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Pathologic Risk Factors In Pediatric And Adolescent Patients With Stage I Testicular Stromal Tumors
Kyle O. Rove, MD1, Paul D. Maroni, MD1, Carrye R. Cost, MD2, Diane L. Fairclough, DrPH, MSPH3, Gianluca Giannarini, MD4, Kris Ann Schultz, MD5, Nicholas G. Cost, MD1.
1Department of Surgery, Division of Urology, University of Colorado, Aurora, CO, USA, 2Department of Pediatrics, Division of Pediatric Oncology, University of Colorado, Aurora, CO, USA, 3Department of Biostatistics and Informatics, University of Colorado, Aurora, CO, USA, 4Department of Urology, University of Bern, Bern, Switzerland, 5Department of Pediatrics, Division of Pediatric Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, USA.

BACKGROUND: Testicular stromal tumors (TSTs) are rare. Fortunately, in the pre-pubertal male, these lesions are almost universally benign, with only rare case reports of metastases. In post-pubertal TSTs, various pathologic risk factors have been identified in patients with clinically-localized disease (Clinical Stage I) that increase the risk of occult metastatic disease (OMD). Puberty has traditionally been felt to alter the natural history of these tumors. We systematically reviewed existing literature to analyze the impact of these risk factors on OMD in pre- (0-12 years old) and post-pubertal (13-21) patients.
METHODS: A literature search using PubMed was conducted using the terms: “testicular stromal tumors,” “testicular leydig cell tumors,” “testicular sertoli tumors,” “testicular interstitial tumors,” “testicular granulosa tumor,” and “testicular sex cord tumors.” Patients 0-21 years old with Clinical Stage I TSTs were included. Study exclusion criteria included: publication pre-1980, non-English language articles, and those lacking data on clinical stage, pathologic risk factors, or post-orchiectomy follow-up. Pathologic risk factors were: tumor > 5 cm, ≥ 3 mitoses per HPF, positive margins, rete testis invasion, lymphovascular invasion, cellular atypia, and necrosis. For analysis we included only those with data on recurrence, survival, and time-to-event. OMD was defined as positive nodes at primary retroperitoneal lymph node dissection (RPLND) or relapse on surveillance.
RESULTS: 100 patients from 33 publications were included with a median age at diagnosis of 5.7 years (range 1.2 months to 21 years). 79 patients were ≤ 12 years (median age 7.2 months) and 21 patients were 13-21 years (median age 16 years). No patients in either group were identified to have OMD at RPLND (2 patients) or during follow up surveillance (median follow up 45.6 months, range 4-360 months). No statistically significant differences were noted in tumor size (median 2.0 vs 1.9 cm, p=0.814). 99% of those ≤ 12 years vs 95% > 12 years had 0-1 pathologic risk factors, and 1% vs 5% had 2+ pathologic risk factors (p=0.378), with ≥ 3 mitoses per HPF representing the most common risk factor (14 patients vs 5 patients, respectively). Sertoli cell tumors represented the largest group in patients ≤ 12 years (n=31 or 39%) followed by granulosa cell tumors (n=28 or 35%), whereas in patients 13-21 years, leydig cell tumors were most common (n=8 or 38%) followed by granulosa cell tumors (n=6 or 29%). Death occurred in 1 patient, age 16, due to other causes.
CONCLUSIONS: Adolescent, post-pubertal patients with Clinical Stage I TSTs appear to behave in a benign manner, similar to pre-pubertal patients and thus may also be amenable to testis-sparing surgery in select circumstances. Further, given the extremely low-risk of relapse in this population, low-cost and low-impact surveillance strategies are paramount and adjuvant surgery or chemotherapy is not indicated. Prospective study of these patients is needed, and entry into a tumor registry such as the Ovarian and Testicular Stromal Tumor Registry is key to learning more about these rare entities.


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