year later, post-mortem examination revealed a well-differentiated epithelial mesothelioma. Immunohistochemical stains for keratin and vimentin were diffusely positive, whereas EMA showed a membranous staining of scattered cells. CEA, Ber-EP4, B72.3 and Leu-M1 were negative. In addition, actin monoclonals decorated groups of cells pertaining to the tumoural component. Immunostains of sections from retrieved paraffin blocks of the previous biopsy showed that the bulk of the spindle-shaped and histiocytic-like cells present in the fibrous streams was strongly labeled by low-molecular-weight keratin, and coexpressed vimentin and actin. EMA showed a membranous staining of sporadic spindle and round cells. The other immunostains were invariably negative. This immunohistochemical pattern closely corresponded to the immunophenotype of the mesothelial tumour detected at autopsy and was very suggestive of myofibroblastic/submesothelial cell origin. The quantitative evaluation of silver nucleolar organizer regions (Ag-NORs) demonstrated high levels of cell proliferation in both surgical and autopsy tissue samples.

• Evaluation of AgNOR count in distinguishing benign from malignant mesothelial cells in pleural fluids. M. Colecchia, O. Leopardi. 1992;188(4-5):541-4. PubMed · Publisher

  Abstract

  The authors have evaluated in eight reactive and eight malignant pleural effusions the number of intranuclear dots representing the nucleolar associated proteins stained with silver colloid technique (interphase nucleolar organizer regions-AgNORs). The mean number per nucleus in benign reactive effusions was 1.56 (SD 0.77) while in mesotheliomatous effusions it was 2.81 (SD 1.44). The statistical analysis of values, by Mann-Whitney U Wilcoxon Rank Sum W Test, revealed a significant difference of AgNOR counts in the two cytological samples. The variability of AgNOR areas and morphologies in reactive and mesotheliomatous nuclei in pleural fluids is evaluated applying automatic image analysis.

• Peritoneal benign cystic mesothelioma. J. Hidvégi, F. Schneider, B. Rohonyi, et al. 1991;187(1):103-6; discussion 106-8. Case report · Review PubMed · Publisher

  Abstract

  A case of a benign cystic peritoneal mesothelioma is reported. A 25-year-old woman presented a 8-year history of recurrent tumor and five operations because of that. On the basis of this case and of 18 cases proved by electron microscopy reported by others, the clinicopathological features and the problems of differential diagnosis are discussed. The ultrastructural examination is essential for the diagnosis of cystic mesothelioma.

• Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia. E.H. Strøm, F. Skjørten, L.B. Aarseth, et al. 1991;187(1):109-13; discussion 114-6. Case report PubMed · Publisher

  Abstract

  We report a patient with recurrent hypoglycemia most likely caused by a solitary fibrous tumor of the pleura. After removal of the tumor, hypoglycemia resolved. The bland histologic picture of this tumor is emphasized. Electron microscopic and immunohistochemical observations support its non-mesothelial derivation. In vitro studies demonstrated that the tumor tissue produced insulin-like growth factor I (IGF-I), and its role as the cause of hypoglycemia is discussed.

• Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum. S. Gonzalez, J. Friemann, K.M. Müller, et al. 1991;187(8):931-5. PubMed · Publisher

  Abstract

  In order to describe the ultrastructural features of the early phases of regenerating mesothelium in rat peritoneum, 69 cases were examined after intraperitoneal injection of 0.05-15 mg crocidolite, chrysotile B and other mineral and synthetic fibers. The findings show the presence of intermediate or transition cells between proliferating submesothelial connective tissue cells bearing the ultrastructural phenotype of myofibroblasts and mature fully regenerated mesothelium. Our results and data accumulated in the literature provide strong support for the hypothesis of submesothelial cells origin for regenerating mesothelium.

• Absence of estrogen immunoreactivity in adenomatoid tumors of male reproductive system. J.I. Lopez, F.I. Aranda. 1990;186(3):395-6. PubMed · Publisher

• Localized fibrous tumors of the pleura: correlation of histopathological, immunohistochemical and ultrastructural features. C. Steinetz, R. Clarke, G.H. Jacobs, et al. 1990;186(3):344-57. PubMed · Publisher

  Abstract

  The histogenesis of localized fibrous tumor of the pleura (LFTP) is controversial. We studied 12 LFTP's by light microscopy; by immunohistochemical staining for cytokeratin (CK), vimentin, muscle-specific actin, desmin, S-100 protein, epithelial membrane antigen (EMA) and factor VIII; by electron microscopy in 6 tumors; and by lung digestion for asbestos bodies in 4 cases. Three histologic patterns occurred in combination: 1) collagenous, 2) cellular and 3) hypocellular/myxoid. Hemangiopericytoma-like foci were prominent in the cellular areas of 9 tumors. Unusual features included diffuse small cells in 3 tumors, microcystic foci in 2, macrocystic areas in 5 and tumor giant cells in 4 tumors. Neoplastic cells in all patterns stained positively for vimentin and actin in 9 and 4 tumors, respectively, and were negative for all other markers. CK and EMA were identified in mesothelial and epithelial invaginations only. Ultrastructurally, neoplastic cells demonstrated intercellular junctions, intermediate or thin filaments, dense bodies and rough endoplasmic reticulum. Basal lamina was focally present in 5 tumors, while tonofilaments, desmosomes and short microvilli were observed in one case. Our results support the conclusion that LFTP is a neoplasm of the multipotential subserosal cell, and usually expresses mesenchymal (fibroblastic/myofibroblastic) differentiation. Coexpression of mesothelial features is rare. Lung asbestos body quantitation in 4 patients suggests that there is no association between LFTP and asbestos exposure.

• Malignant mesothelioma of the tunica vaginalis. M. Kamiya, T. Eimoto. 1990;186(5):680-4; discussion 685-6. Case report · Review PubMed · Publisher

  Abstract

  A case of a malignant mesothelioma of the tunica vaginalis is presented. The patient with an intrascrotal mass was a 32-year-old Japanese male who had no history of asbestos exposure. The tumor was located on the surface of the right testis and was composed of columnar to polygonal cells with glandular and papillary structures. It showed many mitoses and focal invasion of the tunica albuginea. The tumor cells contained alcian blue- and Hale's colloidal iron-positive, hyaluronidase-digestible materials. Immunohistochemical stains for cytokeratin and vimentin were positive, while those for carcinoembryonic antigen, epithelial membrane antigen, Leu-M1, and factor VIII-related antigen were negative. The systemic examinations revealed no other tumors. Based on these findings the tumor was diagnosed as malignant mesothelioma of the tunica vaginalis. The differential diagnosis is discussed under the histologic, histochemical, and immunohistochemical points of view and the previous literature is reviewed.

• Malignant pleural mesothelioma: some aspects of epidemiology, differential diagnosis and prognosis. Histological and immunohistochemical evaluation and follow-up of mesotheliomas diagnosed from 1964 to January 1985. R. Walz, H.K. Koch. 1990;186(1):124-34. PubMed · Publisher

  Abstract

  64 diffuse pleural mesotheliomas diagnosed between 1964 and January 1985 at the Institute of Pathology of the University of Freiburg were analyzed. Since 1980 an increase from one case to 10 cases per year has been observed. The tumor was 3 to 4 times more frequent in men than in women. The age distribution showed a peak between the age of 50 and 60. In 26 cases evidence of exposure to asbestos was detected. In one patient radiotherapy of Hodgkin's disease may have been of etiological significance. The median survival time was 13 months. The five-year survival rate was only 4%. Histologic reevaluation was only possible in cases diagnosed after 1975. Of 43 cases thus evaluated 26 were pure mesothelial, 15 biphasic and 2 of the spindle-cell subtype. A median survival time of 23 months for pure mesothelial mesothelioma in comparison to 13 months for the biphasic mesothelioma indicated a better prognosis for pure mesothelial mesothelioma. Although no other primary tumors were detected, in 10 cases the differential diagnosis of adenocarcinoma had to be considered, and in 3 cases tumors of non-epithelial origin had to be excluded. 35 of 43 mesothelioma were CEA-negative, 38 out of 43 cytokeratin-positive, and 33 out of 43 were EMA-positive. Factor-VIII-related antigen was not demonstrated. 12 of 43 mesotheliomas showed PAS-positive staining, 29 of 43 were stained with Alcian blue. 7 of these 29 showed a positive digestion with hyaluronidase. Although CEA may not be negative in every mesothelioma, this marker seems to be a valid tool for the differential diagnosis of adenocarcinoma. In order to safeguard against a mistaken diagnosis of pleural mesothelioma, the exclusion of other tumors is always indispensable.

• Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum. J. Friemann, K.M. Müller, F. Pott. 1990;186(1):117-23. PubMed · Publisher

  Abstract

  The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.

• Reactive lesions of the pleura. Immunohistochemical characterization. M. Brockmann, I. Brockmann, M. Fischer, et al. 1990;186(2):238-46. PubMed · Publisher

  Abstract

  The visceral pleura of 8 lung tissue specimens with non-tumorous pleural lesions and of 10 specimens with secondary pleural infiltration of different primary tumours were tested by avidin-biotin-method with the following antibodies: anti-keratin KL1, anti-vimentin V9, anti-CEA (BMA 130c), HEA 125, Leu M1, HMFG 2 and anti-collagen type IV. In all cases anti-keratin positive subserosal cells could be proved. Activated mesothelial cells expressed vimentin additionally to keratin. The antibodies Leu M1, HEA 125 and BMA 130c (against CEA) showed no reaction in subserosal and mesothelial cells. With the antibody HMFG 2, however, a weak reaction could be observed. A distinction between reactive and neoplastic pleural lesions is not possible by using these antibodies. The antibodies LeuM1, HEA 125 and BMA 130c can be helpful for differential diagnosis in single cases with pleural carcinosis. The antibody against collagen type IV demonstrates newly developed basal membrane structures in areas with proliferating subserosal cells. Considering our results the entity of mesothelium and submesothelium is discussed with regard to the histogenetical aspect of mesothelioma.

1980s

• A simple "expert system" for morphometric evaluation of cells in pleural effusions. M. Oberholzer, G. Feichter, P. Dalquen, et al. 1989;185(5):647-51. PubMed · Publisher

  Abstract

  Quantitation in diagnostic pathology serves to improve both diagnostic reliability and the prognosis of various malignant tumors. Unfortunately, flexible, user-friendly, reasonably priced and compatible morphometric systems are hardly available on the market. A modular Apple II PC-based system was therefore developed in-house. It records stereologic, planimetric and digital image analysis data and calculates secondary parameters. Detailed statistical analyses can be performed, after data transfer, on larger computers. A typical application of diagnostic morphometry is to determine whether, and with which probability a patient with an unclear histopathologic finding can be assigned to one or more groups of patients with known diseases and prognoses. To this end morphometric data of the patient under investigation are compared with other patient data stored in an expert system. This paper describes the concept of an expert system carried out on the Apple II PC system mentioned above and outlines the evaluation procedures. Invariant moments were used to describe nucleus textures. Results obtained from the cytological analysis of pleural effusions demonstrate that with this approach it is possible to differentiate between normal mesothelium, mesothelioma and metastases of adenocarcinomas.

• What's new in intraperitoneal test on Kevlar (asbestos substitute)?. O.A. Brinkmann, K.M. Müller. 1989;185(3):412-7. PubMed · Publisher

  Abstract

  The intraperitoneal test is a suitable experimental method for studying the different patterns of morphological reaction to foreign body substances of various kinds and concentrations as well as their transport within and elimination from the organism, Kevlar fibres are synthetic aromatic polyamid (aramid) fibres which, investigated by means of the intraperitoneal test in Wistar rats, show distinct pathogenetic reaction patterns: 1. In the early stage after application, the formation of multinucleated giant cells with phagocytosis of the amber-coloured Kevlar fibres, and an inflammatory reaction are foremost features. 2. The typical feature of the second stage is the development of granulomas with central necrosis indicating the cytotoxic nature of Kevlar fibres. 3. The third stage is dominated by the mesenchymal activation with capsular structures of collagenous fibres. Besides granulomatous foci, a slight submesothelial fibrosis is observed. 4. Fragments of Kevlar fibres are drained through lymphatic pathways and stored in lymph nodes where they lead to inflammatory reactions. 5. The reactive granulomatous changes in the greater omentum of rats are accompanied by proliferative mesothelial changes which, in one cases, even led to the development of a multilocular mesothelioma.

• So-called peritoneal implants of ovarian carcinomas. Problems in differential diagnosis. D. Dienemann, H. Pickartz. 1987;182(2):195-201. PubMed · Publisher

  Abstract

  The aim of this paper is the differential-diagnostic distinction of peritoneal 'implants' of serous ovarian tumours from morphologically similar lesions in the peritoneum. The authors investigated 22 cases of ovarian carcinomas, 'implants' of ovarian carcinomas, reactive mesothelial proliferates, endosalpingiosis, benign and malignant mesotheliomas, as well as papillary carcinomas of the pelvic peritoneum with conventional histological stainings and immunohistochemical methods (immunoperoxidase, ABC method). The cells of almost all mentioned lesions express cytokeratin, only the cells of the reactive mesothelial proliferates are partially keratin-negative. CEA was not detected in any of the lesions. Alpha-1-antitrypsin was present in the cells of some ovarian carcinomas and their implants. Lysozyme was found focally in some ovarian carcinomas and in some reactive mesothelial proliferates. An exact differentiation of peritoneal 'implants' as metastases of ovarian carcinomas or autochthonous neoplasias in the course of multifocal tumour development is not possible on the basis of our immunohistochemical findings.

• Coated and uncoated lung mineral fibres in subjects with and without pleural plaques at autopsy. A. Andrion, D. Bellis, E. Bertoldo, et al. 1984;178(6):611-6. PubMed · Publisher

  Abstract

  The lung concentration of coated and uncoated mineral fibres of more than 10 micron in length was determined by light microscopy in 57 autopsied subjects (23 out of which professionally exposed to asbestos) with pleural plaques but no other asbestos-related diseases. Comparisons were made with 57 controls matched for sex, age and smoking habits, who did not show any asbestos-associated diseases or history of previous occupational exposure. Subjects with pleural plaques had a median concentration of coated fibres consistently greater than that observed in those without. However, no substantial differences were found between the two studied groups when uncoated and total fibres were considered. The present study suggests that the factors related to the fibre coating and to the pleural plaque formation may be indirectly connected, but not necessarily restricted to the number and nature of the fibres, or to the professional or environmental conditions of exposure.

• Peritoneal mesothelioma presenting as umbilical tumor. W.S. Kwee, R.W. Veldhuizen, J.B. Vermorken, et al. 1982;174(1-2):159-65. Case report PubMed · Publisher

  Abstract

  The case of a 66 year-old women with a peritoneal mesothelioma is described, which manifested itself as a tumor in the umbilical region. The clinical, cytological, histological and electron microscopical features of the tumor are reported. The diagnostic problems of this tumor are discussed.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Clinical results in the management of patients with uterine sarcoma. K.J. Lohe, J. Baltzer, W. Wolf, et al. 1980;169(2):200-1. PubMed · Publisher

  Abstract

  From 24 Patients which were treated for uterine sarcomas during 1970-1977, 10 patients had a leiomyosarcoma, 6 an endometrial stromal sarcoma, and 8 a mixed mesodermal sarcoma. Surgical treatment was performed in 15 cases, and in 13 cases was followed by postoperative radiation. Eight patients were treated primarily by combined radium and cobalt 60 radiation therapy. Seventeen of 24 patients under control died, 15 of these within on year after onset of therapy. Regarding the histological patterns of sarcomas, both mitotic activity and vascular invasion was without significance in subsequent outcome.

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