Uncommon Cervical Lesions: A Review and Discussion of the Differential Diagnosis

* Context.--While the vast majority of cervical tumors consist of human papillomavirus (HPV)-related squamous cell carcinoma or adenocarcinoma, a subset of rare tumor types, frequently unrelated to HPV, does occur in this location. These tumors vary widely in prognostic and therapeutic implications, and accurate recognition is crucial to providing appropriate treatment. Some are benign or portend a favorable prognosis (adenoid basal carcinoma, ectopic prostate tissue), while others are frankly malignant lesions with a less favorable prognosis (adenoid cystic carcinoma, HPV-negative endocervical adenocarcinoma, mesonephric adenocarcinoma, clear cell carcinoma, small cell carcinoma, and adenosquamous carcinoma). Objective.--To review the morphologic features of uncommon cervical lesions, the utility of immunohistochemistry for distinction between these entities, and the clinical and prognostic implications of accurate diagnosis. Data Sources.--University of Michigan cases and review of the pertinent literature regarding the entities described. Conclusions.--Key morphologic and immunohistochemical features detailed herein will allow for the accurate distinction between these uncommon cervical lesions. Morphology is most useful in discriminating between the entities, as there is frequent immunohistochemical overlap between them; however, in rare instances immunohistochemistry can be useful in resolving the diagnosis. (Arch Pathol Lab Med. 2021;145:891-902; doi: 10.5858/arpa.2020-0327-RA)