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A Case Of Malignant Mesothelioma Pleural Effusion With MOC‐31, BerEP4, And Calretinin Expression

Po Zhao
Published 2019 · Medicine

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To the Editor: Recent guidelines indicate cytologic diagnosis of malignant mesothelioma supported by ancillary techniques to be as reliable as that based on histopathology. It is strongly recommended that all malignant mesothelioma cases to be confirmed by immunocytochemistry (ICC) or immunohistochemistry (IHC). However, none of the ICC or IHC markers is entirely specific, which can sometimes lead to misinterpretation of the results. Here, I report a case of malignant mesothelioma with characteristic imaging findings and malignant pleural effusion that was found to be positive for calretinin, but also MOC-31 and BerEP4 by immunohistochemical stains. The tumor showed sarcomatoid features and focal D2-40 (podoplanin) immunohistochemical reactivity on the subsequent needle biopsy, and was diagnosed as sarcomatoid mesothelioma. Awareness of the expression of MOC-31 and BerEP4 in a small subset of malignant mesotheliomas can prevent misdiagnosis of adenocarcinoma in such cases. The patient is an 80-year-old man with a medical history of gastroesophageal reflux disease and hypertension, who presented with persistent cough for a month, left-sided chest pain, and shortness of breath. Initial computerized tomography (CT) scan of the chest showed a large left pleural effusion with nearly complete collapse of the left lung, as well as 5.2 × 4.2 cm consolidation in the left upper lobe. Initial clinical impression was primary lung cancer. A left thoracentesis removed 2 L of bloody fluid. A ThinPrep and a cellblock were processed for cytologic examination. ThinPrep showed unequivocally malignant cells predominantly in large three-dimensional clusters or tissue fragments with scalloped to smooth surfaces. Malignant cells exhibited finely dispersed chromatin, one to multiple macro nucleoli, and moderate amount of cytoplasm (Figure 1A,B). A panel of immunohistochemical stains was performed on the cell block, including MOC-31, BerEP4, TTF-1, Napsin A, estrogen receptor (ER), CDX2, prostate-specific antigen (PSA), CK7, CK20, calretinin, CK5/6, and D2-40. Malignant cells were positive for MOC-31, BerEP4, calretinin (mostly nuclear staining), and CK7 (Figure 1C-E). Antibodies to other markers were largely nonreactive. A diagnosis of metastatic adenocarcinoma was made based on the MOC-31 and BerEP4 results. However, calretinin expression is unusual to be seen in lung adenocarcinomas, although it has been shown in some breast carcinomas. Subsequent CT scans of the abdomen and pelvis showed diffuse left pleural thickening and enhancement with multiple pleura-based masses. There was no evidence of abdominal metastasis. A positronemission tomography (PET) study revealed hypermetabolic nodular left pleural thickening with small effusion and left hemidiaphragm invasion involving peritoneum, but no hypermetabolic lymph node or other metastasis. These imaging findings were most consistent with mesothelioma. A CT-guided needle biopsy of left peritoneal masses was performed to further clarify the diagnosis. Histologic examination showed sarcomatoid proliferation of malignant cells (Figure 1F). A panel of immunohistochemical stains was performed, including AE1/AE3, cam5.2, CK7, CK20, vimentin, TTF-1, Napsin A, PAX8, CDX2, PSA, PSAP, CD10, CK5/6, calretinin, D2-40, WT-1, EMA, and desmin. Malignant spindle cells were positive for AE1/AE3, CAM 5.2, CK7, vimentin, and CD10. All the other markers were negative. Because all the mesothelial markers tested were negative in the tumor, a diagnosis of poorly differentiated carcinoma with sarcomatoid features was made. This case was subsequently sent to a national academic institution, where immunohistochemical stains showed tumor cells were positive for AE1/AE3 and focally for D2-40, but negative for calretinin, WT1, CK5/6, and mesothelin. BRAC1-associated protein 1 (BAP1) retained nuclear expression. A diagnosis of sarcomatoid mesothelioma was made based on these results. It is possible that there were both epithelioid and sarcomatoid components in this malignant mesothelioma. The epithelioid component was positive for MOC-31, BerEP4, and calretinin as demonstrated in the pleural effusion, whereas the sarcomatoid component was focally positive for D2-40 as shown in the needle biopsy. Immunohistochemical and immunocytochemical stains have been well studied to distinguish between metastatic adenocarcinoma and malignant mesothelioma in malignant effusions. Commonly used antibodies against proteins expressed by adenocarcinomas include MOC31, BerEP4, B72.3, CD15 (Leu-M1), carcinoembryonic antigen (CEA), and claudin-4. Commonly used mesothelial (both benign and malignant) markers include calretinin, CK5/6, D2-40, WT1, and mesothelin. Tissue specific markers can be added when a history of malignancy or a source of suspicion can be identified. MOC-31 and BerEP4 are antibodies both against the epithelial cell adhesion molecule (EpCAM), although it has been shown that MOC-31 performs better than BerEP4 in terms of both detecting carcinomas and reactivity with epithelioid mesotheliomas. B72.3 antibodies identify tumor-associated glycoprotein-72 (TAG-72), a high-molecular-weight mucin-like molecule. TAG-72 is low or nondetectable in normal adult tissues except secretory endometrium, but overexpressed in most adenocarcinomas. Only a small percentage (<10%) of epithelioid mesotheliomas have been found TAG-72 positive. Sarcomatoid mesotheliomas have not been shown to express this marker. CEA consists of a group of highly Received: 27 February 2019 Revised: 14 July 2019 Accepted: 4 September 2019 DOI: 10.1002/dc.24315
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