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

Diagnostic Cytopathology. Volume 32, Issue 3, Pages 145 – 150. Published Online: 2 Feb 2005. [Link]

Alaa M. Afify, M.D. 1 *, Robert Stern, M.D. 2, Claire W. Michael, M.D. 3

1Department of Pathology, University of California, Davis, California
2Department of Pathology, University of California, San Francisco, California
3Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan


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. Diagn. Cytopathol. 2005;32:145-150. © 2005 Wiley-Liss, Inc.