Issues in the Pathology and Diagnosis of the Chronic Myeloproliferative Disorders and the Myelodysplastic Syndromes

Abstract

We have attempted to discuss some of the issues that interest pathologists who are involved in the diagnosis of CMPD and MDS. In most cases, correlation of the clinical findings with the findings in the blood and marrow will allow the morphologist to arrive at a proper diagnosis. Nevertheless, there will continue to be cases that are difficult to classify, or in which the clinical features are out of keeping with the morphologic features. These cases are challenging and thought-provoking, and the application of newer diagnostic techniques, such as molecular genetics, may provide important insights.

Trisomy 14 is a non‐random karyotypic abnormality associated with myeloid malignancies

“…Philadelphia chromosome (Ph)-negative). There is controversy in the literature as to whether atypical CML is an appropriate diagnosis, as myelodysplastic features are usually present and these patients may be more suitably categorized as having MDS (Dickstein & Vardiman, 1993). Interestingly, trisomy 14 was not identified as an additional karyotypic abnormality in patients with CML (i.e.…”

Combination Therapy with Recombinant Human Erythropoietin, Interferon-α-2b and Granulocyte- Macrophage Colony-Stimulating Factor in Idiopathic Myelofibrosis

“…It is thought to arise from a defect in a single stem cell and it is characterized by splenomegaly, immature granulocytes and erythroblasts in the peripher al blood, distorted and teardrop-shaped red blood cells, extramedullary hematopoiesis and marrow Fibrosis [1][2][3], Myelofibrosis may occur as a primary disease of unknown origin, as in the patients described here or it may accom pany other diseases, including myeloproliferative and myelodysplastic disorders [4][5][6][7].…”

Apoptosis (Programmed Cell Death) in Idiopathic (Primary) Osteo-/Myelofibrosis: Naked Nuclei in Megakaryopoiesis Reveal Features of Para-Apoptosis

“…Criteria for eligibility included: (1) no preceding therapy; (2) exclu sion of any other or allied subtype of chronic myeloproliferative dis order and no history of another hematological condition; (3) repre sentative bone marrow biopsies on admission and sequential exami nations in the majority (ratio 30/38) of patients, and (4) complete office and hospital records with follow-up data and life status. In the context of differential diagnosis, it should be emphasized that in 11 patients, clinical and laboratory data on admission showed only some of the features commonly regarded as characteristic for IMF [18][19][20]41], but sequential biopsies and follow-up data were in keep ing with this diagnosis. For this reason, our study encompassed the extreme ranges of initial to advanced stages of IMF without concen tration on 'full-blown' cases, as in most published series (19,41].…”

“…This significant advantage of a direct in situ assessment of cells undergoing programmed death is of particular interest in idiopathic (primary) osteo'/myelofibrosis (IMF). In this chronic myeloprolifer ative disorder, a non-representative aspiration or socalled dry tap is usually found due to the extent of marrow fibrosis [18][19][20]. On the other hand, knowledge about apoptosis is most desirable, since evolution of myelofibro sis was shown to be distinctively linked with degrading processes of the mcgakaryocytic cell lineage resulting in the release of certain growth factors [21][22][23][24][25][26][27][28], Morphologi cal remnants of this fundamental biological process gov erned by a complex cytokine-mediated functional net work are so-called naked (bare, denuded or pyknotic) nuclei [29][30][31][32][33], Hence, naked nuclei (NN) of megakaryo cytes are thought to mark spent stages after exhaustion of platelet production or a premature cell death in certain conditions, like HIV myelopathy and myelodysplastic syndromes [34][35][36][37][38][39], In this terminal stage, NN are finally digested by phagocytic reticular cells [40], Primarily based on ultrastructural features, a conflict of opinions has emerged whether NN reflect apoptosis [35,40] or nonspecific changes [39], For this reason, the present study has focused on a quantification of apoptosis in IMF by using ISEL tech niques and attempts to elucidate its relationship with the NN of megakaryopoiesis.…”