Immunophenotypic differences between neoplastic and non-neoplastic androgen-producing cells containing and lacking...

Area of Science:

• Endocrinology
• Cell Biology
• Oncology

Background:

• Reinke crystals (RCs) are distinctive eosinophilic cytoplasmic inclusions found in Leydig cells and Leydig cell tumors (LCTs).
• The precise composition and formation of RCs remain incompletely understood, particularly their relationship with cellular function and specific proteins.
• Androgen-producing cells, including Leydig cells, are crucial for hormone synthesis and reproductive health.

Purpose of the Study:

• To comprehensively characterize the morphologic, immunophenotypic, and endocrine features of androgen-producing cells with and without RCs.
• To elucidate the molecular nature and cellular origin of Reinke crystals.
• To investigate the role of specific proteins, hormones, and receptors in RC formation and presence.

Main Methods:

• Detailed morphologic and immunophenotypic analysis of neoplastic (Leydig cell tumors, testicular adrenal rest tumors, testicular tumors of adrenogenital syndrome) and non-neoplastic lesions.
• Application of an extensive immunophenotypic panel including markers for sex cord-stromal tumors, androgen hormones, enzymes (3β-hydroxysteroid dehydrogenase - 3BHSD), and receptors.
• Comparative analysis of tissues with and without Reinke crystals, including non-tumoral adrenal glands and Leydig cells from androgen insensitivity syndrome cases.

Main Results:

• Reinke crystals were present in 90% of Leydig cell tumors and all normal Leydig cells, staining specifically with calretinin and 3BHSD.
• RCs were exclusively found in cells co-expressing high levels of both calretinin and 3BHSD, a phenotype unique to Leydig cells and LCTs.
• Leydig cells from androgen insensitivity syndrome cases lacked RCs due to decreased 3BHSD expression, while calretinin was decreased in testicular adrenal-like tumors.

Conclusions:

• Reinke crystals are predominantly crystallized forms of a 3BHSD/calretinin complex, specific to Leydig cells and LCTs.
• The presence or absence of RCs in androgen-producing cells is primarily determined by the expression levels of 3BHSD and calretinin.
• Calretinin expression in these cells is independent of androgen receptors and androgen synthesis, offering insights into cell differentiation and function.