Myeloidtumorsoccurmainlyinadultsandfallintothreemajorgroups: •Aggressivetumorscomprisedofimmaturemyeloidlineageblasts,whichreplacethemarrowandsuppressnormalhematopoiesis •Associatedwithdiverseacquiredmutationsthatleadtoexpressionofabnormaltranscriptionfactors,whichinterferewithmyeloiddifferentiation
Myeloidtumorsinwhichproductionofformedmyeloidelementsisinitiallyincreased,leadingtohighbloodcountsandextramedullaryhematopoiesis
Commonlyassociatedwithacquiredmutationsthatleadtoconstitutiveactivationoftyrosinekinases,whichmimicsignalsfromnormalgrowthfactors.ThemostcommonpathogenickinasesareBCR-ABL(associatedwithCML)andmutatedJAK2(associatedwithpolycythemiaveraandprimarymyelofibrosis).
Allcantransformtoacuteleukemiaandtoaspentphaseofmarrowfibrosisassociatedwithanemia,thrombocytopenia,andsplenomegaly.
The term histiocytosis is an “umbrella” designation for a variety of proliferative disorders of dendritic cells or macrophages. Some, such as very rare histiocytic lymphomas, are highly malignant neoplasms. Others, such as most histiocytic proliferations in lymph nodes, are completely benign and reactive. Between these two extremes lie a group of relatively rare tumors comprised of Langerhans cells, the Langerhans cell histiocytoses. As described in Chapter 5, Langerhans cells are immature dendritic cells found in the epidermis; similar cells are found in many other organs, and they function to capture antigens and display them to T cells.
Langerhans cell proliferations take on different clinical forms, but all are believed to be variations of the same basic disorder. The proliferating Langerhans cells express MHC class II antigens, CD1a, and langerin. Langerin is a trans-membrane protein found in Birbeck granules, cytoplasmic pentalaminar rodlike tubular structures that in electron micrographs have a characteristic periodicity and sometimes a dilated terminal end (“tennis racket” appearance). Under the light microscope, the proliferating Langerhans cells do not resemble their normal dendritic counterparts. Instead, they have abundant, often vacuolated cytoplasm and vesicular nuclei, an appearance more akin to that of tissue macrophages (called histiocytes by morphologists)— hence the term Langerhans cell histiocytosis.
Langerhans cell histiocytoses can be grouped into two major relatively distinctive clinicopathologic entities.
• Multisystem Langerhans cell histiocytosis (Letterer-Siwe disease) usually occurs in children younger than 2 years of age. It typically manifests with multifocal cutaneous lesions that grossly resemble seborrheic skin eruptions and are composed of Langerhans cells. Most affected patients have hepatosplenomegaly, lymphadenopathy, pulmonary lesions, and (later in the course) destructive osteolytic bone lesions. Extensive marrow infiltration often leads to pancytopenia and predisposes the patient to recurrent bacterial infections. The disease is rapidly fatal if untreated. With intensive chemotherapy, 50% of patients survive 5 years.