View source for WBR0326

 {{WBRQuestion
|QuestionAuthor= {{YD}}  {{Alison}} (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology
|Prompt=A 13-year-old girl presents to the physician's office for excessive thirst, frequent urination, and weight loss. She reports that she recently noticed several raised scalp lesions that have been increasing in number. On physical examination, you observe extensive scalp lesions, cervical lymphadenopathy, and exophthalmus. A CT scan displays coalescent osteolytic lesions of the skull with a geographical appearance. Biopsy of the skin lesions demonstrates dermal infiltration of clustering cells, with large ovoid pink cytoplasm under light microscopy with positive immunofluorescence staining for S100 and CD1a. Electron microscopy of the sample reveals the presence of pentalaminar membranous organelles, resembling tennis rackets, near the nuclear membrane. What is the most likely diagnosis based on the findings?
|Explanation=[[Langerhans cell histiocytosis]] is a heterogeneous group of proliferative diseases characterized by the presence of epidermal dendritic cells called Langerhans cells. These cells are often called the "nerve cells of the skin." Langerhans cell histiocytosis was once termed histiocytosis X due to the unclear etiology of the disease.
Hand-Schuller-Christian disease (HSC), eosinophilic granuloma, and Letterer-Siwe disease are all subgroups of [[Langerhans cell histiocytosis]]. The patient in this scenario has the classical clinical presentation of HSC disease, characterized by the triad of: diabetes insipidus, exophthalmus, and lytic bony lesions. Other systemic signs and symptoms may be present, such as lymphadenopathy, pulmonary findings, and hepatosplenomegaly.

Often, light microscopy displays characteristic Langerhans cells, with large ovoid pink cytoplasm that diffusely infiltrate the dermal layer, resembling a granuloma, which exhibit the characteristic staining of Cla and S100 on immunofluoresence. Electron microscopy demonstrates the characteristic tennis racket shaped [[Birbeck granules]]. [[Birbeck granules]] are pentalaminar membranous organelles located near the nuclear membrane. Treatment may include steroids or ultraviolet phototherapy for skin lesions, bisphosphonates for bone lesions, and chemotherapy for systemic involvement.
|AnswerA=Langerhans cell histiocytosis
|AnswerAExp=The findings describe the classical presentation and workup of Langerhans cell histiocytosis characterized by diabetes insipidus, exophthalmus, and lytic bony lesions, presence of Langerhans cells on pathology, and positive staining for CD1a and S100. Electron microscopy displays characteristic Birbeck granules, which resemble tennis rackets.
|AnswerB=Schwannoma
|AnswerBExp=[[Schwannoma]] may exhibit positive S100 staining, but the patient's other clinical findings not typically observed in [[schwannoma]].
|AnswerC=Diabetes insipidus
|AnswerCExp=Although often [[diabetes insipidus]] can be associated with the [[Langerhans cell histiocytosis]] syndrome, it is not the isolated diagnosis in this scenario.
|AnswerD=Mastocytosis
|AnswerDExp=[[Mastocytosis]] can be associated with the [[Langerhans cell histiocytosis]], it is not the isolated diagnosis in this scenario.
|AnswerE=Wiskott-Aldrich syndrome
|AnswerEExp=Patients with [[Wiskott-Aldrich syndrome]] (WAS) often have thrombocytopenic purpura, eczematous skin lesions, and recurrent infections, all of which may be present in Langerhans cell histiocytosis. Although WAS may be in the differential diagnosis of [[Langerhans cell histiocytosis]], WAS does not account for all of the patient's clinical findings.
|EducationalObjectives=Langerhans cell histiocytosis is a proliferative disorder that classically presents with diabetes insipidus, exophthalmus, and lytic bony lesions and is characterized by the presence of Langerhans cells on pathology, positive staining for CD1a and S100, and electron microscopy displaying characteristic Birbeck granules, which resemble tennis rackets.
|References=Cugati G, Singh M, Pande A, et al. Hand Schuller Christian disease. Indian J Med Oncol. 2011; 32(3):183-184.
<br>Badalian-Very G, Vergilio J, Fleming M, et al. Pathogenesis of Langerhans cell histiocytosis. Annu Rev Pathol. 2013; 8:1-20
|RightAnswer=A
|WBRKeyword=Langerhans cell histiocytosis, Histocytosis X, Birbeck granules, S100, Diabetes insipidus, Skull lesions, Eosinophilic granuloma, Hand-Schuller-Christian disease, Proliferative diseases, Exophthalmus, Lytic bone lesions 
|Approved=Yes
}}