Post-irradiation pericardial malignant mesothelioma with deletion of p16: a case report

Abstract

Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.

Keywords: Hodgkin's lymphoma; Pericardial malignant mesothelioma; p16 deletion; post-irradiation.

1

Cytology and immunocytochemistry of pericardial epithelioid mesothelioma. (A) Diff-Quik shows clusters of atypical epithelioid cell proliferation (Diff-Quick staining, 40 x). Immunocytochemical stains show that the tumor cells are positive for calretinin (B) and WT1 (C) and they are negative for MOC31 (D). (B, C, D immunocytochemical staining, 20 x). WT1: Wilms tumor protein; MOC31: epithelial associated monoclonal antibody.

2

Pericardial epitheliod mesothelioma (IHC staining, 20 x). (A) The pericardial biopsy shows nested malignant epithelioid cells invading into fibroadipose tissue. Immunohistochemical stains show the malignant epitheliod cells are positive for WT1 (B), CK 5/6 (C) and calretinin (D). WT1: Wilms tumor protein; CK: cytokeratin.

3

Homozygous deletion in the CDKN2A in pericardial malignant epithelioid mesothelioma. Interphase FISH analysis was performed with dual color chromosome 9 probe, centromere 9 (green)/9p21- CDKN2A (red) (inset), showing bi-allelic deletion (loss of red signals) of 9p21 in the tumor cells.