This case was originally published in 2018. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.
Clinical History
A 55-year-old woman presented with dizziness. MRI showed a 2.5 x 1.5 x 1.7 cm suprasellar mass with associated hemorrhage, expansion of the sella, and superior displacement of the optic chiasm (Image A). The patient denied visual disturbances but admitted to intermittent headaches. There were no clinical signs or symptoms of pituitary dysfunction. All lab results were normal including a 24-hour urine cortisol and the lesion was thought to be a nonfunctioning macroadenoma of the pituitary. An endonasal transsphenoidal resection was performed.
Tissue Site
Pituitary/suprasellar region
Whole Slide Image
The whole slide image provided is a Periodic Acid Schiff stained slide of Suprasellar mass from an Endonasal transsphenoidal resection.
Questions
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What is the MOST likely diagnosis?
-
Aneurysm
-
Craniopharyngioma
-
Crooke cell adenoma
-
Mucormycosis
-
Pituitary apoplexy
-
-
What is the microscopic feature identified by arrows in this image?
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Apoptotic bodies
-
Crooke hyaline change
-
Early necrotic change
-
Fungal organisms
-
Viral inclusions
-
-
It is important to identify this lesion because of which of the following?
-
The radiographic appearance shows infiltration within cortex.
-
This is a slow growing tumor and responds well to radiation therapy.
-
This lesion is almost always endocrinologically silent.
-
This lesion is indolent and does not require treatment.
-
This lesion is invasive and often has an aggressive course.
-
Discussion and Diagnosis
The diagnosis for this case is Crooke cell adenoma (CCA), a relatively rare and poorly understood type of pituitary adenoma with distinct clinical and pathological characteristics. Neuroimaging studies typically describe these neoplasms as large suprasellar masses, often with invasion of the cavernous sinus and adjacent structures. The most common clinical presentation is that of a macroadenoma with invasion into the sphenoid and cavernous sinuses. There is a strong female predominance. Most such tumors are ACTH-secreting adenomas which result in Cushing disease. Patients can also present with symptoms of mass effect (headaches and visual disturbances) caused by endocrinologically silent ACTH-positive adenomas. The patient presented here had no evidence of Cushing disease in the pre- or postoperative periods. CCAs with elevated cortisol levels are much more commonly reported in the literature than those without elevated cortisol levels. Due to their scarcity it is unclear exactly how the functional status of a CCA relates to its clinical course. It remains important for clinicians to be aware of this variant of pituitary adenoma because of its propensity for a more aggressive clinical course.
Crooke hyaline change is a common histologic finding described in nonneoplastic pituitary corticotrophs exposed to persistently elevated cortisol levels. Some corticotroph adenomas show Crooke hyaline change in neoplastic cells, and when more than 50% of adenoma cells exhibit Crooke hyaline change it is known as a CCA. The affected corticotrophs accumulate excessive amounts of cytoplasmic intermediate filaments of cytokeratins along with concomitant displacement and often reduction of cytoplasmic organelles and secretory granules, resulting in a pink hyalinized appearance of the cytoplasm seen on H&E staining of cytologic smears (Image B), frozen sections (Image C), and paraffin sections (Image D). These so-called Crooke cells may have eccentric nuclei pushed to one side by paranuclear collections of displaced normal cellular organelles (Image C, arrow), together encircled by pale hyalinized cytoplasm and often rimmed by amphophilic granular cytoplasm (Image D). The accumulated cytokeratin filaments are best identified as distinct perinuclear rings by IHC for low-molecular-weight cytokeratins such as Cam 5.2 (Image E). Tumor cells in CCA are immunoreactive for ACTH, which decorates peripheral cytoplasm of Crooke cells and negatively highlights non-immunoreactive perinuclear cytokeratin masses (Image F). Although these tumors are clinically aggressive and often invade the cavernous sinuses and nearby structures, they do not display high mitotic activity and MIB-1 (Ki-67) immunolabeling is often very low (Image G).
CCAs are rare, clinically aggressive tumors, with fewer than 100 cases reported in the literature so far. Increased frequency of cavernous sinus invasion makes gross total resection difficult, which contributes to the high recurrence rate of 66%. Patients with CCAs have been reported to have persistent/recurrent visual disturbances and elevated ACTH levels despite multiple resections, aggressive medical management, and stereotactic radiosurgery. In cases of recurrent CCA refractory to conventional methods, there are reports of successful use of temozolamide in obtaining radiographic tumor regression and ACTH level reduction.
Crooke cell adenoma
Take Home Points
- Neuroimaging of Crooke cell adenomas often shows invasion of the cavernous sinus.
- Historically, Crooke cell adenomas were defined as corticotroph adenomas with >50% of cells displaying Crooke hyaline change. However, currently there is no specific classification criterion based on either the number of Crooke cells or the clinical behavior of the neoplasm.
- Crooke hyaline change is a perinuclear ring-like cytoplasmic accumulation of cytokeratin filaments best seen with IHC for low-molecular-weight cytokeratins such as Cam 5.2.
- The typically bland, monomorphic histologic appearance of this tumor with low MIB-1 positive nuclei is at odds with its aggressive invasive behavior.
References
- Asa SL. Practical pituitary pathology: what does the pathologist need to know? Arch Pathol Lab Med. 2008;132:1231-40.
- Di Ieva A, Davidson JM, Syro LV, et al. Crooke cell tumors of the pituitary. Neurosurgery. 2015;76:616-22.
- George DH, Scheithauer BW, Kovacs K, et al. Crooke cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. Am J Surg Pathol. 2003;27:1330-6.
- Mohammed S, Kovacs K, Mason W, Smyth H, Cusimano MD. Use of temozolomide in aggressive pituitary tumors: case report. Neurosurgery. 2009;64:E773-774; discussion E774.
- Oldfield EH, Vance ME, Louis RG, et al. Crooke's changes in Cushing's syndrome depends on degree of hypercortisolism and individual susceptibiility. J Clin Endocrinol Metab. 2015;100:3165-71.
- Takeshita A, Inoshita N, Taguchi M, et al. High incidence of low O(6)-methylguanine DNA methyltransferase expression in invasive macroadenomas of Cushing's disease. Eur J Endocrinol. 2009;161:553-9.
Answer Key
- What is the MOST likely diagnosis?
- A. Aneurysm
- B. Craniopharyngioma
- C. Crooke cell adenoma
- D. Mucormycosis
- E. Pituitary apoplexy
- What is the microscopic feature identified by arrows in this image?
- A. Apoptotic bodies
- B. Crooke hyaline change
- C. Early necrotic change
- D. Fungal organisms
- E. Viral inclusions
- It is important to identify this lesion because of which of the following?
- A. The radiographic appearance shows infiltration within cortex.
- B. This is a slow growing tumor and responds well to radiation therapy.
- C. This lesion is almost always endocrinologically silent.
- D. This lesion is indolent and does not require treatment.
- E. This lesion is invasive and often has an aggressive course.