Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations

Abstract

Malignant mesothelioma (MM) is a rare tumor of mesothelial cells, with an increasing incidence both in developed and developing countries. MM has three major histological subtypes, in order of frequency, according to the World Health Organization (WHO) Classification of 2021: epithelioid, biphasic, and sarcomatoid MM. Distinction may be a challenging task for the pathologist, due to the unspecific morphology. Here, we present two cases of diffuse MM subtypes to emphasize the immunohistochemical (IHC) differences, and to facilitate diagnostic difficulties. In our first case of epithelioid mesothelioma, the neoplastic cells showed cytokeratin 5/6 (CK5/6), calretinin, and Wilms-tumor-1 (WT1) expression, while remaining negative with thyroid transcription factor-1 (TTF-1). BRCA1 associated protein-1 (BAP1) negativity was seen in the neoplastic cells' nucleus, reflecting loss of the tumor suppressor gene. In the second case of biphasic mesothelioma, expression of epithelial membrane antigen (EMA), CKAE1/AE3, and mesothelin was observed, while WT1, BerEP4, CD141, TTF1, p63, CD31, calretinin, and BAP1 expressions were not detected. Due to the absence of specific histological features, the differentiation between MM subtypes could be a challenging task. In routine diagnostic work, IHC may be the proper method in distinction. According to our results and literature data, CK5/6, mesothelin, calretinin, and Ki-67 should be applied in subclassification.

Keywords: asbestos; epithelioid; immunohistochemistry; malignant mesothelioma; sarcomatoid malignant mesothelioma.

FIGURE 1

Case presentation 1—epithelioid mesothelioma. (a) Chest X‐ray examination of the patient showed signs of congestion of the pulmonary circulation, cardiomegaly and fluid accumulation in the left sinus. (b) The tumor consisted of monomorphic, epithelioid cells with severe atypia. Mild cohesion between cancer cells were visible, with small gaps among cellular interactions (HE, 40x). (c) CK5/6 IHC revealed intensive cytoplasmic positivity (CK5/6, 40x). (d) Cancer cells were block positive with calretinin staining (calretinin, 40x). (e) Alongside with positive control, the cancer cells showed expression loss of BAP1, proving mutation (BAP1, 40x). (f) Proliferation factor was 10% (Ki‐67, 40x)

FIGURE 2

Case presentation 2—sarcomatoid mesothelioma. (a) Positron emission tomography/computed tomography (PET/CT) scan after the first surgery revealed tumorous thickening of the pleura and the ribs. (b) Spindle cell morphology cancer cells are visible, with pleomorphism. A large number of mitotic figures are also present (hematoxylin and eosin [HE], 40x). (c) CK5/6 IHC remained negative (CK5/6, 40x). (d) Cancer cells proved to be negative with calretinin staining (calretinin, 40x). (e) Loss of function mutation of BAP1 is visible (BAP1, 40x). (f) Proliferation fraction was 60% (Ki‐67, 40x)