Background: Immunocytochemistry involving single or double antibodies can be used to support or confirm a diagnosis in difficult cytology cases. There are a few reports on the application of a cocktail of 3 antibodies in the literature. We would like to report our experience using this technique in a difficult case of cervical lymph node fine-needle aspiration cytology (FNAC). Case: A 75-year-old woman presented with a left neck mass for which FNAC was performed. The aspirates were cellular comprising atypical cells present in loose aggregates. The cells exhibited an ovoid and spindled morphology with no evidence of keratinization or any other differentiating features. The cytology was suggestive of metastatic poorly differentiated neoplasm; however, the presence of ovoid histiocytic-looking cells required further assessment. Triple immunostaining using a cocktail of CK5/6, CK34, and CD68 was performed. The spindled atypical cells were positive for CK5/6 and CK34 (brown cytoplasmic staining) and the ovoid histiocytic-looking cells were positive for CD68 (red cytoplasmic staining). Based on immunostaining, the cytological diagnosis of metastatic squamous cell carcinoma was confirmed. Conclusion: In view of our findings, the utility of triple immunocytochemical staining in cytology smears of poorly differentiated malignancy and a brief review of the literature are highlighted in this report.

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