Bilateral Osseous Metaplasia of the Ovary in Association with Endometrioma: A Rare Case Report

A 43-year-old primiparous woman presented with heavy menstrual bleeding and dysmenorrhea of 4 years duration. She had a vaginal delivery 25 years back, complicated with eclampsia. She had never conceived after that, but did not seek medical attention for secondary infertility. Her menstrual cycles were regular, lasting for 4–5 days, with heavy flow. She was on tablet tranexamic acid (500 mg) and mefenamic acid (250 mg) during her periods for the last 4 years. She was also a known hypertensive on tablet amlodipine (5 mg) and atenolol (50 mg) for 3 years. An ultrasound performed 5 months back showed bilateral ovarian endometriomas, measuring 4.4 cm × 3.7 cm in the right ovary and 3.0 cm × 2.4 cm in the left ovary. She had been started on hormonal therapy with ethinylestradiol (30 μg) and dienogest (2 mg). However, as there was no improvement in her symptomatology, she presented to us. Upon presentation, her vitals were stable. Perabdominal and bimanual examination revealed a normal sized uterus with a palpable and hard right adnexal lesion measuring approximately 4 cm × 4 cm and a left adnexal cyst measuring 3 cm × 3 cm. There was a tender nodule in the pouch of Douglas. A point of care transabdominal ultrasound revealed a normal sized globular uterus with features of adenomyosis, endometrial thickness of 11 mm, with right ovary measuring 3.3 cm × 3.8 cm and left ovary measuring 2.5 cm × 2.8 cm. With a provisional diagnosis of adenomyosis with bilateral ovarian endometriomas and possible deep infiltrating endometriosis and hypertension, she was planned for medical management. She was treated with tablet dienogest 2 mg once a day. At 3-month follow-up, there was still no improvement in her symptomatology. A repeat ultrasound revealed an adenomyotic uterus, enlarged and calcified right ovary measuring 6 cm × 5 cm [ Figure 1 ] and left ovary measuring 5 cm × 4 cm. Her cancer antigen 125 was 21.8 U/mL She was offered an MRI of the pelvis, but she declined it due to financial constraints. Subsequently, she was planned for total abdominal hysterectomy and bilateral adnexectomy. Transabdominal ultrasound showing right ovary with peripheral calcification (black arrow) measuring 6 cm × 5 cm Intra-operatively, the uterus corresponded to 8 weeks in size. The right ovary was calcified, measuring 6 cm × 5 cm. Right salpingo-oophorectomy was performed and sent for frozen section. The left ovary had a 5 cm × 5 cm endometriotic cyst with adhesions to the bowel. Adhesiolysis was performed, and the left adnexa was removed. Subsequently, total abdominal hysterectomy was done. Frozen section of the right ovary revealed a hard mass measuring 5.5 cm × 3.5 cm × 3.0 cm [ Figure 2 ] with attached soft yellow tissue measuring 1.5 cm × 1.5 cm × 0.8 cm. The microscopic section was suggestive of sex cord stromal tumor, with the possibility of thecoma, fibroma, and leiomyoma also considered. Patient did well postoperatively and was treated with injection leuprolide 11.25 mg on day 3. She was discharged on postoperative day 4 and was asymptomatic at 3-month follow-up. Gross examination of frozen section of right ovary revealed a hard mass measuring 5.5 cm × 3.5 cm × 3.0 cm with a gritty cut surface (black arrow) Histopathology of the right ovary showed ovarian parenchyma along with areas of extensive osseous metaplasia with calcifications [ Figure 3 ]. Sections from the left ovary showed ovarian parenchyma with an endometriotic cyst. The cyst wall contained areas of endometrial glands and stroma with surrounding abundant hemosiderin-laden macrophages, granulation tissue, and moderate to dense inflammation composed of lymphocytes, plasma cells, and polymorphs. Multiple foci of osseous metaplasia with calcifications were also seen in the left ovary [ Figure 4 ]. There was no evidence of malignancy. Sections from myometrium showed adenomyosis, endometrium was in proliferative phase, and cervix showed features of chronic endocervicitis. Bilateral fallopian tubes were within normal limits. Final impression was osseous metaplasia of bilateral ovaries with a left ovarian endometriotic cyst. Photomicrograph from the right ovary showing mature bony tissue formation (black arrow) Photomicrograph from left ovary showing (a) endometrial glands (black arrows) and stroma (b) cyst wall with fibrosis and ossification foci (black arrow) (c) denuded lining epithelium with bands of hemosiderin-laden macrophages (thin black arrow), and bony tissue (thick black arrow)

Osseous metaplasia of nonteratomous ovarian cyst is an extremely rare phenomenon.[ 1 ] The specific incidence rates are difficult to ascertain due to the limited number of documented cases. Till 2020, approximately 33 cases had been reported in the literature.[ 2 ] The exact etiology of osseous metaplasia of the ovary remains unclear. Research is needed to fully understand the pathogenesis and clinical implications of this condition. Hence, we report this case of a 43-year-old woman with left-sided ovarian endometrioma and osseous metaplasia of both ovaries.

Metaplasia is the replacement of one type of adult, mature, differentiated cell type with another mature differentiated cell type that does not typically occur in the tissue in which it is found. Metaplasia in the ovary is rare.[ 1 ] Osseous metaplasia of the ovary is usually found in association with malignant conditions such as low-grade ovarian serous carcinoma and ovarian serous psammocarcinoma.[ 3 4 ] However, it has also been reported in association with nonneoplastic benign conditions of the ovary like endometrioma, serous cystadenoma, ovarian fibroma, and thecoma.[ 2 5 6 7 ] In our case, ovarian endometrioma was demonstrated by histopathology only on the left side. On the right side, while previous ultrasounds had shown an endometrioma, histopathology failed to demonstrate so. It is possible that extensive osseous metaplasia with calcifications may have overshadowed the sonologically demonstrated endometrioma, or that medical treatment with dienogest over 6 months may have shrunk the right-sided endometrioma. However, our case is unique as there was bilateral ovarian osseous metaplasia demonstrated histopathologically in the setting of benign ovarian endometrioma, which is exceedingly rare. Till 2020, approximately 33 cases had been reported in the literature.[ 2 ] Subsequently, Catteau X has reported osseous metaplasia in low-grade ovarian serous carcinoma with a BRAF mutation.[ 3 ] The exact etiology of osseous metaplasia of the ovary remains unclear, although it is thought to be an unusual and benign reaction to chronic inflammation, tissue damage, and tissue repair. The role of overactive growth factor signalling pathway, such as bone morphogenetic proteins (BMPs), in inflammatory conditions marked by ectopic osteogenesis is being increasingly recognized.[ 8 ] BMPs upregulate the expression of adhesion molecules, promoting leukocyte adhesion, with consequent chronic inflammation and tissue fibrosis. Osseous metaplasia in the female genital tract has also been reported in the endometrium. Endometrium may transform into epithelial metaplasia or nonepithelial metaplasia, such as osseous and cartilaginous metaplastic changes. Osseous metaplasia in the endometrium may be explained by (i) endometrial pluripotent stromal cells transforming into osteoblastic cells or (ii) postabortal implantation of fetal tissue growing as a homograft in the endometrium amidst persistent inflammation.[ 9 ] Simultaneous ovarian and endometrial osseous metaplasia has also been reported.[ 10 ] To conclude, osseous metaplasia of nonteratomous ovary is rare. Our case was associated with ovarian endometrioma, which itself is an enigmatic condition. The exact etiology of osseous metaplasia of the ovary is not known. We report this case to shed more light on the subject. Future research should focus on the pathogenesis, clinical implications, associated mutations, and genetics of osseous metaplasia of the ovary. 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 name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. There are no conflicts of interest.