Epididymal cystadenomas (ECA) are uncommon tumors that, even as sporadic lesions, are associated with a somatic mutation in the VHL gene on chromosome 3. In Von-Hippel Lindau disease (VHL) patients, there is a germ-line mutation in the VHL gene, affecting every cell in the patient's body. The presence of bilateral epididymal lesions suggests a germline systemic mutation, rather than a local somatic mutation. Of course, the additional findings of the lesions in the kidney and pancreas provide further evidence of the systemic disease - Von Hippel Lindau disease.
VHL was originally described as the familial association of multiple vascular "angiomas" of the retina (von Hippel disease) with hemangioblastomas (the Lindau tumor). However, it was shortly recognized that these patients had a more complex systemic disease with lesions affecting the solid abdominal organs (kidney and pancreas) with cysts and both benign and malignant neoplasms. Unlike the "classic" phakomatoses, VHL is not associated with cutaneous findings. VHL is autosomal dominant, without racial or sexual predilection. The responsible gene has been identified on chromosome 3p, and the prevalence is estimated at about 1/35,000 to 1/50,000 people in the United States.
The study group at the NIH has suggested subclassifying VHL into 3 subtypes. The most frequent is Type I, VHL without pheochromocytoma. These patients have the "classic" features of renal and pancreatic cysts, and a high risk for developing renal cell carcinoma (RCC).
Type II is VHL with pheochromocytoma, and it is further divided into IIA and IIB. Type IIA has pancreatic islet cell tumors (typically without cysts) and IIB has both Renal and Pancreatic disease.
This patient has evidence of previous adrenal surgery, and has both pancreatic and renal cysts. So this is Type IIB.
More than half of these patients will develop or present with retinal angiomas. These are actually hemangioblastomas of the retina, and cause retinal hemorrhage and detachment. Two-thirds or more of VHL patients will have hemangioblastomas, usually infratentorial, with the cerebellum by far the most common site. Although the hemangioblastoma is a benign nonglial neoplasm, it is hypervascular, and may recur if incompletely resected. In addition, patients with VHL are prone to develop multiple hemangioblastomas, that may be present simultaneously or may appear as metachronous (asynchronous) lesions.
As this patient illustrates, the epididymis may develop benign cystadenomas. The presence of multiple lesions should always suggest a systemic disease. Systemic diseases may be congenital (maldevelopmental and genetic), inflammatory (infectious, autoimmune, etc.), toxic, metabolic, and dissemination of a neoplasm (metastasis). Hematogenous dissemination of neoplasms and infection may create multiple and often bilateral lesions, but they are usually located in asymmetric and somewhat random patterns. However, toxic, metabolic and genetic lesions may show anatomic distributions of lesions that may be bilateral and can be strikingly symmetric.
In the differential diagnosis of this case, the presence of bilateral masses of the scrotum could have been inflammatory or infectious. However, the localization of these masses with anatomic symmetry within the epididymis, might suggest consideration of a syndrome. In addition, the morphology of the masses as heterogeneously solid and cystic also suggests the specific diagnosis of a cystadenoma. These two clues fit together well if the patient has von Hippel-Lindau disease.
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