‘Mucin‐positive’ epithelial mesothelioma of the peritoneum: an unusual diagnostic pitfall

Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signetring cell mesotheliomas were positive for calretinin, keratin 5/6, keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that exhibit signet-ring features. Modern Pathology (2013) 26, 370-384; doi:10.1038/modpathol.2012.172; published online 5 October 2012Keywords: electron microscopy; immunohistochemistry; signet-ring cell carcinoma; signet-ring cell mesotheliomaThe finding of occasional vacuolated cells exhibiting signet-ring-like morphology is not rare in mesotheliomas; however, epithelioid mesotheliomas having a large number of such cells are relatively uncommon and have been subclassified as signet-ring cell mesotheliomas. 1 Signet-ring cell carcinomas can arise in a wide variety of organs, including lung, 2-6 stomach, 7,8 colon, 8-10 breast, 8,11,12 urinary bladder, 13-17 pancreas, 18 salivary glands, 19 and prostate. [20][21][22][23][24][25][26][27][28] The signet-ring configuration seen in adenocarcinomas has traditionally been associated with the accumulation of large amounts of intracytoplasmic mucin. It can also occur as a result of the formation of a true intracytoplasmic lumen with displacement of the nucleus toward the periphery of the cell, in which case, spe...

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confidence: 99%

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confidence: 99%

Mesothelioma with signet-ring cell features: report of 23 cases

Ordóñez

2013

“…Based on their light microscopic features, the 2004 WHO Classification defines four major histologic subtypes of diffuse malignant mesothelioma: epithelioid, sarcomatoid, mixed epithelioid and sarcomatoid (biphasic), and desmoplastic. 1 Although epithelioid mesotheliomas most frequently present a tubulopapillary, adenomatoid (microglandular) or solid pattern, on rare occasions, they may present other histologic patterns, including deciduoid, [2][3][4] clear cell, 5,6 adenoid cystic, 7 pleomorphic, 8,9 small cell, 10,11 rhabdoid, 12 glomeruloid, 13 signet-ring cell 14,15 and oncocytoid. 16 Some of these patterns, such as the pleomorphic, however, have not been well defined.…”

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confidence: 99%

Pleomorphic mesothelioma: report of 10 cases

Ordóñez

2012

Mesotheliomas with pleomorphic features are rare and only a few studies on this mesothelioma variant have been published. Little information regarding the immunoprofile of these tumors and none on their electron microscopic features was included in these studies. Herein are reported 10 cases of pleomorphic mesothelioma that were investigated using a large panel of immunohistochemical markers, 4 of which were also studied by electron microscopy. All of the patients were men and seven had a history of asbestos exposure. Nine of the cases originated in the pleura and one in the peritoneum. Histologically, the tumors were characterized by being composed of large, often discohesive, cells that varied in size and shape, had dense abundant eosinophilic cytoplasm, and single or multiple irregular nuclei, which often contained one or several large nucleoli. Mitotic activity was high and atypical mitoses frequent. Immunoreactivity for pan-keratin and keratin 7 was strong in all of the cases. Expression for calretinin, WT1, podoplanin, mesothelin and keratin 5/6 was also frequent, but variable. All cases were negative for MOC-31, carcinoembryonic antigen, CD15, TAG-72 and thyroid transcription factor-1. Electron microscopy often showed the presence of abundant long, slender microvilli on the cell membrane of the neoplastic cells. These findings demonstrate that, contrary to what has been suggested by some investigators, both immunohistochemistry and electron microscopy can be very helpful in assisting in the diagnosis of pleomorphic mesotheliomas. That the seven patients who underwent extrapleural pneumonectomy had extensive lymph node metastasis and that the median survival of those patients for whom follow-up information was available was only 8.2 months indicates that mesotheliomas with pleomorphic features are associated with highly aggressive clinical behavior. Therefore, when this subtype of epithelioid mesothelioma is present, it should be reported as it can significantly affect the prognosis and treatment of the patient.

“…Most epithelioid mesotheliomas exhibit a tubulopapillary, adenomatoid (microglandular), or solid pattern, but on occasion, may present other histologic patterns, including deciduoid, [1][2][3] clear cell, 4,5 signet-ring, 6 adenoid cystic, 7 rhabdoid, 8 pleomorphic, 9,10 oncocytoid, 11 glomeruloid, 12 and small cell. 13 Some of the variants of epithelioid mesothelioma, such as the small cell variant, have not yet been well-defined and their existence remains somewhat controversial.…”

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confidence: 99%

Mesotheliomas with small cell features: report of eight cases

Ordóñez

2012

Mesotheliomas with small cell morphology are rare and only one study of such cases has been published. As a result of their rare occurrence, some investigators have cast doubt on the existence of such a histologic variant of mesothelioma. This investigator reports a series of eight cases of epithelioid mesothelioma with small cell features, all of which originated in the pleura. Seven of the patients were men and one was a woman. Four patients had a history of asbestos exposure. Histologically, four of the mesotheliomas were epithelioid and four biphasic. The proportion of small cells seen in these cases constituted 80 to 100% of the tumor included in the biopsy material and 15 to 20% of the tumor present in the pneumonectomy specimens. Immunoreactivity for calretinin, keratin 5/6, keratin 7, pan-keratin, WT1, podoplanin, and mesothelin was seen in all cases tested for these markers. All of the cases were negative for MOC-31, Ber-EP4, CEA, CD15, TAG-72, TTF-1, chromogranin A, synaptophysin, CD99, and desmin. The mean survival of the six patients for whom this information was available was 8.2 months. It is important for pathologists to be aware that mesotheliomas can present small cell features and, because of this, they can be confused with other malignancies that can exhibit similar morphology. The value of immunohistochemistry in the differential diagnosis of these tumors is discussed.