A 2-year-old boy presented with persistent fever and massive hepatosplenomegaly. Complete blood count revealed marked leukocytosis (white blood cells, 102 000/μL), anemia (hemoglobin, 5.8 g/dL), and thrombocytopenia (platelets, 59 000/μL). Peripheral blood (PB) smear showed marked neutrophilia with toxic granulation and vacuolation, few variably sized atypical cells with round or irregular nuclei and basophilic vacuolated cytoplasm, and no blasts (panel A). Serum ferritin and soluble interleukin 2 receptor were elevated (1091 ng/mL and 162 090 units/mL, respectively). Bone marrow (BM) showed granulocytic hyperplasia with few atypical cells (same as those seen in PB). Fluorescence in situ hybridization (FISH) analysis showed ALK gene rearrangement in 7% of BM nuclei and in 5.6% of PB nuclei (panel B). Immunostain on the BM clot section showed few CD30+ and ALK-1+ cells (panels C-D). Anaplastic large-cell lymphoma (ALCL) and secondary hemophagocytic lymphohistiocytosis (HLH) were diagnosed.

ALCL is one of the most common pediatric large-cell lymphomas and occasionally shows leukemoid reaction, HLH, or leukemic involvement. Leukemoid reaction and/or HLH can mask the primary tumor. Routine flow cytometry study of the PB or BM may not identify the tumor cells due to “null cell” type and low leukemic involvement. CD30/ALK1 staining and FISH for the ALK gene are necessary to effectively identify the tumor cells and make the diagnosis in these cases.

A 2-year-old boy presented with persistent fever and massive hepatosplenomegaly. Complete blood count revealed marked leukocytosis (white blood cells, 102 000/μL), anemia (hemoglobin, 5.8 g/dL), and thrombocytopenia (platelets, 59 000/μL). Peripheral blood (PB) smear showed marked neutrophilia with toxic granulation and vacuolation, few variably sized atypical cells with round or irregular nuclei and basophilic vacuolated cytoplasm, and no blasts (panel A). Serum ferritin and soluble interleukin 2 receptor were elevated (1091 ng/mL and 162 090 units/mL, respectively). Bone marrow (BM) showed granulocytic hyperplasia with few atypical cells (same as those seen in PB). Fluorescence in situ hybridization (FISH) analysis showed ALK gene rearrangement in 7% of BM nuclei and in 5.6% of PB nuclei (panel B). Immunostain on the BM clot section showed few CD30+ and ALK-1+ cells (panels C-D). Anaplastic large-cell lymphoma (ALCL) and secondary hemophagocytic lymphohistiocytosis (HLH) were diagnosed.

ALCL is one of the most common pediatric large-cell lymphomas and occasionally shows leukemoid reaction, HLH, or leukemic involvement. Leukemoid reaction and/or HLH can mask the primary tumor. Routine flow cytometry study of the PB or BM may not identify the tumor cells due to “null cell” type and low leukemic involvement. CD30/ALK1 staining and FISH for the ALK gene are necessary to effectively identify the tumor cells and make the diagnosis in these cases.

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