Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 6)

This marrow section shows the marrow cavity replaced by fibrous tissue composed of reticulin fibers and collagen. When this fibrosis is due to a primary hematologic process, it is called myelofibrosis. When the fibrosis is secondary to a tumor or a granulomatous process, it is called myelophthisis.Diagnosis While the clinical picture described above is characteristic of chronic IMF, all of the clinical features described can also be observed in PV or CML. Massive splenomegaly commonly masks erythrocytosis in PV, and reports ofintraabdominal thromboses in chronic IMF most likely represent instances of unrecognized PV. ...
Nội dung trích xuất từ tài liệu:
Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 6) Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 6)Figure 103-2 This marrow section shows the marrow cavity replaced by fibrous tissuecomposed of reticulin fibers and collagen. When this fibrosis is due to a primaryhematologic process, it is called myelofibrosis. When the fibrosis is secondary to atumor or a granulomatous process, it is called myelophthisis. Diagnosis While the clinical picture described above is characteristic of chronic IMF,all of the clinical features described can also be observed in PV or CML. Massivesplenomegaly commonly masks erythrocytosis in PV, and reports ofintraabdominal thromboses in chronic IMF most likely represent instances ofunrecognized PV. In some patients with chronic IMF, erythrocytosis hasdeveloped during the course of the disease. Furthermore, since many otherdisorders have features that overlap with chronic IMF but respond to distinctlydifferent therapies, the diagnosis of chronic IMF is one of exclusion, whichrequires that the disorders listed in Table 103-3 be ruled out. A diagnosticalgorithm has been proposed but does not distinguish one disease causing myeloidmetaplasia from another. The presence of teardrop-shaped red cells, nucleated red cells, myelocytes,and promyelocytes establishes the presence of extramedullary hematopoiesis,while the presence of leukocytosis, thrombocytosis with large and bizarreplatelets, and circulating myelocytes suggests the presence of a myeloproliferativedisorder as opposed to a secondary form of myelofibrosis (Table 103-3). Marrowis usually not aspirable due to increased marrow reticulin, but marrow biopsy willreveal a hypercellular marrow with trilineage hyperplasia and, in particular,increased numbers of megakaryocytes in clusters and with large, dysplastic nucleiHowever, there are no characteristic morphologic abnormalities that distinguishIMF from the other chronic myeloproliferative disorders. Splenomegaly due toextramedullary hematopoiesis may be sufficiently massive to cause portalhypertension and variceal formation. In some patients, exuberant extramedullaryhematopoiesis can dominate the clinical picture. An intriguing feature of chronicIMF is the occurrence of autoimmune abnormalities such as immune complexes,antinuclear antibodies, rheumatoid factor, or a positive Coombs test. Whether these represent a host reaction to the disorder or are involved in itspathogenesis is unknown. Cytogenetic analysis of blood is useful both to excludeCML and for prognostic purposes, because complex karyotype abnormalitiesportend a poor prognosis in chronic IMF. For unknown reasons, the number ofcirculating CD34+ cells is markedly increased in chronic IMF (>15,000/µL)compared to the other chronic myeloproliferative disorders, unless they toodevelop myeloid metaplasia. Importantly, approximately 45% of chronic IMF patients, like patients withits companion myeloproliferative disorders PV and ET, express the JAK2 V617Fmutation, often as homozygotes. Such patients had a poorer survival in oneretrospective study but not in another, where they were found to be older and tohave higher hematocrits than those patients who were JAK2 V617F-negative. Complications Survival in chronic IMF varies according to specific clinical features (Table103-4) but is shorter than in patients with PV or ET. The natural history of chronicIMF is one of increasing marrow failure with transfusion-dependent anemia andincreasing organomegaly due to extramedullary hematopoiesis. As with CML, chronic IMF can evolve from a chronic phase to anaccelerated phase with constitutional symptoms and increasing marrow failure.About 10% of patients develop an aggressive form of acute leukemia for whichtherapy is usually ineffective. Important prognostic factors for disease acceleration include anemia,leukocytosis, thrombocytopenia, the presence of circulating myeloblasts, olderage, the presence of complex cytogenetic abnormalities, and constitutionalsymptoms such as unexplained fever, night sweats, or weight loss.