Leukemia in its broadest definition designates malignancies in which the neoplastic cells may be shown to be transformed hematopoietic cells. 'Leukemia' encompasses several discrete diseases which are heterogeneous in their clinical presentation, morphologic features, immunophenotypic, cytogenetic and molecular findings, clinical course, prognosis, and therapeutic management. Acute leukemias are characterized by a maturation arrest of the malignant clone, with accumulation of immature cells and inhibition of normal hematopoiesis. Acute leukemias may be subdivided based on the morphologic, cytochemical, and immunophenotypic features of the neoplastic cells into acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). [1][2][3] Cases not classifiable in this fashion are either undifferentiated (AUL) or biphenotypic. 4,5 In chronic leukemias, the malignant cells are an expanded population of hematopoietic cells without a maturation arrest. These diseases include chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), and hairy cell leukemia (HCL). Loss of cellular maturation may occur as a secondary event in these diseases, as in blast transformation of CML.
We review here uncommon patterns of presentation of leukemia, with an emphasis on the diagnostic and therapeutic challenges that they pose. Leukemias are most commonly bone marrow-based malignancies, eventuating from malignant transformation of hematopoietic progenitors in the bone marrow. Typical presentations of leukemia represent the manifestations of impaired production of normal blood cells and of the presence of an expanded population of hematopoietic cells in the bone marrow. Thus common presenting symptoms and signs of leukemia include fatigue, subjective weakness, fever, bleeding, bruising, and bone pain. Uncommonly, leukemia presents as an extramedullary syndrome rather than as a bone marrow disorder. Extramedullary presentations of leukemia may result from the effects of hyperleukocytosis upon other organ systems, from infiltration of extramedullary tissues by leukemia cells, or from paraneoplastic syndromes with extramedullary manifestations.
Extramedullary syndromes associated with leukemia occur by several mechanisms. First, circulation of large numbers of malignant leukocytes in leukemias with hyperleukocytosis may