Answer: Metastatic clear cell carcinoma of the vagina

Histology: The tumor has a microfollicular appearance, with clear cells surrounding pink proteinaceous material. The clear cytoplasm is due to glycogen, as demonstrated on PAS stains with and without diastase. The tumor cells are non-immunoreactive for both thyroglobulin and thyroid transcription factor 1, which essentially excludes thyroid and pulmonary origin. This patient had a history of vaginal clear cell carcinoma arising from vaginal adenosis as a result of in utero DES exposure. Given the immunoprofile, histologic findings and clinical history, the findings are consistent with a metastasis from the vaginal primary.

Discussion: Clear cell carcinomas of the lung may be either squamous cell carcinoma or adenocarcinoma. One would expect a primary pulmonary adenocarcinoma, in most cases, to demonstrate TTF-1 immunoreactivity. A metastatic well-differentiated thyroid carcinoma should be immunoreactive for both thyroglobulin and TTF-1. An alveolar adenoma is a rare lesion which is multi-cystic, well-circumscribed and consists of delicate septa separating ectatic spaces lined by flattened type 2 pneumocytes. The spaces may contain eosinophilic granular material, similar to that seen in the current case. However, there is virtually no atypia in an alveolar adenoma, which contrasts with the current lesion.

Clear cell carcinoma of the vagina arising in adenosis associated with in utero DES exposure may have a variety of architectural patterns (tubulocystic, solid or papillary) and cell shapes (flat, cuboidal or hobnail). The current case demonstrates an exaggerated tubular pattern with typical clear cell cytology. In its primary site, the differential diagnosis includes microglandular adenosis, the Arias-Stella reaction, and endodermal sinus tumor (yolk-sac tumor).