- Human pathology

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Saturday 19 July 2003

histiocytopathies, histiocytosis, histiocytic disorders, histiocytic tumors, histiocytic proliferations, aggressive histiocytic disorders

Digital cases

- HPC:290 : Nodal Histiocytic infiltration in Rosai-Dorfman disease
- HPC:338 : Nodal Langerhans histiocytosis with tuberculoid granulomatous pattern


- Case 11335: Femoral Langerhans cell histiocytosis
- Case 12691: Faciocranial Langerhans cell histiocytosis

Definition: Histiocytoses are a heterogeneous group of disorders that are characterized by the proliferation and accumulation of reactive or neoplastic histiocytes.

Histiocytosis encompasses a group of diverse disorders characterised by the accumulation and infiltration of monocytes, macrophages, and dendritic cells in the affected tissues.

The nomenclature and classification of paediatric histiocytic disorders is complex but the most recent classification describes three major classes of histiocytoses in which the most common are class I and II.

Class I comprises dendritic cell disorders such as Langerhans cell histiocytosis (LCH) (also known as histiocytosis X), and includes the syndromes Letterer-Siwe disease (MIM.246400) and Hand-Schüller-Christian disease.

Class II consists of macrophage-related disorders including hemophagocytic lymphohistiocytosis (HLH) which is characterised by inherited (Familial haemophagocytic lymphohistiocytosis) (FHLH) (MIM.267700) and sporadic forms of the disease. Additional, less common, histiocytic disorders included in class II are sinus histiocytosis with massive lymphadenopathy (SHML or Rosai-Dorfman syndrome), juvenile xanthogranuloma, reticulohistiocytoma and a familial form previously designated as Faisalabad histiocytosis.

Class III comprises malignant disorders involving histiocytic lineage cells including histiocytic lymphoma and acute monocytic leukaemia.


Three classes of histiocytoses have been defined:
- class I, Langerhans cell disease
- class II, non-Langerhans cell histiocytic disease without features of malignancy
- class III, malignant histiocytic disorders

Although the disorders in classes I and II usually have a benign appearance on histology and are commonly non-aggressive and self-healing, some can cause debilitating or even fatal outcomes.

- dendritic histiocytoses

- other histiocytoses


- xanthogranulomatous histiocytosis

  • Langerhans histiocytosis
  • Erdheim-Chester disease

- histiocytosis with erythrophagocytosis (macrophagic activation syndrome)


- systemic histiocytosis

  • Langerhans histiocytosis
  • Erdheim-Chester disease

- localized histiocytosis

  • splenic histiocytosis
  • cutaneous histiocytosis
  • hepatic histiocytosis
  • pulmonary histiocytosis


- congenital histiocytoses (fetal histiocytoses and neonatal histiocytoses)

  • Langerhans cell histiocytosis
  • generalized juvenile xanthogranuloma
  • congenital self-healing histiocytosis

- familial histiocytoses


- Beverley PC, Egeler RM, Arceci RJ, Pritchard J. The Nikolas Symposia and histiocytosis. Nat Rev Cancer. 2005 Jun;5(6):488-94. PMID: 15928676

- Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer. 2005 Sep;45(3):256-64. PMID: 15547923

- Jaffe R. The other histiocytosis. Pediatr Dev Pathol. 2004 Jan-Feb;7(1):2-4. PMID: 15255029

- Zelger BW, Sidoroff A, Orchard G, Cerio R. Non-Langerhans cell histiocytoses. A new unifying concept. Am J Dermatopathol. 1996 Oct;18(5):490-504. PMID: 8902096

- Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, Bucsky P, Egeler RM, Elinder G, Gadner H, Gresik M, Henter JI, Imashuku S, Janka-Schaub G, Jaffe R, Ladisch S, Nezelof C, Pritchard J. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997 Sep;29(3):157-66. PMID: 9212839