European Journal of Pediatrics

, Volume 135, Issue 2, pp 129–146 | Cite as

Histiocytosis X

  • J. P. M. Bökkerink
  • G. A. M. de Vaan


Histiocytosis X is a spectrum of diseases which should be classified among the wide spectrum of histiocytic disorders, consisting of proliferation of the Mononuclear Phagocyte System (MPS).

The clinical manifestations reflect the site of histiocytic proliferation and may vary from a solitary bone lesion discovered by chance on X-ray film to a disease with a rapidly fatal course affecting almost any organ. The classic classification into eosinophilic granuloma of bone, Hand-Schüller-Christian disease and Letterer-Siwe disease and other related classifications fail to demonstrate the variable course and the smooth transitions, and do not correlate with the histologic findings and prognosis.

The features of the immature and mature macrophage and, in this connection, the histologic findings of non-cutaneous material and the histochemical studies allow a classification into:

  1. 1.

    Benign Histiocytosis X

  2. 1.1

    Solitary or multiple bone lesions

  3. 1.2

    Benign disseminated Histiocytosis X

  4. 2.

    Malignant Histiocytosis X.


The clinical manifestations themselves do not allow a distinction to be made between the two entities, but the latter may lead to severe dysfunction of certain organs. A survey of the clinical manifestations is given. Benign Histiocytosis X comprises a widely variable spectrum, ranging from a solitary bone lesion to disseminated disease, but mostly with favourable outcome; malignant Histiocytosis X has a uniform, rapidly fatal, acute course with severe dysfunction of organs.

This classification is highly correlated with prognosis, which is based on histology, age at onset, dysfunction of liver, lung and hemopoietic system, and a score system.

In differential diagnosis, malignant Histiocytosis X must be distinguished from other histiocytic disorders and combined immunodeficiency, which have very similar symptomatology, but often have a recessive inheritance.

The etiology of Histiocytosis X is still unknown, but histochemical and electronmicroscopic studies point to a response of mature and immature histiocytes to an unidentified antigen.

Treatment of bone lesions consists in curettage or irradiation (600–1000 rads), if the lesions give rise to symptoms. Relapses are frequent. In benign disseminated Histiocytosis X a treatment protocol similar to that of acute lymphoblastic leukemia (ALL) is proposed and a more intensive protocol in malignant Histiocytosis X.

The prognosis of Histiocytosis X has substantially improved with the advent of multiple cytostatic treatment.

Histiocytosis X is a spectrum of diseases of unknown etiology, consisting in a proliferation of differentiated cells of the Mononuclear Phagocyte System (MPS), known as histiocytes. The clinical manifestations are widely variable, mirroring the widespread distribution of the MPS, affecting almost any organ. As a result there are numerous smooth transitions between the three classical entities distinguished in the literature: eosinophilic granuloma, Hand-Schüller-Christian disease and Letterer-Siwe disease.

Because of the variable course of Histiocytosis X, and for prognostic and therapeutic reasons, a classification based on clinical and histologic manifestations is desirable.

The purpose of this report is to review the literature concerning the classification of histiocytic disorders and Histiocytosis X. On the basis of the clinical manifestations, their prognostic value and the histologic findings, a classification (Table 1) is given that will be relatively simple to use in practice as a guide to prognosis and therapy.

Key words

Histiocytosis X Classification Benign and malignant disease Mononuclear Phagocyte System Differential diagnosis Benign and malignant histology Clinical manifestations Score system Organ dysfunction Prognosis ALL-treatment 


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Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • J. P. M. Bökkerink
    • 1
  • G. A. M. de Vaan
    • 1
  1. 1.Division of Pediatric Oncology, Department of PediatricsCatholic University of NijmegenNijmegenThe Netherlands

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