The role of immunohistochemistry in distinguishing squamous cell carcinoma from mesothelioma and adenocarcinoma in pleural effusion

Seminars in Diagnostic Pathology. 2006 Feb;23(1):15-9. [Link]

Li Q, Bavikatty N, Michael CW.

Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.


Background: Distinguishing metastatic squamous cell carcinoma (SCC) from malignant mesothelioma (MM) and adenocarcinoma (ADC) in pleural effusions may be particularly challenging by routine cytologic stains. We explored the utility of using a panel of six antibodies to differentiate SCC from MM and ADC.

Design: 33 cases of pleural cytologic preparations retrieved from our archives consisted of 9 cases of SCC, 12 cases of epithelial MM, and 12 cases of adenocarcinoma of lung. Cell blocks were prepared by the thrombin clot technique followed by formalin-fixation and paraffin-embedding. Tissue sections of 4 microm were stained with hematoxylin and eosin and the immunoperoxidase method visualized by the biotin-streptavidin-peroxidase system. The antibodies used were cytokeratins (CAM 5.2, K903, and CK 5/6), cell membrane glycoproteins (CEA and Ber-EP4), and calretinin. In all cases, the reactivity pattern was graded on a sliding scale from 0 to 4+ according to the percentage of reactive cells.

Results: SCC was positive for K903 (100%), CK 5/6 (89%), CAM 5.2 (78%), and CEA (22%), and negative for Ber-EP4 (100%) and calretinin (100%). MM was positive for calretinin (100%), CAM 5.2 (100%), K903 (92%), CK 5/6 (92%), and negative for CEA (100%) and Ber-EP4 (100%). ADC was positive for CAM 5.2 (100%), CEA (83%), and Ber-EP4 (83%), and negative for calretinin (100%), K903 (92%) and CK 5/6 (92%).

Conclusions: Our studies confirm the role of the above panel of antibodies in distinguishing among these malignancies. Positive staining for K903, CK 5/6, and CAM 5.2 separated SCC and MM from ADC. Positive staining for calretinin separated MM from SCC and ADC. Positive staining for glycoproteins and predominantly negative staining for CK 5/6, K903 and calretinin separated ADC from SCC and MM.