Most patients have been ill only for days or weeks. Bleeding (usually due to thrombocytopenia) occurs in the skin and mucosal surfaces, with gingival bleeding, epistaxis, or menorrhagia. Less commonly, widespread bleeding is seen in patients with disseminated intravascular coagulation (DIC) (in APL and monocytic leukemia). Infection is due to neutropenia, with the risk of infection rising as the neutrophil count falls below 500/mcL (0.5 × 109/L). Common presentations include cellulitis, pneumonia, and perirectal infections; death within a few hours may occur if treatment with appropriate antibiotics is delayed. Fungal infections are also commonly seen.
Patients may also seek medical attention because of gum hypertrophy and bone and joint pain. The most dramatic presentation is hyperleukocytosis, in which a markedly elevated circulating blast count (total white blood count greater than 100,000/mcL) leads to impaired circulation, presenting as headache, confusion, and dyspnea. Such patients require emergent chemotherapy with adjunctive leukapheresis since mortality approaches 40% in the first 48 hours.
On examination, patients appear pale and have purpura and petechiae; signs of infection may not be present. Stomatitis and gum hypertrophy may be seen in patients with monocytic leukemia, as may rectal fissures. There is variable enlargement of the liver, spleen, and lymph nodes. Bone tenderness may be present, particularly in the sternum, tibia, and femur.
The hallmark of acute leukemia is the combination of pancytopenia with circulating blasts (eFigure 13–28). However, blasts may be absent from the peripheral smear in as many as 10% of cases (“aleukemic leukemia”). The bone marrow is usually hypercellular and dominated by blasts (greater than 20%).
Peripheral blood changes in leukemias. In most cases of leukemia, the peripheral blood is involved. Both A and B show a marked increase in the number of leukocytes. In A, which represents chronic lymphocytic leukemia (CLL), the cells resemble small lymphocytes. In B, which is acute lymphoblastic leukemia (ALL), the cells are larger and resemble the lymphoblasts seen in early stages of lymphocytic differentiation. Note the fragmentation of the fragile leukemic cells, which is a common finding in peripheral blood smears of patients with acute leukemia. (Reproduced, with permission, from Chandrasoma P, Taylor CR. Concise Pathology, 3rd ed. Originally published by Appleton & Lange. Copyright © 1998 by The McGraw Hill Companies, Inc.)
Hyperuricemia may be seen. If DIC is present, the fibrinogen level will be reduced, the prothrombin time prolonged, and fibrin degradation products or fibrin D-dimers present. Patients with ALL (especially T cell) may have a mediastinal mass visible on chest radiograph. Meningeal leukemia will have blasts present in the spinal fluid, seen in approximately 5% of cases at diagnosis; it is more common in monocytic types of AML and can be seen with ALL.
The Auer rod, an eosinophilic needle-like inclusion in the cytoplasm, is pathognomonic of AML (eFigure 13–29) and, if seen, secures the diagnosis. The phenotype of leukemia cells is usually demonstrated by flow cytometry or immunohistochemistry. AML cells usually express myeloid antigens such as CD13 or CD33 and myeloperoxidase. ALL cells of B lineage will express CD19, and most cases will express CD10, formerly known as the “common ALL antigen.” ALL cells of T lineage will usually not express mature T-cell markers, such as CD3, CD4, or CD8, but will express some combination of CD2, CD5, and CD7 and will not express surface immunoglobulin. Almost all ALL cells express terminal deoxynucleotidyl transferase (TdT).
Acute promyelocytic leukemia. (Bone marrow aspirate, 100 ×.) Note infiltration with immature myeloid cells characterized by a high nuclear-to-cytoplasmic ratio, open nuclear chromatin, and folding of the nuclei consistent with acute promyelocytic leukemia. Characteristic of this subtype of acute myeloid leukemia is the presence of multiple cells with Auer rods in their cytoplasm. Auer rods are not present in all patients with acute myelogenous leukemia, but their presence is pathognomonic of leukemia that is myeloid rather than lymphoid. This particular subtype of acute myeloid leukemia is associated with acute disseminated intravascular coagulation. (Used, with permission, from L Damon.)