Residency Program - Case of the Month
November 2011 - Presented by Brian Gorospe, M.D.
(Clear Cell) Papillary Cystadenoma of the Epididymis
The sections show a well circumscribed cystic structure surrounded by a fibrous capsule with intracystic papillary projections (figure 1-2). Some of the cystic spaces contain eosinophilic colloid-like material (figure 2). The papillae contain fibrovascular cores and are lined by cuboidal to columnar cells arranged in nests (figure 3). On high power the cells have prominent cell borders, clear cytoplasm, and bland uniform nuclei (figure 4-5). Mitotic activity and necrosis is absent. Immunhistochemical stains were positive for AE1/AE3, CK7, carbonic anhydrase IX, and vimentin; and negative for CD10, RCC, racemase, and calretinin.
Neoplasms of the epididymis are rare, accounting for approximately 5% of intrascrotal neoplasms. Epididymal tumors are usually benign with adenomatoid and leiomyomas representing the majority.1 Papillary cystadenoma of the epididymis (PCE), also referred to as clear cell papillary cystadenoma, is a rare benign epithelial tumor of epididymis that accounts for approximately one-third of all primary epididymal tumors.2 PCE is an important entity to recognize due to its frequent association with von Hippel-Lindau disease (VHLD) and its histologic resemblance to clear cell renal cell carcinoma (RCC).
Ordrzwolski and Mukhopadhyay3 in 2010 performed a detailed analysis of the clinical and pathologic features of the 59 histologically documented cases of PCE in the literature. Based on their analysis PCE occurred mostly in young adults (median 30 years), but patient ages ranged from 16-71 years. Patients most commonly presented with a painless, slow grow mass or swelling. A significant number of cases were asymptomatic and found incidentally during examination of patients for other reasons. A small number of patients presented with pain or were found to have epididymal nodule upon workup for infertility.3 PCEs may by sporadic, but are also seen in approximately 17% of patients with VHLD. PCE may involve one of bilateral epididymis. The lesions are bilateral in 30-40 percent of cases. In VHLD they are more frequently bilateral. The von Hippel-Lindau (VHL) gene has been detected in both sporadic PCEs and also in those patients with VHLD.4
Grossly the tumors range from 0.5 to 8.0 cm, with the majority of tumors measuring less the 5 cm. They appear as a well-circumscribed or encapsulated, solid or cystic, tan nodule located in the head of the epididymis. Microscopically PCE is characterized by cysts filled with intracystic papillary projections with fibrovascular cores. The papillae are lined by a single layer of cuboidal or columnar epithelial cells. The cells are arranged in tubules or nests and have prominent cell borders. Cytoplasmic clearing is a conspicuous feature. In many cases the cystic spaces contain eosinophilic colloid-like material.2,3,4 Immunohistochemically the epithelial cells are consistently positive for AE1/AE3, CAM 5.2, and EMA.1,3
Given the above microscopic description, PCE may be confused with metastatic clear cell RCC. Ayadin et al1, in their analysis of the immunohistochemical profile of 5 cases of papillary cystadenomas, suggest that in cases where there is uncertainty about the histologic diagnosis of papillary cystadenoma and clear cell RCC, a immunohistochemical panel of including AE1/AE3, EMA, CK7, CK20, CD10 and RCC is helpful to rule out metastatic RCC. A majority of clear cell RCCs are immunoreactive for AE1/ AE3, EMA, vimentin, RCC and CD10, but negative for CK7 and CK20. In the analysis by Ayadin et al, papillary cystadenomas were also positive for AE1/AE3 and EMA, and negative for CK20; but (in contrast to clear cell RCC) were strongly positive for CK7, negative for RCC and negative for CD10 (in 4 of 5 cases).1
The treatment of PCE is testicle-sparing surgical excision. The possibility of VHLD should be considered in patients with PCE, since they may be at risk for developing other VHLD-associated tumors. Radiologic or genetic testing for VHLD may be warranted in patient with bilateral PCE given the greater association with VHLD.3
- Ayadin H, Young RH, Ronnett BM, Epstein JI.. Clear cell papillary cystadenoma of the epididymis and mesosalpinx. Am J Surg Pathol. 29: 520-523.
- Bostwick DG, Cheng L. (2008). Urologic Surgical Pathology, 2nd Editon. Elsevier.
- Odywolski KJ, Mukhopadhyay S. Papillary Cystadenoma of the Epididymis. Arch Pathol Lab Med. 2010. 134: 630-633.
- Eble, JN, Sauter G, Epstein JI, Sesterhenn IA (Eds). (2004) World Health Organization: Tumors of the testis and paratesticular tissue. Lyon: IARC Press.