Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report

Abstract

Mesothelioma in situ (MIS) is defined as a preinvasive mesothelioma that forms a single layer of mild atypical mesothelial cells lining on the serosa surface of pleura. The atypical mesothelial cells present loss of BRCA-1 associated protein-1 (BAP-1) and/or methylthioadenosine phosphorylase as examined by immunohistochemistry (IHC) and/or homozygous deletion of cyclin-dependent kinase inhibitor 2A/p16 as examined by fluorescence in situ hybridization. It is difficult to diagnose because of the unremarkable clinical findings except for pleural effusion. The present report describes a case in which MIS was diagnosed at the time of sampling due to the presence of clearly malignant mesothelial cells in the pleural fluid. In 2016, a 74-year-old man with a history of past exposure to asbestos was admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) with dyspnea. Chest CT indicated only right pleural effusion. Malignant mesothelial cells were suspected in a cell block made using pleural effusion; therefore, right pleural biopsy was performed. Pathologically, there was proliferation of mesothelial cells with mild atypia that formed a single-flat layer on the pleural surface; however, there was no invasion. Furthermore, IHC revealed loss of BAP-1 in cells from the biopsied pleura and pleural effusion. MIS was suspected at the time; however, the patient arbitrarily quit his medical check-ups. After 44 months, the patient was readmitted to our hospital complaining of dyspnea. CT indicated a large right pleural mass. A specimen of the mass obtained via CT-guided needle biopsy revealed malignant mesothelioma. The patient continued to deteriorate and eventually died. This case indicated that pleural effusion could be used to demonstrate overtly malignant mesothelial cells and diagnose MIS at the time of sampling. To the best of our knowledge, this is first report of MIS with overtly malignant mesothelial cells in pleural effusion. Pleural effusion may serve an important role in MIS diagnosis.

Keywords: BAP-1; atypical cells; cell block; first obtained pleural fluid; malignant mesothelial cells.

Figure 1.

Chest X ray and CT from the patient's first visit to our hospital showing only right pleural effusion. R, right side; L, left side.

Figure 2.

Cytological specimen of right pleural effusion showing malignant cells. Based on the cell block made using pleural effusion, (A) H&E staining showed malignant cells that formed glomerular or papillary clusters (magnification, ×400). In detail, the cells presented nuclear enlargement, irregular nuclear membranes, frequent binucleation or multinucleation indicated by the blue arrows, humps indicated by the red arrows and cellular pleomorphism. (B) H&E staining also showed nuclear enlargement, binucleation or multinucleation indicated by blue arrows (magnification, ×400). Immunohistochemically, the cells were positive for (C) podoplanin (D2-40) in the cytoplasmic membrane (magnification, ×400), (D) calretinin in the cytoplasm and nucleus (magnification, ×400) and (E) EMA in the cytoplasm and membrane (magnification, ×400), while they were negative for (F) desmin (magnification, ×400) and (G) BAP-1 (magnification, ×400). BAP-1, BRCA-1 associated protein-1; EMA, epithelial membrane antigen.

Figure 3.

Pathological finding in the first right pleural biopsy showing mildly atypical mesothelial cells forming a single layer indicated by black arrows based H&E staining. (A) Magnification, ×100. (B) Magnification, ×200. (C) Loss of BAP-1 (magnification, ×100) and (D) presence of MTAP (magnification, ×100) based on immunohistochemistry, and (E) presence of CDKN2A based on FISH (original magnification, ×63). BAP-1, BRCA-1 associated protein-1; CDKN2A, cyclin-dependent kinase inhibitor 2A; FISH, fluorescence in situ hybridization; MTAP, methylthioadenosine phosphorylase.

Figure 4.

Chest X-ray and CT 44 months after the patient had first visited our hospital showing the appearance of a large mass infiltrating some ribs and thoracic wall in the right lower lung and another mass in the mediastinum. R, right side; L, left side.

Figure 5.

CT-guided needle biopsy of the right large mass was performed. (A) Cytology of needle lavage fluid showing atypical cells with nuclear enlargement indicated by black arrows (magnification, ×600). (B) The pathological findings based on H&E staining included tumor cells with humps on the edge indicated by red arrows (magnification, ×200) and (C) positive for HEG-1 based on IHC (magnification, ×200). Also shown are the results of right pleural biopsy, with (D) loss of BAP-1 (magnification, ×200) and (E) presence of MTAP (magnification, ×200) based on IHC, and (F) presence of CDKN2A based on FISH (original magnification, ×63). BAP-1, BRCA-1 associated protein-1; CDKN2A, cyclin-dependent kinase inhibitor 2A; FISH, fluorescence in situ hybridization; HEG-1, sialylated protein HEG homolog 1; IHC, immunohistochemistry; MTAP, methylthioadenosine phosphorylase.