Primary hypophysitis: Classification review

Primary (idiopathic) hypophysitis is traditionally classified into lymphocytic, granulomatous, necrotizing, or IgG4-related disease types. Secondary hypophysitis occurs in patients with systemic conditions, which if known, often obviate the need for biopsy. Primary idiopathic hypophysitis, in contrast, often mimics tumors and mandates histological confirmation of inflammation. We detail four primary hypophysitis cases, discussing challenges in histological classification. Four women, ages 32 to 76 years, presented with weakness, visual changes, fatigue, weight loss, and/or headache. Preoperatively, pituitary macroadenoma/pituitary neuroendocrine tumor was suspected. Biopsies revealed lymphocytic hypophysitis without (Case 1) and with (Case 2) IgG4+ cells (modest numbers) and granulomatous hypophysitis with necrosis, large numbers of IgG4+ cells (Cases 3 and 4), with multinucleated giant cells (Case 4). Steroid therapy, in one case with rituximab, was administered irrespective of histological classification. Lymphocytic hypophysitis comes to biopsy primarily in patients without known risk factors, eg pregnancy or drug usage. Granulomatous or necrotizing types are less common, less histologically uniform, and may contain large numbers of IgG4+ cells, a feature found both in IgG4-related disease and autoimmune disorders, especially granulomatosis with polyangiitis. In certain cases, the use of steroids, followed by rituximab for all types of hypophysitis based on clinical criteria may obviate the need for precise histological distinction.