COVID-19 (coronavirus)

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
Extensively necrotic pleomorphic and epithelioid malignancy

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
  1. 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.
  2. Arif, Qudsia, and Aliya N. Husain. "Malignant mesothelioma diagnosis." Archives of Pathology & Laboratory Medicine 139.8 (2015): 978-980.
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