Abstract

Cannibalism is a type of “cell-in-cell” phenomenon commonly described in myeloid lineage malignancies. Although lymphocytes and their precursors are inherently non-phagocytic, there are sporadic case reports describing cannibalism by leukemic lymphoblasts. In the current manuscript, we report the case of a pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patient showing cannibalistic lymphoblasts and have reviewed the clinical and laboratory characteristics of similar cases documented in literature. Our manuscript highlights that all reported B-ALL patients showing cannibalistic lymphoblasts had intra-cytoplasmic vacuolations, and all such treatment-naïve pediatric patients were ETV6-RUNX1 fusion positive and had aberrant expression of myeloid lineage antigens.

Introduction

Cannibalism by leukemic blasts is well described in acute myeloid leukemias (AML). Although lymphocytes and their precursors are inherently nonphagocytic, nine cases of leukemic lymphoblasts exhibiting phagocytosis have been documented in literature.[1],[2],[3],[4],[5],[6] Through this manuscript, we report our pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patient who had cannibalistic blasts at diagnosis and review the clinical and laboratory characteristics of similar cases reported in literature. Interestingly, all lymphoblastic leukemia patients with phagocytic lymphoblasts reported till date had unique morphologic features and all pediatric B-ALL patients (100%) of this genre were positive for ETV6-RUNX1 fusion transcript.

Case Scenario

A 14-year-old Indian male presented with extreme fatigue and myalgia for 1 month. He was afebrile and had marked pallor and hepatomegaly. Hemogram revealed hemoglobin of 49 g/L, platelets of 127 × 109/L, and leukocytes of 15.8 × 109/L. Myeloperoxidase (MPO)-negative blasts comprised 75% of circulating leukocytes and 96% of bone marrow nucleated cells. These blasts were 2–4 times the size of a mature lymphocyte, had opened up chromatin and scanty basophilic cytoplasm. Multiple cytoplasmic vacuolations were observed in 88% of the blasts, and 12% of blasts showed erythrophagocytosis or thrombophagocytosis or cannibalism [Figure 1]. Flow cytometric immunophenotyping (FCI) was consistent with B-ALL with aberrant myeloid lineage marker [removed]CD19moderate, CD10bright, HLA-DRmoderate, CD34dim to moderate, CD13moderate, CD33moderate, CD36negative to dim, cytoplasmic CD79amoderate, cytoplasmic CD22moderate, cytoplasmic MPOnegative, and cytoplasmic CD3negative). Qualitative reverse-transcriptase-polymerase chain reaction revealed ETV6-RUNX1 fusion transcript positivity. There was no leukemic central nervous system infiltration at diagnosis.

| Figure. 1Note the presence of prominent vacuolations in the blasts. (a and b) Blasts showing cannibalism; (c) blast with erythrophagocytosis. Inset shows myeloperoxidase-positive erythrocyte engulfed by a blast; (d) thrombophagocytosis by blast. Inset shows myeloperoxidase-negative platelet engulfed by a blast. All slides are May–Grünwald–Giemsa stained, and the insets are cytochemical-myeloperoxidase stained (×100)

After the confirmation of diagnosis, the patient's family was counseled about the disease and treatment options. Due to financial constraints, the family wished to continue therapy at the local place. Hence, he was started on 6-week induction with low-dose chemotherapy protocol comprising weekly vincristine 1.5 mg/m2 and daily prednisolone 60 mg/m2 for 4 weeks followed by taper. The patient never followed up after he was discharged after receiving week 1 induction. As per telephonic information, the patient was shifted to indigenous treatment and succumbed to his illness after 7 months of diagnosis.

Discussion

Cellular cannibalism is a type of “cell-into-cell” phenomenon, wherein a viable cell is irreversibly engulfed by a nonprofessional phagocyte.[7] A cannibalistic cell can engulf a cell of its own lineage (homotypic cannibalism) or of different lineage (xeno-cannibalism).[8] Cannibalism is different from phagocytosis, wherein the latter involves a professional phagocytic cell (histiocyte/macrophage) engulfing a nonviable cell.[7],[8] Though phagocytosis can be seen in both benign and malignant pathologies, cannibalism is pathognomonic of advanced malignancies.[8]

Among acute leukemias, xeno-cannibalism in the form of erythrophagocytosis by neoplastic blasts has been commonly documented in cases of AML with monocyte lineage differentiation, AML with maturation, AML without maturation, acute megakaryoblastic leukemia, mixed phenotype acute leukemia, and acute undifferentiated leukemia.[1],[9] In AMLs, xeno-cannibalism has been associated with t(8;16)(p11;p13), t(16;21)(p11;q22), t(10;17)(p13;p12), inv(8)(p11q13), t(16;21)(p11;q22), t(3;8;7)(q27;p11;q12), del(20)(q11), and t(8;21)(q22;q22).[1]

Although conventional lymphocytes and their precursors are inherently nonphagocytic, cannibalism by leukemic lymphoblasts has been reported in nine patients till date.[1],[2],[3],[4],[5],[6] The first documentation of xeno-cannibalism in lymphoblasts was by Foadi et al. in 1978, where both erythrophagocytosis and thrombophagocytosis were observed in four relapsed ALL patients, but the lineage commitment of these lymphoblasts was not disclosed.[4] In 1984, Colon-Otero et al. reported the first case of erythrophagocytosis by lymphoblasts in a newly diagnosed B-ALL patient.[2] Till date, to our knowledge, cannibalism has been documented in only five treatment-naïve B-ALL patients (one adult and four pediatric) and ours is the sixth case in this genre.[1],[2],[3],[5] The clinical and laboratory characteristics of these six patients are compiled in [Table 1].{Table 1}

| Figure. 1Note the presence of prominent vacuolations in the blasts. (a and b) Blasts showing cannibalism; (c) blast with erythrophagocytosis. Inset shows myeloperoxidase-positive erythrocyte engulfed by a blast; (d) thrombophagocytosis by blast. Inset shows myeloperoxidase-negative platelet engulfed by a blast. All slides are May–Grünwald–Giemsa stained, and the insets are cytochemical-myeloperoxidase stained (×100)

References

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