Infrastructure of Poorly Differentiated Diffuse Epithelial Mesotheliomas

Abstract

In differentiating diffuse epithelial mesothelioma from metastatic adenocarcinoma in pleural and peritoneal biopsies, the number and form of microvilli and the amount and distribution of tonofilaments are thought to be the most useful criteria. This report details 5 cases of diffuse epithelial mesothelioma in which the characteristic fine structural features of neoplastic mesothelial cells were markedly modified. The majority or all tumor cells were poorly differentiated in electron micrographs, particularly with reduced prominence or absence of intermediate filaments, desmosomes, intracytoplasmic lumina, and microvilli. Immunohistochemistry revealed the absence of carcinoembryonic antigen and the presence of cytokeratin in all cases. Comparison with a better differentiated case suggests cytologic details that are useful in distinguishing the poorly differentiated type of epithelial mesotheliomas from adenocarcinoma. These include a mosaic pattern of closely associated tumor cells with a few long, narrow cytoplasmic processes lying parallel to adjacent plasma membranes, abundant cytoplasm with limited organelles usually having a polar arrangement, and nuclei with markedly disaggregated chromatin and prominent nucleolonemal-type nuclei.

Localized malignant mesothelioma of the pleura

“…Ultrastructurally, typical diffuse epithelial mesotheliomas are characterized by long slender sinuous surface microvilli, well‐formed desmosomes, abundant cytoplasmic intermediate filaments, intracellular and intercellular lumina with microvilli, and the absence of microvillous core rootlets 36–39 . These features are depleted in sarcomatoid or poorly differentiated epithelial mesotheliomas 37,39,40 . Although they consist mostly or entirely of poorly differentiated fibroblast‐like cells, most sarcomatoid mesotheliomas contain foci of rudimentary epithelial differentiation in the form of microvillous processes, aggregates of intermediate filaments, or desmosomal junctions 23,24 …”

“…[36][37][38][39] These features are depleted in sarcomatoid or poorly differentiated epithelial mesotheliomas. 37,39,40 Although they consist mostly or entirely of poorly differentiated fibroblastlike cells, most sarcomatoid mesotheliomas contain foci of rudimentary epithelial differentiation in the form of microvillous processes, aggregates of intermediate filaments, or desmosomal junctions. 23,24 In the present case, the tumor showed sarcomatoid histological features.…”

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

“…Sarcomatous mesotheliomas for the most part do not show specific ultrastructural features, and tumors that are poorly differentiated by light microscopy and do not demonstrate a typical pattern of immunohistochemical staining usually lack specific features by electron microscopy as well. 98,99 Occasionally, electron microscopy is useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either MM or serous carcinoma is needed. 65 Formalin-fixed material retrieved from a paraffin block may be satisfactory, since microvilli and tonofilament bundles tend to be preserved.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…However, the diagnostic utility of electron microscopy may be more limited in the setting of poorly differentiated tumors. 75,76 Benign mesothelial proliferations are also in the differential diagnosis of MM. Morphologic features favoring malignancy include dense cellularity, complex papillae, tubules, cellular stratification, and necrosis.…”