Primary Ovarian Leiomyoma with Torsion in a Postmenopausal Woman: A Rare Case with Progesterone Receptor Positivity.

A 73-year-old P3 L3 postmenopausal female presented with complaints of spotting per vaginum along with pelvic pain for 1 month. The pain was dull and aching with no aggravating or relieving factors. The patient had an insignificant past medical and surgical history. She gives no personal and/or family history of gynecologic disorders. The menarche was at the age of 17 years following which she had regular menstrual cycles throughout. She had uneventful vaginal delivery of three full-term healthy babies. The patient attained menopause at the age of 50 years and had no history of any hormone replacement therapy (HRT). Her body mass index (BMI) was 20.4 kg/m 2 . Her vitals were normal. Abdominal examination revealed a firm to hard, globular, nontender mass with irregular surface just palpable above pubic symphysis on the right side. Bimanual examination revealed 10 cm × 8 cm mass of the same consistency occupying the pouch of Douglas and extending above toward the right iliac fossa. Laboratory evaluation including complete blood count, inflammatory markers, and kidney and liver function tests were unremarkable. Her Ca125 and CEA values were 18.8 U/mL and 5.64 ng/mL, respectively. Trans vaginal ultrasound showed a solid, hypoechoic, heterogeneous ovarian mass 9.4 cm × 6.2 cm in size in the right adnexa along with normal size uterus but thick endometrial lining (ET-13 mm). Plain magnetic resonance imaging (MRI) pelvis showed a homogenous solid mass of size 10 cm × 6.7 cm with thick endometrium (ET-12 mm) likely ovarian fibroma [ Figure 1 ]. Her hysteroscopy showed multiple polypoidal growths of the endometrium. An endometrial biopsy was done and histopathological examination revealed disordered proliferative endometrium. A cervical smear cytology Papanicolaou test revealed negative for intraepithelial lesion or malignancy. Magnetic resonance imaging (MRI) showing a homogenous T1 hypointense and T2 hypointense lesion with a tiny focal T2 hyperintense area with diffuse restriction noted in right adnexa likely ORADS MRI 4 with thick endometrium (ET: 11mm) With these investigations, a provisional diagnosis of right ovarian fibroma with thick endometrial lining was made. Intraoperatively a right ovarian solid well circumscribed bosselated mass of 10 cm × 7 cm with no extension/adhesion to surrounding structures was found twisted thrice over infundibulo-pelvic axis [ Figure 2 ]. The uterus, B/L fallopian tubes and left ovary (atrophic) appeared grossly normal. Total abdominal hysterectomy with bilateral salphingo-oophorectomy was done. A frozen section of the resected specimen was not performed due to a strong suspicion of benign pathology, supported by preoperative MRI characterization indicating a likely diagnosis of ovarian fibroma, further corroborated by intraoperative findings. The postoperative period was uneventful and she was discharged on day 5 of surgery. The patient is doing well and has no signs of tumor recurrence after 1 year of follow-up. Histopathological examination of the ovarian mass showed a well-circumscribed tumor of spindle cell morphology arranged in intersecting fascicles with ill-defined cell border, elongated nuclei, blunt ends, and scant-moderate amount of cytoplasm with focal areas of hyalinization. A morphological diagnosis of leiomyoma of the ovary was given which was further confirmed by diffuse immunohistochemical expression of smooth muscle actin and desmin in the tumor cells. Immunohistochemical markers for estrogen and progesterone receptors (ER/PR) were studied [ Figure 3 ]. The tumor cells showed strong expression of PR while ER receptors did not show any positivity. Endometrium showed strong positivity for both ER and PR [ Figure 4 ]. Solid right ovarian tumor twisted thrice over its infundibulopelvic axis Composite picture of histopathology and immunohistochemistry of ovarian mass. (a) Ovarian mass showing intersecting fascicles of smooth muscle bundles, with blunt ends, hyperchromatic nuclei, and indistinct eosinophilic cytoplasm. (b) Diffuse cytoplasmic positivity for smooth muscle actin in >90% of tumor cells. (c) Immunonegativity for Estrogen receptor. (d) Nuclear immunopositivity for progesterone receptor in 80%–90% of tumor cells Composite picture of histopathology and immunohistochemistry of endometrium. (a and b) Variable sized glands, with few of them cystically dilated and filled with secretions in a compact to oedematous stroma indicating disordered proliferative endometrium. (c) Strong nuclear immunopositivity for estrogen receptor in both endometrial glands and stroma. (d) Moderate nuclear immunopositivity for progesterone receptor in both endometrial glands and stroma

Leiomyomas are benign tumors of smooth muscle commonly found in the uterus but can occasionally develop in other locations too. Leiomyomas of the ovary are rare, accounting for <1% of benign ovarian tumors.[ 1 ] These tumors are typically seen in premenopausal women and their occurrence in postmenopausal women often raises concerns about malignancy.[ 2 ] Imaging and clinical features are frequently nonspecific, making histopathological analysis essential for an accurate diagnosis. We present here a rare case report of torsion of ovarian leiomyoma in a 73-year-old woman presenting with postmenopausal bleeding with immunohistochemistry analysis of tumor cells revealing strong positivity for progesterone receptors. The index case underscores the possible role of progesterone in stimulating the growth of ovarian leiomyoma, even in a postmenopausal woman.

Ovarian leiomyomas are extremely rare whereas uterine leiomyomas are among the most common pelvic tumors in women of reproductive age. Approximately 70 cases have been reported in literature till now[ 2 ] and about only one-sixth of cases are discovered in postmenopausal women.[ 3 ] The precise origin of ovarian leiomyomas remains unclear and several hypotheses have been proposed regarding their pathogenesis. They are presumed to arise from the smooth muscle cells of the ovarian blood vessels, ovarian ligament, or even from ectopic smooth muscle tissue possibly derived from Müllerian or Wolffian duct remnants. There is another theory of its development through metaplastic transformation of the stromal cells within the ovary.[ 4 ] The closest differential diagnosis includes the fibroma-thecoma group of tumors which can be differentiated by immunohistochemistry workup. Some ovarian leiomyomas are associated with conditions such as ovarian fibromas, endometriosis, or pregnancy, suggesting that hormonal factors may play a role in their development, particularly in premenopausal women however the growth of the entity in postmenopausal women remains a mystery. In postmenopausal women, where the incidence of leiomyomas should generally decrease due to the decline in estrogen, finding of this benign ovarian tumor raises concern about the origin and trigger of growth after cessation of ovarian function in them. In our case even if we assume the leiomyoma originated during her premenopausal years, such long-standing tumors would have shown features of degeneration which was absent in our case. Eventually, we evaluated the ER and PR status of the tumor cells which showed strong positivity for PR only. Endometrium was strongly positive for both ER and PR. A review of the literature on published cases [ Table 1 ] of ovarian leiomyoma in postmenopausal women shows that they were aged between 50 and 68 years. Most of them presented with abdominal pain with no other pathologies of the uterus. The size of the leiomyomas varied, ranging from as small as 1 cm to as large as 16 cm. Histopathological analysis of all cases revealed an absence of mitosis or nuclear atypia. Tumor markers were insignificant in almost all of them. However, none of the studies included immunohistochemical analysis (ER and PR) of the tumor cells. Published cases of ovarian leiomyoma in postmenopausal women YSM: Years since menopause, UP: Uterine pathology, TMs: Tumor markers, NA: Nuclear atypia, CEA: Carcinoembryonic antigen, NK: Not known, SM: Surgical menopause, PMB: Postmenopausal bleeding, P: Parity, A: Abortion, MA: Mitotic activity Brodowska et al . conducted an immunohistochemical analysis of steroid receptors in the ovaries of postmenopausal women operated for benign uterine disease. They found that PR, ER-α, and androgen receptor (AR) were present in the normal ovaries of postmenopausal women. While the expression levels of PR and AR remained unchanged, the expression of ER-α gradually decreased after menopause.[ 13 ] However, they included patients between 48 and 60 years. Our patient was 73 years old with positive progesterone receptors. Studies indicate that progesterone may promote the growth of fibroids by increasing cell proliferation and decreasing cell death (apoptosis) within fibroid tissue. It also stimulates the production of growth factors that support fibroid development as well as regulates the production of growth factors like transforming growth factor-beta, which contributes to extracellular matrix production, further increasing fibroid size.[ 14 15 ] This effect helps explain why fibroids often enlarge during pregnancy when progesterone levels are elevated. This may also explain the growth of ovarian leiomyoma in our case. Though the levels of progesterone decrease significantly after menopause, leiomyomas may continue to grow in women where ovarian function has ceased due to the activity of extra-ovarian sources of hormones (e.g., adrenal or adipose tissue-derived androgens converted to estrogen) or HRT. The presence of progesterone receptors suggests that even minimal levels of progesterone could potentially influence the growth of leiomyomas in these women.[ 16 ] We discovered thick endometrium with positive ER and PR in this woman and histopathology was suggestive of disordered proliferative endometrium. It has been substantiated that all postmenopausal endometria preserve their entire complement of ER and PR, regardless of their functional status.[ 17 ] Endometrial proliferative activity in postmenopausal women is also not inherently abnormal. Archer et al .[ 18 ] along with Korhonen et al .,[ 19 ] found proliferative activity in approximately 25% and hyperplastic disease in <5% of endometrial biopsy specimens of asymptomatic postmenopausal women. Sivridis and Giatromanolaki also identified weakly proliferative patterns in approximately 26.2% of disease-free endometria from asymptomatic postmenopausal women who had undergone hysterectomy for prolapse.[ 20 ] This proliferative pattern observed is likely a response of the uterine mucosa to continuous low-level estrogenic stimulation. This aligns with the reported increased capacity of postmenopausal women to convert androstenedione, primarily of adrenal origin, into estrone in adipose tissues through the action of the enzyme aromatase obtained by peripheral aromatization.[ 20 ] The conversion increases with higher body weight due to a greater number of fat cells and with advanced age due to increased specific activity of aromatase.[ 21 ] However, the precise quantitative variation of this activity with age remains poorly understood. In our case, involving a postmenopausal woman of 73 years with a BMI of 20.4 kg/m 2 , the theory of peripheral aromatization of adrenal androgens in fat tissue leading to estrone synthesis and subsequent endometrial growth does not fully account for the observed context and remains inadequately understood. To conclude, this rare case of torsion of an ovarian leiomyoma in a postmenopausal woman with postmenopausal bleeding underscores the need to consider ovarian leiomyomas in the differential diagnosis of pelvic masses in older women. The strong progesterone receptor positivity in this tumor suggests that hormonal influences may still contribute to tumor growth even after menopause. Histopathological examination and immunohistochemical analysis are crucial for accurate diagnosis and understanding the underlying mechanisms of tumor growth. The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity. There are no conflicts of interest.