Cytomorphology of unusual primary tumors in the Pap test

Rare entities in the Pap test, which include neoplastic and non-neoplastic conditions, pose challenges due to the infrequent occurrence of many of these entities in the daily practice of cytology. Furthermore, these conditions give rise to important diagnostic pitfalls to be aware of in the Pap test. For example, cases with adenoma malignum (AM) have been called benign. Recognition of these conditions can help correctly interpret Pap tests as abnormal and thereby ensure that patients get appropriately diagnosed. In this paper, we illustrate and discuss selected uncommon primary neoplastic lesions of the cervix and the vagina that may be seen in Pap test, with a focus on cytomorphology, differential diagnosis and the role of possible ancillary studies. These cases include high-grade squamous intraepithelial lesion cells with small cell morphology; small cell carcinoma; large neuroendocrine carcinoma; glassy cell carcinoma; AM; malignant mixed Müllerian tumor; clear cell carcinoma and primary malignant melanoma. Recognition of these rare variants/neoplasms is important so that involved Pap tests are not diagnosed as benign and that patients with these conditions get additional follow-up.