Quantification of Leydig cells and stromal hyperplasia in the postmenopausal ovary of women with endometrial carcinoma

Hum Pathol. 2019 Mar;85:119-127. doi: 10.1016/j.humpath.2018.10.022. Epub 2018 Nov 11.


Endometrioid endometrial carcinomas (EECs) are correlated with high serum levels of androgens and estrogen. We hypothesized that Leydig cells and ovarian stromal hyperplasia contribute to postmenopausal ovarian androgen production and are observed more frequently in EEC patients. Ovaries of postmenopausal women with EEC (n = 36) or non-endometrioid endometrial carcinoma (NEEC; n = 19) were examined for the presence of hilar Leydig cells and compared with ovaries resected for benign conditions (n = 22). Leydig cells were counted manually, and a Leydig cell density was calculated per millimeter squared hilar surface. Ovarian stromal hyperplasia was scored as atrophic, moderate hyperplastic, or marked hyperplastic. In all endometrial carcinomas, these findings were correlated with the serum levels of sex steroids and hormone receptor expression in their endometrial carcinomas. In EEC patients, mean number of Leydig cells was 282.8 cells compared with 76.3 cells in NEEC patients and 66.4 cells in controls. Leydig cells, marked stromal hyperplasia, and combined presence were observed more frequently in EEC patients compared with NEEC and controls. Combined presence was associated with higher serum sex steroid levels and increased tumor expression of estrogen and progesterone receptor. A cutoff value for Leydig cell hyperplasia could be proposed at a total of 300 Leydig cells bilaterally, examining a representative cross section of both hili. Concluding, we have quantified hilar Leydig cells and demonstrated that Leydig cells may contribute to the development of EEC by increased androgen production in postmenopausal women. The correlation between sex hormone levels and Leydig cell hyperplasia may support endometrial pathology screening in these women.

Keywords: Endometrial neoplasms; Hormone receptors; Leydig cell hyperplasia; Leydig cells; Serum sex steroids; Stromal hyperplasia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenedione / blood
  • Carcinoma, Endometrioid / blood
  • Carcinoma, Endometrioid / pathology*
  • Dehydroepiandrosterone Sulfate / blood
  • Endometrial Hyperplasia / blood
  • Endometrial Hyperplasia / pathology*
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / pathology*
  • Endometrium / pathology
  • Estradiol / blood
  • Female
  • Humans
  • Leydig Cells / pathology*
  • Male
  • Middle Aged
  • Ovary / pathology*
  • Postmenopause / blood
  • Retrospective Studies
  • Stromal Cells / pathology*
  • Testosterone / blood


  • Testosterone
  • Androstenedione
  • Estradiol
  • Dehydroepiandrosterone Sulfate