The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement

Diagnostic Cytopathology. 2006 Dec;34(12):801-6. [Link]

Reda S. Saad, M.D., Ph.D. 1 *, Jennifer L. Lindner, D.O. 2, Xiaoqi Lin, M.D. 2, Yulin L. Liu, M.D., Ph.D. 1, Jan F. Silverman, M.D. 1

1Department of Pathology, Drexel University College of Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania
2Department of Pathology, Allegheny General Hospital, Pittsburgh, Pennsylvania

email: Reda S. Saad (

*Correspondence to Reda S. Saad, Department of Pathology and Laboratory Medicine, Assistant Professor, Drexel University College of Medicine, Allegheny General Hospital, 3rd floor South Tower, 320 East North Avenue, Pittsburgh, PA 15212


Differentiating malignant mesothelioma (MM) from pulmonary carcinoma in pleural fluid cytology can be challenging. Recent studies have suggested that D2-40, a novel lymphatic marker, may be a useful marker for mesothelial differentiation in surgical specimens. However, there are no available data regarding its utility in effusion cytology specimens. We investigated the utility of D2-40 in pleural fluid cytology in differentiating MM from pulmonary carcinomas. Twenty cases of pleural effusion smears of surgically confirmed MM with their corresponding cell blocks were retrieved from the database of the hospital computer system. We also included 10 cases of metastatic pulmonary adenocarcinoma (PA) and 10 cases metastatic pulmonary squamous cell carcinoma (PSCC) involving the pleural fluid. Cell blocks were formalin-fixed, paraffin embedded, and immunostained for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40. Cases were scored as negative (<5% positivity) or positive (>5% moderate/strong positivity). The positive rates for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40 were as follows: MM (0/20), (0/20), (17/20), (18/20), (19/20), (17/20), for PA (8/10), (0/10), (3/10), (0/10), (0/10), (0/10), and for PSCC (1/10), (10/10), (6/10), (10/10), (0/15), (0/10). The staining pattern for D2-40 was characterized by thick membranous staining. Diffuse cytoplasmic staining by D2-40 was seen in 2 cases of pulmonary carcinoma, counted as negative. Our study showed that in differentiating MM from PA, CK5/6, WT-1, and D2-40 have high specificity and sensitivity for MM. Although calretinin is a sensitive IHC marker for MM, it is not specific since it stained 30% of PA. Conversely, to differentiate between MM and PSCC, p63 and WT-1 are the best available markers. We recommend a panel of CK5/6, p63, D2-40, and WT-1 to differentiate MM from pulmonary carcinomas in effusion cytology specimens.