Paratesticular Papillary Cystadenoma of the Epididymis in the Setting of von Hippel-Lindau

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An individual with von Hippel-Lindau disease presented with bilateral paratesticular masses. Prior germline testing had revealed the presence of a pathogenic VHL c.620T>C alteration. His past medical history was significant for right cerebellar hemangioblastoma, laser photocoagulation procedures for bilateral retinal hemangioblastomas, as well as multiple partial nephrectomies for clear cell renal cell carcinoma. In addition, he had also undergone a distal pancreatectomy for a well-differentiated neuroendocrine tumor. He was evaluated for worsening bilateral scrotal pain and a bilateral epididymectomy was performed for a 3.0-cm mass on the left and a 3.6-cm mass on the right. Representative images of the tumor arising within the epididymis (A) have been depicted. Specifically, this tumor exhibited papillary architecture (B) and was comprised of cells with clear cytoplasm that exhibited reverse polarity (ie, oriented away from the basement membrane; C). Immunohistochemistry for carbonic anhydrase IX, which is upregulated secondary to hypoxia-dependent signaling in tumors that have loss of function alterations of VHL, demonstrated a constitutive pattern of expression characterized by diffuse membranous localization (D). What is the most likely diagnosis?a. Metastatic clear cell renal cell carcinoma involving the epididymisb. Primary papillary cystadenoma of the epididymisc. Metastatic clear cell (tubulo-) papillary renal cell carcinoma involving the epididymisd. Primary adenocarcinoma of the epididymis Answer: b. Primary papillary cystadenoma of the epididymis. Papillary cystadenomas are benign tumors and are thought to arise from epididymal ducts.1Odrzywolski K.J. Mukhopadhyay S. Papillary cystadenoma of the epididymis.Arch Pathol Lab Med. 2010; 134: 630-633Crossref PubMed Google Scholar The mean age at presentation is approximately 35 years, and these tumors range in size from 0.5 to 8.0 cm.1Odrzywolski K.J. Mukhopadhyay S. Papillary cystadenoma of the epididymis.Arch Pathol Lab Med. 2010; 134: 630-633Crossref PubMed Google Scholar Although solitary tumors are identified more frequently, the presence of bilateral tumors should raise the possibility of von Hippel-Lindau disease.1Odrzywolski K.J. Mukhopadhyay S. Papillary cystadenoma of the epididymis.Arch Pathol Lab Med. 2010; 134: 630-633Crossref PubMed Google Scholar These tumors have significant morphologic and immunophenotypic overlap with both clear cell renal cell carcinoma as well as clear cell (tubulo-) papillary renal cell carcinoma.2Cox R. Vang R. Epstein J.I. Papillary cystadenoma of the epididymis and broad ligament: morphologic and immunohistochemical overlap with clear cell papillary renal cell carcinoma.Am J Surg Pathol. 2014; 38: 713-718Crossref PubMed Scopus (20) Google Scholar For instance, neither the expression of PAX8 or diffuse membranous localization of carbonic anhydrase IX (a surrogate marker of hypoxia-dependent signaling in tumors that have loss of function alterations of VHL) can be used to reliably distinguish clear cell type renal cell carcinoma from primary papillary cystadenoma of the epididymis.2Cox R. Vang R. Epstein J.I. Papillary cystadenoma of the epididymis and broad ligament: morphologic and immunohistochemical overlap with clear cell papillary renal cell carcinoma.Am J Surg Pathol. 2014; 38: 713-718Crossref PubMed Scopus (20) Google Scholar The diagnosis of papillary cystadenoma of the epididymis is therefore established based on a combination of histopathologic examination as well as the clinical context, including tumor site.