Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature

Abstract

Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma "misclassification", "misdiagnosis", "diagnostic challenge" or "diagnostic pitfall" and on unsolved questions about its histogenesis and possible risk factors.

Keywords: asbestos; mesothelioma; misdiagnosis; ovarian mesothelioma; talc.

Figure 1

Case 1. Histological section of papillary ovarian mesothelioma ((a) hematoxylin and eosin stain, original magnification ×200). The neoplastic cells were strongly positive for calretinin ((b) immunohistochemistry, original magnification ×200). FISH analysis showed CDKN2a (p16) heterozygous deletion (c). Upon ultrastructural examination, the neoplastic cells showed microvilli-like expansion (arrow, inset) on the luminal surface ((d) original magnification ×4400; inset original magnification ×30,000). The SEM micrograph of foliated talc crystals ((e) arrow) and EDX analysis spectrum of the particle (f) were compatible with its general chemical formula (Mg₃Si₄O₁₀(OH)₂). SEM image of quartz crystal and EDX analysis spectrum (g,h).

Figure 2

Case 2. Histological section of ovarian mesothelioma with solid and trabecular patterns ((a) hematoxylin and eosin stain, original magnification ×200) and diffusely immunoreactive calretinin ((b) immunohistochemistry, original magnification ×200). Lack of nuclear expression of BAP1 ((c) immunohistochemistry, original magnification ×400). The neoplastic cells showed numerous elongated and branching microvilli on the luminal surface ((d) original magnification ×4400). At higher magnification, desmosome-like junctions and intracytoplasmic tonofilaments were evident (inset, original magnification ×10,000). The SEM micrograph (e) and EDX analysis (f) spectrum were morphologically and chemically (chemical formula: Ca2Mg5Si8O22(OH)2) compatible with tremolite fiber. In the same specimen, quartz ((g) arrow) and talc crystals ((g) dashed lines) were also evident with the respective EDX analysis spectrum ((h left) quartz; (h right) talc crystal).

Figure 3

Case 3: Histological section of ovarian mesothelioma with papillary pattern ((a) hematoxylin and eosin stain, original magnification ×200) and diffusely immunoreactive calretinin ((c) immunohistochemistry, original magnification ×200), and D2-40 ((e) immunohistochemistry, original magnification ×200). Case 4: Histological section of ovarian mesothelioma with solid pattern and deciduoid cytology ((b) hematoxylin and eosin stain, original magnification ×200) and diffusely immunoreactive calretinin ((d) immunohistochemistry, original magnification ×200), and D2-40 ((f) immunohistochemistry, original magnification ×200).