Myelodysplastic syndromes (MDSs) and acute myeloid leukemias (AMLs), although most frequently occurring sporadically and in adult populations, have additionally been noted to occur in association with predisposing germline genetic abnormalities, with such cases commonly occurring in children and young adults. With the utilization of advanced diagnostic methodologies in clinical practice and the recognition of the significance of this set of conditions for clinical management, the spectrum of syndromic conditions has continued to expand in the medical literature.

Table 5.1 provides an overview of the inherited leukocyte disorders covered in this chapter.

Juvenile myelomonocytic leukemia (JMML) is a clonal myelomonocytic neoplasm of childhood with prominent granulocytic and monocytic proliferation, characteristically driven by RAS-pathway gene mutations. (See Table 10.1.)

Bone marrow failure syndromes comprise a heterogeneous group of disorders that may be inherited or acquired; may be static or progressive; and may affect any one hematopoietic lineage individually, multiple lineages, or all lineages collectively. The unifying feature consists of the failure of the bone marrow to supply the body with normal quantities of the mature forms of any of the three hematopoietic-lineage elements. Although bone marrow failure syndromes may engender a predisposition to the development of associated malignancies, and primary neoplastic processes involving the bone marrow and peripheral blood may meet the criteria of impaired hematopoiesis, discussion of neoplastic processes associated with cytopenias will be largely covered elsewhere.

Blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are an aggressive hematopoietic malignancy derived from precursors to plasmacytoid dendritic neoplasms, with a predilection toward involvement of the skin, bone marrow, and peripheral blood.1

Childhood myelodysplastic syndromes (MDSs) are clonal myeloid neoplasms characterized by impaired production of circulating hematopoietic elements (generally, hemoglobin concentration < 10 g/dL, platelet count < 100 × 109/L, or absolute neutrophil count < 1.8 × 109/L), frequently accompanied by morphologic dysplasia and recurrent genetic abnormalities and lacking features of overproduction of additional hematopoietic lineage elements. In light of its rarity in comparison to its clinicopathologic mimics, minimal diagnostic criteria have been proposed (see Table 13.1).

Hematolymphoid malignancies represent an area in which ancillary studies offer particularly valuable information for diagnosis, classification, and prognosis, as well as risk-stratified and targeted therapy. The results of multiple test modalities, including flow cytometry, immunohistochemistry, and cytogenetic and molecular genetic analyses, should be integrated and interpreted within the context of morphologic evaluation. In this chapter, the principles, general technical aspects, and clinical applications of these ancillary tests are discussed.

Chronic myeloid leukemia (CML), BCR-ABL1+, is a clonal myeloproliferative neoplasm (MPN) with a hyperabundance of granulocyte forms, defined by the presence of the BCR-ABL1 fusion gene, most frequently due to the chromosomal translocation t(9;22)(q34.1;q11.2) resulting in the Philadelphia (Ph) chromosome.

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement are clonal neoplasms with characteristically prominent eosinophilic proliferation and defining cytogenetic rearrangements. (See Table 11.1.)