Differentiation of mesothelioma from adenocarcinoma in serous effusions: The role of hyaluronic acid and CD44 localization

Abstract

Differentiating cells of mesothelial origin from adenocarcinoma (ACA) based on morphology alone can be a diagnostic challenge, especially in cytological specimens. Malignant mesothelioma (MM) is characterized by accumulation of abundant intracellular hyaluronic acid (HA), a feature that is not reported in ACA. The purpose of this study was to evaluate the significance of cellular HA using an HA-specific binding peptide (HABP) and the expression of its principal receptor, the standard CD44 molecule (CD44S). Archival paraffin-embedded cell blocks of serous fluids from 28 cases of reactive mesothelial cells, 14 cases of MM, 20 cases of metastatic ovarian carcinomas, 17 cases of metastatic breast carcinomas, 12 cases of metastatic lung ACA, and 12 cases of metastatic gastrointestinal ACA were stained with HA using a biotinylated HABP and CD44S. Positive staining was defined as droplet to diffuse cytoplasmic staining for HA and uniform membranous staining for CD44S. All MMs and 93% (26/28) of the benign mesothelial cells were positive for intracytoplasmic HA vs. none of ACAs. CD44S was expressed in 100% (28/28) of mesothelial hyperplesia, 86% (12/14) of MMs, 70% (14/20) of ovarian carcinomas, 29% (5/17) of breast carcinomas, 25% (3/12) of gastrointestinal ACAs, and 8% (1/12) of lung ACAs. In MM and reactive mesothelial cells, CD44S stained cell membranes diffusely with highlights on the villous surfaces and in ACA it was focal and confined to cell membranes. Immunostaining with HA is a reliable marker that can distinguish between cells of mesothelial origin (reactive mesothelial cells and MM) and ACA. The CD44S staining pattern of cells of mesothelial origin is of diagnostic significance. CD44 may prove useful in conjunction with other stains in the differential diagnosis of mesothelioma and ADA.

Diagnostic Utility of MOC-31, HBME-1 and MOC-31mRNA in Distinguishing Between Carcinoma Cells and Reactive Mesothelial Cells in Pleural Effusions

“…Such errors in diagnosis usually are caused by misinterpretation of adenocarcinoma cells as reactive mesothelial cells. 9 The rate of false positive diagnoses also is significant and often caused by overinterpretation of reactive mesothelial cells as malignant cells. 5 ICC can greatly aid in such diagnostic dilemmas, but, currently, available markers have varying sensitivities and specificities for mesothelial cells or cells of epithelial differentiation.…”

Early cytological diagnosis of diffuse malignant mesothelioma of the peritoneum: A case report

“…27,28 Many studies have reported the use of different immunocytochemical panels comprising various antibodies in the differential diagnosis between reactive mesothelial, adenocarcinoma, and malignant mesothelioma cells in serous effusions. 13,29,30 Some authors reported about the role of DNA-ICM (DNA-ploidy) in effusion cytology. The results have shown that nonmalignant mesothelial lesions (reactive mesothelial proliferations) were all DNAdiploid or -polyploid, and all DNA-aneuploid lesions in contrast corresponded to malignant tumors.…”

Preparation of the methyl ester of hyaluronan and its enzymatic degradation

“…16 Recent studies have indicated that hyaluronan can also exist intracellularly, however, the intracellular functions of hyaluronan are unknown. 17 Chondroitin has a structure similar to that of hyaluronan in which the 2-acetamido-2-deoxy-D-glucopyranose residue of hyaluronan is replaced with a 2-acetamido-2-deoxy-D-galactopyranose residue.…”