Bone marrow cellular cannibalism by medulloblastoma
Authors: Virginia Escamilla, Emilio Franco‐Macías, Cristina Calderón‐Cabrera, Eloy Rivas, Rosario M. Morales‐Camacho, Maria Teresa Vargas, Ricardo Bernal, José A. Pérez‐Simón
Journal: American Journal of Hematology (2014)

Cellular cannibalism consists on the internalization of a cell into another of the same lineage. Internalized cells can maintain unaltered form (emperipolesis), suffer from degenerative passive changes, or be digested when the receptor cell is phagocytic (phagocytosis). A six-year-old girl started with endocranial hypertension due to IV ventricle tumor complicated with obstructive hydrocephalus. Tumor resection and placement of a ventriculoperitoneal shunt were accomplished. Histological diagnosis was established for large cell/anaplastic medulloblastoma (Image 1, panel 1a,b), WHO grade IV, belonging to high risk no Wnt/SHH group, probably group 3, according to international consensus 1. Panel 1: Histological brain section. H&E stain, 400× (a). The inset shows complex cannibalism (wrapping o cannibalism) (b). Panel 2: Bone marrow aspirate. MGG stain, 1,000×. Classical morphological features of cannibalism phenomenon in various stages: approximation (a); gradual penetration (b–e), and complete internalization (f). Panel 3: Bone marrow aspirate. MGG stain, 1,000×. One malignant cell is internalizing into another cell and this complex is engulfed by another cell (a–c). One cell internalizing into two cells at a the same time (d–e), and in other area, two cells were seen internalizing into one another (f). Panel 4: Bone marrow aspirate. MGG stain, 1,000×. Three erythrocytes are internalized by a malignant cell (a), two erithrocytes are internalized by one malignant cell, and this complex is internalized by another cell (b). Erythroblast internalization (c). Three months later craniospinal magnetic resonance images (MRI) and cerebral spinal fluid (CSF) demonstrated that meningeal infiltration and hyper-fractioned radiotherapy was administered. A month later the patient had to be readmitted due to neurologic deterioration, abdominal pain, and pancytopenia. A bone marrow aspirate was performed, which was hyper-cellular and showed 97% of pleomorphic undifferentiated cells (15–30 μm), with round nuclei, without nucleoli, basophil agranular cytoplasm, vacuolation, and clasmatosis phenomenon. They were of malignant appearance and non-hematopoietic lineage. These cells showed scarce cohesion (isolated clusters of 3–4 cells). Features showing cannibalism were observed in up to 0.6% of tumor cells. Nearly half of the cannibalism images showed tumor cells on their way to internalization but not having completed the engulfment yet. Full sequence of successive steps in the process of cannibalism could be observed (Image 1, panel 2a–f), even the interaction of three cells with successive internalizations (Image 1, panel 3a–c), two cells internalized by a third one (Image 1, panel 3d-e), or two cells internalizing another one simultaneously (Image 1, panel 3f). Most of internalized cells were unaltered. Moreover, 0.1% of internalized erythrocytes were observed, occasionally more than one in the same cell (Image 1, panel 4a), where they could coexist with cannibalism phenomenon (Image 1, panel 4b). Internalization of erythroblasts was seen exceptionally (Image 1, panel 4c). Cytogenetic bone marrow analysis revealed a karyotype: 45,XX,dic(10;11)(p10;p10),i(17)(q10),70∼120dmin[20]. Fluorescence in situ hibridization (FISH) analyses confirmed a c-myc (MYC) amplification in dmins. Two weeks after hospitalization, the patient died in the context of disseminated disease. Due to the fact that medulloblastoma rarely metastasizes outside the central nervous system (CNS) 2, cytological descriptions of bone marrow dissemination are exceptional 3. Differential diagnosis with acute leukemia was raised because of the scarcity of genuine metastatic nests 4. Cannibalism has already been reported in brain tissue samples from anaplastic medulloblastomas 5, 6. A high cellular bone marrow (BM) aspirate allowed us to observe this phenomenon thoroughly. Although degenerative changes in the wrapped or receptor cell could rarely be seen, both cells were usually preserved. Emperipolesis rather than a true phagocytosis would be a more accurate term to describe this phenomenon. A few images of cannibalism showed even more than two cells simultaneously involved. This finding known as bizarre or complex cannibalism has infrequently been described histologically in other tumors 7. Less common is erythrocyte internalization 8, and even more exceptional when involving erythroblasts.