CASE 1. Langerhans cell histiocytosis of the thyroid.

A 46-year-old woman presented to her physician with an enlarging , painful neck mass, mild dysphagia, and right otalgia. Her other health problems included diabetes mellitus, hypertension, and dyslip-idemia. She had been diagnosed with diabetes insipidus 15 years earlier after experiencing polyuria and polydypsia, and this disorder was controlled by desmopressin, 0.1 mg by mouth three times per day. Pertinent findings on physical examination were an asymmetrically enlarged and tender goiter (Fig 1). Thyroid panel was normal. Thyro-globulin level was elevated to 9,235 ng/mL (normal range, 1 to 40 ng/mL). Computed tomography scan of the neck revealed heterogeneous enlargement of both thyroid lobes with anterior lobulated projections (Fig 2A). There was no evidence of enlarged lymph nodes. Magnetic resonance imaging of the brain, nuclear bone scan, and chest computed tomography scan were normal. Attempted thyroidectomy was aborted because of a significant hemorrhage (2 L of blood) during the initial part of the surgery, but a biopsy of the thyroid gland was obtained. It demonstrated histiocytes (Fig 3, arrow) infiltrating the space between the thyroid lobules (Fig 3, star), with phenotypic features and immunohistochemical profile (positive for S100, CD1A, and CD68-PGM1) consistent with Langerhans cell histiocytosis (LCH). The patient was treated initially with interferon-alfa 1 ϫ 10 6 units subcutaneously three times per week, for 4 months. This treatment was ineffective, as reflected by enlargement of the size of her goiter, worsening of the tenderness and dysphagia, and an increase in thyroid size on computed tomography scan. Subsequently, she was treated with two courses of cladribine, with initial response followed by progressive regrowth. The patient was then treated with pentostatin (2Ј-deoxycoformycin), a purine analog with adenosine deaminase inhibitory activity, at a dose of 4 mg/m 2 by intravenous infusion once every 2 weeks. The patient achieved a partial remission and continues to respond to this regimen 6 months (11 cycles) later, with ongoing shrinkage of her goiter (Fig 2B). LCH is most commonly a pediatric disease, but it can affect the adult population. It usually presents as a multisystem granulomatous infiltrate (in two thirds of cases) in adults. 1 Bone involvement predominates (80% of cases) with osteolytic and asymmetric lesions,