Cytokeratin CK20 is a sensitive marker for Crooke's cells and the early cytoskeletal changes associated with hypercortisolism within pituitary corticotrophs

Abstract

Crooke's cells are nonneoplastic corticotroph cells found in the adenohypophysis of patients who have an endogenous or exogenous excess of glucocorticoids. Classic Crooke's cells have a prominent hyaline cytoplasmic ring that displaces the basophilic granules of the normal cell. This characteristic appearance is produced by a perinuclear accumulation of cytokeratin filaments. Immunohistochemistry for cytokeratins is a sensitive way to identify Crooke's cells, but a keratin antibody specific for Crooke's hyaline change has not been reported. Normal pituitary epithelial cells are variably reactive for many keratin antibodies but are negative for cytokeratin 20 (CK20) expression. We evaluated the use of CK20 immunohistochemistry as a marker for Crooke's cells. We examined sections from 25 pituitary glands resected from 15 patients who had undergone exogenous glucocorticoid administration and from 10 patients with an endogenous source of hypercortisolism; sections from 10 normal pituitary glands obtained at autopsy were used as controls. CK20 immunoreactivity was observed only in corticotrophs. A staining pattern consistent with classic Crooke's cells was seen in pituitary gland sections from 15 of the cases. Cells with less intense CK20 positivity were present in sections from all 25 cases. We found CK20 to be a sensitive and specific marker for Crooke's cells and also for the previously unrecognized, subtle, cytoskeletal changes that occur in corticotrophs in response to hypercortisolism.