Ovarian Endometrioma with Osseous Metaplasia: A Case Report and Review of the Literature

Abstract

Background:

Osseous metaplasia of the nonteratomatous ovary is extremely rare. This condition has been reported in association with endometriosis and certain ovarian neoplasms.

Case:

A 35-year-old nulliparous patient presented with new-onset severe abdominal pain associated with abdominal fullness, nausea, and vomiting. She had a large, tender pelvic mass anterior to the cervix. Computed tomography showed a midline pelvic mass, measuring 13.1 × 12.3 × 9.3 cm, located anteriorly and superiorly to the uterine fundus, with partially calcified septations as well as an eccentric soft-tissue nodule The uterus was enlarged and lobulated, containing multiple fibroids. There was a complex cystic mass superior to the uterus producing low-level internal echoes and having a few septations with areas of calcification. The patient underwent an exploratory laparotomy during which the pelvic mass was identified as an endometrioma arising from the left ovary. The cyst was densely adherent to the superior aspect of a leiomyomatous uterus with a large fundal fibroid measuring ∼7 cm. Intraoperative pathologic evaluation revealed that this cyst was benign. Lysis of adhesions, followed by myomectomy, was performed, removing 19 fibroids weighing 235 g in aggregate.

Results:

The patient had an uncomplicated postoperative course and was referred for infertility evaluation. Pathologically, this lesion was consistent with an endometriotic cyst (endometrioma) with focal osseous metaplasia.

Conclusions:

It has been theorized that chronic inflammation might be a driving force in the formation of bone within these lesions.

Introduction

Osseous metaplasia of the nonteratomatous ovary is rare. A few case reports have previously described ossification of ovarian neoplasms, osseous metaplasia without any associated abnormalities, and osseous metaplasia associated with endometriosis.^1–16 Osseous metaplasia should not be confused with pathologic calcification of tissue or with formation of teratomas. This article describes a case of osseous metaplasia within an endometrioma and reviews the literature.

Case

A 35-year-old nulliparous patient presented with a 4-day history of new-onset severe abdominal pain associated with abdominal fullness, nausea, and vomiting. Her history was significant for regular menstrual periods with dysmenorrhea. She had been attempting to become pregnant for the prior 2 years without success. A pelvic examination revealed a large, tender pelvic mass anterior to the cervix. Computed tomography showed a midline pelvic mass, measuring 13.1 × 12.3 × 9.3 cm, located anteriorly and superiorly to the uterine fundus, with partially calcified septations as well as an eccentric soft-tissue nodule (Figs. 1 and 2). The uterus was enlarged and lobulated, containing multiple fibroids. Ultrasonography showed the uterus measuring 14.4 × 7.5 × 8.4 cm with multiple fibroids, and the right ovary measured 3.4 × 1.4 × 2.7 cm. There was a complex cystic mass superior to the uterus producing low-level internal echoes and having a few septations with areas of calcification measuring 9.2 × 13.2 × 11.5 cm (Figs. 3 and 4).

FIG. 1.

A computed tomographic image on the transverse plane showed a midline pelvic mass, measuring 13.1 × 12.3 × 9.3 cm, with partially calcified septations as well as an eccentric soft-tissue nodule.

FIG. 2.

A computed tomography image on the sagittal plane also showed a midline pelvic mass, measuring 13.1 × 12.3 × 9.3 cm, with partially calcified septations as well as an eccentric soft-tissue nodule, which was consistent with the image seen on the transverse plane.

FIG. 3.

A sagittal midline view of transabdominal ultrasound (US) image showed a complex cystic mass that was superior to the uterus and producing low-level internal echoes. The US also showed a few septations with areas of calcification measuring 9.2 × 13.2 × 11.5 cm, sagittal view.

FIG. 4.

A sagittal midline view of a transabdominal ultrasound (US) image also showed a complex cystic mass that was superior to the uterus and producing low-level internal echoes. The US also showed a few septations with areas of calcification measuring 9.2 × 13.2 × 11.5 cm. This was consistent with the sagittal US view.

The patient underwent an exploratory laparotomy during which the pelvic mass was identified as an endometrioma arising from the left ovary. The cyst was densely adherent to the superior aspect of a leiomyomatous uterus with a large fundal fibroid measuring ∼7 cm. The right fallopian tube and ovary appeared to be normal. The left fallopian tube was partially adherent to the left adnexal mass, which was carefully separated to maintain tubal integrity. The cyst ruptured during dissection and dark brown material was noted within the cyst, consistent with an endometrioma. A fragment of hard tissue measuring 1 × 0.5 × 0.2 cm was noted within the endometrioma. The cyst was excised from the ovary, and intraoperative pathologic evaluation revealed that this cyst was benign. Lysis of adhesions, followed by myomectomy, was performed, removing 19 fibroids weighing 235 g in aggregate.

Results

The patient had an uncomplicated postoperative course and was referred for infertility evaluation.

Additional Pathology

The specimen received in the pathology laboratory was a disrupted red–tan cyst measuring 11 × 6.5 × 0.7 cm. On the outer surface, a focal area of thickening, with grossly recognizable small fragments of bony tissue measuring 1 × 0.5 × 0.2 cm, was seen. The inner surface of the unilocular cyst was hemorrhagic. Histologically, this lesion was consistent with an endometriotic cyst (endometrioma) with focal osseous metaplasia (Fig. 5).

FIG. 5.

Well-formed bone was seen within the cyst wall. Away from the bone, an endometriotic cyst was noted that was lined by endometrial glandular epithelium with underlying stroma (inset, upper right). Color images are available online

Discussion

Osseous metaplasia is a rare finding in nonteratomatous ovaries, and, in particular, ovarian endometriomas. A review of the literature yielded an article on osseous metaplasia within an endometrioma of a supernumerary ovary¹ and another article showing complete ossification of the ovary; however only microscopic foci of endometriosis were identified.² Heterotopic bone in the ovary has also been associated with extensive endometriosis.³ These researchers theorized that osseous metaplasia was a response to constant inflammatory insults to the tissues secondary to endometriosis. This theory of inflammation was supported further by Campo et al.,⁴ who described osseous metaplasia within the uterus and ovaries bilaterally in a patient with an intrauterine device.

There are several case reports describing ossification associated with ovarian neoplasms including luteinized thecomas,^5,6 Sertoli–Leydig tumors,⁷ mucinous cystadenomas,^8,9 and a fibroma (Table 1).¹⁰ Other case reports have shown calcification surrounding the ovaries rather than ossifications.^11–13 There have also been other isolated case reports of ossification without any associated abnormalities. Rosa e Silva et al.¹⁴ and Shipton et al.¹⁵ both described this phenomena.

Table 1.

Reported Cases of Ossification in Nonteratomatous Ovaries

Case	Patient's age	Case details	Pathology	Theorized pathogenesis	Other considerations
1¹	32	Known stage II endometriosis, complex left cystic mass, & patient previously underwent LSO for recurring pain; 8 months later had left back pain & had a retroperitoneal mass; laparotomy revealed retroperitoneal endometrioma densely adherent to surrounding vessels & ureter	5 × 4 × 3–cm retroperitoneal cyst found to be supernumerary ovary; solid red–brown tissue, 2-cm corpus luteum cyst & smaller <1 cm tan–white nodule; light microscopy showed ovarian stroma & endometriosis & foci of osseous metaplasia adjacent to areas of endometriosis scattered throughout the ovarian stroma	Osseous metaplasia hypothesized to be secondary to endometriosis	—
2¹⁰	21	Pelvic mass on laparotomy 7 × 5 cm; round, stony hard mass completely replacing left ovary	Solid, ovoid nodular structures, measuring 7 × 6 × 5cm; mass encapsulated with glistening white surface; cut surfaces were trebeculated & gritty; no residual ovarian tissue identified; multiple sections after decalcifications showed replacement of entire ovarian tissue with a fibroma composed of interlacing & whorled bundles of dense connective-tissue cells	—	Fibromas had not previously been described with ossification
3¹¹	30	Dysmenorrhea & lower abdominal pain; 7-cm calcified mass; laparoscopic oophorectomy with posterior colpotomy to remove the mass	Ossification with dystrophic calcification	—	—
4¹²	42	G1, P1 with severe abdominal pain & dysmenorrhea for 15 years, pelvic pain occurred intermittently & worsened; well-defined calcified mass 4 × 5 cm located in the pelvis found on examination & imaging; TAH & BSO showed, right ovary was enlarged, ovoid & pale brown	Pathology showed endometriosis with extensive calcification & ossification	Considered torsion with subsequent infarction of an ovarian endometrioma	—
5¹³	50	G5, P5 with cervical dysplasia had TAH & BSO; all pelvic organs appeared normal & imaging did not show any calcifications beforehand	Right ovary measured 3.0 cm, left ovary measured 3.3 cm; solid & stony hard with diffuse gritty texture & granular yellow sectioned surfaces; uterus & fallopian tubes unremarkable; histology showed ovarian cortical & medullary stroma replaced by uniformly distributed, closely spaced spherical foci of calcifications; ∼50% of ovarian tissue; foci were 0.1–0.2 mm, with largest being 1.5 mm; slightly ragged, densely eosinophilic periphery & weakly basophilic interior; occasional psammoma bodies found, most were surrounded by hyalinized collagen	Laminated structures resembling psammoma bodies could have served as initial nidus of focus	—
6¹⁴	31	Patient with DM since age 15 with oligomenorrhea due to chronic anovulation caused by ovarian hypofunction secondary to DM; found to have 2.5-cm suspected dermoid cyst on right side; underwent LSO	Ovary enlarged with smooth surface & hardened; histology showed osseous metaplasia in the ovarian stroma; adjacent parenchyma presenting primordial follicles & corpus albicans; no other abnormalities	Osseous metaplasia might be a reaction to “tissue aggression in an attempt to repair”; in this case, might have been due to ovarian stimulation by hyperinsulinemia	—
7¹⁵	63	Right thigh pain; right pelvic calcified mass seen on X-ray; patient underwent laparotomy with TAH–BSO; right ovarian mass with brown fluid found	5-cm ovarian cyst, filled with thick brown material could not be cut with scalpel; after decalcification showed cyst containing altered blood without definite lining; foreign-body giant cells present & bone with marrow spaces present in the cyst wall; no evidence to suggest teratoma	Heterotopic bone formation can occur with possible stimuli. such as blood clot, inflammation, or trauma	—
8¹⁶	Not reported	Specimen of TAH & BSO, measuring total 9 × 6 × 4 cm	Ovaries measured 2.5 × 2.5 × 1 & 2.5 × 1.5 × 1 cm; 1 ovary had small cyst 1 × 0.5 cm & a “whitish well defined nodule” measuring 0.7 cm; which showed sclerosis & heterotopic bone formation; otherwise normal ovary; uterus with simple hyperplasia	—	Rare, as this occurred in otherwise normal ovaries; did not report endometriosis
9²	46	P3 with history of endometriosis & chronic pelvic pain; patient underwent TAH & BSO	3-cm solid heavily calcified mass with stony hard consistency in right ovary; showed extensive calcification of the right ovarian stroma with formation of mature bone, adjacent to small focus of endometriosis	Ovarian endometriosis with inflammatory response is a stimulus for calcifications followed by osseous metaplasia of undifferentiated stromal cells	—
10³	33	G2, P2, with history of abdominal pain, dysmenorrhea & dyspareunia & nodularity in cul-de-sac; patient underwent TAH & BSO, appendectomy; 90% of left ovary involved in endometriosis with periovarian implants, scarring & fibrosis	Left ovary was 3 × 2 cm; surfaces showing hemorrhagic fibrosis; 1 cm nodule of ossification; endometriosis	Areas of ovarian stromal tissue might revert to a more-embryonic state, with osteoblastic capability under certain abnormal conditions, such as blood clot organization, infections, or traumatic inflammation	—
11⁴	42	G2, P2, with IUD, presented with AUB; TVUS showed widespread, minute calcifications in the endometrial cavity & both ovaries; patient underwent laparoscopic resection of 3- & 5-mm calcific nodules on the left & right ovaries & hysteroscopic blunt resection of calcific nodules; had adhesions of bowel to posterior wall of uterus & ovaries; normal menses returned after surgery, but nodules remained	Histology showed bone tissue in the ovaries & endometrium & no inflammation of the surrounding tissue	Osseous metaplasia might be secondary to totipotential stromal cells, activated by inflammatory stimuli or prolonged estrogen hyperstimulation, giving rise to osteoblasts, or IUD promoted local inflammatory reaction that induced transformation of totipotent cells to osteoblasts	—
12⁵	66	Postmenopausal bleeding; CT with 10 × 7 × 4–cm bony density on the left; EMB showing endometrial adenocarcinoma; patient underwent TAH & BSO	Right ovary 4 × 3 × 1 cm, cut section showed fibrous white & focal yellow & calcified areas; left ovarian tumor weighed 2.5 kg & measured 10 × 8 × 4 cm; cut with bone saw; cut section showed dense, brown, well-formed compact bone separated by fibrous septa; endometrial with high-grade endometrial adenocarcinoma without LVI; found to be luteinized thecoma with decalcified sections showing replacement of architecture by mature lamellar bone; Haversian canals noted	Final diagnosis of luteinized thecoma	No endometriosis seen
13⁶	51	Lumbar back pain; pelvic mass found on CT & US findings showed right adnexal mass with calcifications; patient underwent right oophorectomy	Ovarian thecoma with luteinized thecoma cells & partly typical thecoma cells; foci of calcifications scattered in the stroma with no psammoma bodies noted; metaplastic bone seen adjacent to typical thecoma cells at the periphery of the tumor; bone rimmed with osteoblasts & osteoclasts with bony spicules	Transforming factor or unknown osteoinductive factors could play a role in promoting osseous metaplasia of undifferentiated mesenchymal stromal cells with pluripotent ability for differentiation	—
14⁷	20	20-year-old, G1, P0, underwent cesarean delivery at 38 weeks; had left ovarian mass that was removed intraoperatively	Measured 6.0 × 3.5 × 3.2cm, weighed 52 g; Sertoli–Leydig tumor identified with central area of hyalinization, ossification & calcifications; psammoma bodies were not identified; there were also mast cells & adherent fibrin thrombi were seen in blood vessels within the tumor	Case is different because of the distinct pattern of hyalinization, central calcification & ossification	—
15⁸	75	Pelvic mass; patient underwent excision of mass	Grossly 10-cm cyst mucinous cystadenoma; firm-elastic wall was 2–5 mm thick, with inner lining shining & undulating; loosely textured fibrous tissues lined with columnar cells with small, round-to-oval, bland monotonous nucleus in 10 sections; several thin plates of lamellar-fibered bone identified in the ovarian stroma, surrounded by elongated cells with spindled nuclei	Osteoinductive agent made by tumor cells; TGF-ß has been implicated in osteogenesis	—
16⁹	19	G1, P1 with 5.7-cm complex mass on ovary; laparoscopy revealed cystic mass involving the ovary & no endometriosis present; cyst removed intact	Mass was identified as a mucinous cystadenoma, 6 × 5 × 3–cm smooth-surfaced cystic mass, multiloculated with several fibrotic-appearing areas; several thickened septae with most prominent one measuring 1.3 cm; cyst walls had spicules of mature trabecular bone embedded in a fibrotic stroma; no endometriosis, psammoma bodies, or necrosis presentCyst wall surrounded mostly by fibrotic ovarian stroma.	Osteoblasts might differentiate from fibroblasts; conditions in the connective tissue must be “favorable” for ossification	—
Current case	35	G0, with 13-cm complex pelvic mass & fibroids underwent exploratory laparotomy & had endometrioma with 1 × 0.5 × 0.2–cm hard mass	Endometrioma with focal osseous metaplasia	Might be a reaction to endometriosis	—

LSO, left salpingo-oophorectomy; G, gravida; P, para; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; DM, diabetes mellitus; IUD, intrauterine device; AUB, abnormal uterine bleeding; TVUS, transvaginal ultrasound; CT, computed tomography; EMB, endometrial biopsy; LVI, lymphovascular invasion; US, ultrasound; TGF, tumor growth factor.

Conclusions

Osseous metaplasia is described in the literature infrequently. This condition might be associated with chronic inflammation or irritation.

Footnotes

Author Disclosure Statement

No financial conflicts of interest exist.

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