Tuesday, November 29, 2011

Histiocytic Disorders

A new classification scheme for histiocytic disorders has been promulgated by the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society.

The new classification scheme is based on the biological behavior of the disease and the lineage of the predominant cell type.

A very cursory review of immunology is helpful before proceeding to the classification. A histiocyte is a cell of the mononuclear phagocyte system (formerly the reticuloendothelial system). The histiocytes we'll be concerned with are monocytes, macrophages, and dendritic cells. Precursor cells in the marrow give rise to circulating monocytes, which differentiate into the tissue-resident phagocytes, macrophages and dendritic cells under the proper cytokine milieu. Langerhans cells are a class of dendritic cells that typically reside in the epidermis.

Under the new classification scheme, histiocytic disorders are classified based on biologic behavior into those with malignant behavior and those with varied biological behavior, and based on predominant cell type into monocyte-, dendritic cell-, or macrophage-related disorders. The term varied biological behavior is meant to convey the spectrum of behavior in this class, which can range in severity from self-limited to lethal.

Langerhans cell histiocytosis, the most well known of the histiocytic disorders by radiologists, is classified as a dendritic cell-related histioctyic disorder of varied biological behavior. Terms such as eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease are now (> 10 years) considered obsolete or unnecessary, and should be avoided unless you're trying to be difficult during case conference.

Erdheim-Chester disease, an extremely rare disorder that somehow pops up during radiology residency and on boards, is classified as part of Juvenile xanthogranuloma and related disorders.

The outline below summarizes the current classification scheme:

Disorders of Varied Biological Behavior
  • Dendritic cell-related
    • Langerhans cell histiocytosis
    • Secondary dendritic cell processes
    • Juvenile xanthogranuloma and related disorders
      • Erdheim-Chester disease
      • Solitary histiocytomas with juvenile xanthogranuloma phenotype
    • Solitary histiocytomas of various dendritic cell phenotypes
  • Macrophage-related
    • Hemophagocytic syndromes
    • Primary hemophagocytic lymphohistiocytosis (familial , sporadic)
    • Secondary hemophagocytic syndromes (infection-associated, malignancy-associated, other)
    • Rosai-Dorfman disease (sinus histiocytosis with massive adenopathy)
    • Solitary histiocytoma with macrophage phenotype
Malignant Disorders
  • Monocyte-related
    • Leukemias (Monocytic leukemia M5A and B, acute myelomonocytic leukemia M4, chronic myelomonocytic leukemia)
    • Extramedullary monocytic tumor or sarcoma
  • Dendritic cell-related histiocytic sarcoma (localized or disseminated) based on phenotype
    • Langerhans cells
    • Follicular dendritic cell
    • Interdigitating dendritic cell
    • Others
  • Macrophage-related histiocytic sarcoma (localized or disseminated)


  • Chow A, Brown BD, Merad M. Studying the mononuclear phagocyte system in the molecular age. Nat Rev Immunol. 2011 Oct 25;11(11):788-98.
  • 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.
  • Lieberman PH, Jones CR, Steinman RM, Erlandson RA, Smith J, Gee T, Huvos A, Garin-Chesa P, Filippa DA, Urmacher C, Gangi MD, Sperber M. Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years. Am J Surg Pathol. 1996 May;20(5):519-52.

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