| Abstract|| |
Hypophysitis of the pituitary gland is a rare inflammatory disorder and broadly classified as primary and secondary hypophysitis. Primary hypophysitis is mainly of lymphocytic, granulomatous, and xanthomatous types. Among the various primary hypophysitis, granulomatous hypophysitis is rare type with an incidence of 1 in 10 million. The various forms of hypophysitis are misdiagnosed as pituitary adenoma in 40% cases. Idiopathic granulomatous hypophysitis is even rarer inflammatory disorder accounting for <1% of cases involving panhypopituitarism with headache and visual disturbances. We report idiopathic granulomatous hypophysitis in a 28-year-old female presenting with blurring of vision and headache.
Keywords: Granulomatous hypophysitis, idiopathic, pituitary
|How to cite this article:|
Agale SV, Binayke R, Kumari G, D'Costa GF. Idiopathic granulomatous hypophysitis: A report of an uncommon disorder. Indian J Pathol Microbiol 2018;61:389-92
|How to cite this URL:|
Agale SV, Binayke R, Kumari G, D'Costa GF. Idiopathic granulomatous hypophysitis: A report of an uncommon disorder. Indian J Pathol Microbiol [serial online] 2018 [cited 2019 Dec 12];61:389-92. Available from: http://www.ijpmonline.org/text.asp?2018/61/3/389/236629
| Introduction|| |
Inflammatory lesions of the pituitary are uncommon and may mimic sellar tumors and can be misdiagnosed as pituitary adenomas in 40% of patients.,,,, Hypophysitis is a rare pituitary inflammatory disorder with an incidence of 1 in 10 million , and may involve adenohypophysitis, neurohypophysitis, infundibulum, or combined sites. Hypophysitis is basically classified into primary and secondary hypophysitis.,,, Secondary hypophysitis may be caused by systemic inflammatory disorders and infectious processes.,
According to Cheung et al., there are three major subtypes of hypophysitis: (1) lymphocytic hypophysitis, (2) granulomatous hypophysitis, and (3) xanthomatous hypophysitis.
Rao et al. described four histological subtypes of primary hypophysitis which include lymphocytic, granulomatous, xanthomatous, and necrotizing.
Recently, in 2015, Kong et al. categorized hypophysitis histologically into five subtypes: lymphocytic, granulomatous, xanthomatous, xanthogranulomatous, and necrotizing.
All together inflammatory hypophysitis comprises nearly 0.5% of lesions treated in major series with lymphocytic hypophysitis being more common than granulomatous or xanthomatous hypophysitis.
| Case Report|| |
A 28-year-old P2 L2 female presented with complaints of gradual loss of vision and headache for 10 days. There was a history of amenorrhea for 4 months. The patient was a known case of hypothyroidism and was on regular medication (thyroxin).
There was no history of convulsion, vomiting, loss of consciousness, and trauma to head. There was no history of hypertension, diabetes mellitus, ischemic heart disease, tuberculosis, allergy, or addiction.
General condition of the patient was satisfactory with normal vitals. On systemic examination, no abnormality was detected. The patient was alert, conscious, and cooperative.
On ophthalmological examination, bilaterally pupils were reactive to light, and on examination of fundus, no abnormality was detected.
Magnetic resonance imaging (MRI) brain showed a relatively well-defined sellar and suprasellar homogeneously enhancing mass with widening of the sella measuring approximately 2.1 cm × 1.5 cm × 1.8 cm. The lesion showed a mild constriction at the level of diaphragma sellae. The pituitary gland was not seen separate from the mass. A tiny focus of cystic lesion was seen within the mass, more toward the left. There was resultant mass effect along the undersurface of the optic chiasma which was displaced superiorly. Laterally, the mass was abutting and encasing the medial aspect of the cavernous segment of the bilateral intracranial internal carotid artery. The features were suggestive of pituitary macroadenoma. There was no obvious necrosis and hemorrhage within the mass [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Magnetic resonance imaging brain: A lesion measuring 2.1 × 1.5 × 1.8 cm with widening of sella. (b) Magnetic resonance imaging brain: A relatively well-defined sellar and suprasellar homogenously enhancing mass lesion|
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The relevant hematological and hormonal investigations are mentioned in [Table 1].
The routine hematological investigations (complete blood count, renal function test, liver function test, and immunological tests) were unremarkable. On hormonal study, luteinizing hormone (LH) and adrenocorticotropic hormone levels were found to be low.
Grossly, multiple fragmented bits aggregating to 0.8 cc were received. Microscopic examination revealed destruction and infiltration of hypophyseal parenchyma by noncaseating epithelioid cell granulomas with lymphocytes and few plasma cells. Both Langhans-type and foreign body-type giant cells were seen. Eosinophils were not seen. There was no evidence of vasculitis, necrosis, and fibrosis [Figure 2]a and [Figure 2]b. Special stains for acid-fast bacilli (Ziehl–Neelsen [ZN] stain) and fungus (periodic acid–Schiff [PAS] stain and Grocott methenamine silver [GMS] stain) were negative.
|Figure 2: (a) Microphotograph showing granulomatous inflammation involving pituitary parenchyma (H and E, ×40). (b) Microphotograph showing granulomas comprised epithelioid cells, foreign body-type giant cells, and lymphocytes (H and E, ×100)|
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| Discussion|| |
Hypophysitis, the inflammatory lesion of the pituitary gland, is very rare and is known to occur less commonly than primary tumors.,,,
Granulomatous hypophysitis can mimic pituitary adenoma clinically and radiologically and may result in hypophyseal dysfunction due to the destruction of the gland. It is difficult to diagnose granulomatous hypophysitis preoperatively.,,,, Granulomatous hypophysitis was first described by Simmonds in 1917 and has annual incidence of 1 in 10 million., Clinically, granulomatous hypophysitis presents with diffuse enlargement of the pituitary gland with enhanced sellar mass extending into the suprasellar area. It can be idiopathic and secondary type. Secondary granulomatous hypophysitis can be caused by systemic tuberculosis, syphilis, or fungal infections and Wegener's granulomatosis.
Idiopathic granulomatous hypophysitis is a rare inflammatory disorder accounting for <1% of cases involving panhypopituitarism with headache and visual disturbances. Headache is the most common presenting feature.,,, These patients may have amenorrhea-galactorrhea, hyperprolactinemia, fatigue, diabetes insipidus, nausea and vomiting, aseptic meningitis, and/or blurred vision., In our case, the patient presented with headache and gradual loss of vision and was having a history of amenorrhea. She was found to have hypothyroidism also. Due to the presence of amenorrhea and hypothyroidism, an autoimmune etiology was considered.
Hunn et al. reviewed cases of idiopathic (primary) granulomatous hypophysitis till 2014 and found a total of 82 cases. Recently, in 2016, eight cases of granulomatous hypophysitis have been described by Xu et al.
Granulomatous hypophysitis is less common than the lymphocytic hypophysitis and relationship between the two is unclear. Granulomatous hypophysitis differs from lymphocytic hypophysitis as it lacks female predominance, association with pregnancy, and occasional spontaneous resolution.
According to Rao et al., granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%), and in GH, the infiltrate had almost equal proportions of CD3+ T-cells and CD68+ histiocytes. They have studied immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis.
Secondary hypophysitis is seen in the background of systemic inflammatory diseases such as sarcoidosis, Wegener's granulomatosis, Takayasu disease, and Langerhans cell histiocytosis and infections such as tuberculosis, fungal infections, and syphilis. In the setting of systemic inflammatory diseases, the diagnosis of secondary hypophysitis can be made easily as patients present with other systemic manifestations of the underlying diseases.,
In our case, there was no such systemic manifestation of other underlying disorder, and other conditions were ruled out based on the histological features. Wegener's granulomatosis is characterized by necrotizing vasculitis with granulomas involving vessels. These features were absent in this case. In syphilis, the inflammatory infiltrate is mainly of plasma cells with panarteritis. Granulomatous inflammation of fungal etiology was ruled out based on the absence of eosinophilic infiltrate, necrosis, vasculitis, and PAS and GMS negativity for fungal hyphae.
Pituitary tuberculosis is extremely rare, and a reported incidence of 4% in patients with tuberculosis has been quoted in the literature. Despite the high incidence rates of systemic tuberculosis, intracranial tuberculomas account for 0.15%–5% of intracranial space-occupying lesions, sellar tuberculomas, as isolated manifestations of the disease are extremely rare. Indian literature review revealed that it is indeed a diagnostic challenge to differentiate between idiopathic granulomatous hypophysitis and tuberculosis. However, in our case, the patient did not show signs of active tuberculosis nor of a systemic disease nor had a previous history of tuberculosis. Tuberculosis was ruled out microscopically on the basis of the absence of caseation necrosis and acid-fast bacilli on ZN stain. However, because the patient was from an endemic zone of tuberculosis, Mantoux test was performed and was negative in our case. Therefore, a diagnosis of idiopathic granulomatous hypophysitis would be appropriate in this case. Polymerase chain reaction for Mycobacterium tuberculosis was not available on paraffin block at that time so was not done.
MRI in case of pituitary hypophysitis shows pituitary enhancement which is usually intense, homogeneous, and symmetrical, and the invasive changes of the sella turcica are rare.
According to Chung et al., the clinical and radiological presentations are similar in different histological types of hypophysitis, and definitive diagnosis is only possible on pathological examination.,
Morphologically, various types of hypophysitis have variable morphology.
Lymphocytic hypophysitis is characterized by diffuse infiltration of the inflammatory cells in the pituitary comprised predominantly lymphocytes. Formation of lymphoid follicles along with variable fibrosis may also be present. Pathogenesis is considered as autoimmune phenomenon; however, it is unclear.
Granulomatous hypophysitis has histiocytes, multinucleated giant cells, and variable number of lymphocytes along with plasma cells in the pituitary.
Xanthomatous hypophysitis is the least common form of hypophysitis and is characterized by the presence of lipid-rich foamy histiocytes with variable number of lymphocytes. Histologically, it has a similar appearance of xanthomatous inflammatory process as in other organs.,
The optimal therapeutic course for the treatment of idiopathic granulomatous hypophysitis is currently disputed. Surgery is an effective method for removal of mass, but corticosteroid therapy is an alternative treatment option in idiopathic granulomatous hypophysitis.,
| Conclusion|| |
Idiopathic granulomatous hypophysitis is a very rare lesion of pituitary gland. The pathologist plays an important role in the diagnosis of pituitary hypophysitis and its subtypes as it can be diagnosed only on biopsy.
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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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Shubhangi Vinayak Agale
Department of Pathology, Grant Government Medical College, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]