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Nov 2, 2010 - Imprint cytology revealed distinct cytologic features which helped arriving at the specific diagnosis of pituitary adenoma intraoperatively. Subse-.
Role of Imprint Cytology in the Intraoperative Diagnosis of Pituitary Adenomas Nishat Afroz,

M.D.,

Nazoora Khan,

M.D.,

Jaseem Hassan,

The cytologic touch imprint alone can be diagnostic of pituitary adenomas and meningiomas, etc. A 45-year-old man was operated upon for intracranial meningioma. Imprint cytology revealed distinct cytologic features which helped arriving at the specific diagnosis of pituitary adenoma intraoperatively. Subsequent histopathology and immuno-histochemistry confirmed the diagnosis. Thus intraoperative touch preparations are of immense help in arriving at a diagnosis as well as in excluding other possible differential diagnoses and therefore can replace frozen section for intraoperative consultations of sellar and parasellar tumors. Diagn. Cytopathol. 2011;39:138–140. '

2010 Wiley-Liss, Inc.

Key Words: imprint cytology; pituitary adenomas; sellar; para sellar tumors; differential diagnoses

The utility of cytodiagnosis in intraoperative consultation for pituitary surgery is widely recognized and cytodiagnosis has replaced the use of frozen sections for the diagnosis of pituitary tumors at many institutions.1 Since the vast majority of pituitary surgical specimens are pituitary adenomas (PA), the primary purpose of the intraoperative consultation is to confirm the diagnosis of pituitary adenoma as well as to exclude other sellar and parasellar tumors compressing the pituitary gland.2 Despite the fact that PA are very common tumors, there are only a few international literatures on the cytological appearances of intraoperative analysis of PA and other tumors occurring in sellar and parasellar region. In the same line here we describe the intraoperative cytological findings of pituitary adenoma of a case who was operated upon with the clinical impression of meningioma. A brief discussion of possible differential diagnosis is also included.

Department of Pathology and Surgery, J.N. Medical College, Aligarh Muslim University, Aligarh *Correspondence to: Nishat Afroz, M.D., Department of Pathology, J.N. Medical College, Aligarh Muslim University, Aligarh 202002. E-mail: [email protected] Received 22 January 2010; Accepted 17 February 2010 DOI 10.1002/dc.21394 Published online 2 November 2010 in Wiley Online Library (wileyonlinelibrary.com).

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M.D.,

and M. F. Huda, M.S., Mc.H.*

Case Reports A 45-year-old man presented clinically with complaints of headache and blurring of vision of three-months duration. Contrast CT (Fig. 1) and MRI revealed an enhancing sellar and suprasellar mass compressing the optic chiasma. A tentative diagnosis of meningioma was rendered. An open craniotomy was performed and the neoplasm was resected in toto. Touch imprints and crush preparations were made. Alcohol-fixed smears were stained with Haematoxylin and Eosin (H&E) and Papanicolaou (Pap) stain. At low power cytology showed cellular pattern comprising of numerous monolayered discohesive sheets, small cell nests exhibiting vague to wellformed acini and papillary formation (Fig. 2). At high power cells exhibited mild nuclear pleomorphism, fine chromatin, and occasional small nucleoli. Cytoplasmic tinctorial properties ranged from pale pink to clear or vacuolated. Some binucleate forms were also seen without any mitoses (Fig. 3). Based on above findings a cytological diagnosis of pituitary adenoma was rendered. Subsequent paraffin embedded H&E sections confirmed the cytodiagnosis and showed mostly round cells in sheets with abundant eosinophilic cytoplasm and vesicular nuclei which were mildly pleomorphic and contained prominent nucleolus (Fig. 4). The cytoplasm was finely granular. There were no mitoses. The stroma consisted of small thin walled blood vessels. Periodic acid Schiff (PAS) stain was negative. The final histological diagnosis rendered was acidophilic adenoma of the pituitary. Immunohistochemically cells were diffusely positive for growth hormone only and were negative for cytokeratin and EMA thus contributing to the specific diagnosis of a pure adenoma of GH cell type. Serum levels of growth hormone and prolactin were insignificant.

Discussion Of all prolactinoma is the most common neoplasm arising in adenophysis, accounting for 50% of tumors found incidentally at autopsy and for about 30% of those encountered '

2010 WILEY-LISS, INC.

Diagnostic Cytopathology DOI 10.1002/dc

CYTODIAGNOSIS OF PITUITARY ADENOMAS

Fig. 1. CT SCAN (Contrast): a well circumscribed enhancing sellar mass compressing the optic chiasma.

Fig. 2. Imprint smear: papillary sheets of cells with discohesive ends (Papanicolaou, 3100). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

by the neurosurgeons3 while pure adenoma of GH type account for about 14% of all surgically resected PA4 Pituitary adenomas can be nonfunctional (about 1/3) or canbe functional which secrete a broad variety of hormones. Imprint cytology is favored over smear methods because not only the cytologic features but the cellularity of the imprint is very informative in pituitary adenoma, because it is usually hypercellular due to acinar disruption.5 Moreover pituitary adenomas possess distinct cytologic features that are important in intraoperative differential diagnoses from normal pituitary tissues, meningiomas, craniopharyngiomas, germinomas, and oligodendrogliomas.6 Other rare entities like granular cell tumor, chordoma, and metastatic carcinoma can also be confused with PA Similar to the Ng et al. we also observed that architecturally cells of pituitary adenoma typically exhib-

Fig. 3. Imprint smear: papillary sheet with vague acini formation. Cells exhibiting mild nuclear pleomorphism, fine chromatin, pink to vacuolated cytoplasm (Papanicolaou, 3400). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Fig. 4. Tissue section: papillary sheets and acini of round cells with abundant eosinophilic cytoplasm and mildly pleomorphic nuclei (H&E, 3400). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

ited discohesive cell clusters, short trabeculae, and small papillary structures occasionally with relatively uniform nuclei with mild to moderate nuclear pleomorphism without frank anaplasia or mitoses.6 Whereas the presence of cohesive sheets of cells (some with intranuclear cytoplasmic pseudo-inclusions) or of meningiothelial whorls, slender uniform spindle cells, fibroblastic areas or even of psammomatous calcifications can be diagnostic of a meningiomas.5,7,8 The cytologic features of adamantinomous craniopharyngioma comprise of a cyst filled with the socalled wet or plump keratin with anucleate squames.5,7 This type of keratin is diagnostic of the lesion and is visible on histologic sections as well.5 In difficult cases immunostaining for keratin may be necessary to identify Diagnostic Cytopathology, Vol 39, No 2

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Diagnostic Cytopathology DOI 10.1002/dc

AFROZ ET AL.

the squamous cells for the demonstration of craniopharyngioma. The use of immunohistochemistry can be helpful in confirming the diagnosis of a prolactinoma or other adenomas of pituitary. However, it is often far more clinically relevant for the endocrinologist, internist or neurosurgeon to follow the serum hormone levels that are obtained after the surgery compared with those obtained preoperatively to determine the success of the surgical procedure. Germinomas are usually suprasellar masses occasionally extending to the sellar region. They have dimorphic cellular population of small lymphocytes and large primitive germ cells with prominent and often angular nucleoli.9 Oligodendrogliomas cytologically may exhibit uniform, round cells but are usually arranged in patternless, diffuse sheets of completely discohesive cells, and lack the epithelial and glandular architecture of pituitary adenomas.10,11 Cytologically granular cell tumor consists of sheets of polyhedral cells with abundant granular cytoplasm that is PAS positive and diastase resistant. The use of immunohistochemistry can be helpful in confirming the diagnosis of a prolactinoma or other adenomas of pituitary. However, it is often far more clinically relevant for the endocrinologist, internist or neurosurgeon to follow the serum hormone levels that are obtained after the surgery compared with those obtained pre-operatively to determine the success of the surgical procedure. To conclude, imprints of pituitary adenomas possess distinct cytologic features that distinguish it from normal pituitary tissues, germinomas, meningiomas, craniopha-

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ryngiomas, oligodendrogliomas, and other tumors of sellar and parasellar region therefore imprint cytology can alone be diagnostic and of immense help during intraoperative consultation.

References 1. Hidehiro T, Hiroyoshi S, Naomi T, Powell SZ. Utility of cytodiagnosis (imprint cytology) in the intraoperative consultations for pituitary surgery. J Jpn Soc Clin Cytol 2005;44:333–337. 2. Bigner SM, Johnston WW. Cytopathology of the central nervous system. 1st ed. Chicago: American Society of Clinical Pathologists (ASCP publisher); 1994. p 134. 3. Kovacs K, Hovrath E. Tumors of Pituitary gland. In: Hartmann WH, editor. Atlas of tumor pathology series 2 fasc. XXI. Washington D.C.: Armed Forces Institute of Pathology; 1986. p 264. 4. Asa SL, Kovacs K. Pituitary pathology in acromegaly. Endocrinol Metab Clin North Am 1992;21:553–574. 5. Powell SZ. Intraoperative consultation. Cytologic preparations, and frozen section in the central nervous system. Arch Pathol Lab Med 2005;129:1635–1652. 6. Ng H-K. Smears in the diagnosis of pituitary adenomas. Acta Cytol 1998;42:614–618. 7. Chandrasoma PT. Nonastrocytic primary neopplasms. In: Chandrsoma PT, Apuzzo MLJ, editors. Stereotactic brain biopsy. New York: Igaku-Shoin; 1989. p 119–162. 8. Nguyen G-K, Johnson ES, Mielke BW, Phong N-H. Cytology of intracranial tumors in crush preparations. Pathology Annu 1991;28: 233–258. 9. Ng H-K. Cytologic diagnosis of intracranial germinomas in smear preparations. Acta Cytol 1995;39:693–697. 10. Nguyen G-K, Johnson ES, Mielke BW. Comparative cytomorphology of pituitary adenomas and ologodendrogliomas in intraoperative crush preparations. Acta Cytol 1992;36:661–667. 11. Timperley WR. Tumors of the central nervous system. In: Gray W, editor. Diagnostic cytopathology. Edinburgh: Churchill Livingstone; 1995. p 919–924.