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Year : 2017  |  Volume : 13  |  Issue : 3  |  Page : 580-582

Intratumoral granulomatous reaction in recurrent pituitary adenoma: A unique presentation

Department of Pathology, Advanced Medicare and Research Institute Hospitals, Kolkata, West Bengal, India

Date of Web Publication31-Aug-2017

Correspondence Address:
Subhashis Mitra
Department of Pathology, Advanced Medicare and Research Institute Hospitals, Kolkata - 700 029, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_677_16

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 > Abstract 

Pituitary adenoma is one of the most common intracranial neoplasms, usually presenting with endocrinopathies or visual field defects. Granulomatous hypophysitis, one of the subtypes of primary hypophysitis, is a rare neurological entity presenting as a sellar lesion with mass effect symptoms and endocrinological dysfunction. Majority of cases of primary hypophysitis are misdiagnosed as pituitary adenomas preoperatively, and histopathology is required for a definitive diagnosis. Granulomatous hypophysitis can be primary/idiopathic or secondary to a variety of causes such as infection, foreign body reactions, and systemic inflammatory conditions. The presence of tumoral microgranulomas in pituitary adenoma is exceedingly rare, having been documented only twice previously. We present a unique case of recurrent pituitary macroadenoma in a 59-year-old woman with histopathological features of idiopathic intratumoral noncaseating granulomatous inflammation. The presence of a granulomatous response in the absence of a systemic infectious or inflammatory disorder is suggestive of a local tumoral response to an as-yet unidentified antigen.

Keywords: Adenoma, granuloma, hypophysitis, pituitary, visual defects

How to cite this article:
Mitra S, Chakraborty H. Intratumoral granulomatous reaction in recurrent pituitary adenoma: A unique presentation. J Can Res Ther 2017;13:580-2

How to cite this URL:
Mitra S, Chakraborty H. Intratumoral granulomatous reaction in recurrent pituitary adenoma: A unique presentation. J Can Res Ther [serial online] 2017 [cited 2020 May 27];13:580-2. Available from: http://www.cancerjournal.net/text.asp?2017/13/3/580/208757

 > Introduction Top

Pituitary adenoma is one of the most common causes of sellar lesions causing mass effect symptoms and can cause hormonal abnormalities. Granulomatous hypophysitis is a rare sellar lesion and mimics pituitary adenoma on both clinical and radiological investigations.[1] Granulomatous hypophysitis arising in a pituitary adenoma is extremely rare, with only two previous reports of tumoral microgranulomas present in conjunction with adenoma.[2],[3]

 > Case Report Top

A 59-year-old woman presented to the hospital with complaints of visual problems and chronic headaches for the preceding 5 months. She had been operated upon 3 years previously in another institution for a pituitary tumor. The tumor excised earlier was a pituitary macroadenoma causing similar symptoms. The patient had no other significant medical history, physical examination was unremarkable, and visual perimetry studies showed features of early bitemporal hemianopia. Routine hematological and biochemical parameters were within normal ranges.

Serum prolactin at 13.85 ng/ml, serum cortisol (a.m.) at 17.88 μg/dl, and serum cortisol (p.m.) at 11.01 μg/dl levels were normal. Adrenocorticotrophic hormone estimation was not done, due to the absence of any clinical features of hypercortisolism. Thyroid-stimulating hormone was slightly elevated at 7.91 μIU/l, while free thyroxine (0.75 ng/dl) and free triiodothyronine (1.71 pg/ml) were decreased. Total thyroxine and triiodothyronine levels were normal.

Chest roentgenograms as well as Doppler study of carotid and vertebral arteries of both sides were within normal limits. Routine electrocardiogram and echocardiographic investigations showed no significant abnormality. Routine serological examination and Mantoux tuberculin sensitivity test were nonreactive.

Computed tomographic scan of the brain showed a well-defined enhancing lesion with smooth outline in sellar and suprasellar regions abutting optic chiasma. There was no intralesional calcification and no midline shift. Magnetic resonance imaging (MRI) scan demonstrated an enlarged sella and a large well-marginated patchily enhancing soft tissue mass within sellar and suprasellar regions. There was no parasellar extension, and no necrosis or hemorrhage. Optic tracts and optic chiasma were stretched over the lesion. A presumptive clinicoradiological diagnosis of recurrent pituitary tumor was done [Figure 1].
Figure 1: (a) Coronal computed tomographic scan showing contrast-enhanced sellar mass. (b) Axial computed tomographic scan showing contrast-enhanced sellar mass. (c) T1-weighted sagittal magnetic resonance scan showing sellar mass (pituitary region). (d) T1-weighted sagittal magnetic resonance scan showing contrast (gadolinium) enhancement of sellar mass

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Endonasal endoscopic-assisted microsurgery was scheduled for removal of lesion, and a transnasal, transphenoidal excision of pituitary tumor was done. Microscopic examination of the excised tissue revealed a tumor composed of nests of cells with round-to-oval uniform nuclei and abundant acidophilic cytoplasm, separated by thin fibrovascular septae. Multiple intratumoral noncaseating epithelioid granulomas with Langhans' giant cells, surrounded by lymphocytes, were found. There was no necrosis or appreciable mitotic activity [Figure 2]. Ziehl–Neelsen acid-fast bacilli (AFB) and periodic acid–Schiff's stain were done but showed no evidence of AFB or fungal elements. A final histopathological diagnosis of pituitary adenoma with intratumoral granulomatous inflammation was given. Polymerase chain reaction studies for Mycobacterium tuberculosis were negative, and detailed clinical, radiological, and ancillary investigations revealed no systemic inflammatory or infectious disease. The patient recovered well with resolution of visual symptoms and remains symptom free after 1 year of follow-up.
Figure 2: (a) Section showing pituitary adenoma interspersed with numerous granulomas and absence of necrosis (H and E, ×100). (b) Section showing granuloma closely abutting pituitary adenoma (H and E, ×400). (c and d) Section showing noncaseating epithelioid granulomas with giant cells and collar of mononuclear leukocytes (H and E, ×400)

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 > Discussion Top

Pituitary adenomas are most frequently found in women in their third to sixth decades and represent 15% of all intracranial neoplasms. The most common clinical complaints are endocrinopathies and visual defects, but one-third of adenomas are functionally silent. Size ranges from microadenomas to large tumors causing sellar enlargement. Dural, vascular, and sinus invasion can be associated with 50% of pituitary adenomas. As seen in this case, adenomas are usually constituted of monomorphic cells in a nested arrangement. Mitoses and nuclear pleomorphism are usually not prominent.[4]

Nonsecretory adenomas present with mass effects, typically visual defects and headaches. In the absence of any endocrinological symptoms, differential diagnosis of such sellar masses also includes craniopharyngioma, arachnoid cyst, Rathke's cleft cyst, meningioma, gliomas, metastatic tumors, chordoma, and inflammatory lesions. Inflammation of the pituitary exists as a spectrum ranging from lymphocytic hypophysitis to granulomatous hypophysitis, as well as xanthomatous and necrotizing forms. Primary hypophysitis has no discernible etiology, while causes of secondary hypophysitis include tuberculosis, sarcoidosis, syphilis, foreign body reactions, mycotic granulomas, and systemic immunologic diseases. High-dose corticosteroid therapy with clinical, endocrinological, and radiological monitoring is a possible therapeutic option for primary hypophysitis in the absence of any identifiable causative agent. Transsphenoidal surgery is recommended for all cases to aid unequivocal diagnosis, disease-specific therapy, rapid decompression and resolution of symptoms, and to obviate unnecessary steroid therapy. Histopathological examination of the excised tissue remains the gold standard of diagnosis.[2],[5],[6]

Pituitary tuberculosis is preceded by tubercular meningitis, hematogenous spread, or paranasal sinus involvement. MRI findings of stalk enhancement, sellar floor erosion, and apoplexy are not unique to pituitary tuberculomas.[1],[7] Pituitary apoplexy is a condition in which hemorrhagic necrosis of a pituitary adenoma is followed by intense inflammatory reaction, histiocytic infiltration, and cholesterol cleft formation, with no granulomas. It is exceedingly rare to find idiopathic noncaseating granulomatous inflammation in the substance of a pituitary adenoma, and the current case is the first report of granulomatous reaction in a recurrent adenoma. There has been an earlier report of microgranulomas seen in a pituitary adenoma presenting as a primary tumor.[2] Two cases of systemic sarcoidosis have also been reported in which the patients presented with a pituitary adenoma and intratumoral or peritumoral granulomas.[3],[8]

Neurosarcoidosis is associated with posterior pituitary and leptomeningeal involvement and diabetes insipidus, none of which are present in this case. In the absence of any evidence of any local or systemic causes of granulomatous inflammation, an immune etiology has to be considered.

Granulomatous inflammation is initiated by macrophages ingesting foreign antigens and presenting peptides to T-lymphocytes, leading to cytokine and interferon production. Epithelioid cell transformation of macrophages, giant cell formation, and lymphocytic infiltration are seen. Central caseous necrosis is a hallmark of M. tuberculosis infection and rare in other granulomatous diseases.[9] Postsurgical chronic inflammatory reaction and granuloma formation are associated with identifiable retained foreign bodies such as suture material, surgical glove starch, gauze, or similar materials; none of which were present in the current case.[10] Noncaseating granulomas in a pituitary adenoma can be either due to a systemic immune response or local immune reaction to a tumoral antigen or by-product. The current report of granulomatous response in a recurrent pituitary tumor, with no previous histopathological evidence of granulomatous hypophysitis at initial presentation, supports the hypothesis of an unspecified tumoral antigen provoking an immune response.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Bhansali A, Velayutham P, Radotra BD, Pathak A. Idiopathic granulomatous hypophysitis presenting as non-functioning pituitary adenoma: Description of six cases and review of literature. Br J Neurosurg 2004;18:489-94.  Back to cited text no. 1
Scheithauer BW, Silva AI, Atkinson JL, Nippoldt TB, Kaufmann TJ, Kovacs K, et al. Pituitary adenoma with tumoral granulomatous reaction. Endocr Pathol 2007;18:86-90.  Back to cited text no. 2
Saeger W, Hofmann BM, Buslei R, Buchfelder M. Silent ACTH cell adenoma in coincidence with granulomatous hypophysitis – A case report. Pathol Res Pract 2007;203:221-5.  Back to cited text no. 3
Cochran EJ. Central nervous system. In: Gattuso P, Reddy VB, David O, Spitz DJ, Haber MH, editors. Differential Diagnosis in Surgical Pathology. Philadelphia: Saunders, Elsevier; 2010. p. 1028-30.  Back to cited text no. 4
Su SB, Zhang DJ, Yue SY, Zhang JN. Primary granulomatous hypophysitis: A case report and literature review. Endocr J 2011;58:467-73.  Back to cited text no. 5
Gundgurthi A, Kharb S, Garg MK, Brar KS, Bharwaj R, Gupta S, et al. Combined granulomatous and lymphocytic hypophysitis presenting as pituitary incidentaloma in a middle-aged woman. Indian J Endocrinol Metab 2012;16:846-9.  Back to cited text no. 6
Jain A, Dhanwal DK, Kumar J. A rare case of pituitary tuberculoma-diagnosed and managed conservatively. Pituitary 2015;18:579-80.  Back to cited text no. 7
Rubin MR, Bruce JN, Khandji AG, Freda PU. Sarcoidosis within a pituitary adenoma. Pituitary 2001;4:195-202.  Back to cited text no. 8
Kumar V, Abbas AK, Aster JC, editors. Robbins & Cotran Pathologic Basis of Disease. Philadelphia: Saunders, Elsevier; 2014. p. 97-9.  Back to cited text no. 9
De Marco JK, McDermott MW, Dillon WP, Bollen A, Edwards MS. MR appearance of postoperative foreign body granuloma: Case report with pathologic confirmation. AJNR Am J Neuroradiol 1991;12:190-2.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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