Cellular Fibroma Ovary with Minor Sex Cord Elements Associated with Endometrial Adenocarcinoma: a Rare Entity

Sir,

Cellular fibromas account for 10% of all fibromatous tumors of the ovary. They are nearly always endocrine inert and are very rarely associated with hormone production. Hence, it is imperative to look for minor sex cord elements in cellular fibromas if they are associated with endometrial changes of excess estrogen like endometrial hyperplasia or adenocarcinoma [1].

Ovarian fibroma with minor sex cord element is a rare tumor comprising of sex cord elements forming less than 10% of the tumor area. The histological differential diagnosis includes adenofibroma, fibromatosis, and Brenner’s tumor [2, 3]. However, the undifferentiated/primitive sex cord-type cells are the hallmark of this tumor and help in differentiating it from other differentials [4]. The reticulin stain is also useful in highlighting the distinct components of this tumor since it has a distinct pericellular staining pattern in fibroma which is lost in the minor sex cord elements [5]. Immunostains like inhibin and calretinin are strongly positive in the minor sex cord elements in contrast to their weak and patchy staining in the fibromatous component [4].

A 60-year-old lady, P3L3 presented with complaints of postmenopausal bleeding. An endometrial biopsy was performed, and she was diagnosed with a moderately differentiated endometrioid adenocarcinoma of the endometrium. The patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Per operatively, the uterus was enlarged to 10 to 12 weeks’ size. The right ovary was unremarkable, and the left ovary was bulky. The pelvic lymph nodes were not enlarged and were sent for frozen section examination which was negative for metastasis. There was no ascites. Specimen of the uterus (11 cm × 19 cm × 6 cm) with the right (3.5 cm × 3 cm × 1.0 cm) and left (5.5 cm × 4.5 cm × 2.5 cm) ovaries and right (7.5 cm) and left (4.5 cm) fallopian tubes were received. On the cut section of the uterus, a growth was seen in the endometrial cavity which was grey-brown and friable measuring 9 cm × 8.5 cm × 2 cm [Fig. 1A]. On the cut section, the right ovary showed atrophic changes, and the left ovary showed solid grey-white areas with yellowish nodules [Fig. 1B]. Microscopy of the left ovary showed spindle-shaped cells arranged in intersecting fascicles with a variable amount of collagen and intermingled sex cord elements forming less than 10% of the area [Figs. 1D, 2A, and 2B]. The stromal cells had elongated nuclei with tapering ends and no prominent nucleoli. There was minimal pleomorphism and only occasional mitotic Figs. (0 to 1 mitosis per ten high power fields). Section from endometrial growth showed features of a moderately differentiated endometrioid carcinoma invading less than half of the myometrial thickness [Fig. 1C]. On reticulin staining, the fibroma component showed a pericellular pattern of staining which was lost in the minor sex cord component [Fig. 2C and 2D]. Inhibin immunostain was very weak to negative in the fibroma component and was strongly positive in the minor sex cord element [Fig. 2E and 2F]. The final histopathological diagnosis was moderately differentiated endometrioid adenocarcinoma uterus with left-side cellular ovarian fibroma with minor sex cord elements. The patient was lost to follow-up.

Fig. 1.

A Total abdominal hysterectomy with bilateral salpingo-oophorectomy specimen showing the endometrial growth. B Left ovary showed grey-white areas with yellowish nodules. C (hematoxylin and eosin, 100 ×) moderately differentiated endometrioid adenocarcinoma. D (hematoxylin and eosin, 40 ×) Left ovarian tumor showing the cellular fibroma component

Fig. 2.

A (hematoxylin and Eosin, 100 ×) ovarian cellular fibroma with minimal pleomorphism and only occasional mitosis. B (hematoxylin and Eosin, 400 ×) minor sex cord element showing poorly defined tubular structures. C (reticulin Stain, 100 ×) cellular fibroma with pericellular arrangement of reticulin fibers. D (reticulin stain, 400 ×) loss of pericellular reticulin pattern in the small nests of minor sex cord element. E (inhibin immunostaining, 400 ×) negative inhibin immunostain in the fibroma component. F (inhibin immunostaining, 400 ×) strong immunopositivity in the small nests of minor sex cord component

This case is only the fifth case in the world reporting the association of “ovarian fibroma with minor sex cord elements” with endometrial adenocarcinoma. Mathur A et al. [4] reviewed the literature and found that a total of 17 cases of ovarian fibroma with minor sex cord element had been reported till 2018. Out of these 17 cases, only 4 cases had coexistent endometrioid adenocarcinoma. Three cases had endometrial hyperplasia without atypia. The rest of the cases had unremarkable or proliferative endometrium. One case showed the transformation of the fibroma component to fibrosarcoma [6]. The criteria for malignancy in a fibroma include severe nuclear atypia and mitosis in more than 4 per 10 high-power fields.

Cellular fibromas need to be differentiated from the diffuse type of adult granulosa cell tumor. Reticulin stain is found to be very useful in this differential as it gives a distinct pericellular staining pattern in fibroma as opposed to the nested pattern in granulosa cell tumors [5]. In our case too, the reticulin stain showed a pericellular staining pattern which was lost in the area of the minor sex cord element. Stall JN et al. have also highlighted the utility of reticulin staining in differentiating granulosa cell tumors from thecoma [5]. Fibromas are generally weakly positive to immunonegative for inhibin. In our case too, inhibin was negative in the fibroma component and strongly positive in the minor sex cord element.

The minor sex cord element in our case comprised of undifferentiated and poorly defined tubular structures and dispersed cells and did not resemble any particular lineage of sex cord cells like granulosa, Sertoli, or Leydig cells. Minor sex cord elements have also been reported in the stroma of mucinous neoplasms [7].

It is important to document the minor sex cord elements in ovarian fibromas so that their prognostic relevance can be fully elucidated. All cases reported to date have behaved in a benign fashion. In a recent review of sex cord-stromal tumors of the ovary, Young RH stressed the importance of the 10% cut-off for minor sex cord elements as tumors having more than 10% component of granulosa cell tumor are categorized as granulosa cell tumor with stromal predominance [8]. These tumors may have a better prognosis than epithelial-rich tumors. Sometimes, the cells of the granulosa cell component have a moderate amount of pale cytoplasm which is very difficult to differentiate from the thecoma component. In such cases, the reticulin staining pattern is particularly useful [8].

This case highlights the importance of careful examination of ovaries in all cases of endometrial hyperplasias and adenocarcinomas. This would help in documenting small islands of minor sex cord elements which would help in explaining the hyper-estrogenic state in the patient.

Data Availability

The authors confirm that the data supporting the findings of this study are available within the article.

Declarations

Ethics Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed Consent

Informed consent was obtained from the patient for publication of case details and images. Patient confidentiality was maintained in all aspects.

Conflict Interest

The authors declare no competing interests.