The controversial issue of malignant histiocytic disorders personal observations and review of the literature

There are few disease entities so confusing as those related to the histiomonocytic cells and their malignant proliferations, defined either as Malignant Histiocytosis or histiocytic lymphoma. Both terms have been considered synonymous and employed indifferently by most Authors, although certain differences in the clinical manifestations have sometimes been outlined. The term “malignant-histiocytosis” was applied to a hematological condition first described by Scott and Robb-Smith [1] as histiocytic medullary reticulosis on the basis of its clinical features. Rappaport [2] introduced the term “malignant histiocytosis” in 1966 and reviewed the pathological features of this condition. Malignant histiocytosis has been considered a most aggressive disease. It was characterized by the systemic proliferation of malignant cells [3] and presented with fever, wasting, pancytopenia, hepatosplenomegaly and adenopathy. Reevaluation of cases formerly considered malignant histiocytosis, however, disclosed that the malignant cells were not histiocytes but various other cell types, including T-cells, B-cells, CD30+ anaplastic lymphoid cells and possibly others [4-5-6-7-89-10-11-12]. Notwithstanding these results, there remain case reports and descriptions of small series of lymphomas with features suggestive of a true histiocytic derivation [13-14-15-16-17-18]. In view of these conflicting reports, it seems justifiable to provide further contribution to this intriguing issue and to attempt a definition of the biological and clinical features which characterize these unusual and atypical malignant proliferations. A substantial improvement in the recognition and definition of these histiocytic disorders derives from the results of a study carried out by a group of Pathologists and haematologist/oncologists who have recently proposed an updated classification of the proliferative histiocytic disorders of childhood, which replaces that of the Histiocyte Society, published a decade ago [19]. According to these Authors, under the heading of “histiocytes” are included both macrophages and monocytes as “antigen processing cells” and dendritic cells as “antigen presenting cells” of the mononuclear phagocytic system (MPS). The Authors furthermore propose the abandoning of the confusing terms “histiocytic lymphoma” and “malignant histiocytosis”. Lymphomas are malignant tumours of different lymphoid cell types and therefore cannot be “histiocytic”. There are instead very rare tumors that may mimic large cell anaplastic lymphomas (LCAL) by morphology but the tumor cells show clear markers of monocytes and/or macrophages without any lymphoid properties. They should be designated as monocyticor macrophage-related histiocytic sarcomas (MMHS) [20]. These different entities differ only in phenotype, so that the signs and symptoms of these rare malignant histiocytic disorders cannot be differentiated on the Abstract. The Authors describe two cases, initially diagnosed on morphological and clinical grounds, as malignant histiocytic proliferations, in which cytochemical, immunocytochemical and genotypic investigations demonstrated a probable histiocytic malignancy in one case and a B lymphoma in the other. While the results of the studies on IgG and TCR rearrangements have not provided a definite answer with regards to their usefulness in separating lymphoid proliferations from the so-called histiocytic disorders, a panel of immunocytochemical techniques, especially that employed for demonstrating lysozyme, together with a number of cytochemical reactions may be helpful in establishing a correct diagnosis towards one disorder rather than another. The Authors outline all the diagnostic problems which underline hystiocytic proliferations and take the opportunity for a critical review of the most recent literature. caso clinico