title: Granulomatous and lymphocytic hypophysitis - are they immunologically distinct?
abstract: Hypophysitis includes three histopathologically distinct entities - granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis. Demographic, clinical, endocrine function and radiological features of 33 histologically confirmed cases of hypophysitis were reviewed. Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms. Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism was the most common endocrine abnormality (33.33%) followed by hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar mass with variable contrast enhancement was observed. On histology, granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells accompanied GH. LH in contrast, had CD4+ T-helper cell predominance [CD4: CD8 > 1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5-40% of the infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich infiltrate in contrast to CD4+ T-cell predominance in LH suggesting that the two forms have distinct immunological mechanisms in evolution, an autoimmune process in LH and type IV hypersensitivity response in GH.
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Mahadevan
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Maiti
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Ranjan
authors.affiliation: Human Brain Tissue Repository, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Shivayogi Durgad
authors.initials: SD
authors.lastname: Shwetha
authors.affiliation: Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Arimappamagan
authors.initials: A
authors.lastname: Arivazhagan
authors.affiliation: Neuroimaging and Intervention Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Jitender
authors.initials: J
authors.lastname: Saini
mesh_terms: D000293:Adolescent; D000328:Adult; D000069281:Autoimmune Hypophysitis / Q000473:pathology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: Granulomatous hypophysitis; cytotoxic T cells; helper T cells; immunopathogenesis; lymphocytic hypophysitis