Abnormal white blood cells: Leukemia or not? (Proceedings)
Leukemia = the presence of neoplastic cells in circulation. Leukemia can arise independently of, or concurrently with tissue neoplasia. The opposite is also true. A hematopoietic cell neoplasm can be localized to the BM or tissue without being seen in circulation.
Lymphoproliferative disease is the general term to describe an abnormal expansion (often neoplastic, but occasionally reactive) of the lymphoid line. Lymphoma or lymphosarcoma describes a solid, sarcomatous lymphoid tumor which may involve a variety of organs, such as lymph nodes, liver, spleen, kidney, and intestines. Bone marrow is involved in a small percentage of cases.
Myeloproliferative disease (MPD) is the proliferation of granulocytic, megakaryocytic, erythrocytic, and/or stromal connective tissue (fibrous and osseous) cells in the bone marrow and includes the following:• Undifferentiated MPD or blastic form
• Myelomonocytic (neutrophils and monocytes)
• Erythemic myelosis (RBC)
• Erythroleukemia (RBC and WBC)
Myelofibrosis is a poorly understood entity characterized by proliferation of hemic cells, as well as diffuse fibrosis in the bone marrow. Extramedullary hematopoiesis accompanies these changes. Myelofibrosis is a form of MPD and may also be a terminal stage of other forms of MPD.
Leukemia is suspected when the white cell count is high with increased numbers of blasts cells and/or atypical cells. The bone marrow should be sampled when the blood is not definitive or when trying to identify the specific type of leukemia. A bone marrow aspirate provides more information on cell morphology. A bone marrow core biopsy provides more information regarding bone marrow architecture. This is best used to identify focal lesions, fibrosis, and cellularity.
If the bone marrow contains greater than 30% blast cells and lack orderly maturation, it is consistent with myeloproliferative disease. If less than 30% blast, the process is classified as dysmyelopoiesis. Cytochemistry and electron microscopy may be necessary to identify the cell type. Focal aggregates of neoplastic cells can be seen with lymphoma, myeloma, and mast cell tumors.
Leukemia can be classified by several processes. The terms acute, subacute, and chronic have been used to describe the degree of cellular differentiation.
1. Acute very little differentiation of neoplastic cells (mostly blasts).
2. Subacute more differentiated cells (intermediate).
3. Chronic welldifferentiated neoplastic cells.
Acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) are relatively easy to diagnose due to the presence of significant numbers of blasts or other atypical cells. In the dog, acute leukemia appears slightly more likely to be of myeloid than lymphoid origin. However, it may be difficult to differentiate AML from ALL through examination of hematologic or cytologic features. In addition, AML in dogs and cats is difficult to diagnose through flow cytometry immunophenotyping as the available antibody panels do not provide lineage specific myeloid or myelomonocytic markers. While combinations of antibodies, coupled with flow scatter patterns can be used to help characterize myeloid precursors, no currently available panel of antibodies can consistently identify myelomonocytic leukemia or AML. CD34 is detected on both AML and ALL. There is also no PCR test for clonality for AML. One of the best markers for AML is myeloperoxidase. Currently, this is detected by most labs through cytochemistry on cytology or histology slides.
Subtle signs that are often used to differentiate AML from ALL on the blood film include the presence of granules or vacuoles in the cytoplasm, a finer nuclear chromatin pattern and as slightly more centralized nuclear placement. If there is even a slight continuum to more differentiated cells, this can be helpful but many blastic or intermediate leukemias are poorly differentiated.
Acute lymphoid leukemia may be comprised of cells of B, T, or NK origin. CD34 is often detected on AML and ALL, but is rarely (or not) detected on lymphoma and therefore serves as a useful marker to differentiate ALL with tissue involvement from lymphoma with marked leukemia. Flow phenotyping and PCR for antigen receptor rearrangement (PARR) are very useful for the characterization of lymphoproliferative processes. However a negative result does not exclude the possibility of a lymphoid (versus myeloid) neoplasia.