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

We performed a detailed morphologic,

immunophenotypic, and endocrine characterization of neoplastic

and non-neoplastic lesions of androgen-producing cells

known to harbor or lack Reinke crystals (RCs) with an aim to

provide further insight into the nature of these cells and crystals.

Study cases were selected from the files of participating

hospitals and subclassified according to current classifications:

20 with Leydig cell tumors (LCTs), 2 with testicular

adrenal rest tumors (TARTs), 2 with testicular tumors of

adrenogenital syndrome (TTAGS), and 2 with androgen insensitivity

syndrome (AIS). An extensive immunophenotypic

panel including markers used in sex cord-stromal cell tumors,

androgen hormones, enzymes, and receptors was applied to

the cases and 10 non-tumoral adrenal glands. Non-tumoral

tissues were scored separately. RCs were present in 90 % of

LCTcases and all cases with normal Leydig cells; RCs stained

specifically with calretinin and 3β-hydroxysteroid dehydrogenase

(3BHSD) and were present only in cells with high

concomitant expression of both proteins, a phenotype unique

to Leydig cells and LCTs. Leydig cells from AIS cases lack

RCs due to decreased expression of 3BHSD. Calretinin is

decreased in testicular adrenal-like tumors and absent in normal

adrenocortical cells, which explain why they lack RCs.

Calretinin expression in androgen-producing cells is independent

from androgen receptors and androgen synthesis. RCs

represent for the most part, if not exclusively, crystallized

forms of a 3BHSD/calretinin complex. Androgen-producing

cells containing and lacking RCs differ mainly in the level of

expression of these proteins and androgen receptors.