MALIGNANT HISTIOCYTOSIS: Histologic, Cytochemical, Chromosomal, and Molecular Data with a Nosologic Discussion
Section snippets
HISTOPATHOLOGY
MH is characterized by the proliferation of large (from 10 to 20 μm), atypical, clear, “histiocyte-like” cells according to Rappaport72 and Cazal.14 Better seen on smears, these cells have a basophilic, finely or grossly vacuolated cytoplasm. The nucleus is large and irregular and exhibits prominent and dense nucleoli and a thick nuclear membrane (Fig. 1). Mitotic figures, sometimes multipolar, are frequent and provide a crucial element for distinguishing this condition from a reactive process.
CYTOCHEMISTRY
Because the neoplastic cells are extremely immature, usually necrotic, and frequently intermingled with locally activated lymphoid and histiocytic cells, the interpretation of the cytochemical data is sometimes difficult. As anticipated, the MH cells react positively with acid phosphatase, nonspecific esterase, and most lysosome-associated enzymes.13, 63 The results of the immunostaining are more characteristic, exhibiting most typically a CD30 positivity as revealed by Ki-1 or BerH2 specific
MALIGNANT HISTIOCYTOSIS PERMANENT CELL LINES
In view of certain conflicting data regarding the true nature of the proliferative cells, cell culture appeared to be a reliable method for selection of the cell in question and study of its behavior and its capacity for differentiation, as well as of the nature of the biologic products released. To date, only a few MH-derived permanent cell lines are available. Most of them have been isolated from pleural effusions in children with a disseminated disease identified as MH by their pediatricians
CHROMOSOMAL ABNORMALITIES: THE t(2;5) AND THE 5q35 BREAKPOINT
Following the first report by Morgan et al56 in 1986, chromosomal investigations performed on several MH cell lines revealed the occurrence of a constant breakpoint located on the long arm of chromosome 5 (5q35bp). Most often, this abnormality has been found associated with a second breakpoint involving the short arm of chromosome 2 and a reciprocal translocation t(2;5). Moreover, translocations involving various regions of chromosomes 1, 3, and 6 were also reported, underscoring the value of
DIFFERENTIAL DIAGNOSIS
Because MH cells express CD30 antigen, as do Reed-Sternberg cells, MH has sometimes been regarded as a disseminated variety (Stage IV) of Hodgkin's disease.35 This assumption has recently been supported by molecular studies— that is, the presence of NPM/ALK chimeric transcript in 11 of 13 patients with Hodgkin's disease.67 These results, however, have not been confirmed by most of the investigators using the NPM/ALK probe elaborated by Morris et al.11, 25, 27, 44, 50, 51, 97, 103 Of note,
NOSOLOGIC DISCUSSION
The main diagnostic problem remains the distinction between MH and lymphoma, and more precisely ALCL. As already stated, it is more a nosologic than a differential discussion. The opinion that MH belongs to the ALCL group is based on the following arguments (Table 3): (1) the CD30 positivity, considered as a reliable marker of Reed-Sternberg cells; (2) the frequent expression of lymphoid markers such as CD3, CD2, CD4, CD7, CD8, CD43, and CD45R021, 55, 97; and (3) the frequent underlying
SUMMARY
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
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Address reprint requests to Jean Gogusev, MD, Chargé de Recherche à l'INSERM, U 90 Hôpital Necker Enfants Malades, 149, rue de Sèvre, 75743 PARIS Cedex 15, France
Work supported by a grant from the Histiocytosis Association of America.