Granulosa cell tumors of the testis are very rare neoplasms. While most appear to have a benign course, they occasionally metastasize. Risk factors in the primary tumor for the development of metastasis include tumor size, mitotic rate, vascular invasion, tumor necrosis, infiltrating margins, and cytologic atypia. In the presence of retroperitoneal metastasis, lymphadenectomy is the treatment of choice and there is no accepted adjuvant chemotherapy. Extrapolating from the ovarian cancer literature, cisplatin-based combination chemotherapy may be occasionally effective.
These standard approaches were ineffective in the patient cared for by the authors. On the other hand, the major response of a testicular granulosa cell tumor to pazopanib—an investigational multitargeted receptor tyrosine kinase (TK) inhibitor of all three vascular endothelial growth factor receptors in addition to other TKs—is very interesting.[2,3] A completed phase I trial of this drug was recently reported.
Reasonable Research Direction
The embryologic origin of granulosa cells is controversial. In the ovary, granulosa cells appear to be involved in the formation of the capillary bed of the corpus luteum.[5,6] Therefore, treatment of a granulosa cell tumor with an antiangiogenesis agent has a possible pathophysiologic basis.
The authors’ anecdotal observation of the activity of a multitargeted antiangiogenic TK is supported by a retrospective review of eight patients with metastatic granulosa cell tumors of the ovary who were treated with bevacizumab (Avastin). One complete and two partial responses were reported. Clinical trials are the backbone of drug discovery and are encouraged for the treatment of both common and uncommon tumors. Drugs with antiangiogenic activity might be effective against this rare tumor type.
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Schumer ST, Cannistra SA: Granulosa cell tumor of the ovary. J Clin Oncol 15:1180-1189, 2003.
2. Harrison MR, Huang W, Liu G, et al: Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor. Oncology (Williston Park) 23:792-795, 2009.
3. Kumar R, Knick VB, Rudolph SK, et al: Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 6:2012–2021, 2007.
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6. Reynolds LP, Grazul-Bilska AT, Redmer DA: Angiogenesis in the corpus luteum. Endocrine 1:1-9, 2000.
7. Tao X, Sood AK, Deavers MT, et al: Anti-angiogenesis therapy with bevacizumab for patients with ovarian granulosa cell tumors. Gynecol Oncol June 12, 2009 (epub ahead of print).