Testicular lipomatosis in Cowden's syndrome

Abstract

Cowden's syndrome is either familial or sporadic and is associated with the predominantly postpubertal development of a variety of cutaneous, stromal and visceral neoplasms. The syndrome is associated with mutations of the PTEN gene and is closely related to Bannayan's syndrome in which macrocephaly and benign tumors, especially lipomas and hemangiomas are pathognomic. In PTEN knockout mice testicular tumors have been reported and for this reason we felt it prudent to examine the testes of our patients with genetically proven Cowden's syndrome. Seven of eight patients who underwent testicular ultrasound were found to have diffuse bilateral hyperechoic lesions. Four patients consented to testicular biopsy and on histological examination multiple foci of adipocytes were found within the testicular interstitium, with no evidence of dysplasia or preclinical malignancy. Immunohistochemical assessment of adipocytes suggested a stromal derivation without evidence of metaplasia from Leydig cells. In one case there was focal atrophy of seminiferous tubules, while in two others there was nodular periorchitis of the tunica albuginea. Biochemical evaluation of testicular function (luteinizing hormone, follicle-stimulating hormone, testosterone, sex hormone binding globulin and free androgen index), prostate-specific antigen and testicular tumor markers were normal, while seminal fluid analysis showed only minor abnormalities. The high incidence of testicular lipomatosis in our adult subjects suggests this to be an important diagnostic criterion for Cowden's syndrome.

Testicular Hamartomas in a Patient With Bannayan-Riley-Ruvalcaba Syndrome

“…In 2003, Lindsay et al 5 reported a patient with Cowden syndrome who had multiple testicular echogenic foci on sonography and tiny high-signal lesions on T1-weighted magnetic resonance imaging, similar to the findings in our patient, which were described as testicular hamartomas. Woodhouse et al 8 found similar sonographic findings in 8 patients with Cowden syndrome; these underwent biopsy and were found to be lipomatous lesions without malignant potential; as such, they do not warrant biopsy when they have classic imaging characteristics. In a subsequent analysis, these authors proposed the term "lipomatosis of the testis" and suggested that it may be pathognomic for Cowden syndrome.…”

“…Our patient, with a pure anaplastic seminoma, could add a small amount of weight to that argument. Given the work by Woodhouse et al, 8 however, the pathologic mechanisms behind the characteristic testicular lesions of BRRS and Cowden syndrome are not likely to be precursors to seminomas. In this case, no proof exists that this did not merely represent a sporadic case of a seminoma.…”

“…4 PTEN mutations have also been described in other sporadic malignancies. 8 Visualization of a testicular lesion on sonography raises concern for malignancy; in a patient with a history of a seminoma, there should be concern for recurrent disease. Multiple hyperechoic lesions are more rare and are typical of testicular microlithiasis; however, microlithiasis presents as smaller, more echogenic foci.…”

Testicular Mixed Germ Cell Tumor in an Adolescent with Cowden Disease

“…Woodhouse and Ferguson [9] described benign testicular lipomatosis in Cowden syndrome. They identified testicular lipomatosis in 7 of 8 men who had investigation for subfertility [10].…”

Fettvev i testiklene

“…Testikulaer lipomatose er et patognomonisk funn som kan relateres til Cowdens syndrom, en sjelden, arvelig tilstand som er assosiert med økt risiko for utvikling av flere typer kreft (2,3). På bakgrunn av dette funnet ble derfor pasienten henvist til utredning ved Seksjon for arvelig kreft, Oslo universitetssykehus.…”