The classification of acute leukemias into lymphoid leukemia (ALL) and nonlymphoid leukemia (ANLL) is of critical therapeutic importance. The differentiation of ALL from ANLL is usually achieved through morphologic, cytochemical and immunophenotypic analysis of leukemic blasts. One of the main morphologic criteria in the differentiation between the two types is the presence of granules in the cytoplasm of ANLL blasts. There have been scattered reports of patients with ALL who have lymphoblasts with azurophilic cytoplasmic granules. We describe two cases of granular ALL with review of the literature.
Case Report
Case 1A 22-year-old Saudi male was referred to King Khalid University Hospital (KKUH) in April 1995 with a diagnosis of ALL. He presented with malaise and shortness of breath for one month prior to admission. On examination, he was pale with no jaundice or cyanosis. He had generalized lymphadenopathy and hepatosplenomegaly. Chest and central nervous system (CNS) examinations were unremarkable. The diagnosis of ALL was confirmed (see below) and chemotherapy was started using hydroxyurea 2 g, p.o., q.i.d., for three days, followed by mitoxantrone 12 mg/m 2 intravenously (IV) daily for three days, vincristine 1.4 mg/m 2 IV weekly for seven weeks, and methylprednisolone 60 mg/m 2 IV daily for 21 days. Because of CNS involvement, he was started on intrathecal (IT) methotrexate (MTX) 10 mg, cytosine arabinoside (Ara-C) 50 mg and hydrocortisone 50 mg three times a week for a total of 10 doses. Induction was complicated by fever and neutropenia and he was managed with broad spectrum antibiotics and amphotericin-B. He did not achieve complete remission. Reinduction was started, but the patient died of neutropenia and septic shock.
Hematological EvaluationOn admission, complete blood count (CBC) revealed a white blood count (WBC) of 23.8xl0 9 /L, hemoglobin (Hb) of 107 g/L, and platelet count of 59xl0 9 /L. The WBC differential count showed 8% neutrophils, 70% lymphocytes and 20% blasts. Bone marrow (BM) aspirate revealed hypercellular marrow with 55% blasts. The blasts were variable in size with some showing high nuclear cytoplasmic (N/C) ratio, while others were larger with low N/C ratio and prominent nucleoli. The morphology was that of L2 by the French American British (FAB) classification of ALL.1 Fifteen percent of the blasts contained cytoplasmic granules that were variable in size and stained purple by May-Giemsa stain. The number of granules was also variable, but most of the blasts contained more than three granules. Occasional hand mirror cells were also present. Auer rods were absent.The blasts were negative for Sudan black (SBB) and chloroacetate esterase (CAE) and positive for periodic acid Schiff (PAS), nonspecific esterase (NSE) without inhibition by sodium fluoride (NaFl), and weakly positive for acid phosphatase (AP). Flow cytometry was performed on the bone marrow aspirate and showed the blasts to be positive for CD10 (CALLA), CD19, CD20, CD22 and HLADR and negative for CD7, CD3, CD13 and CD33. T...