Diagnostically Confusing Aspects of the Physiologic Ovarian Follicle: A Report of 57 Cases and Brief Review of Selected Other Non-neoplastic Ovarian Lesions

We performed a retrospective review of cases sent in consultation wherein physiological ovarian follicles, corpora lutea, or their constituent cells raised concern for malignancy based on architectural or cytologic features. The 57 cases were broadly divided into 4 groups. The largest (n=31) showed tangential sections through the granulosa (n=18) or theca (n=13) layers of developing follicles. The irregular appearance, high baseline mitotic activity (median: 20 mitoses/10 high-power fields), and occasional Call-Exner–like spaces (n=6) contributed to concern. The second group (n=20) consisted of corpora lutea in which tangential sectioning or partial involution imparted an unusually complex architecture; mitoses were prominent in 8 of these cases, and endocrine-type atypia was seen in 5. The third group consisted of 2 cases in which corpora albicantia formed an appreciable mass. The final group consisted of 4 cases where artifactually detached granulosa cells from developing follicles were present within vascular spaces, mimicking intravascular malignancy. Extensive sampling revealed no associated ovarian neoplasm. In discussing these unusual appearances of physiological granulosa and theca cells, we briefly review the histology of developing follicles and other benign proliferations that may mimic sex cord-stromal neoplasia. Awareness of these variations of normal histology is critical to prevent misdiagnosis of malignancy.