What is the pathophysiology of granulosa cell tumors (GCTs) of the ovaries?

Updated: Aug 30, 2018
  • Author: David C Starks, MD, MPH; Chief Editor: Warner K Huh, MD  more...
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Answer

Two theories exist to explain the etiology of sex cord–stromal tumors. The first proposes that these neoplasms are derived from the mesenchyme of the developing genital ridge. The second purports that sex cord and stromal cells of the mature ovary are derived from precursors found within the mesonephric and coelomic epithelium.

Reports of extraovarian GCTs can be found in the literature and may lend support to the derivation of this class of tumors from epithelium of the coelom and mesonephric duct.

Various theories propose explanations for the differentiation of normal granulosa and/or stromal cells into neoplastic entities. To date, no clear etiologic process has been identified. However, the most recent molecular data regarding these tumors have linked a missense point mutation (C402G) in the FOXL2 gene to granulosa cell tumors. [2] Using whole transcriptome sequencing of 4 adult GCTs, the mutation in FOXL2 was identified. They confirmed this mutation was present in an additional 86 of 89 adult GCTs, 3 of 14 thecomas, and 1 in 10 juvenile-type GCTs. Moreover, the mutation was not found in any of 49 sex cord stromal tumors of other types or in epithelial ovarian tumors. This suggests a potential pathogenic mutation and raises the possibility of identifying novel targeted therapies. [3]

GCTs are thought to be tumors of low malignant potential. Most of these tumors follow a benign course, with only a small percentage showing aggressive behavior, perhaps due to early stage at diagnosis. Metastatic disease can involve any organ system, although tumor growth usually is confined to the abdomen and pelvis.


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