Pathology International

About the journal

Publisher: Published by Blackwell Scientific Publications for the Japanese Society of Pathology
Published: 1994 to the present, Australia
Language: English
ISSN: 1320-5463 (print), 1440-1827 (electronic)
Continues: Acta Pathologica Japonica
Its record in the NLM Catalog

2020s

Digital PCR for Detecting Loss of BAP1 and MTAP in Pleural Fluids of Mesothelioma Patients: Perspectives in the Diagnosis. G. Rosini, G. Alì, R. Bruno, et al. 2026;76(9):e70172. PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) often presents loss of BAP1 and MTAP genes. Digital PCR (dPCR) can accurately measure gene copy numbers (CNs). We hypothesized that cell-free DNA (cfDNA) extracted from the supernatant of pleural fluids (SPFs) could allow an efficient detection of these genetic events. BAP1/MTAP CN was measured with dPCR in SPFs and in solid tumor biopsies (STBs) of 37 PM patients. Results were compared with immunohistochemistry (IHC) carried out in STBs. IHC alone detected BAP1/MTAP-losses in 32/37 (86.5%). However, the sensitivity improved to 34/37 (91.9%) when low CN of BAP1/MTAP was included. Among 20 patients presenting SPFs, dPCR alone detected a low CN in 18 samples (sensitivity = 90%). Finally, this two-gene signature was applied on SPFs in a prospective series of six consecutive patients presenting an undefined diagnosis (negative for PM) and two showed reduced CN. After 7 months of follow-up, these subjects were further re-evaluated for the persistence/worsening of the symptoms and were diagnosed for PM. We highlighted dPCR's potential for detecting subtle BAP1/MTAP losses in SPFs of PM patients. This appears as a complementary approach for a more accurate diagnosis in specific contexts, when high-risk patients receive negative results after IHC analysis.

© 2026 The Author(s). Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Pleural Mesothelioma With Unusual Squamous Differentiation: A Clinicopathological Case Report With Molecular Insights From Whole-Exome Sequencing. J. Bodemeyer, M.E. Mierzwa, J. Seraphin, et al. 2026;76(10):e70190. Case report PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is an aggressive tumor with a poor prognosis and limited therapeutic options. While histological heterogeneity is common, true squamous differentiation is extremely rare and diagnostically challenging. We report an 81-year-old man with asbestos exposure who presented with recurrent right-sided pleural effusion. Thoracoscopic biopsies revealed two distinct tumor components. The first expressed mesothelial immunohistochemical markers, whereas the second showed a squamous profile. Both components demonstrated loss of BAP1 expression and homozygous deletion of CDKN2A, supporting a common mesothelial origin. Whole-exome sequencing revealed a tumor mutational burden above the average reported for mesothelioma (8-9 mutations per megabase), with 69 somatic mutations in total, 43 shared between the two components. In addition to canonical mesothelioma alterations (BAP1, CHEK2), the squamous component harbored 18 unique variants, including oncogenic alterations in NFE2L2 and PIK3CA. A novel SOX9 missense variant of uncertain significance (p. Thr243Pro) was also identified within the transactivation middle (TAM) domain; its functional consequence remains unknown. This case highlights a rare histological variant of pleural mesothelioma with partially squamous differentiation, characterized by a mutational burden above the mesothelioma average and squamous carcinoma-associated alterations. Integrated histology, immunohistochemistry, and genomic profiling are essential to avoid misdiagnosis and to improve understanding of tumor plasticity in mesothelioma.

© 2026 The Author(s). Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Expression of Heart Development Protein With EGF-Like Domains 1 (HEG1) Decorated With Low-Sulfated Keratan Sulfate in Human Malignant Pleural Mesothelioma. K. Nakashima, H. Hoshino, Z. Zhang, et al. 2025;75(10):504-512. PubMed · Publisher · Free full text

Abstract

The glycoform of heart development protein with EGF-like domains 1 (HEG1) recognized by the SKM9-2 monoclonal antibody is a useful diagnostic marker for malignant pleural mesothelioma (MPM). The putative glycoform includes core 2 O-glycans carrying sialyl poly-N-acetyllactosamine (LacNAc), but sulfation modifications are undetermined. Since sialyl 6-sulfo LacNAc-capped core 2 O-glycans are expressed in MPM and their structure overlaps with low-sulfated keratan sulfate (KS), we asked whether low-sulfated KS is expressed in MPM and whether HEG1 is decorated with low-sulfated KS. We performed immunohistochemical analysis of 41 MPM cases using anti-KS monoclonal antibodies and endoglycosidases, reversed-phase ion-pair high-performance liquid chromatography analysis of KS/sulfated LacNAc isolated from human pleural tissue, and western blot analysis of HEG1·IgG recombinant fusion proteins secreted from low-sulfated KS-expressing human embryonic kidney cells. Most MPM tissues were stained with anti-low-sulfated KS antibodies and staining was eliminated by endo-β-galactosidase and keratanase II but not by peptide-N-glycosidase F. Disaccharide composition analysis revealed that mono-sulfated LacNAc disaccharide and di-sulfated LacNAc disaccharide accounted for 83.1% and 16.9% of pleural KS/sulfated LacNAc, respectively. Western blot analysis of HEG1·IgG glycoforms indicated that HEG1 functions as a core protein for low-sulfated KS. Thus, HEG1 protein decorated with low-sulfated KS is expressed in MPM.

© 2025 The Author(s). Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species. Y. Okazaki. 2022;72(2):83-95. Review PubMed · Publisher

Abstract

Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.

© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
PCBP2 knockdown promotes ferroptosis in malignant mesothelioma. L. Yue, Y. Luo, L. Jiang, et al. 2022;72(4):242-251. PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is still increasing worldwide. The pathogenesis depends on asbestos-induced iron accumulation, which eventually leads to ferroptosis-resistance of mesothelial cells via somatic mutations. Poly (rC)-binding proteins 1 and 2 (PCBP1/2) are recently recognized cytosolic Fe(II) chaperones. Here we studied the role of PCBP1/2 in rat/human mesothelial and MM cells as well as rat/human MM specimens. Normal peritoneal mesothelial cells in rats exhibited PCBP1 but not PCBP2 immunopositivity whereas primary/immortalized mesothelial cells showed PCBP1/2 immunopositivity. Rat MM specimens induced by intraperitoneal injection of chrysotile, including in situ lesion, revealed PCBP1/2 immunopositivity (90% for both) in the nucleus and cytoplasm with a tendency of higher expression in epithelioid subtype. Knockdown of PCBP2 but not PCBP1 significantly decreased both TfR1 and FTH expression in MM cells with inhibition of proliferation, indicating stagnation of intracellular iron transport. Erastin, a cysteine-deprivation type ferroptosis inducer, decreased the expression of both PCBP1/2 in MM cells. Furthermore, PCBP2 knockdown significantly increased the sensitivity of MM cells to erastin-induced ferroptosis with increased catalytic Fe(II). In conclusion, PCBP2 works for ferroptosis-resistance not only during mesothelial carcinogenesis but also in MM, which warrants further investigation as a novel therapeutic target.

© 2022 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas. K. Hiroshima, D. Wu, E. Koh, et al. 2021;71(9):604-613. PubMed · Publisher · Free full text

Abstract

Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.

© 2021 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Clinicopathological significance of intelectin-1 in colorectal cancer: Intelectin-1 participates in tumor suppression and favorable progress. N. Katsuya, K. Sentani, Y. Sekino, et al. 2020;70(12):943-952. PubMed · Publisher

Abstract

Intelectin-1 (ITLN1) is an adipokine with an anti-inflammatory function that is involved in neoplastic diseases such as pleural mesothelioma and gastric and prostate cancers. However, the expression and function of ITLN1 in colorectal cancer (CRC) remain unknown. To identify novel prognostic markers or therapeutic targets for CRC, we focused on ITLN1 protein. By immunohistochemistry, 87 (59%) of 148 CRC cases showed reduced expression of ITLN1. ITLN1-reduced CRC cases were associated with higher M grades (P = 0.0017) than ITLN1-retained CRC cases. Furthermore, the cases with ITLN1 retained expression tended toward a more favorable prognosis than those with reduced expression. Cell growth of the CRC cell lines transfected with ITLN1 siRNA were greater than those of the negative control cell lines transfected with siRNA. Levels of phosphorylated epidermal growth factor receptor, Erk and Akt were higher in the CRC cells transfected with ITLN1 siRNA than in control cells. Immunohistochemical analysis of human colorectal polyp specimens also revealed a sequential decrease in the expression of ITLN1 through both the conventional adenoma-carcinoma pathway and the serrated pathway. These results indicated that ITLN1 might play an important role in regulating colorectal tumorigenesis.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Development of mesothelioma in situ and its progression to invasive disease observed in a patient with uncontrolled pleural effusions for 15 years. K. Hidaka, T. Takeda, Y. Kinoshita, et al. 2020;70(12):1009-1014. Case report PubMed · Publisher

Abstract

Mesothelioma in situ (MIS) has recently been investigated as a distinct phase of mesothelioma carcinogenesis. The diagnostic criteria proposed for MIS include a loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC). However, the length of time that MIS typically remains an in situ lesion before progression to invasive disease is still unclear. Herein, we report a case of a Japanese woman in her early seventies who had suffered from recurrent pleural effusions for 15 years, during which MIS developed and progressed to invasive mesothelioma. Retrospective diagnosis of partial MIS, fully developed MIS, and invasive disease was made using BAP1 IHC on three biopsy specimens and via clinical observations with radiological images. MIS and invasive lesions revealed BAP1 loss. The interval from partial or full MIS to invasive disease was 14 and 7 years, respectively. These results support a diagnostic strategy combining histomorphology with genomic-based assays including BAP1 IHC in biopsy tissues from a patient with recurrent pleural effusions.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Expression status of PD-L1 and B7-H3 in mesothelioma. E. Matsumura, K. Kajino, M. Abe, et al. 2020;70(12):999-1008. PubMed · Publisher

Abstract

Mesothelioma is a rare, aggressive malignancy with poor outcome, and has limited treatment options. The aim of this study was to perform a comprehensive analysis of programmed death ligand 1 (PD-L1) and B7 homolog 3 (B7-H3) expression in mesothelioma. We investigated the protein expression of PD-L1 and B7-H3 and their potential correlation with histological subtype, which might help to develop new therapies targeting these immune checkpoint molecules. Expression analysis of PD-L1 and B7-H3 was performed by immunohistochemistry using serial tissue sections of specimens obtained from 31 patients with mesothelioma. Tumors were classified into 22 epithelioid, 6 sarcomatoid, and 3 biphasic types. Of the 31 patients, 13 (41.9%) were positive for PD-L1 and 28 (90.3%) were B7-H3 positive. Twelve of the 13 PD-L1 positive patients were positive for B7-H3. PD-L1 and B7-H3 were widely co-expressed in biphasic and sarcomatoid type tumor cells. These findings might provide a rationale for the use of combination therapy for mesothelioma by targeting PD-L1 and B7-H3, as well as the development of anti-B7-H3 or anti-PD-L1 single agents.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Genomic profiling of multiple primary cancers including synchronous lung adenocarcinoma and bilateral malignant mesotheliomas: Identification of a novel BAP1 germline variant. A. Shinozaki-Ushiku, S. Kohsaka, H. Kage, et al. 2020;70(10):775-780. Case report PubMed · Publisher

Abstract

We report a case with a rare combination of synchronous lung adenocarcinoma and bilateral malignant pleural mesotheliomas in a 70-year-old male without asbestos exposure. He metachronously developed peritoneal malignant mesothelioma, intrahepatic cholangiocarcinoma, urothelial carcinoma of the bladder and prostatic adenocarcinoma. Immunohistochemistry revealed complete loss of BAP1 expression in all seven lesions. Targeted next generation sequencing using Todai OncoPanel identified a novel germline variant (c.1565_1566del, p.P522Rfs*14) of BAP1. Additionally, different nonsynonymous somatic mutations of BAP1 were identified in four lesions including lung adenocarcinoma, malignant pleural and peritoneal mesotheliomas, and bladder cancer. The remaining two lesions had different somatic mutations in genes other than BAP1. Multiple BAP1-deficient cancers that developed in a single patient suggest the newly identified germline variant of BAP1 gene to be pathogenic and this case expands the clinical spectrum of BAP1-tumor predisposition syndrome. Screening for BAP1 status is highly recommended in cases with a similar combination of cancers.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Peritoneal adenomatoid (microcystic) mesothelioma. D. Mori, S. Kido, M. Hiraki, et al. 2020;70(11):876-880. Case report PubMed · Publisher

Abstract

There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Pleural sarcomatoid mesothelioma with an interstitial growth pattern. K. Miyakawa, M. Yamamoto, N. Akiyama, et al. 2020;70(2):126-128. Case report · Letter PubMed · Publisher
Utility of highly expressed EZH2 in pleural effusion cytology for the diagnosis of mesothelioma. M. Yoshimura, M. Hamasaki, Y. Kinoshita, et al. 2020;70(10):831-833. Letter PubMed · Publisher

Summary

In this letter, the authors examined whether high expression of enhancer of zeste homolog 2 (EZH2), detected by immunohistochemistry (IHC), helped distinguish malignant pleural mesothelioma (MPM) from reactive mesothelial cells (RMC) in pleural effusion cytology cell blocks. They tested EZH2 alone and combined with BAP1 IHC, MTAP IHC and 9p21 fluorescence in situ hybridization (FISH). They studied 40 MPM cases (33 male, 7 female; mean age 69.8 years) and 20 RMC cases (11 male, 9 female; mean age 70.6 years). All were diagnosed between 2010 and 2019 at Fukuoka University Hospital and Hyogo College of Medicine, Japan. All RMC cases showed low EZH2 expression (<30%), while 45% of MPM cases showed high expression. Sensitivities were 57.5% for 9p21 FISH, 55.0% for BAP1 IHC, 55.0% for MTAP IHC and 45.0% for EZH2 IHC, each with 100% specificity. Combining EZH2 IHC with 9p21 FISH, BAP1 IHC or MTAP IHC gave sensitivities of 72.5%, 77.5% and 72.5%, respectively. Adding EZH2 IHC to BAP1 IHC plus 9p21 FISH or MTAP IHC raised sensitivity from 85% (34/40) to 87.5% (35/40). In six MPM cases, the other assays showed no abnormality; in one of these, high EZH2 expression helped diagnose MPM. The authors also described practical difficulties in evaluating IHC in cell blocks. They concluded that adding EZH2 IHC increased sensitivity in separating MPM from RMC. Because the sample was small, they said further validation was needed.

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2010s

A case of lung adenocarcinoma complicated by pulmonary talcosis occurring in a patient employed in the confectionery industry. K. Kobayashi, N. Watanabe, T. Oka, et al. 2019;69(4):229-234. Case report PubMed · Publisher

Abstract

A 73-year-old Japanese man, who worked at a confectionery company for more than 20 years, was diagnosed with a 28 mm nodular lesion in the superior lobe of the right lung by whole-body computed tomography examination. A biopsy revealed the presence of adenocarcinoma. With a diagnosis of a primary lung cancer, a right upper lobectomy was performed. A nodular lesion, 25 × 23 mm in size, was observed in the upper right lobe lung field, and was diagnosed histopathologically as a papillary adenocarcinoma. In addition, fibrous scars in the central part of the tumor showed numerous Langhans and/or foreign body giant cells, and histiocytic cells that had phagocytized numerous small transparent crystals, together with coal powder deposition. The extracted crystals were observed with a scanning electron microscope, and although plate-like structures were observed, ferruginous bodies suggestive of asbestos were not found. The crystals were demonstrated to be talc by powder X-ray diffraction. Herein, we investigated a case of lung adenocarcinoma in a patient with talcosis, with discussions based on a literature search. This collision of talcosis and lung adenocarcinoma adds to an increasing body of knowledge on an apparent association between talc and cancer cases.

© 2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Morphological difference between pleural mesothelioma cells in effusion smears with either BAP1 loss or 9p21 homozygous deletion and reactive mesothelial cells without the gene alterations. S. Matsumoto, M. Hamasaki, Y. Kinoshita, et al. 2019;69(11):637-645. PubMed · Publisher

Abstract

We previously characterized the morphological characteristics of malignant pleural mesothelioma (MPM) cells with 9p21 homozygous deletion (HD) using a combination of the virtual microscopy and fluorescence in situ hybridization (FISH). In this study, we investigated whether MPM cells with BRCA1-associated protein 1 (BAP1) loss show the same morphological characteristics identified in MPM cells with 9p21 HD. MPM cells with either BAP1 loss detected by immunocytochemistry (ICC) or 9p21 HD detected by FISH were identified via virtual microscopy prior to ICC or FISH, followed by analysis and quantification of their morphological characteristics. MPM cells with BAP1 loss or 9p21 HD exhibited significantly more frequent cell-in-cell engulfment, multinucleation, and larger multicellular clusters composed of more than 10 cells than reactive mesothelial cells. In conclusion, MPM cells with BAP1 loss or 9p21 HD share similar cytological features, indicating that the same morphological criteria can be used to detect MPM cells harboring such genetic aberrations.

© 2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
A case of cytokeratin-negative sarcomatoid malignant pleural mesothelioma. K. Inafuku, Y. Tsuura, T. Morohoshi, et al. 2018;68(6):391-393. Case report · Letter PubMed · Publisher
Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells. S. Aida, J. Aida, M. Naoi, et al. 2018;68(9):503-508. PubMed · Publisher

Abstract

We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-). Telomere length was measured using the tissue quantitative fluorescence in situ hybridization method, and expressed as normalized telomere-to-centromere ratio. NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P < 0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp- cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases with shorter telomeres tended to show aberrant expression of epithelial membrane antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA-binding protein 3 (IMP3). These results suggest that telomere shortening and subsequent genetic instability play an important role in the development of MM. Measurement of telomere length of cells in pleural effusion might be helpful for earlier detection of MM.

© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features. N. Kimura, M. Hasegawa, K. Hiroshima. 2018;68(2):128-132. Case report PubMed · Publisher

Abstract

Malignant mesothelioma (MM) with rhabdoid features is an MM variant. Fifteen cases have been reported previously, all of which were combined with other types of MM. Herein, we report an autopsy case of pleural MM with monomorphic rhabdoid features. The patient was a 62-year-old male without a history of asbestos exposure. An autopsy revealed a soft, granular tumor that replaced the entire left pleura and had invaded to the diaphragm and lower lobe of the lung. The tumor cells, which had eosinophilic plump cytoplasm and eccentric nuclei, were loosely cohesive. Immunohistochemistry showed that the cells were diffusely positive for calretinin, D2-40, vimentin, CAM5.2, and AE1/AE3; and negative for WT-1, TTF-1, CK7, CEA, desmin, CD34, BCL-2, S100 protein, and p40. Neither homozygous deletion of p16 nor BAP-1 protein loss was observed. Loss of INI1/BAF47 protein, an indicator of malignant rhabdoid tumor, was observed. Therefore, MM with rhabdoid features was confirmed.

© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
A Case of Solitary Well-Differentiated Papillary Mesothelioma with Invasive Foci in the Pleura. S. Shimizu, H.E. Yoon, N. Ito, et al. 2017;67(1):45-49. Case report PubMed · Publisher

Abstract

Well-differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor consisting of mesothelial cells with a papillary architecture, bland cytological features, and a tendency toward superficial spread without invasion. Rare cases with superficial invasion are termed WDPM with invasive foci. We report a case of solitary WDPM with invasive foci in the pleura. A 61-year-old woman presented with a lung adenocarcinoma. A small papillary lesion measuring 29 × 10 × 8 mm was incidentally found in the parietal pleura during a lobectomy for the lung adenocarcinoma. The fibrovascular core of the small papillary lesion was surrounded by a single layer of cuboidal cells with mild to moderate atypia and large nucleoli. Atypical mesothelial cells focally invaded the submesothelial layer. The cells of the papillary lesion were positive for cytokeratins and mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on fluorescence in situ hybridization. We could not detect atypical mesothelial cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci is prone to multifocality; however, our case represents a solitary case in the pleura.

© 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Primary malignant pericardial sarcomatoid mesothelioma: An autopsy report. H. Muta, Y. Sugita, K. Ohshima, et al. 2017;67(6):311-315. Case report PubMed · Publisher

Abstract

Primary malignant pericardial sarcomatoid mesothelioma (PMPSM) is an extremely rare tumor with poor prognosis. We present an autopsy case in an 80-year-old man admitted for heart failure after one month of treatment at an outpatient clinic. He died three months after symptom onset. A complete autopsy revealed localization of the tumor to the pericardium without other lesions. Histologically, mainly spindle-shaped atypical cells with hyperchromatic nuclei and nucleoli were observed. Immunohistochemical markers for mesothelioma were positive for calretinin, cytokeratin AE1/AE3, and cytokeratin CAM5.2. Thus, we diagnosed primary sarcomatoid malignant mesothelioma of the pericardium. To our knowledge, only four PMPSM cases have been reported in the English literature in the past 30 years. Although PMPSM is rare, clinicians and pathologists should recognize it as a possible diagnosis of pericardial tumors. It is necessary to accumulate clinical and pathological diagnostic findings to establish early detection methods for this extremely rare disease.

© 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests. T. Hida, M. Hamasaki, S. Matsumoto, et al. 2016;66(10):563-570. PubMed · Publisher

Abstract

Differentiation of malignant pleural mesothelioma (MPM) from benign mesothelial proliferation remains problematic. Loss of nuclear staining of BRCA1-associated protein 1 (BAP1; detected using immunohistochemistry (IHC)) and homozygous deletion (HD) of p16 (detected using fluorescence in situ hybridization (FISH)) are useful for differentiation of MPM from reactive mesothelial hyperplasia (RMH), but the correlation between BAP1 expression loss and p16 HD has not been fully described. We performed BAP1 IHC and p16-specific FISH for 40 MPM and 20 RMH cases, and measured proportions of cells showing BAP1 expression and p16 HD for each case. The diagnostic accuracy for MPM and the cut-off values of the two methods were assessed using receiver operating characteristic (ROC) analysis. BAP1 expression loss, p16 HD and coexistence of both were present in 27 (67.5 %), 27 (67.5 %) and 17 (42.5 %) MPM cases, respectively. Three MPM cases (7.5 %) and all 20 RMH cases had neither BAP1 loss nor p16 HD. There was no correlation between the results of the two methods. Their combination showed higher sensitivity (92.5 %, 37/40) and estimated probability than BAP1 IHC and p16-specific FISH used alone. BAP1 IHC and p16-specific FISH have independent diagnostic value, and have increased reliability when used in combination, for MPM diagnosis.

© 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy. S. Toyokuni. 2016;66(5):245-59. Review PubMed · Publisher

Abstract

Helmut Sies established the concept of oxidative stress in 1985. However, it took some time to introduce this concept into pathology, where investigators count on formalin-fixed paraffin-embedded tissue sections. I sought out antigens for this purpose based on an oxidative stress-induced rat renal carcinogenesis model, which revealed that 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins are ideal. These two monoclonal antibodies successfully revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis. Shigeru Okada established the aforementioned ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model, which thus far has answered many questions regarding the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also in human carcinogenesis. Furthermore, excess iron is a major pathology in asbestos-induced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases.

© 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary nodules: A case report. T. Hida, M. Hamasaki, S. Matsumoto, et al. 2015;65(6):318-23. Case report PubMed · Publisher

Abstract

A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.

© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung. Y. Hattori, A. Yoshida, M. Yoshida, et al. 2015;65(6):286-92. PubMed · Publisher

Abstract

Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas.

© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Primary pleural angiosarcoma associated with pneumoconiosis: An autopsy case. K. Matsuda, T. Yamaryo, Y. Akazawa, et al. 2015;65(11):603-7. Case report PubMed · Publisher

Abstract

We report a case of pleural angiosarcoma in an adult male patient confirmed by autopsy and possibly associated with pneumoconiosis. The lesion was characterized by thickened pleura of both lungs with nodular tumors. Histologically, the tumor was composed of spindle-to-polygonal epithelioid cells that were positive for CD31, CD34, vimentin, and cytokeratin on immunohistochemical staining but were negative for calretinin. Further examination revealed mix-dust pathological findings consistent with the existence of pneumoconiosis; dystrophic ossification, anthracosis, and fractal small dust particles were observed in the lung parenchyma and a hilar lymph node. The current case suggests that pneumoconiosis-associated pathologies may be risk factors for the development of angiosarcoma in the pleura.

© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Sarcomatoid pleural mesothelioma with osteosarcomatous, chondrosarcomatous and rhabdomyoblastic elements: an extremely rare autopsy case. Y. Tsukamoto, H. Hao, N. Kajimoto, et al. 2015;65(1):51-3. Case report · Letter PubMed · Publisher
Malignant pleural mesothelioma mimicking the intrapulmonary growth pattern of epithelioid hemangioendothelioma. Y. Muramatsu, K. Isobe, K. Sugino, et al. 2014;64(7):358-60. Case report · Letter PubMed · Publisher
Practical utility of insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1, and epithelial membrane antigen for distinguishing malignant mesotheliomas from benign mesothelial proliferations. S. Chang, M.H. Oh, S.Y. Ji, et al. 2014;64(12):607-12. PubMed · Publisher

Abstract

The differentiation of malignant mesotheliomas and benign mesothelial proliferations is crucial in determining patient care and prognosis. But, this distinction can be extremely difficult, particularly in small biopsies. Recently, insulin-like growth factor II mRNA-binding protein 3 (IMP3) and glucose transporter 1 (GLUT-1) have been reported as specific and sensitive markers in the distinction of mesotheliomas from benign mesothelial proliferations. The purpose of this study is to evaluate the utility of IMP3, GLUT-1, and epithelial membrane antigen (EMA) immunohistochemistry for distinguishing mesotheliomas from benign mesothelial proliferations. Immunoexpression of IMP3, GLUT-1, and EMA was evaluated in 88 malignant mesotheliomas, 35 adenomatoid tumors, and 20 benign lung tissues with reactive mesothelial cells. The sensitivity for IMP3, GLUT-1, and EMA was 37%, 21%, and 41%, respectively. The specificity for IMP3, GLUT-1, and EMA was 100%. When IMP3, GLUT1, and EMA combined, the sensitivity was 66% for IMP3/EMA staining, 53% for GLUT-1/EMA staining, and 45% for IMP3/GLUT-1. Use of IMP3 and EMA together is more helpful to distinguish malignant mesotheliomas from benign mesothelial proliferations than the use of IMP3 or EMA alone.

© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats. H. Nagai, Y. Okazaki, S.H. Chew, et al. 2013;63(9):457-62. PubMed · Publisher

Abstract

Multiwalled carbon nanotubes (MWCNTs) have attracted public attention not only for their potential applications in engineering and materials science but also for possible environmental risks. MWCNTs share similar properties with asbestos, a definite human carcinogen causing malignant mesothelioma (MM), in that they are both biopersistent thin fibers with a high aspect ratio. Certain types of MWCNTs do induce MM in animal experiments. Though there are many different types of MWCNTs awaiting use in industry, there is little evidence about what types of MWCNTs present a high risk for MM in vivo. We have previously shown that the diameter of MWCNTs is one of the critical factors for mesothelial injury, which eventually leads to MM. Because of the extensive commercial use of MWCNTs, the properties of MWCNTs that determine carcinogenic activity should be clarified. Here we report that a high dose (10 mg) of a tangled form of pristine MWCNT (with a diameter of 15 nm) did not induce MM after intraperitoneal administration in rats, which were followed for up to 3 years after injection. This observation strengthens our previous finding that the rigidity, diameter, length and surface properties of MWCNTs are important factors in MM induction in vivo.

© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Well-differentiated papillary mesothelioma, possibly giving rise to diffuse malignant mesothelioma: a case report. K. Washimi, T. Yokose, Y. Amitani, et al. 2013;63(4):220-5. Case report PubMed · Publisher

Abstract

Well-differentiated papillary mesothelioma (WDPM) is a distinct subtype of mesothelial tumor from diffuse malignant mesothelioma (DMM), with an uncertain malignant potential. The relationship between WDPM and DMM, with regard to the ability of the former to develop into the latter, is also unknown. A 58-year-old woman, diagnosed with a rectal carcinoid tumor, underwent removal of the lymph nodes via the abdomen in 2004. A large number of white miliary nodules were identified on the mesentery and peritoneum, which were histologically diagnosed as WDPM. No further therapy was administered, but the patient was followed-up using imaging methods. Seven years later, an abdominal wall mass was discovered using positron emission tomography-computed tomography, and a laparotomy biopsy was performed. DMM was diagnosed, because mesothelioma with extended invasion had been histologically identified. Mesothelioma similar to papillary proliferation was present on the outer layer of the peritoneum, and an infiltrating lesion with continuous restiform or solid-like structures was noted. WDPM was believed to have undergone malignant transformation. Compared to DMM, WDPM has a good prognosis and is considered a benign or borderline neoplasm. Our findings suggest that WDPM does have malignant potential, however, because histological findings indicated a malignant transformation of WDPM to DMM.

© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma. Y. Enomoto, T. Kasai, M. Takeda, et al. 2012;62(4):226-31. PubMed · Publisher

Abstract

An evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.

© 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Case reports of primary pulmonary adenocarcinoma with pleural spread: so-called pseudomesotheliomatous adenocarcinoma. R. Saito, A. Kasajima, S. Taniuchi, et al. 2012;62(10):709-15. Case report PubMed · Publisher

Abstract

We report two autopsy cases of primary pulmonary adenocarcinoma associated with unusual pleural spread. Both patients had confirmed history of asbestos exposure. In the first patient the tumor was localized in one pulmonary lobe with marked infiltration into pleura, chest wall and diaphragm. In the second patient the entire right lung was covered by irregularly thickened tumor. Both tumors were mainly located in the extrapulmonary area and the intrapulmonary portions represented only minor components. Histologically, tumor cells demonstrated glandular and papillary growth patterns associated with focal hobnail-like features. Immunohistochemical evaluation revealed diffuse and marked immunoreactivity of TTF-1, CEA, CD15 and MOC31 in both cases, while calretinin, CK5/6, vimentin, thrombomodulin and HBME-1 were broadly positive in one case. D2-40 was not detected in either case. Examination using electron microscopy revealed the presence of sparse and short microvilli in tumor cells. All of the above findings are consistent with adenocarcinoma of the lung. Primary adenocarcinoma with a characteristic pleural extention grossly resembling malignant mesothelioma has been previously reported in the literature as pseudomesotheliomatous adenocarcinoma. This is the first report of pseudomesotheliomatous adenocarcinoma displaying variable immunoprofile with a diagnosis using electron microscopical examination. Additionally, we performed quantitative analysis of asbestos bodies in pseudomesotheliomatous adenocarcinoma.

© 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
The recurrence of malignant pleural mesothelioma 14 years after extrapleural pneumonectomy: possible histological transformation. T. Kinoshita, G. Ishii, Y. Matsumura, et al. 2012;62(11):754-7. Case report PubMed · Publisher

Abstract

A 56-year-old man underwent extrapleural pneumonectomy for malignant pleural mesothelioma (MPM). The histological diagnosis was epithelioid mesothelioma with T2N0M0, and no sarcomatoid component was observed. Subsequently, 14 years after complete resection, screening computed tomography detected a rapidly growing right thoracic mass, which was diagnosed as a recurrence of MPM on resection. However, it was composed of both epithelioid (50%) and sarcomatoid (50%) components, suggesting possible histological transformation. Although there have been some previous reports on the recurrence of MPM, to the best of our knowledge, this is the first clinical case which indicated that histological transformation of MPM might occur.

© 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Combined adenomatoid tumor and well differentiated papillary mesothelioma of the omentum. Y. Hatano, Y. Hirose, K. Matsunaga, et al. 2011;61(11):681-5. Case report · Review PubMed · Publisher

Abstract

Herein is reported a highly rare case of combined adenomatoid tumor and well differentiated papillary mesothelioma of the omentum. A 45-year-old Japanese man was incidentally found to have a mesenteric mass during abdominal ultrasonography. Grossly, a well-circumscribed and non-encapsulated tumor, measuring 24 × 23 × 22 mm, was located in the omentum with no obvious invasion to the surrounding stomach and pancreas. Microscopically, the tumor consisted of two histological distinct components; the majority of it showed irregular arrangement of numerous cysts lined by a single layer of flattened or epithelioid cells and the multifocal minor component exhibited prominent papillary protrusions lined by a single layer of cuboidal cells with relatively uniform nucleus. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin (AE1/AE3), vimentin, calretinin, D2-40 and WT-1, and negative for epithelial membrane antigen (EMA), desmin, S-100 protein and CD68. Ki-67 labeling index of the tumor cells was <5%. The postoperative course was uneventful, though he has not received any adjuvant therapy. Despite the rarity, recognition of such combined cases of mesothelial lesions is important to prevent overdiagnosis.

© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Inactivation of Merlin in malignant mesothelioma cells and the Hippo signaling cascade dysregulation. Y. Sekido. 2011;61(6):331-44. Review PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumor arising primarily from pleural or peritoneal cavities, which is caused by asbestos exposure after long latency. One of the most frequently mutated genes detected in MM cells is the neurofibromatosis type 2 (NF2) tumor suppressor gene which is located at chromosome 22q12. The NF2 gene encodes Merlin, an ERM (Ezrin/Radixin/Moesin) protein. The underphosphorylated form of Merlin is active and acts as a tumor suppressor by regulating several distinct cellular signaling pathways. One of the downstream pathways regulated by Merlin is the Hippo signaling pathway, which is conserved from Drosophila to mammalian cells and plays important roles in organ size control and cancer development. Recent studies have identified alterations of the components in the Hippo signaling cascade in MM cells, including overexpression of Yes-associated protein (YAP) and inactivation of large tumor suppressor homolog 2 (LATS2). Dysregulation of the Merlin-Hippo signaling cascade is one of the frequent and key events of MM cell development and/or progression. Thus, a strategy to normalize this signaling cascade may be the rationale for developing a new target therapy against MM.

© 2011 The Author. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Mucin-positive epithelial mesothelioma of the peritoneum: small bowel involvement. J.H. Kim, K.Y. Kwon, Y.K. Jeon, et al. 2011;61(12):756-61. Case report PubMed · Publisher

Abstract

Mucin-positive epithelial mesothelioma has been reported in the peritoneum only once, and that mainly involved the stomach wall. We report the second peritoneal case and this is the first case mainly involving the small bowel wall. A 65-year-old man showed diffuse involvement from the duodenum to the ileum and metastatic masses in the left adrenal gland. Segmental resection of the small bowel was performed; 2 months later the patient died. Light microscopy showed diffusely anaplastic epithelioid cell proliferation and foci of glandular formation with granular mucinous materials in the cytoplasmic vacuoles or within glandular lumina. Histochemically, these mucin materials were PAS-positive and diastase-resistant. Immunohistochemically, the various mesothelial markers were positive, and a few adenocarcinoma markers were focally positive. Ultrastructurally, the tumor cells showed long slender microvilli on the apical surface, consistent with mesothelioma. Electron microscopy can play a decisive role in the case of ambiguous histochemical and immunohistochemical results.

© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Multicystic mesothelioma of the pericardium. S. Morita, A. Goto, T. Sakatani, et al. 2011;61(5):319-21. Case report PubMed · Publisher

Abstract

Multicystic mesothelioma is a well recognized but rare serosal tumor which mainly arises from the peritoneum in women and is considered as a benign lesion. This is the second case report of pericardial multicystic mesothelioma, which took a fatal clinical course. A 63-year-old man presented with pitting edema, shortness of breath, and hoarseness. Radiological investigations revealed solid and cystic tumor of the pericardium which was continuously extending into the mediastinum and the liver. Pericardial biopsy showed micro-cystic tumor lined by single layer of mesothelial cells without atypia, and the diagnosis was multicystic mesothelioma. Curative surgery could not be performed, and three years and four months later, the patient died because of the direct compression of the heart by the tumor. At autopsy, the tumor was found to be directly extending into the right pleural cavity and the right lung, besides the mediastinum and the liver. Neither malignant transformation nor metastatic tumor was identified.

© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
9p21 deletion in the diagnosis of malignant mesothelioma, using fluorescence in situ hybridization analysis. M. Takeda, T. Kasai, Y. Enomoto, et al. 2010;60(5):395-9. PubMed · Publisher

Abstract

Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as one of the most common genetic alterations in malignant mesotheliomas (MMs). Previous studies showed that this alteration might be useful for differentiating benign from malignant mesothelial tumors in cytology and surgical specimens. Although the diagnostic utility of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH) analysis has been reported only recently, it has not been well demonstrated. The purpose of this study is to evaluate the diagnostic utility of 9p21 homozygous deletion assessed by FISH in mesothelial neoplasm and hyperplasia of Japanese patients using paraffin-embedded tissue. Simultaneously, p16 protein immunoexpression was explored as a potential diagnostic aid. FISH analysis demonstrated 9p21 deletion in 35 of 40 cases with MM (88%) (P < 0.001). In contrast, no cases of adenomatoid tumor, benign mesothelial multicystic tumor, reactive mesothelial hyperplasia or pleuritis showed 9p21 deletion (P < 0.005). 9p21 homozygous deletion correlated well with p16 protein expression in the tumor cells. Our study suggests that 9p21 homozygous deletion assessed by FISH on paraffin-embedded tissue may be very useful for differentiating MM from reactive mesothelial proliferation.
Lymphohistiocytoid mesothelioma of the pleura. T. Kawai, S. Hiroi, K. Nakanishi, et al. 2010;60(8):566-74. PubMed · Publisher

Abstract

Lymphohistiocytoid mesothelioma (LHM), reported to be a rare variant of sarcomatoid mesothelioma, is challenging to differentiate from non-Hodgkin's lymphoma due to marked lymphocytic infiltration. To aid accurate recognition of LHM, we examined immunohistochemical, in situ hybridization (ISH) of Epstein-Barr virus RNA (EBER-1) mRNA, fluorescence ISH (FISH) for homozygous deletion of 9p21, and asbestos analysis in four cases (three men and 1 woman). Three patients died, while Case 4 was still alive 19 months after extrapleural pneumonectomy. Histologically, these cases were characterized by heavy lymphocytic infiltration. All neoplastic cells were positive for calretinin, AE1/AE3, and epithelial membrane antigen, but negative for CEA. EBER1 factor was negative. FISH analysis demonstrated homozygous deletion of the 9p21 locus in three of the four cases. In Case 1: (i) autopsy findings showed mesothelioma primarily located in the right parietal pleura, but metastasized into the left lung and abdominal organs; (ii) the histological findings at autopsy indicated sarcomatoid mesothelioma; and (iii) we found asbestos bodies and fibers in extracts from lung tissue (Cases 1 & 4) using digestion with bleaching fluid. LHM, an infrequent variant of sarcomatoid mesothelioma, displayed homozygous deletion of the 9p21 locus (three of four cases), and has a relatively favorable prognosis for the sarcomatoid type.
Pleural malignant mesothelioma with osteoclast-like giant cells. H. Itami, C. Ohbayashi, Y. Sakai, et al. 2010;60(3):217-21. Case report PubMed · Publisher

Abstract

Reported herein is the first case of malignant mesothelioma with osteoclast-like giant cells (OGC) in a 55-year-old man, a building contractor. Open thoracoscopic biopsy from the left parietal pleura showed a pleomorphic tumor composed of round to spindle cells mixed with numerous OGC; focal hemorrhage and necrosis were observed, but neither bone nor osteoid tissue was seen. The tumor cells had eosinophilic cytoplasm and round to oval nuclei with varying degrees of atypia. OGC had multiple small uniform nuclei without atypia and large eosinophilic cytoplasm, similar to giant cells of the so-called giant-cell tumors. On immunohistochemistry the tumor cells stained positive for AE1/AE3 and mesothelial markers, including calretinin, thrombomodulin, D2-40, and negative for carcinoma markers, including CEA, MOC31, and thyroid transcription factor-1. Consequently the tumor was diagnosed as malignant mesothelioma with OGC. Because malignant mesothelioma with OGC has not been reported to date, described herein are the histopathology and immunohistochemistry findings of this tumor, and a review of the literature.
Simple quantitative analysis of asbestos body using the sediment of formalin injected into surgically resected lung cancers. Y. Sakai, C. Ohbayashi, H. Itami, et al. 2010;60(2):78-86. PubMed · Publisher

Abstract

A simple screening method for quantitatively analyzing asbestos bodies that can be carried out even in community hospitals, is needed in order for laborers and neighborhoods in the vicinity of asbestos factories to apply for compensation for asbestos-related injury. Eighty-eight consecutive cases of surgically resected primary lung cancer were analyzed for asbestos bodies using two methods, and the correlation between them was statistically examined. The first was the conventional technique using lung tissue digestion and phase-contrast scanning, and the second was the authors' method using light microscopy to scan the sediment of formalin-injected lung specimens. The overall correlation coefficient of the concentration of asbestos bodies between the authors' method (C(AB/SED)) and the conventional method (C(AB/DLT)) was 0.4576, a weak statistically significant correlation; in patients with occupational asbestos exposure, however, the correlation coefficient was 0.7341. Despite the cost, it may be prudent to use the conventional method under the present law for patients with C(AB/SED)>or=3.5/mL. C(AB/DLT) >3000/g dry lung tissue when C(AB/SED) is >or=3.5/mL suggests the potential for the accumulation of asbestos absorption by lung tissue.

2000s

Adenomatoid tumor of the pleura. H. Minato, T. Nojima, N. Kurose, et al. 2009;59(8):567-71. Case report PubMed · Publisher

Abstract

A case of adenomatoid tumor of the pleura is reported, and its differential diagnosis from benign and malignant pleural lesions is discussed. A small pleural nodule was incidentally found during a thoracic operation in a 54-year-old woman with esophageal cancer. The patient had no history of exposure to asbestos, and was well with no sign of recurrence 14 months after the operation. A 7 mm, circumscribed tumor had characteristic features of adenomatoid tumor. The tumor was composed of an aggregation of irregularly shaped tubulocystic spaces with fibrous stoma. The spaces were lined by flattened and occasional cuboidal epithelioid cells with cytoplasmic vacuolization, and several spaces contained pale blue mucinous fluid. On immunohistochemistry the tumor cells were positive for AE1/AE3, CAM5.2, vimentin, cytokeratin 5/6, D2-40, calretinin, thrombomodulin, and WT-1, but negative for CEA, Leu M1 (CD15), thyroid transcription factor-1, epithelial membrane antigen, desmin, glucose transporter-1 (GLUT-1), CD31, and CD34. The MIB-1 (Ki-67) labeling index was 1-2%, indicating low proliferative activity. Adenomatoid tumor of the pleura is rare, and the pathogenesis has not been elucidated. Recognition of these benign mesothelial lesions in the pleura is important to avoid misdiagnosis. The immunohistochemistry in the present case supports its mesothelial origin.
Malignant peritoneal mesothelioma: quantitative analysis of asbestos burden. R. Kurimoto, T. Kishimoto, Y. Nagai, et al. 2009;59(11):823-7. Case report PubMed · Publisher

Abstract

Malignant mesotheliomas develop commonly in the pleural cavity and rarely arise in the peritoneal cavity. It is well established that asbestos exposure is related to malignant pleural mesothelioma, but the asbestos burden in the abdominal cavity in patients with malignant peritoneal mesothelioma has not been well studied. The purpose of the present study was therefore to report on an autopsy case of malignant peritoneal mesothelioma with quantitative analysis of the asbestos burden in tissues from the pleura and organs in the abdominal cavity. The patient was a 67-year-old man with a history of asbestos exposure. The peritoneum was thickened with diffuse tumor proliferation. This patient was diagnosed as having malignant peritoneal epithelioid mesothelioma. The number of asbestos fibers was >10,000/g dry tissue in all samples examined except in the small intestine. The number of asbestos fibers in the stomach was 53,000/g, which was higher than that in a control asbestosis subject. The existence of numerous asbestos fibers found in the abdominal cavity suggests that asbestos stimuli are related to the tumorigenesis of malignant peritoneal mesothelioma.
Malignant pleural mesothelioma initially diagnosed on cervical lymph node biopsy. S. Ogata, S. Hiroi, A. Tominaga, et al. 2009;59(8):592-4. Case report PubMed · Publisher

Abstract

Reported herein is a case of malignant pleural mesothelioma, initially diagnosed on cervical lymph node biopsy. A 58-year-old man, without obvious evidence of asbestos exposure, exhibited repeated pleural effusion (cause unclear), which was resolved by diuretics. A neck mass was apparent and was identified pathologically as a lymph node metastasis of malignant mesothelioma. F-18 fluorodeoxyglucose positron emission tomography/CT established the diagnosis of malignant pleural mesothelioma. Two conclusions emerge from this report: (i) cervical lymph node metastasis of pleural mesothelioma, although rare, should be included in differential diagnosis; and (ii) positron emission tomography/CT is useful for establishing a diagnosis of mesothelioma.
Malignant pleural mesothelioma: clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features. K. Hiroshima, T. Yusa, T. Kameya, et al. 2009;59(8):537-45. Case report PubMed · Publisher

Abstract

The earliest pathological events in the development of malignant pleural mesothelioma (MPM) are not understood. The aim of the present study was to elucidate the early histopathological features of MPM. A total of 16 extrapleural MPM pneumonectomy patients were investigated. Early stage mesothelioma was arbitrarily defined as a tumor < or =5 mm in thickness regardless of the nodal status or other organ involvement. Eight of these patients (six with epithelioid, two with biphasic) had early stage mesothelioma by this definition. Macroscopically there was no visible tumor, but the parietal and visceral pleura were thickened and there was focal adhesion between them. Microscopically, the mesothelioma lesions were multifocal and discontinuous on the pleura. In extremely early cases of epithelioid mesothelioma, tumor cells were generally arrayed in a single layer, but papillary proliferation was observed elsewhere. In sarcomatoid mesothelioma, mesothelioma cells proliferated, forming multiple small polypoid nodules on the pleura. Epithelial membrane antigen was helpful to distinguish reactive from neoplastic mesothelium, but glucose transporter-1 was not. Mesothelioma cells disseminate diffusely throughout the parietal and visceral pleura and mediastinal fat tissue before becoming visible. Stage Ia mesothelioma (neoplasm limited to the parietal pleura) would not be observed in daily practice.
Rosai-Dorfman disease presenting as a solitary mediastinal mass. A.I. Hida, S. Yagi, Y. Obase, et al. 2009;59(4):265-8. Case report PubMed · Publisher

Abstract

Rosai-Dorfman disease (RDD) involving an extranodal site is a diagnostic challenge. Reported herein is the case of a 67-year-old man who presented with a solitary superior mediastinal mass. The lesion was clinically suspected of malignancy including lymphoma because of its high uptake during a (67)Ga-scintigram and (18)F-fluorodeoxyglucose-positron emission tomography. There was no evidence of spread of the disease. Histology of thoracoscopic biopsy specimens indicated granulomatous lesion with infiltration of lymphocytes, plasma cells, and histiocytes with lymphocytes engulfed in their cytoplasm. The lesion did not contain lymph node or thymic elements. On immunohistochemistry the histiocytes were positive for S-100 protein, CD68, and CD163 but were negative for CD1a. These findings suggested a diagnosis of RDD. Despite lack of intervention, the lesion remained almost the same size for 3 years. To the best of the authors' knowledge this is the first case of RDD presenting as a solitary mediastinal mass.
Coalescent pleural malignant mesothelioma and adenocarcinoma of the lung, involving only minor asbestos exposure. T. Tsuzuki, H. Ninomiya, Y. Natori, et al. 2008;58(7):451-5. Case report PubMed · Publisher

Abstract

Coexistence of pulmonary adenocarcinoma and pleural malignant mesothelioma is extremely rare, although both are asbestos-related. Herein is presented a rare case of coalescent lung tumor made up of a malignant mesothelioma and a pulmonary adenocarcinoma in a 62-year-old Japanese man, a high-school teacher with only minor asbestos exposure. Preoperative diagnosis of adenocarcinoma was made on transbronchial biopsy. At surgery, multiple small white nodules were observed on the parietal pleural surface, opposite to the lung tumor. They were confirmed to be malignant mesothelioma on histopathology of paraffin section. The pulmonary tumor mass itself consisted of two distinct portions. The major part contained papillary proliferation of hobnail and columnar cells. Peripherally, neoplastic cells grew in a lepidic fashion and micropapillary growth was also detected. The other component featured tubular structures. The former was positive for adenocarcinoma markers such as CEA, Ber-EP4, PE-10, thyroid transcription factor-1 and Napsin A, and negative for mesothelial markers including calretinin, D2-40, WT-1 and HBME, while the latter was the opposite, resulting in a diagnosis of coalescing malignant mesothelioma and adenocarcinoma. The panel of antibodies used for immunohistochemistry was useful to distinguish the two different components in the one tumor.
Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma. A.R. Zekri, A.A. Bahnassy, W.S. Mohamed, et al. 2007;57(8):493-501. PubMed · Publisher

Abstract

The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. Univariate analysis showed a significant correlation between OS and stage (P = 0.03), performance status (P = 0.04), p53 overexpression (P = 0.05), asbestos exposure (P = 0.002) and SV40 (P = 0.001). Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.
Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic markers. M. Maeda, O. Hino. 2006;56(11):649-54. Review PubMed · Publisher

Abstract

Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30-40 years, and the prognosis is dismal. In addition to immunohistochemical markers, recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In contrast, the expression in renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It has also been found that N-ERC/mesothelin is very stable and plentiful in the blood. In the present paper the potential utility of molecular diagnostic markers is reviewed, including ELISA systems for asbestos-related mesothelioma.
Desmoplastic malignant mesothelioma of the pleura: autopsy reveals asbestos exposure. R. Ishikawa, E. Kikuchi, M. Jin, et al. 2003;53(6):401-6. Case report PubMed · Publisher

Abstract

Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma, and is often difficult to distinguish from reactive pleural fibrosis because of associated extensive collagen fibrosis. An 82-year-old woman with a severe cough was revealed to have pleural effusion and diffuse pleural thickening on the right side. Antibiotics were ineffective, and a compression fracture of the ninth and tenth thoracic vertebral bodies was recognized on X-ray. Autopsy revealed a diffuse pleural thickening with hyalinized collagen tissue in the central part of the pleura. However, the peripheral part of the fibrous tissue was composed of spindle and polygonal cell proliferation that were immunohistochemically positive for antibodies against cytokeratin and vimentin. In addition, the ninth and tenth thoracic spines were infiltrated by similar cells. The condition was diagnosed as desmoplastic mesothelioma with bone metastases. Asbestos bodies were detected in the thickened pleura and fibrosed alveolar septa, and it was suggested retrospectively that the patient had been exposed to asbestos. Thus, autopsy analyses of fibrous pleurisy are necessary to detect a desmoplastic variant of mesothelioma of the pleura and its association with asbestos exposure.
Malignant mesothelioma of the pericardium: case reports and immunohistochemical studies including Ki-67 expression. H. Hirano, T. Maeda, M. Tsuji, et al. 2002;52(10):669-76. Case report PubMed · Publisher

Abstract

Pericardial malignant mesothelioma (PMM) is extremely rare compared with pleural cases of mesothelioma. We present the clinical and pathological features of three autopsy cases with PMM. All three cases showed rapid progress and died of heart failure. Detailed examination was obtained from the autopsy. Macroscopic appearances of each case showed a thickened pericardium due to tumor invasion. Microscopic observations of all cases led to a diagnosis of epithelial-type malignant mesothelioma (MM). The results of immunohistochemical examinations were similar to the previous published work on pleural mesothelioma. To disclose the pathological characteristics of PMM, we analyzed Ki-67 labeling index (LI) of three cases of PMM and five cases of pleural MM that died within 2 years. The difference of Ki-67 LI between PMM and pleural MM was not significant (P > 0.05). The poor prognosis of patients with PMM must be caused by restricted cardiac wall motion due to tumor involvement, in addition to the tumor proliferation itself.
Microcystic variant of localized malignant mesothelioma accompanying an adenomatoid tumor-like lesion. H. Umezu, K. Kuwata, Y. Ebe, et al. 2002;52(5-6):416-22. Case report PubMed · Publisher

Abstract

The case of a 70-year-old man with a hitherto undescribed pleural mesothelioma is reported. The tumor was localized in the left lung apex and had invaded the parietal pleura. Histologically, the tumor was characterized by a proliferation of epithelioid cells and the formation of microcysts. The tumor cells were positive for calretinin and vimentin, and possessed abundant microvilli, indicating a mesothelial cell origin for the tumor. A high Ki-67 index and mitotic index, and the recurrence of the tumor after surgery, indicated malignancy. Based on the evidence, we propose that the tumor is a microcystic variant of a localized malignant mesothelioma.
Localized malignant mesothelioma of the pleura. H. Okamura, T. Kamei, A. Mitsuno, et al. 2001;51(8):654-60. Case report PubMed · Publisher

Abstract

We describe a case of malignant pleural mesothelioma appearing as a solitary pleural tumor in a 56-year-old Japanese man with no history of exposure to asbestos. A chest radiograph revealed an isolated extrapulmonary mass in the left hemithorax. The patient underwent tumor resection, but the tumor later recurred on the contralateral pleura. The patient developed cerebral metastases and died 16 months after the initial surgery. The resected tumor was sessile with broad-based pleural attachment. Microscopically, the tumor was composed of interlacing fascicles of plump spindle cells intermixed with few polygonal cells. Most of the tumor cells showed positive immunoreactivity for cytokeratins (AE1 and AE3) and vimentin. Many of the tumor cells were positive for epithelial membrane antigen, and a few were positive for desmin. In contrast, the tumor cells were consistently negative for carcinoembryonic antigen, epithelial antigen BerEP4, calretinin, S-100 protein, neuron-specific enolase, muscle actin antigen HHF35, alpha-smooth muscle actin antigen and CD34. Ultrastructurally, the tumor cells had diffusely distributed cytoplasmic intermediate filaments, desmosome-like junctions, and a few microvilli. Some tumor cells contained cytoplasmic tonofilaments. Immunohistochemical and ultrastructural findings supported the mesothelial nature of the tumor, and led us to diagnose this tumor as a sarcomatoid localized malignant mesothelioma.
Localized pleural malignant mesothelioma. S. Erkiliç, I. Sari, B. Tunçözgür. 2001;51(10):812-5. Case report PubMed · Publisher

Abstract

Pleural malignant mesothelioma (PMM) is a rare tumor and it is commonly seen in the form of multiple nodules or a diffuse tumor. A localized tumor mass in the pleura is extremely rare. Only seven cases have been reported. In this report, we present an additional case of localized PMM and describe the immunohistochemical and flow cytometric findings. A 61-year-old woman, without a history of smoking or asbestos exposure, presented with a severe pain in her right shoulder and arm. Chest radiography showed a solitary mass in the right upper lung field. Computed tomography showed a 5 cm right upper lung mass. Magnetic resonance imaging showed that the mass extended to the wall of the thorax. The patient underwent surgery for total removal of the tumor. Pathology revealed a localized malignant mesothelioma. Immunohistochemical analysis showed that the tumor was strongly and diffusely positive for cytokeratins with high and low molecular weight, and focally positive for vimentin and epithelial membrane antigen (EMA), but it was negative for carcinoembryonic antigen, Factor VIII, alpha-fetoprotein and Leu-M1. Flow cytometry showed an aneuploid DNA content in the tumor. The final diagnosis was localized malignant mesothelioma (epithelial type). The patient showed signs of local recurrence 5 months after surgery, and radiotherapy was given.

1990s

An autopsy case of a malignant pericardial mesothelioma in a Japanese young man. M. Watanabe, H. Suzuki, K. Fukutome, et al. 1999;49(7):658-62. Case report PubMed · Publisher

Abstract

An autopsy case of a malignant pericardial mesothelioma in a 27-year-old man with no history of exposure to asbestos is reported. He was admitted for heart failure due to pericardial effusion of unknown origin and surgically drained, but later died. The diagnosis of a malignant pericardial mesothelioma was made on the basis of histologic, immunohistochemical and ultrastructural findings. The tumor was located on the pericardium, but autopsy revealed that it had spread extensively in the mediastinum and the lungs. Microscopically, the tumor cells were epithelial like and contained histochemically demonstrable glycogen and hyaluronic acid. Immunohistochemical studies of the tumor demonstrated positive immunoreactivity for cytokeratin 19, muscle actin HHF35, epithelial membrane antigen, CA125, p53 and p21WAF1/CIP1 whereas the tumor was negative for cytokeratins 10 and 17, carcinoembryonic antigen, vimentin, epithelial antigen BerEP4, S-100, c-erbB2 and bcl-2. A high MIB-1 labeling index was noted. Under the electron microscope the tumor cells exhibited long, thin villi. The operation and autopsy findings thus revealed this to be a very rare case of malignant pericardial mesothelioma in a young man.
Cystic renal cell carcinoma: arose as a simple cyst, recurred repeatedly as a multicystic mass and finally presented as a solid mass. Y. Shishikura, M. Furusato, S. Aizawa. 1998;48(8):623-8. Case report PubMed · Publisher

Abstract

An unusual case of cystic renal cell carcinoma in a 70-year-old Japanese male is reported. He had had a simple renal cyst removed 1 year ago. On presentation the right kidney was surrounded by multiple translucent cysts, which varied in size from 1 to 50 mm. The cyst walls were lined by single-layered cuboidal epithelium. The differential diagnosis included cystic mesothelioma, cystic lymphangioma and multicystic dysplastic kidney. An immunohistochemical and ultrastructural study and flow cytometric analysis of DNA ploidy were performed. The tumor was differentiated to such an extent that it was difficult to diagnose as carcinoma; however, it recurred repeatedly. Three and a half years after initial presentation the tumor had invaded the ileum with the pathological change to be almost solid when viewed grossly and, microscopically, showed tubulo-papillary structures in addition to a cystic pattern. The DNA ploidy pattern revealed a near-diploid aneuploid in the early specimen and a polyploid aneuploid in the last specimen.
An autopsy case of diffuse malignant mesothelioma of the pericardium. N. Sakuma, T. Kamei, T. Unoki, et al. 1997;47(1):64-7. Case report PubMed · Publisher

Abstract

A report is presented of an autopsy case of a 71-year-old Japanese man with a diffuse malignant epithelial mesothelioma of the pericardium with massive pericardial effusion and a thickened pericardium. He had no history of exposure to asbestos. He suffered severe heart failure and later died. Autopsy revealed that the tumor had developed over the pericardium. Microscopically, the tumor cells were arranged in an epithelial form, and histochemically, the cytoplasm of these cells contained glycogen and hyaluronic acid. The tumor tissue showed immunohistochemical positivity for cytokeratin, epithelial membrane antigen, vimentin, cancer antigen 125, thrombomodulin, mesothelial antigen, muscle actin and human milk fat globule. In contrast, all the tumor cells were negative for human carcinoembryonic antigen and epithelial antigen. Ultrastructurally, the tumor cells had long, thin microvilli, abundant intermediate filaments, intracytoplasmic lumina and long desmosomes. It is considered that the patient had a typical malignant epithelial mesothelioma of the pericardium.
Nodular pulmonary amyloidosis associated with asbestos exposure. K. Hiroshima, H. Ohwada, M. Ishibashi, et al. 1996;46(1):66-70. Case report PubMed · Publisher

Abstract

A 71 year old man was admitted for the purpose of diagnosis of a right solitary pulmonary nodule. The size of the nodule was 18 x 18 mm in diameter 2 years ago, but it has become large, 25 x 25 mm in diameter. The nodule was resected by thoracotomy. Microscopically, eosinophilic amorphous, acellular substances were surrounded by inflammatory infiltrates. It stained with Congo red stain and showed green birefringence with polarizing microscopy. Amyloid fibrils were observed electron microscopically. Asbestos bodies were observed in the lung parenchyma around the nodule. This case shows that a nodule in nodular pulmonary amyloidosis can grow gradually and suggests the possibility of asbestos fibers as one of the etiologic factors in nodular pulmonary amyloidosis.
Solitary fibrous tumor of the nasal cavity and orbit. M. Fukunaga, S. Ushigome, K. Nomura, et al. 1995;45(12):952-7. Case report PubMed · Publisher

Abstract

Solitary fibrous tumors (SFT) are rare spindle cell neoplasms generally associated with the serosal surface, especially the pleura. Two SFT are reported arising in the nasal cavity and orbit, occurring in a 33 year old female and a 21 year old male, respectively. The lesions lacked the characteristic features of other recognized neoplasms that occur in these regions. Immunohistochemically, the tumors cells were diffusely and strongly positive for vimentin and CD34 and some or many tumor cells expressed neuron-specific enolase and Leu-7. Ultrastructurally, the tumor cells showed no distinct features although they were suggested to be primitive mesenchymal or fibroblast-like cells. Both tumors were diploid by flow cytometry. The two patients have had benign clinical courses with limited follow-up. Our findings suggest that SFT is of mesenchymal cell origin and support another location for SFT, indicating additional evidence against mesothelial origin. SFT should be included in the differential diagnosis of spindle cell tumors arising in the nasal cavity and orbit.
An autopsy case of malignant mesothelioma associated with asbestosis. M. Watanabe, N. Kimura, M. Kato, et al. 1994;44(10-11):785-92. Case report PubMed · Publisher

Abstract

An autopsy case of malignant mesothelioma with asbestosis caused by asbestos exposure for 17 years is reported. Autopsy revealed that mesothelioma spread extensively in all serosal tissues including pleura, pericardium, diaphragm, peritoneum and tunica vaginalis testis. Histopathologically, most of the tumor showed an epithelial form, but sarcomatous and microcystic patterns were also observed. The tumor cells had abundant glycogen and hyaluronic acid and, immunohistochemically, they were positive for cytokeratin, vimentin and epithelial membrane antigen (EMA). Long, slender microvilli were characteristically observed in these tumor cells. All of these data were compatible with malignant mesothelioma. Procollagen type I (procol.l) immunostaining was performed to reveal the mesenchymal character of mesothelioma. Both epithelial-type cells and sarcomatous-type cells showed positive staining for procol.l, although the latter showed stronger immunoreactivity. Immunostaining for procol.l was found to be one of the useful tools for distinguishing mesothelioma from adenocarcinoma. Using an extraction method for asbestos fibers, asbestos bodies were found in many tissues including lymph nodes, liver, small intestine, spleen, kidney, testis and pleura, in addition to lung parenchyma. Although multiple tumor metastases from an undetermined primary site is not ruled out, 'multifocal tumorigenesis' is suspected from the widespread deposit of asbestos fibers.

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