Case Study Discuss the pathpyysiology of Myelofibrosis - Essay Example

This disease is characterized by fibrosis and sclerosis of bone marrow. To compensate for the hematopoietic cell population, extramedullary hematopoiesis takes place in the spleen, accounting for the massive enlargement of the spleen. This disease occurs predominantly in subjects over the age of 54 years. The bone marrow fibrosis is the hallmark of pathological findings in such cases, where extensive fibrosis with resultant peripheral blood leukoerythroblastosis is expected as a typical histopathologic picture on bone marrow biopsy (Tefferi, 2000, p.

1255-1265). This clinically heterogeneous group of diseases stems from clonal proliferation of stem cell origin and is characterized at least initially by marrow hypercellularity with varying degrees of marrow fibrosis and an increase in the production of one or more terminally differentiated cell types. These differentiated elements may accumulate in the bone marrow, in the peripheral blood, and in other organs, such as, spleen. All these diseases demonstrate a variable tendency to undergo disease progression that may terminate in bone marrow failure or in transformation to an acute phase malignant disease.

The evaluation of bone marrow histology holds an important role in defining the pathology of this disease, by mainly ruling out unsuspected pathology. The pathologic changes are subtle until the disease has progressed, and therefore, classification of these disorders benefits from the integration of the morphologic features with clinical, hematologic, and cytogenetic findings. Of major importance is the presence or absence of Philadelphia chromosomes (BCR/ABL or translocation9;22). This group of diseases constitutes the classical group of BCR/ABL-negative chronic myeloproliferative disorders.

The disease is regarded as one of the chronic myeloproliferative disorders. Recently considerable progress has been made in understanding its pathogenesis, although this has yet to result in significant therapeutic advances. Indeed, its prognosis remains poor when compared to other BCR-ABL-negative chronic myeloproliferative disorders with death resulting from cardiac failure, infection, hemorrhage, and leukemic transformation (Barosi, 2003, p. 1211-1226).Hemapoetic Components It has been appreciated for many years that MF is a clonal disorder and that the disease arises from the proliferation of malignant pluripotential stem cells.

Recently, using fluorescent in situ hybridization (FISH), there is evidence that both B and T cells can be involved, while karyotypic analysis has shown that the stromal proliferation is polyclonal, or reactive, and not part of the underlying clonal hematopoiesis. An increased number of circulating hematopoietic precursors, including pluripotent and lineage restricted progenitor cells is a feature of MF and is likely to result from the proteolytic release of stem cells from the marrow. It is also possible that the spleen and liver contribute to the circulating progenitor pool as splenectomy temporarily normalizes levels.

The high level of circulating progenitor cells is reflected in the significantly increased peripheral