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Year : 2023  |  Volume : 66  |  Issue : 3  |  Page : 618-620
A unique coexistence of a plurihormonal pituitary adenoma with granulomatous hypophysitis

Department of Oncopathology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

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Date of Submission05-May-2021
Date of Decision26-Oct-2021
Date of Acceptance30-Oct-2021
Date of Web Publication15-Dec-2022


Dual pathology in the pituitary gland is a unique phenomenon. Coexistence of a pituitary adenoma with primary hypophysitis has been reported rarely with very few cases in the literature. Among the primary hypophysitis, primary granulomatous subtype has been proposed to be idiopathic and autoimmune in nature. Plurihormonal pituitary adenomas produce hormones of more than one different pituitary cell lineage. Pituitary adenoma with a single hormonal content has been documented with concurrent primary granulomatous hypophysitis. The present case describes the unique coexistence of a plurihormonal adenoma showing somatotroph, lactotroph, and corticotroph lineage with primary granulomatous inflammation in the sellar region in a 36-year-old woman.

Keywords: Immunohistochemistry, pituitary adenoma, plurihormonal, primary granulomatous hypophysitis

How to cite this article:
Patra S, Trivedi P. A unique coexistence of a plurihormonal pituitary adenoma with granulomatous hypophysitis. Indian J Pathol Microbiol 2023;66:618-20

How to cite this URL:
Patra S, Trivedi P. A unique coexistence of a plurihormonal pituitary adenoma with granulomatous hypophysitis. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Sep 27];66:618-20. Available from:

   Introduction Top

Pituitary adenoma (PA), a neoplastic proliferation of anterior pituitary hormone-producing cells, is the most common sellar neoplastic lesion.[1] It can be functioning, requiring medical treatment, or nonfunctioning managed surgically.[2] Hypophysitis is a rare inflammatory disorder mostly affecting middle-aged women and broadly classified into primary and secondary types.[3] Primary hypophysitis is thought to be autoimmune or idiopathic in nature and it has been classified into four subtypes as lymphocytic (LyH), granulomatous (GrH), xanthomatous, and necrotizing. Among the primary hypophysitis, GrH with coexistent PA is exceedingly rare with four cases published till date.[4],[5],[6],[7] Here, we present a case of plurihormonal pituitary adenoma coexisting with primary granulomatous hypophysitis.

   Case Description Top

A 36-year-old woman had galactorrhea for 1-month duration along with mild headache and difficulty in reading for 10 days. On laboratory evaluation, her serum prolactin level was found to be increased (64 μg/L, normal: up to 20 μg/L) with a mild increase in serum cortisol (800 nmol/L, normal: 137.9–634.5 nmol/L) and normal levels of other pituitary hormones. On ocular examination, she was found to have decreased visual acuity (6/9, both eyes), bitemporal loss of visual field, and central scotoma. A contrast-enhanced magnetic resonance imaging (MRI) of the brain showed intensely and heterogeneously enhancing enlarged pituitary gland with convex superior margin (maximum height of 1.5 cm), associated with some deepening and widening of floor of sella turcica, mild thickening of the stalk of pituitary gland, and compression over bilateral optic chiasma suggesting the possibility of pituitary hyperplasia or macroadenoma likely [Figure 1]a and [Figure 1]b. The initial therapy was started with Cabergoline tablets 0.25 mg twice weekly and she had been closely followed up for any improvement or deterioration of her symptoms. After 4 weeks, she had a little improvement of galactorrhea but ocular symptoms worsened. She underwent transsphenoidal resection of the lesion and the tissue was submitted for histopathological examination. Light microscopy of the submitted tissue showed an adenomatous lesion with monomorphic round cells arranged in cords, solid nests, and small sheets with a variably pale eosinophilic to amphophilic to pale basophilic cytoplasm and round regular nuclei with finely stippled chromatin and small nucleoli in some of them. Necrosis or mitosis was not evident. Adjacent to the adenoma, there were noncaseating epithelioid granulomas with Langhan's-type multinucleated giant cells and dense lymphoplasmacytic cell infiltrate [Figure 2]a, [Figure 2]b, [Figure 2]c. Special stains for acid-fast bacilli and fungus did not reveal any organism. Immunohistochemistry for pituitary hormones showed strong immunoreactivity for prolactin (PRL) [Figure 2]d, adrenocorticotrophic hormone (ACTH) [Figure 2]e, and thyroid-stimulating hormone (TSH) [Figure 2]f. MIB-1 index was <1% and p53 was negative. A reticulin stain showed preserved reticulin framework in the normal pituitary gland with granuloma and giant cells [Figure 3]a, whereas the adenomatous component completely lacked the reticulin fibers [Figure 3]b. Hence, a diagnosis of plurihormonal pituitary adenoma with coexisting granulomatous hypophysitis was rendered. Pit-1 transcription factor study was not done.
Figure 1: Contrast-enhanced MRI: (a and b) showing an enhancing lesion in pituitary gland (yellow arrow), compressing optic chiasma (white arrow).

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Figure 2: (a) Coexistent epithelioid granuloma (left) with adenomatous proliferation of anterior pituitary cells (right) [H&E, 40×]; (b) Epithelioid granuloma (left) with pituitary adenoma (right); tumor cells arranged in clusters having small round nuclei and abundant cytoplasm [H&E, 20×]; (c) Langhan's-type multinucleated giant cells and dense lymphoplasmacytic cell infiltration [H&E, 40×]; (d) Prolactin (PRL); (e) Adrenocorticotrophic hormone (ACTH) and (f) Thyroid-stimulating hormone (TSH) [IHC, 20×]. H and E, Hematoxylin and eosin; IHC, Immunohistochemistry.

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Figure 3: (a) Preserved reticulin framework in normal pituitary gland with presence of granuloma and giant cells (white arrow) (Reticulin stain, 20×); (b) Loss of reticulin framework, as presumptive evidence of pituitary adenoma (Reticulin stain, 20×).

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   Discussion Top

Pituitary adenomas are the most common sellar neoplasms. They have been classified according to their hormone content and pituitary cell lineage.[1] Plurihormonal adenomas are adenohypophyseal tumors that produce more than one hormone. They can be monomorphous, consisting of a single-cell type producing two (or rarely more) hormones, or plurimorphous, consisting of two or more different cell lineages.[1] The hypophysitis commonly occurs in young women. It mimics PA and is often misdiagnosed as an adenoma on imaging.[8] It is very difficult to differentiate from nonfunctioning PA clinically and radiologically without the help of histopathology.[4] Primary GrH has been thought to be incited by an unknown exogenous or endogenous antigen eventually developing autoantibodies against nonsecretory proteins in the pituitary by an immunological reaction.[9] The clinical and histopathological findings of the reported four cases of PA with concurrent GrH have been provided in [Table 1]. None of those cases was associated with an adenoma of more than one hormonal lineage as in the present study. Hypophysitis needs special attention as it results in persistent deficiency of pituitary hormones. Management includes control of the inflammatory reaction. The mainstay of medical treatment is glucocorticoids, but in some cases, immunosuppressive agents like azathioprine or rituximab may be required.[10]
Table 1: Studies demonstrating PA with concurrent GrH

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In conclusion, dual pathologies involving the master endocrine gland are extremely rare. The present case is one such rare example occurring in a middle-aged woman having granulomatous hypophysitis with concurrent plurihormonal (lactotroph, thyrotroph, and corticotroph) PA. The inflammatory reaction is usually underrecognized before surgery and misdiagnosed as a PA. Even after removing the PA, coexisting hypophysitis needs medical attention to control the immune-mediated reaction.

Ethical approval


Declaration of patient consent

Informed consent was taken from the patient to publish her laboratory investigations and histopathology images.


We acknowledge all the technical staff of histopathology and immunohistochemistry sections in our department.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Osamura RY, Grossman A, Korbonits M, Kovacs K, Lopes MB, Matsuno A, et al. Pituitary adenoma. In: Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO Classification of Tumors of Endocrine Organs. 4th ed. Lyon: IARC; 2017. p. 13-40.  Back to cited text no. 1
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: A systematic review. Cancer 2004;101:613-9.  Back to cited text no. 2
Gutenberg A, Hans V, Puchner MJ, Kreutzer J, Brück W, Caturegli P, et al. Primary hypophysitis: Clinical-pathological correlations. Eur J Endocrinol 2006;155:101-7.  Back to cited text no. 3
Sivakoti S, Nandeesh BN, Bhatt AS, Chandramouli BA. Pituitary adenoma with granulomatous hypophysitis: A rare coexistence. Indian J Endocr Metab 2019;23:498-500.  Back to cited text no. 4
[PUBMED]  [Full text]  
Mitra S, Chakraborty H. Intratumoral granulomatous reaction in recurrent pituitary adenoma: A unique presentation. J Cancer Res Ther 2017;13:580-2.  Back to cited text no. 5
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. 6
Holck S, Laursen H. Prolactinoma coexistent with granulomatous hypophysitis. Acta Neuropathol (Berl) 1983;61:253-7.  Back to cited text no. 7
Hunn BH, Martin WG, Simpson S, Mclean CA. Idiopathic granulomatous hypophysitis: A systematic review of 82 cases in the literature. Pituitary 2014;17:357-65.  Back to cited text no. 8
Moskowitz SI, Hamrahian A, Prayson RA, Pineyro M, Lorenz RR, Weil RJ. Concurrent lymphocytic hypophysitis and pituitary adenoma. Case report and review of the literature. J Neurosurg 2006;105:309-14.  Back to cited text no. 9
Joshi MN, Whitelaw BC, Carroll PV. Mechanisms in endocrinology: Hypophysitis: Diagnosis and treatment. Eur J Endocrinol 2018;179:151-63.  Back to cited text no. 10

Correspondence Address:
Priti Trivedi
Department of Oncopathology, The Gujarat Cancer and Research Institute, New Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_439_21

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