Distinguishing Cystic Degeneration from Other Aging Lesions in the Adrenal Cortex of Sprague-Dawley Rats

Abstract

Cystic degeneration of the adrenal cortex is a common age-related finding in the Sprague-Dawley (SD) rat strain occurring more frequently in females. Compression of the adjacent cortex, a common hallmark of benign adrenal cortical tumors, often accompanies foci of cystic degeneration, creating a diagnostic challenge. Accurately differentiating these relatively common degenerative changes from proliferative lesions is critical in safety assessment studies. Cystic degeneration typically arises in the zona fasciculata of the adrenal cortex and often causes compression along the margin of the lesion. The degenerating cells are large, with abundant eosinophilic cytoplasm, or contain clear cytoplasmic vacuoles. Mitotic figures are generally uncommon. In many cases, cystic degeneration appears to arise in areas of hypertrophy in the zona fasciculata. In contrast, adrenal cortical hyperplasia and adrenal cortical adenoma are frequently comprised of smaller cells that cause compression of adjacent cortex, and in some cases mitotic figures are observed. Cytological detail and growth patterns should be considered more useful criteria than compression alone for separating degenerative cystic lesions from proliferative lesions in the adrenal cortex of SD rats.

Findings in Historical Control Harlan RCCHan™

“…Cystic degeneration in the adrenal cortex represented a continuum of features ranging from foci of few vacuolated cortical cells with associated congestion at minimal severity to larger areas with confluent vacuolated cells, cell loss, cystic spaces, and hemorrhage at higher severity (Figure 13). Cystic degeneration demonstrated a markedly higher incidence (Table 22) in females (64.2%) than in males (6.1%) similar to what was reported in Sprague-Dawley rats by Laast et al (2014). Similarly, focal hypertrophy of the zona glomerulosa was more common in females (49.7%) than males (24.4%) while, in contrast, focal vacuolation was more common in males (40.6%) than females (10.1%).…”

Stress-induced changes in the aged-rat adrenal cortex. Histological and histomorphometric study

“…Stress induces pronounced changes at the interphase between ZR and medulla where connective tissue cords loosened, cell count decreased and cell-to-cell spaces extended [18]. These vacuolated areas might denote an early stage of cystic degeneration [21].…”

Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System

“…( Chandra et al 2013 ; Elmore et al 2013 ; Frith et al 2000 ; Greaves and Faccini 1992 ; Hamlin II and Banas 1990 ; Laast et al 2014 ; Nyska and Maronpot 1999 ; Yarrington 1996 )…”