Sertoli cell proliferations of the infantile testis - An intratubular formof Sertoli cell tumor?

We report on six boys with intratubular Sertoli cell proliferations (ISCPs) , studied by routine histologic methods, electron microscopy, and immunohis tochemistry of anti-mullerian hormone (AMH), inhibin alpha -subunit, 3 beta -hydroxysteroid dehydrogenase (3 beta -HSD), proliferative cellular nuclea r antigen, and p53, and carefully followed for extended periods with period ic clinical examinations, testicular ultrasonographies, and determinations of serum levels of AMH and inhibin B. Peutz-Jeghers syndrome was found in f our of six patients, and gynecomastia occurred in five of six patients. One boy had isosexual pseudoprecocity. ISCPs were observed as multiple foci of seminiferous tubules with large and proliferated Sertoli cells replacing g erm cells and limited by the basement membrane. Mitotic figures, atypia, an d/or interstitial invasion were not observed. Bilateral ISCPs were the only pathologic finding in three patients (patient nos. 1-3) and were associate d with a microscopic tumor that resembled a large-cell calcifying Sertoli c ell tumor (LCCSCT) in a fourth patient (patient no. 4). In the two remainin g patients (patient nos. 5 and 6) ISCPs and LCCSCT were found in both teste s. Ultrastructural examination showed large Sertoli cells, with round nucle i, sparse organelles, and some glycogen. Inhibin alpha -subunit immunolocal ization was positive in the five patients in whom it was determined (patien t nos. 2-6), AMH was positive in those ISCPs associated with tumors (patien t nos. 4-6) and negative in isolated ISCPs (patient nos. 2 and 3); 3 beta - HSD and PCNA were variable, and p53 was negative in all ISCPs. Patient nos. 1-4 have been followed for 2-19 years. One of them is currently entering p uberty, the other two have already completed puberty and have testes of nor mal size, and the remaining one is an adult with clinically normal testes a nd sperm production. None of these patients had evidence of tumor developme nt during follow-up as shown by serial ultrasonographies and serum levels o f AMH and inhibin B. Patient nos. 5 and 6 who had bilateral ISCPs and LCCSC T were orchidectomized and evolved for 2-10 years after surgery without tum or recurrence. The prognostic significance of ISCPs, particularly when they are the only pathologic finding in a testicular biopsy, is a matter of con troversy, Based on the long normal evolution, we recommend a conservative a pproach to therapy. The bilateral and multicentric character of ISCPs and t heir association with Sertoli tumors and Peutz-Jeghers syndrome suggest tha t they represent either proliferative lesions with tumorigenic potential or the intraepithelial stage in the evolution of some testicular Sertoli cell tumors.