September 2022 – Neuropathology

A 37-year-old man with a history of multiple endocrine neoplasia 1, Hurthle cell neoplasm, pancreatic neoplasm, and pituitary adenoma, presented after an episode of syncope. Imaging revealed a pituitary mass replacing the clivus, opacifying the right sphenoid sinus and extending into the left sinus and posterior right nasal cavity. His cortisol and adrenocorticotrophic hormone levels were elevated. The histopathologic findings of the pituitary mass are shown below. T-Pit immunostain was also positive, while SF-1 and PIT-1 were negative (not shown). 

Figure 1: A1 ACTH 20x
Figure 2: PIT CAM 5.2.2
Figure 3: Pit 20x

What is best diagnosis for the patient’s pituitary mass?

  • Crooke cell adenoma
  • Sparsely granulated corticotroph adenoma
  • Densely granulated corticotroph adenoma
  • Acidophilic stem cell adenoma

The correct answer is ...

Crooke’s cell adenoma.

The expression of T-PIT transcription factor and adrenocorticotrophic hormone (ACTH) (image above) support the diagnosis of a corticotroph pituitary adenoma. There are three subtypes of corticotroph adenomas: densely granulated, sparsely granulated, and Crooke cell adenoma. The histology shows glassy eosinophilic cytoplasm with granules noted at the periphery, which is characteristic of a Crooke cell adenoma. The CAM 5.2 stain (image above) shows strong perinuclear and ring-like expression of low molecular weight cytokeratin corresponding to the accumulation of hyaline material and is required for diagnosis of the Crooke cell adenoma. Of note, the nomenclature within the 2022 WHO Classification of Tumors, 5th edition, Endocrine and Neuroendocrine Tumors will change from pituitary adenoma to PitNET (pituitary neuroendocrine tumor).

Crooke cell adenomas are a rare subtype of pituitary adenoma, representing <1% of pituitary adenomas, and typically are silent macroadenomas at the time of diagnosis. They can however produce Cushing disease symptoms, and this is a well-known presentation of patients. Crooke cell adenomas show more aggressive behavior with an estimated 60%-66% risk of recurrence. The subtype also typically invades into the cavernous sinus and is resistant to radiotherapy.

Pituitary adenomas can be a manifestation of multiple endocrine neoplasia (MEN) syndrome, which is a hereditary syndrome of the endocrine glands. MEN1 tumors include pituitary gland tumors, parathyroid tumors, and pancreatic neuroendocrine tumors. The most frequent types of pituitary adenoma in MEN1 syndrome are lactotroph, somatotroph, and non-secreting tumors.


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Nadarra Stokes, M.D.

Resident, Anatomic and Clinical Pathology
Mayo Clinic

Rachael Vaubel, M.D., Ph.D.

Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.