cow-2022-29

CASE OF THE WEEK

Editor: Mahmut Akgul (akgulm@amc.edu)

2022-29/July 25

Contributors: Vandana Panwar, Rajal Shah

A young male in his 20s with a known cancer syndrome presented with bilateral epididymal masses.

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Quiz

a) Primary adenocarcinoma of the epididymis

b) Metastatic clear cell renal cell carcinoma to the epididymis

c) Papillary cystadenoma of the epididymis

d) Serous borderline tumor of the epididymis

e) Paratesticular papillary mesothelioma

a) Von Hippel Lindau

b) Lynch

c) Multiple endocrine neoplasia

d) Li-Fraumeni

e) Birt-Hogg-Dube

1. c; 2. a

Papillary cystadenoma of the epididymis

Papillary cystadenoma of the epididymis (PCE) is a benign epithelial tumor located in the head of the epididymis and is thought to arise from epididymal ducts. It is the second most common benign tumor of epididymis after the benign adenomatoid tumor. Although solitary tumors are identified more frequently, the presence of bilateral tumors should raise the possibility of von Hippel-Lindau disease (VHL). von Hippel-Lindau syndrome, an autosomal dominant condition is characterized by cerebellar, retinal, and spinal hemangioblastoma, clear cell renal cell carcinoma, multiple renal cysts, pheochromocytoma, pancreatic cysts, and endocrine pancreatic tumors, endolymphatic sac tumors of the ear and papillary cystadenoma of epididymis. (1) Most cases of papillary cystadenoma of the epididymis are incidental findings in patients with VHL, while some cases are found in patients who seek consultation for infertility (oligozoospermia or obstructive azoospermia) or hydrocele. Among symptomatic patients, the most common presentation is a painless, slowly growing scrotal swelling. A small number of patients present with pain or tenderness in the scrotum or are found to have an epididymal nodule during workup for infertility. (4)

Most cases of PCE occur in young adults, but patients may range in age from 16 to 76 years and these tumors range in size from 0.5 to 8.0 cm. These clinical findings are actually considered sufficient to justify the diagnosis (2) however, genetic testing is the standard method to diagnose VHL. (3)

PCE forms a well-circumscribed or encapsulated, variably cystic nodule, which may be tan or yellow. Histologically, PCE is characterized by cysts filled with prominent intracystic papillary projections The papillae contain fibrovascular cores and are lined by a single layer of bland cuboidal or columnar epithelium. Cells with clear cytoplasm may exhibit reverse polarity (i.e., oriented away from the basement membrane).

Immunohistochemically, the epithelial cells of PCE are consistently positive for cytokeratin AE1/AE3, CAM 5.2, and epithelial membrane antigen (EMA). The keratin profile is CK7 positive and CK20 negative. Renal cell carcinoma marker, carcinoembryonic antigen, vimentin, and S100 are variably positive. PAX8 has been reported to be positive in 1 case. CD10 has been negative in all cases tested.

Differential diagnosis of PCE is metastatic clear cell RCC and clear cell papillary RCC. Clear cell papillary RCC is a biologically indolent tumor that does not metastasize. Features common to clear cell RCC include cystic, tubular, and nested architecture; prominent vascular stroma; and clear cells. Both may occur in patients with VHLD. A CK7-positive and CD10-negative profile has been shown to differentiate PCE from metastatic RCC.PAX8 and CA 9 are not reliable in this distinction. Papillary cystadenoma of the epididymis must also be distinguished from paratesticular papillary mesothelioma, which can involve the epididymis and is positive for epithelial markers. Features that distinguish papillary mesothelioma from PCE include the absence of clear cells and the presence of calretinin positivity. Another epithelial lesion with papillary architecture is a serous borderline tumor of the para testes. This lesion can be differentiated from PCE by the absence of clear cells, the presence of a stratified lining, and the occasional presence of psammoma bodies. Papillary cystadenoma of the epididymis is easily differentiated from the recently described serous (nonpapillary) cystadenoma of the epididymis by the lack of papillary architecture in the later.

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 the tumor site.

1. Boratto SDF, Cardoso PAS, Priolli DG et al. von Hippel-Lindau Syndrome: Genetic Study of Case with a Rare Pathogenic Variant with Optic Nerve Hemangioblastoma, a Rare Phenotypic Expression. Front Oncol. 2020 feb 14;10:139.

2. Maher ER, Sandford RN et al. Von Hippel-Lindau Disease: an Update. Curr Gen Med Rep. 2019;7:227–35.

3. Dumitriu R, Burcea I, Dusceac R et al. Von Hippel-Lindau Syndrome: Clinical Features, Genetics and Surveillance of a Family. Arch Intern Med Res. 2020;3:146–55.

4. S Glasker, MGB Tran, S B Shively et al. Epididymal cystadenomas and epithelial tumourlets: effects of VHL deficiency on the human epididymis. J Pathol. 2006 Sep;210(1):32-41.

Vandana Panwar, PGY3
UT Southwestern Medical Center, Department of Pathology
Dallas, TX

Rajal B. Shah, MD
Dr. Charles T Ashworth Professor of Pathology
Clements University Hospital
Department of pathology
UT Southwestern Medical Center
Dallas, TX

Paratestis

Kidney, diabetes, emphysematous pyelonephritis.