Chronic myelomonocytic leukemia (CMML). In the WHO classification scheme CMML has been placed in the “Myelodysplastic/myeloproliferative diseases” category. Patients with predominantly myeloproliferative features have a hypercellular marrow (shown in the image) than patients with Myelodysplastic features. However, both categories can share a number of histopathologic features such as dysplasia in marrow elements resulting in anemia and thrombocytopenia. This particular case showed the following karyotype: 46,XY,add(2)(p23),add(5)(q22),-10,add(11)(p15).
Chronic myelomonocytic leukemia (CMML). Cells of both myeloid and monocytic lineages are increased in the hypercellular form of CMML. In the routine H&E stain it may be difficult to differentiate myeloid precursors from monocytic elements. In general, monocytes have scant finely granular cytoplasm and convoluted and folded nuclei without prominent nucleoli (three arrows). Promonocytes show nuclear grooves and creases that may not be apparent in biopsy sections. Monoblasts are indistinguishable from myeloblasts in routine H&E histology sections. Granulocytic elements show obvious granulation and pose little problem in identification.
Chronic myelomonocytic leukemia (CMML). Dysplasia is often present in megakaryocytes and manifests itself by hypolobation and abnormal nuclear lobation (arrowhead). Thrombocytopenia is usually the result of megakaryocytic dysplasia but the number of megakaryocytes may also be low contributing to thrombocytopenia. Some normal appearing megakaryocytes are always present in contrast to cases of chronic myelogenous leukemia (CML) where almost all megakaryocytes are small and hypolobated (micromegakaryocytes).
Chronic myelomonocytic leukemia (CMML). Bone marrow core biopsy staining with PAS stain (shown in the photomicrograph) is very helpful in highlighting magenta granules of granulocytes and lack of granules in monocytes and precursors. Note the presence of abundant granules in band and segmented neutrophils, myelocytes and metamyelocytes. The monocytes indicated by arrows do not show any significant amount of PAS-positive cytoplasmic granules and show folded and convoluted nuclei without prominent nucleoli.
Chronic myelomonocytic leukemia (CMML). Bone marrow reticulin fibrosis is variable but is present in up to 30% of patients with CMML. The presence of fibrosis does not favor a diagnosis of CML or idiopathic Myelofibrosis but chromosomal studies including routine karyotyping and FISH/PCR studies for bcr-abl and PCR for Jak-2 mutation must be performed to rule out the possibility of those disorders. In fact, exclusion of CML is a required criterion in the WHO scheme. The reticulin fibrosis, however, is almost never to the extent of the fibrotic phase of idiopathic Myelofibrosis.
Chronic myelomonocytic leukemia (CMML). Bone marrow aspirate smears are often diagnostic in the right clinicopathologic context. However, because of marrow fibrosis, aspirate smears may not be obtained but touch imprints of the core biopsy should be obtained in such situations. When obtained, the aspirate smears are often hypercellular and show increased numbers of both myeloid elements (yellow arrowheads) and monocytic elements. Monoblasts are very similar to myeloblasts and may not be identified as such. However, Promonocytes can be identified by their characteristic nuclear creases and grooves and fine nuclear chromatin (black arrows) and lack of any cytoplasmic vacuolation. Mature monocytes have somewhat more convoluted nuclei and may be cytoplasmic vacuoles.
Chronic myelomonocytic leukemia (CMML). Since hypercellular CMML is a chronic myeloproliferative disorder, increased numbers of both eosinophils (top arrowhead) and basophils (center arrow) and their precursors are identified. The increase is generally mild in a typical of CMML and not to the degree seen in cases of CML. However, in a subset of CMML moderately to markedly increased numbers of eosinophils are seen and such cases are designated as “CMML with eosinophilia.”
Chronic myelomonocytic leukemia (CMML). Red cell dysplasia is a feature in CMML, almost always in the hypocellular CMML with Cytopenias (the myelodysplastic form) but also commonly in the hypercellular CMML (myeloproliferative form). The dysplasia may be mild and subtle in the myeloproliferative form and is identified by the presence of nucleated red cell precursors shows nuclear budding and contour irregularity (two arrows). Also note that some of the red cell precursors are large and appear megaloblastic. The red cell dysplasia is a contributing factory to anemia which may be the presenting clinical finding.
Chronic myelomonocytic leukemia (CMML). In the peripheral blood, not only monocytes are increased (>1.0 x 109/L) but also immature myeloid elements including myelocytes and metamyelocytes are increased in addition to increased neutrophils and bands. The monocytes show abundant cytoplasm with fine granulation and nuclei may still show nuclear creases and folds (two arrowheads on the left). The myelocytes show moderate to abundant cytoplasmic granulation and condensed nuclear chromatin without any nuclear creases and folds (two arrows on the right). The myelocytes and metamyelocytes are generally <10% of all white cells. Myeloblasts/Monoblasts must be less than 20% in the peripheral blood or bone marrow.
Chronic myelomonocytic leukemia (CMML). Another area showing clusters of monocytic elements (arrows). Two neutrophils are also seen. Monocytosis may also be seen in a variety of both reactive conditions including chronic infections and chronic inflammatory conditions. However, promonocytes and monoblasts are not increased. Monocytosis is also a feature of acute myelomonocytic and monocytic leukemia.
Download all images in this set