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LETTER TO EDITOR
Year : 2014  |  Volume : 62  |  Issue : 2  |  Page : 216-217

Crooke's cell adenoma of the pituitary: A histological, immunocytochemical, and electron microscopic study of a rare case


1 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
2 Department of Neurosurgery, Dr. Dil Hospital-Neurocare, Ludhiana, Punjab, India

Date of Submission24-Aug-2013
Date of Decision19-Jan-2014
Date of Acceptance31-Mar-2014
Date of Web Publication14-May-2014

Correspondence Address:
Vani Santosh
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.132435

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How to cite this article:
Sathiyabama D, Asha U, Shwetha SD, Thakkar R, Dil JS, Santosh V. Crooke's cell adenoma of the pituitary: A histological, immunocytochemical, and electron microscopic study of a rare case. Neurol India 2014;62:216-7

How to cite this URL:
Sathiyabama D, Asha U, Shwetha SD, Thakkar R, Dil JS, Santosh V. Crooke's cell adenoma of the pituitary: A histological, immunocytochemical, and electron microscopic study of a rare case. Neurol India [serial online] 2014 [cited 2021 Apr 19];62:216-7. Available from: https://www.neurologyindia.com/text.asp?2014/62/2/216/132435


Sir,

Crooke's hyaline change, first described by Crooke, represents intracytoplasmic accumulation of cytokeratin (CK), usually noted in non-tumorous corticotrophs in response to excess glucocorticoids. [1] Rarely this change is seen in corticotroph adenomas, termed Crooke's cell adenomas (CCA). CCA is a rare form of adrenocorticotropic hormone (ACTH)-producing adenoma, known for its aggressive behavior and tendency to recur. Few cases are reported in literature, with the largest series comprising 36 cases, reported by George et al. [2] In this study, the recurrence rate was in 61%, suggesting the aggressive nature of this tumor. We report an additional case of CCA, probably the first case from India.

A 58-year-old lady presented with features of Cushing's disease of 2-years duration. Magnetic resonance imaging (MRI) revealed a lobulated, partially enhancing, solid, and cystic sellar/suprasellar tumor [Figure 1]a-c. Serum ACTH level was 102 pg/ml (normal 7.2-63 pg/ml). She underwent a transethmosphenoidal microsurgical excision of the pituitary tumor. No mass lesion was noted on ultrasound examination of abdomen. Histology revealed features of an ACTH-secreting pituitary adenoma. Most tumor cells exhibited characteristic Crooke's hyaline [Figure 2]a, which was positively stained for pan cytokeratin (AE1/AE2), variably for CK-7 [Figure 2]b and c, and displaced the ACTH secretory granules to the periphery of the cells [Figure 2]d. These findings matched with the study of Rotondo and colleagues. [3] The tumor showed a variable expression of markers of tumor aggressiveness such as MIB-1 [Figure 3]a, topoisomerase-2 alpha [Figure 3]b, and p53 [Figure 3]c, suggesting that these markers may not consistently indicate the inherent aggressive nature of CCAs. On the other hand, diffuse staining for p27 and O 6 methyl guanine methyl transferase (MGMT) was noted [Figure 3]d and e. Even though most studies have shown decreased p27 expression in aggressive pituitary adenomas, in the present study and in the study of Rotondo et al., a high expression of p27 was noted in CCA, suggesting its dual tumor suppressor and oncogenic role. 4 Our case was immunopositive for MGMT, probably suggesting that CCAs are not good candidates for temozolomide (TMZ) treatment. Ultrastructurally, Crooke's hyaline corresponds to 'microfilaments', as we have observed [Figure 3]f, which belongs to the CK class, and this process has been likened to a metaplastic change.
Figure 1: Shows the MRI features of CCA. T1W image shows a sellar/ suprasellar lesion with hypointense solid and a hyperintense cystic component. (a) T2W image highlights the hyperintense cyst with fluid level and isointense solid component. (b) Post contrast T1W image shows moderate homogenous enhancement of the solid component. (c) MRI = magnetic resonance imaging, CCA = Crooke's cell adenomas

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Figure 2: Shows the histological features of CCA. The tumor cells contain perinuclear dense Crooke's hyaline inclusion, (a) which are diffusely positive for pan CK. (b) and variably express CK7. (c) ACTH-positive granules are pushed to the periphery. (d) Original magnification ×160. CK = cytokeratin, CCA = Crooke's cell adenomas, ACTH = Adrenocorticotropic hormone

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Figure 3: Shows expression of markers of tumor aggressiveness in CCA. Occasional tumor cell nuclei are labeled by MIB-1, (a) anti-topoisomerase-2 alpha, (b) while more cells show p53 labeling. (c) A diffuse immunopositivity is seen for p27 (d) and MGMT. (e) All figures are original magnification ×160. (f) Shows ultrastructural characteristics of Crooke's hyaline. Numerous perinuclear intermediate filaments are seen obscuring rough ER and golgi bodies, displacing the secretory granules peripherally. Original magnification ×9300. CCA = Crooke's cell adenomas, ER = Endoplasmic reticulum

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To summarize, we report a rare case of CCA with a varied expression of markers of tumor aggressiveness. These markers may not reflect the aggressive potential of the tumor, as earlier studies have highlighted these tumors to be resistant to treatment and prone for recurrences.

 
  References Top

1.Crooke AC. A change in the basophil cells of the pituitary gland common to conditions which exhibit the syndrome attributed to basophil adenoma. J Pathol Bacteriol 1935;41:339-49.  Back to cited text no. 1
    
2.George DH, Scheithauer BW, Kovacs K, Horvath E, Young WF Jr, Lloyd RV, et al. Crooke′s cell adenoma of the pituitary: An aggressive variant of corticotroph adenoma. Am J Surg Pathol 2003;27:1330-6.  Back to cited text no. 2
    
3.Rotondo F, Cusimano M, Scheithauer BW, Coire C, Horvath E, Kovacs K. Atypical, invasive, recurring Crooke cell adenoma of the pituitary. Hormones (Athens) 2012;11:94-100.  Back to cited text no. 3
    


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  [Figure 1], [Figure 2], [Figure 3]

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[Pubmed] | [DOI]



 

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