C-MYC rearrangements are frequent in aggressive mature B-Cell lymphoma with atypical morphology

Abstract

Diagnosis and classification of aggressive mature B-cell lymphoma with atypical morphology remains a challenge. To identify factors that may contribute to the atypical morphology, we selected eight such cases and evaluated their morphologic, immunophenotypic and cytogenetic features and clinical outcomes. The neoplastic cells showed a diffuse monotonous infiltrating pattern with a spectrum of morphology including: 1) L1 lymphoblastic; 2) centroblastic; 3) immunoblastic; and 4) mixed centroblastic and immunoblastic. The lymphoma cells in most cases were positive for CD10 and/or BCL6, and showed BCL2 expression. 6 of 8 cases showed C-MYC rearrangements, and interestingly, all 6 cases demonstrated a proliferation index of < or =90%. 3 of the 6 cases also demonstrated t(14;18). Clinical follow-up indicated that aggressive mature B-cell lymphoma may benefit from more intensified chemotherapeutic regimens used for BL. Our study suggests that aggressive mature B-cell lymphoma with atypical morphology may be another "grey zone lymphoma" lying in the spectrum between Burkitt lymphoma and diffuse large B-cell lymphoma.

Keywords: Aggressive mature B-cell lymphoma; Burkitt lymphoma; C-MYC rearrangement; diffuse large B-cell lymphoma; grey zone lymphoma.

Figure 1

Morphologic variations in aggressive mature B-cell lymphomas with atypical morphology (H&E, × 400 magnification). A. L1 lymphoblastic morphology: a monotonous population of medium-sized neoplastic cells with scant cytoplasm, round nuclei and small nucleoli (from patient 3); B. Centroblastic morphology: large cells with abundant cytoplasm, vesicular nuclei and small nucleoli; C. Immunoblastic: large cells with abundant cytoplasm and single centrally located prominent nucleolus; D. Centroblastic and immunoblastic morphology: with features of (B) and (C).

Figure 2

Aggressive mature B-cell lymphoma with atypical morphology in bone marrow (from patient 6). The bone marrow aspirate showed several large lymphoid cells with abundant basophilic and vacuolated cytoplasm, irregular nuclei and multiple prominent nucleoli (Wright-Giemsa, × 1000 magnification). These cells have sizes similar to the adjacent promyelocyte and myelocytes.

Figure 3

FISH analysis using the c-MYC break-apart probe set. A. A c-MYC rearrangement is present (patient 1) as indicated by splitting apart of the normal red-green fusion signal into one red (centromeric end of MYC) and green (telomeric end of MYC) signal (arrows); B. An c-MYC rearrangement is absent (patient 8) as evidenced by the presence of normal red-green fusion signals only.