Moderate to poorly differentiated Sertoli-Leydig cell tumor.
Sertoli-Leydig cell tumors (SLCT) belong to the group of sex-cord stromal tumors of the ovary. They account for less than 0.5% of all ovarian tumors and are almost always unilateral. The clinical characteristics are related to the degree of histological differentiation. Up to 50% of SLCTs have endocrine functions (androgenic or estrogenic), and the prognosis is correlated most meaningfully with the degree of differentiation and stage of the tumor. The age at diagnosis averages 25 years (range 2 to 75 years) with 70-75% of these tumors presenting during the second and third decade of life, and less than 10% occurring either prior to menarche or after the menopause.
Our case represented a diagnostic challenge, giving the unusual clinical presentation (lack of hormonal symptoms) and the late age of presentation. The gross appearance and unilaterality favored the diagnose of SLCT. Over 97% of SLCTs are unilateral and they present most often as solid to solid-cystic mass with a yellow to brown appearance on sectioned surface. The size ranges from not detectible to 35 cm (mean 12-14 cm). Additionally, the case presented with poorly differentiated features including: predominantly spindle cell growth pattern, high nuclear grade and almost absence of recognizable Sertoli tubule formation and Leydig cells. Our case showed some tubule representing intermediately differentiated component, thus suggesting the diagnosis of SLCT.
In older patients, the differential diagnosis with other sex cord/stromal tumors, endometrioid adenocarcinoma and carcinoid tumors is aided by the use of immunohistochemistry to discern the final diagnosis. Zhao et al. very elegantly determined the best immunohistochemical panel to differentiate SLCT from other sex cord/stromal and epithelial ovarian tumors. The authors concluded that inhibin is the most discriminatory sex cord marker (2% positivity in carcinoid and 4% positivity in well-differentiated endometrioid carcinoma) followed by calretinin with CD10 being much less useful and CD99 not being discriminatory (up to 40% positivity in carcinoid and 33% positivity in well-differentiated endometrioid carcinoma). EMA is the best epithelial marker with no sex cord tumors showing positivity, followed closely by CK7, ER and PR. It is important to mention that up to 65% of the analyzed sex cord tumors were positive for pan-keratin antibody rendering it of no use for ruling out sex cord ovarian tumors. Chromogranin and synaptophysin are excellent discriminatory markers for carcinoid tumor with CD56 being neither sensitive nor specific for this differential diagnosis. In a more recent paper, the same authors concluded that in addition to inhibin and calretinin, SF-1 and WT1 are also excellent options for ruling in sex cord tumors.
In our case, positivity for inhibin and calretinin and negativity for EMA and ER, together with the H&E appearance ruled out the main differential diagnoes, i.e. endometrioid/clear cell adenocarcinoma, carcinoid tumor and the less likely adult granulosa cell tumor.
The prognosis of SLCTs is good, although poorly differentiated tumors may recur. Conservative surgery is acceptable for young patients wishing to preserve fertility, and postoperative adjuvant chemotherapy and long-term follow up are recommended in those with high-risk factors. Our patient presents with several risk factors including: older age, no androgenic symptoms, poor differentiation and stage pT2a at the time of diagnosis; giving her a poorer prognosis.
In summary, the left adnexal mass presented in our 65-year-old patient was highly concerning for malignancy. The main differential diagnosis was between poorly differentiated adenocarcinoma (endometrioid or clear cell), carcinoid tumor and sex-cord/stromal tumors. Even though age favored an epithelial neoplasia, the gross appearance (yellow-to-brown cut surface) and unilaterality favored a sex cord tumor. Ultimately, the combined use of inhibin, calretinin and EMA antibodies helped in ruling out an epithelial ovarian cancer and carcinoid tumor. Another important differential diagnosis to consider would have been adult granulosa cell tumor, giving the age and the gross appearance of the tumor; however, the lack of histological features of granulosa cell tumor, including the absence of Call-Exner bodies ruled out that diagnosis. For more detailed information and other differential diagnosis please refer to Zhao et. al 2009.
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Contributed by Humberto Trejo Bittar, MD; R. Marshall Austin, MD, PhD and Chengquan Zhao, MD.