Squamous cell carcinoma in serous effusions: Avoiding pitfalls in this rare encounter.

Background: With advent of personalized medicine, precise classification of malignant tumors becomes essential. Squamous cell carcinoma (SCC) is rarely found in serous effusions and has morphologic and immunohistochemical (IHC) overlap with other neoplasms.

Methods: 17-year review identified 49 fluids from 26 patients where SCC was recognized.

Results: SCC was more frequent in pleural fluid (84%) and rare in other effusions. Lung SCC was common (65%), followed by head and neck (16%), with other origins less represented. 19 samples were diagnosed positive for SCC, 12 were reported as non-small cell carcinoma and 13 were atypical/suspicious. Two were false negative (on hypocellular smears) and one was false positive (smear with small orangeophilic squamous-like cells). Two fluids were diagnosed as adenocarcinoma on smears and SCC on cellblocks after IHC. A chi-square test showed the correct diagnosis more often on cellblocks than smears (P-value = .0005) and all false positive, negative or misclassifications were done on cytology smears. Ber EP4 and MOC 31 immunostains were positive in most cases when performed, and the most specific immunostains for SCC were p63 and p40. Negative mucin stains were helpful. Cytology smears are imperfect tools in evaluation of body fluids and SCC can be misclassified as adenocarcinoma on smears alone. Orangeophilic cytoplasm can lead to false positive results. The most useful stains for identification were p40, p63, and mucicarmine.

Conclusion: The combination of clinical history with cellblock preparation and appropriate IHCs is the best method to ensure a correct diagnosis.