Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Congenital Adrenal Hyperplasia in the Testis

  • Manuel NistalEmail author
  • Pilar González-Peramato
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4794-1

Synonyms

Definition

Testicular adrenal rest tumors (TARTs) are nodular formations, macro or microscopic, benign, located in the vicinity of the rete testis, constituted by cells similar to those of the adrenal cortex. They develop in patients with congenital adrenal hyperplasia (CAH) who have followed inappropriate treatment.

Clinical Features

Patients with TARTs are carriers of a CAH, an autosomal recessive process characterized by deficit of enzymes involved in the synthesis of glucocorticoids. The deficit of corticoids causes an increase in ACTH secretion, resulting in adrenal hyperplasia. The stimulation of ectopic adrenal tissue in the testicle or the stimulation of pluripotent cells of the testicular hilum leads to the development of TARTs. In children, they may debut with symptoms of precocious puberty and generally bilateral increase in testicular size. In adults, seek consultation due to infertility (Tanaka et al. 2017). Ultrasonography is the best tool to detect initial lesions, not yet palpable, and to modify the treatment in those diagnosed (Yu et al. 2015).
  • Incidence

    Clinical incidence of TARTs ranges from 27% to 47%. These figures rise to 30–94% of adults and 18.3–48% of children with CAH using testicular ultrasounds. The discordance is based on the fact that only TARTs greater than 2 cm are palpable. They are more frequent in patients with inadequate treatment, but they can also be observed in well-controlled or even over-treated patients. Most TARTs develop in patients with the classic form of CAH. TARTs develop in all genetic groups of CAH although with variable incidence.

  • Age

    TARTs are most common between 20 and 30 years. Most cases in childhood occur in the first four years.

  • Sex

    Male

  • Site

    Right and left testes

  • Treatment

    Seventy five percent of the tumors return or stabilize by increasing the doses of hydrocortisone. When these results are not obtained, testis sparing surgery is warranted. In some of these cases, they may reappear months after surgery (Kocova et al. 2018).

  • Outcome

    Oligozospermia is common in patients with TARTs (66%) (Reisch et al. 2009). It is practically a constant in patients with p.1172 N genotype. The causes of oligozoospermia are multiple. Because of the abnormal hormonal status in CAH, there is a dysfunction of Leydig cells secondary to the high production of androgens by the adrenal and a high rate of conversion of these into estrogen. Oligozospermia can also be caused by a mechanical obstruction of the rete testis by the tumoral nodules.

Macroscopy

The size of TARTs varies from microscopic to several centimeters. They are well-defined, nonencapsulated yellowish nodules located in the testicular mediastinum.

Microscopy

Currently, testicular biopsy is rarely used because when clinical data, ultrasounds, or MRI coincides, the biopsy is not indicated. TARTs are composed of cells with spherical nucleus and large cytoplasm that is reminiscent of Leydig cells, although lacking Reinke crystals (Fig. 1). No mitosis is observed and in general the pleomorphism is low. The nodules have thick trabeculae of highly collagenized connective tissue. In the periphery, adipose tissue and lymphocytic infiltrates can be recognized (Rutgers et al. 1988).
Fig. 1

Testicular adrenal rest tumor. Nodular formation of cells with eosinophilic cytoplasm. The tumor presents thick trabeculae of highly collagenized connective tissue and adipose metaplasia. The nodule peripherally displaces the testicular parenchyma

Immunophenotype

The cells of TARTs express synaptophysin (88%), CD56, inhibin, Melan A, vimentin, and calretinin. They have receptors for angiotensin II and ACTH and variable immunosuppression for RA. They are negative for insulin-like 3 (Wang et al. 2011).

Differential Diagnosis

The most important differential diagnosis must be established with Leydig cell tumor, since the treatment of these two pathologies is quite different. It requires, in many cases, the sum of the clinical, laboratory, imaging, histological, and immunohistochemical data (Nistal et al. 2017).

Criteria in favor of TARTs are: bilateralism, lower testosterone levels than in Leydig cell tumors, poor estrogen activity (absence of gynecomastia), elevated serum ACTH, and involution when treated with hydrocortisone. The imaging tests show location of the nodules between the rete testis and the testicular parenchyma. TARTs show hypoechoic areas in tumors smaller than two cm and heterogeneous and hyperechoic areas in larger tumors, probably due to existence of fibrous septa (Deshpande et al. 2017). Immunohistochemically, the only marker that TARTs do not share with Leydig cell tumors is Insulin-like 3 (Lottrup et al. 2015).

References and Further Reading

  1. Deshpande, S. S., Shetty, D., & Saifi, S. (2017). Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia. Pol J Radiol, 82, 526–529.Google Scholar
  2. Kocova, M., Janevska, V., & Anastasovska, V. (2018). Testicular adrenal rest tumors in boys with 21-hydroxylase deficiency, timely diagnosis and follow-up. Endocr Connect, 7, 544–552.Google Scholar
  3. Lottrup, G., Nielsen, J. E., Skakkebæk, N. E., Juulm, A., & Rajpert-De Meyts, E. (2015). Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours. European Journal of Endocrinology, 172, 491–499.CrossRefGoogle Scholar
  4. Nistal, M., Gonzalez-Peramato, P., & Serrano, A. (2017). Differential diagnosis of tumors in the adrenogenital syndrome. In Clues in the diagnosis of non-tumoral testicular pathology (pp. 51–57). Cham: Springer.CrossRefGoogle Scholar
  5. Reisch, N., Flade, L., Scherr, M., Rottenkolber, M., Pedrosa Gil, F., Bidlingmaier, M., Wolff, H., Schwarz, H. P., Quinkler, M., Beuschlein, F., & Reincke, M. (2009). High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. The Journal of Clinical Endocrinology and Metabolism, 94, 1665–1670.CrossRefGoogle Scholar
  6. Rutgers, J. L., Young, R. H., & Scully, R. E. (1988). The testicular “tumor” of the adrenogenital syndrome. A report of six cases and review of the literature on testicular masses in patients with adrenocortical disorders. The American Journal of Surgical Pathology, 12, 503–513.CrossRefGoogle Scholar
  7. Tanaka, M., Enatsu, N., Chiba, K., & Fujisawa, M. (2017). Two cases of reversible male infertility due to congenital adrenal hyperplasia combined with testicular adrenal rest tumor. Reprod Med Biol, 17, 93–97.Google Scholar
  8. Wang, Z., Yang, S., Shi, H., Du, H., Xue, L., Wang, L., Dong, Y., & Han, A. (2011). Histopathological and immunophenotypic features of testicular tumour of the adrenogenital syndrome. Histopathology, 58, 1013–1018.CrossRefGoogle Scholar
  9. Yu, M. K., Jung, M. K., Kim, K. E., Kwon, A. R., Chae, H. W., Kim, D. H., & Kim, H. S. (2015). Clinical manifestations of testicular adrenal rest tumor in males with congenital adrenal hyperplasia. Ann Pediatr Endocrinol Metab, 20, 155–161.Google Scholar

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Authors and Affiliations

  1. 1.Department of Anatomy, Histology and NeuroscienceUniversidad Autónoma de MadridMadridSpain
  2. 2.Department of PathologyUniversidad Autónoma de MadridMadridSpain
  3. 3.Department of PathologyUniversity Hospital La PazMadridSpain