Bone marrow infiltration of CD20-negative follicular lymphoma after rituximab therapy: a histological mimicker of hematogones and B-cell acute lymphoblastic leukemia/lymphoma

Abstract

Rituximab is a monoclonal antibody against CD20. Rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, termed R-CHOP, have improved the overall survival of patients with B-cell lymphoma in comparison with that of CHOP therapy. However, as with other molecularly-targeted therapies, resistance to rituximab could emerge sooner or later after rituximab administration. A number of mechanisms for rituximab resistance have been proposed, including downregulation of CD20 protein expression. Differential diagnosis of B-cell proliferation with reduced or lost CD20 expression includes not only B-cell lymphomas with CD20 downregulation, but also other tumorous and non-tumorous lesions. These include precursor B-cell neoplasms such as B acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) and hematogones, a normal precursor B-cell proliferation during regeneration of hematopoiesis, typically observed following bone marrow suppression by chemotherapy. It is important to distinguish these possibilities because distinct therapies are required for each. In this paper, we report a case where bone marrow infiltration of follicular lymphoma histopathologically mimicked hematogones or B-ALL/LBL when CD20 expression was downregulated in follicular lymphoma after R-CHOP therapy.

Keywords: B acute lymphoblastic leukemia/lymphoblastic lymphoma; CD20; Rituximab; follicular lymphoma; hematogones.

Figure 1

Representative histological images of the tumor cells in the bone marrow. (A, B) Hematoxylin and eosin (HE) stain. (C-I) Immunohistochemistry. (C) CD20. (D) CD79a. (E) BCL2. (F) BCL6. (G) CD10. (H) CD34. (I) TdT. Positive cells were stained brown in immunohistochemistry. At low power view in HE stain, the tumor cell nodules were found in the vicinity of the bone trabeculae (A). High power view showed centrocyte-like appearance of the tumor cells (B). The proliferating tumor cells were positive for CD79a (D), BCL2 (E), and BCL6 (F), weakly positive for CD10 (G), but negative for CD20 (C), CD34 (H), and TdT (I). (A) Original magnification: × 12.5. Bar: 2 mm. (B-H) Original magnification: × 400. Bar: 50 μm.