August 2014

A 13-year-old female presented with intermittent episodes of abdominal pain

Maggie Yell, MD, Melina Flanagan, MD

Overview

A 13-year-old female presented with intermittent episodes of abdominal pain.  Pelvic ultrasound revealed a 15.6 x 12.6 x 8.9 cm right adnexal complex cystic mass.  An exploratory laparotomy with left ovarian cystectomy was performed.

Gross Description

A 425g, 17.0 x 11.0 x 6.0 cm left ovarian mass was received.  The outer surface was tan-white and shaggy with no excrescences.  On sectioning the mass was solid with cystic degeneration.  No definitive ovarian tissue was identified.  Microscopic examination showed the following:

Figure 1: 20x magnification. At low power the mass demonstrates a pseuolobular pattern with alternating hypo- and hyper-cellular areas, as well as prominent thin-walled blood vessels.
Figure 2: 100x magnification. Round to oval spindle cells can be appreciated at this power.
Figure 3: 100x magnification. Theca-like cells with vacuolated cytoplasm can also be appreciated at this power.
Figure 4: 40x magnification. The spindle cells are immunoreactive for smooth muscle actin (shown above), and are negative for desmin, CD117, inhibin, calretinin, and PLAP.

Diagnosis

What is the most likely diagnosis ?

Answer

Please select an answer above.

Discussion

Sclerosing stromal tumor (SST) of the ovary is a rare and benign entity that tends to occur in young women [23].  It was initially described by Chalvardjian and Scully in 1973 and termed sclerosing stromal tumor due to a propensity of the cellular regions to form collagenous sclerosis [24].  Sclerosing stromal tumor most likely originates from the ovarian stroma as it is composed of spindle-shaped and rounded cells that are similar to tumor cells found in a fibroma, thecoma, or lipid cell tumor.  In addition, it contains a large amount of pericellular reticulin and intracellular lipid [4].   It is normally hormonally inactive, but there have been some cases associated with pregnancy, androgenic expression, and endometrial carcinoma [2].

Grossly, the tumor is well circumscribed with a smooth, somewhat bosselated surface and usually replaces most of the ovarian tissue [34].  The cut surface is grey-white with yellow foci and can have firm, rubbery, edematous and mucoid textures [4].  Tumors can have solid and cystic components [2], and the cysts may be single or  multiple  and may contain mucoid or serous fluid [4].  Focal calcifications have been noted [24].  Microscopically, the tumor is well demarcated and surrounded by fibrous tissue [2].  The architecture is characterized by cellular areas arranged in pseudolobules, as well as hypocellular, edematous, or collagenous areas, and thin-walled blood vessels that resemble those seen in hemangiopericytomas (“hemangiopericytoma-like vasculature”) [2]. The cellular areas are composed of two populations of cells: luteinized theca-like cells with vacuolated cytoplasm and round nuclei and fibroblast-like spindle cells with elongated nuclei [2-4].  As mentioned previously, the cellular areas have a propensity for sclerosis.  On high power, the nuclei can be round or spindle-shaped, sometimes vesicular with prominent nucleoli, dark and shrunken, or binucleate [4].  Mitoses are rare [24]. Signet ring-like cells can be seen occasionally [23].

Immunohistochemically, sclerosing stromal tumors stain positively for vimentin.  The spindle cells stain positively for smooth muscle actin and desmin.  The positive staining for smooth muscle actin suggests that this entity originates from pluripotent immature stromal cells of the ovarian cortex. The theca-like cells stain positively for inhibin-alpha, show variable staining for CD99, and are negative for smooth muscle actin and desmin.  Overall, the tumor is negative for estrogen receptor and has variable focal staining of the theca-like cells for progesterone receptor [2].  In general, the morphologic and clinical features of SST are sufficiently distinct enough to make the diagnosis without immunostains.

The differential diagnosis for SST includes other sex cord stromal tumors such as fibroma-thecoma tumors or the diffuse/ sarcomatoid pattern of granulosa cell tumors, as well as leiomyomas and dysgerminoma (especially ones with distinct fibrosis). These are discussed in the question section above.  In addition, the theca-like cells may resemble signet ring cells, and thus mimic Krukenberg tumors or signet-ring stromal tumor of the ovary.  Differentiation from Krukenberg tumors is usually possible on clinical grounds, as patients have a primary tumor elsewhere and tend to be older. In addition, the metastatic signet-ring cells are positive for keratin and EMA while signet ring like cells in sclerosing stromal tumor contain lipid [2].

Most sclerosing stromal tumors occur in the 2nd to 3rd decade of life [2]. Clinically, the most common presenting symptoms include menstrual irregularity (metrorrhagia or menometrorrhagia) and pelvic discomfort or pain [4].  Tumors are typically unilateral and most are found on the right side [23].  The vast majority of cases do not show hormonal activity, although this has been seen in pregnant women, possibly due to hCG stimulating the stromal lutein cells during pregnancy [3], and there has been one case associated with virilization [5]. To date all reported cases have been benign.

References

1. Rajabi P, Hani M, Bagheri M, Mirzadeh F. Large ovarian leiomyoma in young woman. Advanced biomedical research. 2014;3:88. 
2. Zekioglu O, Ozdemir N, Terek C, Ozsaran A, Dikmen Y. Clinicopathological and immunohistochemical analysis of sclerosing stromal tumours of the ovary. Archives of gynecology and obstetrics. 2010;282(6):671-6. 
3. Marelli G, Carinelli S, Mariani A, Frigerio L, Ferrari A. Sclerosing stromal tumor of the ovary. Report of eight cases and review of the literature. European journal of obstetrics, gynecology, and reproductive biology. 1998;76(1):85-9. 
4. Chalvardjian A, Scully RE. Sclerosing stromal tumors of the ovary. Cancer. 1973;31(3):664-70. 
5. Yen E, Deen M, Marshall I. Youngest Reported Patient Presenting with an Androgen Producing Sclerosing Stromal Ovarian Tumor. Journal of pediatric and adolescent gynecology. 2014.