Clinicopathological Features of Acute Promyelocytic Leukemia: an Experience in One Institute Emphasizing the Morphological and Immunophenotypic Changes at the Time of Relapse

Acute promyelocytic leukemia (APL) has two morphological variants, namely macrogranular (M3) and microgranular (M3v). M3v, characterized by the presence of neoplastic promyelocytes with only sparse fine azurophilic granules, accounts for 10-25% of all APL and has unique biological characteristics. Relapse occurs in approximately 20% of patients with APL. The morphological type of the leukemic cells at relapse is usually identical with the primary disease, and only one case of morphological change at relapse has been reported. Here, we analyzed the clinicopathological features of APL, including 4 relapsed cases emphasizing morphological changes at the time of relapse. The unique finding of the present study is that 2 of 4 relapsed cases changed from M3 to M3v at relapse. The morphological features of these were different in each case (one had blastic features and the other resembled monocytoid leukemic cells). Cytogenetic analyses revealed the continued presence of t(15;17)(q22;q12) at the time of relapse and morphological change. Moreover, the immune phenotype of the leukemic cells changed from CD2(-)/CD34(-) to CD2(+)/CD34(+) at that time. These findings suggest that morphological change at relapse in APL may not be a rare event, and that the leukemic cells can show variable morphological features at the time of relapse, which could result in misdiagnosis as a different type of acute myeloid leukemia. Therefore, a comprehensive approach with emphasis on combined morphological, immunophenotypic, and cytogenetic analyses is important for diagnosis and appropriate treatment of relapsed APL.