Extensive Bilateral Adrenal Rest Testicular Tumors in a Patient With 3 β-Hydroxysteroid Dehydrogenase Type 2 Deficiency

Abstract

Testicular adrenal rest tumors (TARTs) are presumably derived from ectopic adrenocortical tissue in the testis, affecting up to 49% to 94% of males with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Few reports have described TARTs in rarer forms of CAH such as 3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D). A man with 3βHSD2D presented with massive bilateral testicular tumors. He had been treated with glucocorticoids and mineralocorticoids since infancy, with difficulties in suppressing dehydroepiandrosterone sulfate. At the age of 13 years, bilateral testicular lumps were found, and a radiologic diagnosis of TARTs was proposed. Subsequent sonographic examinations showed progression, despite intensifying his glucocorticoid therapy with metabolic complications. Following an open testicular biopsy, concerns of a Leydig cell tumor and risk of malignant transformation were raised, and because the patient also had local symptoms and azoospermia, he underwent bilateral orchiectomy at age 33 years. Histopathology was consistent with bilateral TARTs, exhibiting widespread immunoreactivity for adrenocortical markers, whereas no histological features of Leydig cell tumors were seen. The distinction between TARTs and Leydig cell tumors is important but can be challenging, and in our case, orchiectomy was needed to rule out the latter diagnosis. TART should be considered a differential diagnosis also in patients with 3βHSD2D who have testicular lumps.

Keywords: 3β-hydroxysteroid dehydrogenase deficiency; congenital adrenal hyperplasia; fertility; sperm quality; testicular adrenal rest tumors.

Figure 1.

Long-term follow up in a male with 3βHSD2D deficiency. The TARTs were revealed by age 13 years, when the patient’s height began to flatten (progressed bone age), and they gradually enlarged. Despite the depicted intensification in treatment (glucocorticoids and fludrocortisone), minimal response to DHEAS levels was observed. The increasing weight reflected the negative metabolic control. Finally, a bilateral orchiectomy was performed when the patient was 33 years old. The DHEAS concentrations were still markedly elevated at the last follow-up at 34 years of age.

Figure 2.

Histology of extensive TARTs in a man with 3βHSD2D. (A) Routine hematoxylin and eosin staining of the left TART. The tumor cells have a large nuclear-to-cytoplasmic ratio, and tumor nuclei are round to elliptical with a loose chromatin. The cytoplasm is eosinophilic and granulated. (B) Associated TART features such as adipose tissue metaplasia (asterisk) and focal lymphocytic infiltrates (arrow) are noted. (C) The tumor is seen with a massive peritubular fibrosis and hyalinization (arrow). (D) Tumor within the rete testis (asterisk), the hypothesized origin of TARTs. (E) Immunohistochemical markers for adrenal tissue; from left to right: inhibin A, Melan A, calretinin, and synaptophysin. (F) Additional immunohistochemical markers (CD56, CYP11B1, and CYPP11B2) supporting the TART diagnosis. Widespread CD56 immunoreactivity and focal CYP11B1 and CYP11B2 positivity. All photomicrographs are magnified ×100, except A and inserts of CYP11B1/2 immunostainings (×400).