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Langerhans cell histiocytosis (LCH); histiocytosis X

A group of disorders characterized histologically by proliferation & infiltration of Langerhans histiocytes that fuse into multinucleated giant cells & form granulomas with eosinophils. Classification: 1) eosinophilic granuloma (unifocal LCH) 2) Hand-Schuller-Christian syndrome (multifocal LCH) 3) Letterer-Siwe syndrome (most aggressive form) 4) pulmonary Langerhans cell granulomatosis Staging: 1) localized disease - bone (1 or 2 adjacent lesions) - lymph node - skin 2) disseminated disease - bone, multifocal - bone & soft tissue or soft tissues alone (except skin & isolated lymph node) - organ dysfunction (liver, lungs, hematopoietic system) Etiology: - abnormal proliferation of histiocytes Epidemiology: 1) most commonly occurs in children (toddlers) [3] 2) males > females 3) incidence: rare Pathology: 1) proliferation of Langerhans cells a) abundant, pale eosinophilic cytoplasm with indistinct cell borders b) folded, indented, kidney-shaped nucleus, with finely dispersed chromatin 2) stimulation for proliferation of Langerhans cells unknown Clinical manifestations: 1) lytic bony lesions 2) cutaneous abnormalities a) scalp, chest, upper back [3] b) soft tissue swelling c) eczema d) seborrheic dermatitis-like changes e) erythematous papules & nodules with purpura, crusting & ulceration, necrosis 3) lymphadenopathy - posterior cervical, submandibular, supraclavicular [3] 4) serous drainage from ears [3] Laboratory: - immunohistochemistry (biopsy: skin, bone, soft tissue) 1) diagnosis (2 or more) a) ATPase+ b) S-100 protein+ c) alpha-D-mannosidase d) peanut agglutinin+ 2) definite diagnosis a) CD1a+ b) Birbeck granules - complete blood count may show anemia of chronic inflammation Management: - prednisone, vinblastine, & mercaptopurine [3]

Related

eosinophilia vinca alkaloid

Specific

eosinophilic granuloma Hand-Schuller-Christian syndrome (lipoid histiocytosis) Letterer-Siwe syndrome pulmonary Langerhans cell granulomatosis

General

granulomatous disease histiocytic neoplasm histiocytosis

References

  1. Color Atlas & Synopsis of Clinical Dermatology, Common & Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 556-561
  2. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
  3. Mehta B, Venkatramani R Langerhans'-Cell Histiocytosis N Engl J Med 2014; 371:1050September 11, 2014 PMID: 25207768 http://www.nejm.org/doi/full/10.1056/NEJMicm1312532
  4. Allen CE, Merad M, McClain KL Langerhans-Cell Histiocytosis. N Engl J Med 2018; 379:856-868. Aug 30, 2018 PMID: 30157397 https://www.nejm.org/doi/full/10.1056/NEJMra1607548