Papillary cystadenoma of the epididymis is the only benign epithelial tumor of the epididymis.1 This benign tumor is seen in about 17% of patients with von Hippel-Lindau (VHL) disease2, which also includes retinal, spinal, and cerebellar hemangioblastomas, renal cysts and carcinomas, pheochromocytomas, and solid organ cysts. Interestingly, this patient had no signs of VHL disease or infertility.
In females, the counterpart of papillary cystadenoma of the epididymis is represented by papillary tumors of the broad ligament and peritoneum. Most of these tumors are usually solid, although they may have distinct cystic spaces. Distinctive microscopic features were described by Price.3
The distinction between cystadenoma and adenocarcinomas of the epididymis can be difficult. High nuclear grade and high proliferation index together with invasive growth and presence of necrosis is most consistent with adenocarcinoma. None of these features were seen in our patient. The finding of adenocarcinoma of the epididymis requires a metastatic workup because of the rarity of primary epididymal adenocarcinomas.4
Clear cell papillary cystadenoma is histologically similar to renal cell carcinoma. There are several reported cases where clear cell papillary cystadenoma of the epididymis was confused with metastatic renal cell carcinoma.5 The differential diagnosis is further complicated by the fact that both renal cell carcinoma and papillary cystadenoma of the epididymis are known to develop in VHL. Lectin histochemistry studies are helpful in distinguishing papillary cystadenoma and metastatic renal cell carcinoma - the former staining for soybean agglutinin.6 Allelic loss of the VHL gene, located on the short arm of chromosome 3, has been demonstrated in all benign papillary tumors developing in VHL patients (papillary cystadenoma of the broad ligament, endometrioid cystadenoma of the broad ligament, papillary cystadenomas of the epididymis, papillary tumor of the retroperitoneum).7 Several hypoxia-inducible genes are regulated by protein encoded by the VHL gene, including platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), erythropoietin, and vascular endothelial growth factor (VEGF).8 VEGF overexpression has been demonstrated in VHL-associated tumors and may explain the cyst formation and vascularized stroma present in these tumors.8
To our knowledge this is the first reported case of coexistent testicular seminoma and papillary cystadenoma of the epididymis. Both seminoma and papillary cystadenoma of the epididymis are characterized by clear cell cytoplasmic alteration. Other examples of such neoplasms with clear cell change include the clear cell type of renal cell carcinoma, clear cell adenocarcinoma of the urethra and bladder, the classic type of seminoma (as in this patient), papillary cystadenoma of the epididymis, and well-differentiated adenocarcinoma of the prostate. Knowledge of the neoplastic entities displaying clear cell change in the genitourinary tract aids in the differential diagnosis of these conditions.9
Contributed by Simion Chiosea, MD and Anil Parwani, MD, PhD