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.

Epithelial and organ‐related marker expression in pituitary adenomas

“…9 This pattern of reactivity has also been described in neoplastic cells of corticotroph tumors and in non-neoplastic cells of patients with endogenous and exogenous hypercortisolism. 11 In our CK20-positive tumors, Crooke's hyaline change was not prominently identified, reflecting the fact that most tumors, including corticotrophs, were macroadenomas.…”

“…Thus, we found this more frequently than in prior studies reporting no CK20‐positive tumors but less frequently than in studies where CK20 reactivity was a frequent finding . This pattern of reactivity has also been described in neoplastic cells of corticotroph tumors and in non‐neoplastic cells of patients with endogenous and exogenous hypercortisolism . In our CK20‐positive tumors, Crooke's hyaline change was not prominently identified, reflecting the fact that most tumors, including corticotrophs, were macroadenomas.…”

“…9 A subsequent study demonstrated CK20 expression in neoplastic and normal pituitary cells under the influence of endogenous and exogenous cortisol. 11 To our knowledge, the markers CK7 and CK20 have received little further investigation beyond these initial studies. This is somewhat surprising because these markers are most frequently used in contemporary surgical pathology (and neuropathology) in the work-up of metastases.…”

“…However, the frequency of CK20 immunoreactivity differed between these studies, with the larger study reporting immunoreactivity in corticotrophs and somatotrophs . A subsequent study demonstrated CK20 expression in neoplastic and normal pituitary cells under the influence of endogenous and exogenous cortisol …”

Keratin Expression in Endocrine Organs and their Neoplasms

“…The distinction between densely granulated and sparsely granulated growth hormone producing tumors is of clinical importance, as densely granulated somatotroph adenomas are more likely to respond to somatostatin analog therapy compared with sparsely granulated adenomas [55,56]. In normal and hyperplastic anterior pituitary tissue, corticotroph secreting cells (Crooke's cells) are positive for K20 [57]. Coons et al reported that 13 of 15 cases of corticotroph adenomas constantly expressed K20 with a diffuse cytoplasmic pattern, making K20 a very useful marker for this specific type of adenoma [58].…”