2019-4 / MARCH 11

A 43-year-old male presented with a painless testicular mass. Representative histopathologic images and results of molecular testing are shown.


Identify the tumor and what syndromal association should this patient be tested for.

a) Sex Cord Stromal Tumor with Annular Tubules, Peutz-Jeghers Syndrome

b) Large Cell Calcifying Sertoli Cell Tumor, Carney Complex

c) Large Cell Calcifying Sertoli Cell Tumor, Carney-Stratakis Syndrome

d) Leydig Cell Tumor, no syndromal association

Q1. B

Large Cell Calcifying Sertoli Cell Tumor, Carney Complex

Large cell calcifying Sertoli cell tumor can occur in a sporadic or syndromic setting. Up to 60% of cases are thought to be sporadic. Tumors that occur in a syndromal setting are typically bilateral, multifocal and tend to be diagnosed in younger patients compared to their sporadic counterparts. Histologically, the neoplastic cells are characterized by granular eosinophilic cytoplasm, round to oval nuclei and moderate-sized nucleoli. These cells are arranged in variable architectural patterns ranging from nests to cords and tubules and intratubular tumor is frequently seen. As the name of this tumor indicates, small psammomatous to large plaque-like calcifications are often seen as well. Immunophenotypically, these cells label for both Inhibin and SF-1. Some features that correlate with malignant behavior include: increased mitotic activity (>3/10 high power fields), cytologic atypia, necrosis, lymphovascular invasion, size>4cm and extra-testicular growth.

In the syndromic setting, Large Cell Calcifying Sertoli Cell Tumor is often associated with Carney Complex. Common genetic alterations involve the PRKAR1A gene. Other implicated genes include PRKACB. Large Cell Calcifying Sertoli Cell Tumor constitutes a major diagnostic criterion, while inactivating mutations of PRKAR1A constitutes a supplemental diagnostic criterion for the diagnosis of Carney Complex. Either 2 major criteria or a combination of 1 major and 1 minor criteria is required to establish the diagnosis of Carney Complex. Some of the other major criteria include cardiac myxomas, growth hormone producing pituitary adenomas and psammomatous melanotic schwannoma.

Sex cord stromal tumor with annular tubules can be seen in as a part of Peutz-Jeghers Syndrome. This syndrome occurs secondary to alterations of the STK11 tumor suppressor gene. Carney-Stratakis syndrome involves a dyad of paragangliomas and gastrointestinal stromal tumors. This syndrome occurs secondary to germline alterations of succinate dehydrogenase (SDH) subunit genes.

Kirschner LS, Carney JA, Pack SD et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet. 2000 Sep;26(1):89-92.

Forlino A, Vetro A, Garavelli L et al. PRKACB and Carney complex.
N Engl J Med. 2014 Mar 13;370(11):1065-7.

Kratzer SS, Ulbright TM, Talerman A et al. Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature. Am J Surg Pathol. 1997 Nov;21(11):1271-80.

Sounak Gupta, MD, PhD
Memorial Sloan Kettering Cancer Center


Carney, Large Cell, Calcifying, Sertoli, Testis