ALK-positive anaplastic large-cell lymphoma with marked leukemoid reaction and hemophagocytic lymphohistiocytosis

Abstract

A 2-year-old boy presented with persistent fever and massive hepatosplenomegaly. Complete blood count revealed marked leukocytosis (white blood cells, 102 000/mL), anemia (hemoglobin, 5.8 g/dL), and thrombocytopenia (platelets, 59 000/mL). 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 1 and ALK-1 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.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

A case of a 22-month-old boy with necrotizing pneumonia presenting with leukaemoid reaction misdiagnosed as leukaemia: A case report and review of the literature

“…Additional testing of peripheral blood and bone marrow specimens include immunophenotyping for clonal disorders such as leukaemia and the presence of polyclonal mature neutrophils in LR (CD13 and CD15 positivity) and negative CD34, CD117, CD10, CD19 and HLA-DR in leukemia28. Another confusing entity for LR is chronic granulocytic leukaemia (CNL) which overlaps with LR in a morphological sense, but its clonal pattern on immunophenotyping clearly distinguishes the two conditions29. In order to exclude chronic myeloid leukaemia (CML), it is possible to investigate bone marrow morphology, which shows an arrest in the maturation of myeloid lineage.…”

Pathogenesis and Pathology of Pediatric Lymphoma

“…IHC staining for ALK is very useful to detect scattered tumor cells in bone marrow for staging or to monitor residual disease after treatment. ALCL can present in a leukemic phase mimicking acute monocytic leukemia morphologically (Figure 6J), or occasionally cause leukemoid reaction mimicking juvenile myelomonocytic leukemia morphologically (Figure 6K) (49).…”

Multiple myeloma coexisting colon carcinoma as the presenting symptom of a neutrophilic leukemoid reaction: a rare case report with genetic analysis

“…It is characterized by an increase in mature neutrophils and a marked "left shift", which refers to the presence of immature granulocytic forms (1). The main causes of LR are severe infection, neoplasms, toxin exposure, severe hemorrhage and acute hemolysis (2)(3)(4). Cancer is an important cause of LR, which can be identi ed at either diagnosis or prior to it by as much as 4 years (5).…”