Molecular Pathology of Histiocytic Disorders

Abstract

Histiocytic disorders are diseases characterized by the proliferation and/or accumulation of histocytic cells in bone marrow (BM), peripheral blood (PB), and a variety of extramedullary tissues, associated with variable local and systemic symptoms, which depend on the disease subtype. Histiocytes are hematopoietic cells that derive from BM progenitors and have important functions in the immune system, including antigen presentation and antigen processing. Normal histiocytes include multiple functional subsets with distinct morphology, immunophenotype, and tissue localization. Histiocytic dis-orders are currently classified according to their morphologic and immunophenotypic resemblance to these normal counterparts, as well as according to their clinical presentation and biologic behavior (Table 42.1). The immunohistochemical classification of the tumors of histiocytes and accessory dendritic cells proposed by the International Lymphoma Study Group comprises two major categories: disorders of varied biologic behavior and malignant disorders. This chapter will focus on the former category, which includes clonal and non-clonal entities, none of which may be definitively classified as malignant, although their clinical behavior may be aggressive and even fatal (Table 42.2). The malignant disorders include sarcomas with histiocytic or dendritic cell differentiation, as well as acute myeloid leukemias (AMLs) with monocytic or monoblastic differentiation. Due to the rarity and thus lack of a significant amount of molecular data, sarcomas with histiocytic or dendritic cell differentiation will not be addressed in this chapter. For a discussion of AMLs with monocytic or monoblastic differentiation, see Chaps. 34 and 35.