Crooke’s cell adenoma
38F presenting with one week history of gradual onset global headache. Recent diagnosis ACTH-dependent Cushing’s disease (based on a three-year history of hot flushes, diaphoresis, generalized joint pain, lethargy, truncal obesity, moon facies, recurrent non-traumatic fractures in feet, abdominal striae, depression, hirsutism and amenorrhea. Confirmed with hormonal testing). Past medical history of WFNS grade 1 SAH secondary to right PCA aneurysm; managed by right craniotomy and clipping of aneurysm.
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There is evidence of prior right sided craniotomy and there is metallic artefact in a right paraclinoid location compatible with prior surgery for aneurysm. Multiple foci of increased T2 signal are seen in the periventricular white matter. The lateral ventricles have an abnormal squared configuration with no septum pellucidum identified, likely developmental in nature.
There is an abnormal ovoid area of hypoenhancement in the central-right pituitary gland measuring 8 x 4 mm in the coronal dimension. There is a small area of T2 hyperintensity in the right side of the pituitary. The infundibulum is minimally deviated toward the left. The cavernous sinuses and optic nerves have a normal appearance.
Impression: The findings suggest a microadenoma in the central right sided pituitary gland. Right cranial surgery, possibly for an aneurysm. Likely developmental abnormality involving the ventricles.
The patient underwent a transsphenoidal resection of the pituitary lesion.
MACROSCOPIC DESCRIPTION: "Pituitary tumour": Soft red tissue fragments 5mm in maximum dimension. Frozen section DIAGNOSIS: Pituitary adenoma.
MICROSCOPIC DESCRIPTION: Paraffin sections show a moderately hypercellular tumour composed of cells with mildly pleomorphic round and oval hyperchromatic nuclei and a variable amount of pale eosinophilic cytoplasm. These are arranged in trabeculae and diffuse sheets within a vascular stroma. No mitotic figures or areas of necrosis are seen and no normal anterior pituitary tissue is included. Reticulin staining shows a diffuse non-acinar pattern typical of adenoma. No staining for growth hormone, prolactin, ACTH, LH, FSH, TSH, GFAP or S-100 protein is seen in tumour cells. CAM5.2 staining shows strong perinuclear staining in the majority of tumour cells with circumferential perinuclear staining, strongly suggestive of Crooke's hyaline, noted in many cells. The topoisomerase labelling index is <1%.
DIAGNOSIS: Pituitary tumour: Features suggestive of Crooke's adenoma.
The patient received no further treatment. She has remained under radiological surveillance, with no disease recurrence.
This case demonstrates Crooke cell adenoma, a particularly rare form of ACTH-producing pituitary gland tumor.
Endocrinologically functional ACTH-producing pituitary adenomas are associated with Cushing disease 1. Most occur in women, at a mean age of 35 to 44 years 2, and majority are microadenomas (75-90%) 3.
Corticotrophs of the anterior pituitary normally contain small numbers of perinuclear cytokeratin filament bundles 1. Persistently elevated blood cortisol levels causes cytoplasmic accumulation of cytokeratin resulting in a distinctive cellular alteration termed Crooke hyaline change 1,4: cell cytoplasm of hyalinized appearance on hematoxylin-eosin and periodic acid–Schiff stains 5. Rarely this change is seen in corticotroph adenomas, termed Crooke’s cell adenoma 4.
Case courtesy of Associate Professor Pramit Phal
- 1. Rotondo F, Cusimano M, Scheithauer BW et-al. Atypical, invasive, recurring Crooke cell adenoma of the pituitary. Hormones (Athens). 2012;11 (1): 94-100. Pubmed citation
- 2. George DH, Scheithauer BW, Kovacs K et-al. Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. Am. J. Surg. Pathol. 2003;27 (10): 1330-6. Pubmed citation
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- 4. Sathiyabama D, Asha U, Shwetha SD et-al. Crooke's cell adenoma of the pituitary: a histological, immunocytochemical, and electron microscopic study of a rare case. Neurol India. 2014;62 (2): 216-7. doi:10.4103/0028-3886.132435 - Pubmed citation
- 5. Felix IA, Horvath E, Kovacs K. Massive Crooke's hyalinization in corticotroph cell adenomas of the human pituitary. A histological, immunocytological, and electron microscopic study of three cases. Acta Neurochir (Wien). 1982;58 (3-4): 235-43. Pubmed citation