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Distinguishing reactive mesothelial cells from metastatic disease, typically adenocarcinoma, in effusion cytology can be challenging at times. We currently use a panel of immunocytochemical markers for select cases including MOC-31 and BerEp4, but difficulties still exist. Enhancer of zeste homologue 2 (EZH2) plays important roles in epigenetic silencing and cell cycle regulation and is upregulated in a wide variety of malignancies. Thus, we hypothesized that EZH2 immunocytochemistry, which to our knowledge has not yet been reported on cytology material, might serve as a unique marker of malignancy in morphologically equivocal effusion specimens by highlighting aberrant protein expression in malignant cells. A total of 96 (48 benign and 48 malignant) effusion cases were selected retrospectively from our department archives. All malignant cases were metastatic adenocarcinomas except for three high grade neuroendocrine carcinomas (two lungs and one ovary), one cervical squamous cell carcinoma, and one epithelioid endometrial stromal sarcoma. The 48 benign cases were all negative for EZH2, and 43 of 48 malignant effusions were positive. As a solitary marker, EZH2 exhibited a sensitivity of 90% and a specificity of 100% (P < 0.0001). EZH2 functioned as a unique and accurate marker of malignancy in this series of effusions. Relative to published data, EZH2 demonstrated a sensitivity comparable to MOC-31 and superior to BerEp4, and a specificity superior to both of these commonly used immunostains. Thus, EZH2 is likely to be of great value as an adjunct to morphology in diagnosing malignancy in effusion specimens., (Copyright © 2013 Wiley Periodicals, Inc.)

Multicystic peritoneal mesothelioma (MPM) is an uncommon cystic mesothelial proliferative lesion. It occurs predominantly in women of reproductive age and most commonly arises in the pelvis. The preoperative diagnosis of MPM is difficult to establish based on clinical and radiographic findings, and has therefore traditionally been diagnosed following surgical resection. Due to differing management of MPM and its differential diagnoses including both benign and malignant lesions, it would be beneficial to diagnose MPM preoperatively. We report a case of MPM in a middle aged female that was diagnosed by fine needle core biopsy and touch preparations, allowing for appropriate clinical management. The cytomorphologic features of needle core biopsy, immunocytochemical studies and differential diagnosis are discussed. Furthermore, despite its infrequency, the current case emphasizes the importance of the inclusion of this entity in the differential diagnosis of cystic lesions of the abdomen and pelvis at the time of on-site evaluation and final diagnosis, in order to avoid misinterpretation of strips of benign mesothelial cells as inadequate for diagnosis.

Mesothelioma is a neoplasm arising from the mesothelial cells lining the body serosal surfaces. The frequent primary sites include the pleura followed by the peritoneum and rarely the pericardium. Pleural mesothelioma encases the lung and fills the pleural space, which limits the lungs' ability to expand. The initial diagnosis requires the presence of characteristic clinical, radiological, and pathological features. A thorough review of the English language literature found no reports where a diagnosis of mesothelioma was made on material originating from bronchioalveolar lavage (BAL). We report a case of lung parenchymal involvement by mesothelioma shedding cells in BAL specimen.

Malignant mesothelioma with deciduoid features (MMWDF) is a recently characterized morphologic variant of epithelioid malignant mesothelioma, which frequently is misdiagnosed as peritoneal deciduosis or florid mesothelial hyperplasia. We report on the cytological, histological, immunohistochemical, and autopsy findings of a case of MMWDF arising in the pericardium of a 71-yr-old female patient. Cytology showed large, polygonal to round cells with pale to bright, eosinophilic cytoplasm, occasionally showing xantomatous pattern, containing a pleomorphic and vesicular nucleus with a single prominent nucleolus. Autopsy examination showed a neoplasm encasing the heart and great vessels. No other primary neoplasm was found. The histological analysis disclosed the typical features of MMWDF. Immunohistochemistry showed diffuse immunoreactivity for cytokeratin MNF116, HBME-1, and calretinin in the neoplastic cells, as well as focal positivity for epithelial membrane antigen positivity in a brush border-like pattern. All other markers were negative. We would like to stress that pathologists must be aware of the cytological and histological features of this rare variant of epithelioid malignant mesothelioma in order to avoid a misdiagnosis of a benign process or a metastatic malignancy.

Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of malignant mesothelioma. The oncogenic capacity of SV-40 is a function of a nuclear protein, the large T antigen (Tag). SV-40 Tag DNA sequences are detected by the polymerase chain reaction in 40-80% of malignant mesothelial proliferations. However, the role of immunohistochemistry (IHC) in demonstrating the nuclear localization of Tag is controversial. We sought to determine the clinical utility of SV-40 Tag IHC in pleural effusion cytology as an ancillary tool in the cytologic diagnosis of malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell block sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101. Despite strong and consistent immunoreactivity in positive controls, no nuclear immunostaining was observed in any case. We believe the small sample size in cytology cell block sections, the low viral copy number in infected cells, and the effect of formalin fixation may have resulted in absence of immunoreactivity. The role of SV-40 Tag IHC in diagnostic cytopathology remains unclear unless further studies reliably show its detection., (Copyright 2001 Wiley-Liss, Inc.)

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material., (Copyright 2001 Wiley-Liss, Inc.)

Cytological slides of serous fluids of 41 malignant mesotheliomas, 88 metastatic adenocarcinomas, and 25 reactive effusions were immunostained with the antibodies anti-CEA, MOC-31, Leu-M1, Ber-EP4, and B72.3. Most mesotheliomas and all reactive fluids failed to stain with these antibodies. The sensitivity of the five markers to detect carcinoma cells differed remarkably. Especially MOC-31, Ber-EP4, and B72.3 stained with a high number of carcinoma cases and the complemetary value of Ber-EP4 and B72.3 to immunostain carcinoma cells was impressive: 94% of the metastatic adenocarcinoma cases reacted with Ber-EP4 or B72.3 in contrast to 1 of 41 malignant mesotheliomas.