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Although myelomonoblastic leukemia is thought to originate from a malignant transformation of the stem cell of the mononuclear phagocyte system, malignant histiocytosis (MH) is classically assumed to represent a malignant change of the terminal and fixed elements of this system. Indeed, MH is characterized by the proliferation of large, clear, pleomorphic, "histiocytic-like" HLADR and CD30+ cells resulting in a nodal and extranodal disseminated neoplasm affecting preferentially and severely children and young adults. Although there is broad agreement on the clinicopathologic presentation of this condition, there is currently quite a controversy over the T-lymphoid or histiocytic origin of the proliferative cells that results in a nosologic discussion between the anaplastic large cell lymphoma (ALCL) advocates and the MH supporters. This article has dealt mainly with this nosologic discussion and with the contributions provided by the investigations performed on MH permanent cell lines. These in vitro studies have demonstrated that the proliferation is characterized by a unique chromosomal abnormality, the 5q35bp usually associated with a t(2;5) translocation generating a fusion gene NPM/ALK and the subsequent translation of p80 protein. Although it is known that no single chromosomal abnormality is strictly restricted to a cell lineage, this 5q35bp and associated translocations seem today to represent the hallmark for this condition. In view of these chromosomal aberrations, the CD30+ ALCLs represent a heterogeneous group because 15% to 50% express the NPM/ALK fusion gene. In addition, these in vitro investigations have shown that 5q35bp proliferative cells are glass-adherent, can develop an immunodependent phagocytosis, and are able to reduce NBT and produce TNF-alpha. More significantly, they express constitutively the c-fms (the receptor of the macrophage growth factor) and, under TPA stimulation, are able to modulate the expression of this receptor and its ligand, as well as TNF-alpha and IL-1. None of these cell lines express CD3, but several express CD68 and CD71. In contrast, genomic investigations have shown the underlying existence of monoallelic and even biallelic gene rearrangements for TCR beta and IgJH. In view of these discrepancies between the genomic and phenotypic features of these cells, the histogenetic debate should remain open but must take into account these new chromosomal and molecular data.

Malignant histiocytic disorders, other than leukemias, are extremely rare in childhood. Despite unresolved nosologic and terminologic difficulties, they should be classified according to the lineage of the aberrant cells in a given tumor. There are no common and typical clinical presentations, nor are there established treatment modalities available. For the disseminated forms, aggressive systemic treatment modalities--similar if not identical to those used for large cell anaplastic lymphomas--appear to be the best treatment option. For the localized forms, which are primarily dendritic cell sarcomas, a more localized and individualized therapy is appropriate.