A 14-year-old male student was hospitalized and seen in our department for the first time on September 6, 2010 with the chief complaint of polyuria, dry mouth and polydipsia over the past 3 months and worsening of these symptoms for one month or so. During his hospital stay, a series of investigations were ordered as follows: (1) urinalysis, showing 24-h urine volume between 8 000 ml and 9 000 ml and specific gravity of morning fasting urine between 1.0 and 1.001; (2) fluid deprivation-vasopressin test, positive; (3) dynamic contrast-enhanced MR imaging of the pituitary gland, showing loss of high signal intensity in the posterior pituitary lobe (Figs.1–3); (4) whole-body PET-CT, showing a nodular mass with normal glucose metabolism in the anterior mediastinum, which was suspected to be the hyperplastic thymus pending carcinoid to be excluded; and (5) whole-body bone scan, unremarkable. Neither evidence of myasthenia gravis nor evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes was found.
Based on these findings, the provisional diagnosis for this case was (1) complete central diabetes insipidus and (2) isolated thymic nodules of unknown etiology, to be differentiated between physiological and pathological. After treatment with oral desmopressin, the patient experienced amelioration in polyuria and dry mouth, and was discharged home. Six months later, follow-up with plain and contrast-enhanced CT scanning of the chest demonstrated growth of the previously-detected nodular mass in the upper part of anterior mediastinum that was probably consistent with thymus hyperplasia or thymoma (Fig. 4). By MR imaging, thickening of the pituitary stalk, in addition to loss of high signal intensity of the posterior pituitary lobe, was revealed (Figs. 5–7). On April 26, 2011, the patient underwent video-assisted thoracoscopic exploration of the right pleural cavity plus thymectomy under general anesthesia. At surgery, the thymus appeared thickened and tenacious, located anterior to the superior vena cava and superior to the heart. Inside the upper part of thymus, a soft tumor measuring 1.5 cm× 1.2cm in size was found. Pathological study revealed a large number of thymic corpuscles in the resected tissues. In lymphatic tissues at the margin of the tumor, a distinct type of cells with focal and light staining cytoplasm, irregular and grooved nuclei, and 0 to 6 mitotic figures per 10 high-power fields (HPF), was juxtaposed against a backdrop of numerous eosinophils. Immunohistochemical assay demonstrated that the tumor tissue was positive for S-100, CD1a (weakly), CD68 (diffusely), CD20 and CD3 (focally) and CK19 (in epithelium), but was negative for TdT. These results correlated well with the histology in Langerhans cell histiocytosis (Figs. 8–10).
Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized, bone marrow-derived Langerhans cells and mature eosinophils. LCH may occur in any age groups, in particular, children aged 1–3 years, with an annual incidence of 4–5 per million[
1]. Depending on organ involvement, LCH is traditionally classified into single organ involving (unifocal), multifocal unisystem and multifocal multisystem LCH. The latter typically causes lesions in the lungs, liver, lymph nodes, bone, skin, and the pituitary. Osteolytic lesions may be present in virtually all patients with LCH. Skin lesions frequently appear as the initial symptom, manifested by a rash which varies from erythematous, scaly to dark brown seborrheic papula. Damages to the liver and spleen usually include hepatomegaly or splenomegaly, hypoproteinemia and hyperbilirubinemia. Pulmonary LCH often gives rise to cough and dyspnea, and diffuse nodular opacities on chest X-ray that may progress to a honey-comb lung [
2]. According to the clinical data summarized in China, children account for 72.7% of all LCH patients; and the tissues/organs frequently involved were bones (45.5%), lymph nodes (45.5%), skin (36.4%), liver and spleen (36.4%), lung (31.8%), bone marrow (13.6%), ear (9.1%), eyes (4.5%), pituitary (4.5%) and thymus (in a single case). Owing to a wide range of clinical pictures [
3,
4], LCH can be misdiagnosed in as many as 59.1% of the patients [
5]. Involvement of the pituitary stalk was consistently noted in many reported cases of LCH with diabetes insipidus as the initial symptom [
6], while in thymic LCH, the patients were reported to have symptoms of myasthenia gravis [
7,
8] or remain asymptomatic [
9]. Diagnosis of LCH mainly relies on pathological and cytological findings which are characterized by a variable number of aberrantly proliferating Langerhans cells admixed with polymorphous population of numerous eosinophils, multinucleated giant cells, lymphocytes, neutrophils, plasma cells and fibroblasts. The Birbeck granule found in cytoplasm represents the distinctive ultrastructural hallmark of Langerhans cells. The present report described a case of adolescent-onset, rapid-progressing LCH which was manifested by complete central diabetes insipidus and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. Thickening of pituitary stalk was not associated with any clinical signs on the patient’s first visit. The only finding was the thymus hyperplasia indicated by PET-CT, which was considered to be pathological after a half-year of serial follow-up. After surgery, the diagnosis of LCH was determined by positive immunohistochemical assays for S-100 and CD1a. The present case may have important clinical implications that Langerhans cell histiocytosis should be listed as a differential diagnosis for patients with unexplained diabetes insipidus as the first symptom. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs.
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