Background:
The histiocytic disorders are a group of inflammatory myeloid neoplasias. Abnormal proliferation of histiocytes accumulate in many tissues, including the pituitary, and are a rare cause of pituitary dysfunction (particularly diabetes inspidus). Langerhan’s cell histiocytosis has an incidence of 1-2 per million adults; Erdheim Chester disease has about 500 case reports in the literature. There are broad systemic manifestations including bony infiltration, cutaneous, lung, cardiac, or retroperitoneal involvement. Therapies may include cytotoxic chemotherapy, radiotherapy and interferon. There is increasing evidence that MAPK pathway mutations (including BRAF and MEK) are the driver of these neoplastic conditions; these are currently being explored as therapeutic targets.
Cases:
A 36 year-old female presented with confusion, thirst, polyuria, amenorrhoea and headaches. She was found to have pan-hypopituitarism with diabetes insipidus, in association with an isolated suprasellar mass. She underwent a craniotomy with partial resection. Histopathology revealed a histiocytic infiltrate with immunohistochemistry consistent with Langerhan’s cell histiocytosis. Further staging investigations did not reveal any systemic involvement. Treatment with chemo- and radiotherapy was hampered by worsening hypothalamic dysfunction. She developed adipsia with extreme hypernatremia, hyperphagia and subsequent diabetes mellitus, and marked behavioural disturbance. The patient ultimately passed away within 9 months due to hyperosmolar state.
A 47 year-old female presented with thirst and polyuria. A water deprivation test confirmed complete cranial diabetes insipidus. No other pituitary hormone abnormalities were identified and initial MRI pituitary was normal. Approximately 15 months later a repeat MRI found new nodular thickening of the pituitary stalk, suspicious for an infiltrative process. Bone scan was performed due to an incidental complaint of knee pain, and the pathognomonic appearance of Erdheim Chester disease (a non-Langerhan’s histiocytosis) was seen. Bone biopsy revealed histiocytic infiltrate with confirmatory immunohistochemistry. BRAF mutational status was negative. Treatment with interferon-based therapy is now being contemplated.