July 2019 Case Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions July 2019 Case Authors Yagi, DO (PGY-3); Dr. Stacey Kim (Faculty) Subject Pulmonary pathology Clinical History 66-year-old female with hypertension, diabetes mellitus and a history of tobacco use presents to the emergency department with shortness of breath. Initial imaging showed a large right-sided pleural effusion. She then underwent thoracentesis demonstrating an exudative effusion suspicious for malignancy, however, cytologic evaluation was negative for malignant cells. Subsequent imaging revealed a new right lower lobe atelectasis vs. underlying consolidation. The patient was ultimately taken to the operating room for a video-assisted thorascopic surgery (VATS) where a thickened pleural peel was identified and sent for intraoperative consultation (see figure 1). This specimen was extensively necrotic but categorized as "pleomorphic and epithelioid malignancy". Enough tissue was preserved for further histologic evaluation and work-up. Figures Figure 1 (H&E, 20x): Frozen section, "Extensively necrotic pleomorphic and epithelioid malignancy" Figure 2 (H&E, 20x): Permanent section Figure 3 (20x): Immunohistochemical stains, Positive mesothelial markers Figure 4 (20x): Immunohistochemical stains, Negative carcinoma markers Diagnosis Epithelioid malignant mesothelioma Discussion Malignant mesothelioma is a rare malignancy that arises from the mesothelial-lined surfaces of the pleura, peritoneum, pericardium or tunica vaginalis. Pleural mesothelioma is the most common form and is highly associated with asbestos exposure. Patients typically present with nonspecific respiratory symptoms such as cough, dyspnea and pleural effusions. Although in the right clinical setting malignant mesothelioma may be highly suspected, a tissue diagnosis is required. Microscopically, malignant mesothelioma appears as a cellular proliferation of mesothelial cells which may demonstrate a wide range of cytologic atypia. The key diagnostic feature is the presence of invasion of these atypical cells, often into fat. Malignant mesothelioma exhibits three distinct histology subtypes: epithelioid, sarcomatoid or a mixed (biphasic) pattern. Epithelioid mesothelioma is the most common subtype and is composed of polygonal, oval or cuboidal cells that appear similar to their benign counterparts. Within this group, there are multiple secondary growth patterns that can be appreciated. Sarcomatoid variants predominantly consist of spindled cells while the mixed (biphasic) mesotheliomas show both epithelioid and sarcomatoid areas. The use of immunohistochemical stains is extremely helpful when evaluating a potential case of malignant mesothelioma. Due to its often epithelioid features, the most important differential diagnosis to exclude is metastatic carcinoma. Based on sensitivity and specificity, the best markers for confirming mesothelioma are calretinin, cytokeratin 5/6, WT1 and podoplanin (D2-40). Conversely, the carcinoma markers of MOC31 and BEREP4 should be negative. Tissue specific markers may also be of help in evaluating for metastatic disease. However, the breast marker GATA3 can be positive in up to one-half of epithelioid mesotheliomas and PAX8, which indicates Mullerian or renal origin, may sometimes stain peritoneal mesotheliomas and benign mesothelial cells. In general, it is recommended that concordance of two positive mesothelioma markers and two negative carcinoma markers be present for a definitive diagnosis of malignant mesothelioma. References Husain, Aliya Noor, et al. "Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the International Mesothelioma Interest Group." Archives of Pathology & Laboratory Medicine 142.1 (2017): 89-108. Arif, Qudsia, and Aliya N. Husain. "Malignant mesothelioma diagnosis." Archives of Pathology & Laboratory Medicine 139.8 (2015): 978-980. 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