Diffuse large B-cell lymphoma with composite germinal center and non-germinal center types: A report of two cases.

We report two cases of diffuse large B-cell lymphoma (DLBCL) with composite germinal center B-cell (GCB) and non-GCB types. Case 1 was a 72-year-old woman with inguinal lymph node swelling. Two morphologically different lesions were concurrently observed in needle biopsy specimens. One lesion was DLBCL with centroblastic morphology and a GCB phenotype (CD10+, BCL6+, and MUM1-), according to the Hans algorithm. The other lesion was DLBCL with anaplastic morphology and a non-GCB phenotype (CD10-, BCL6+, and MUM1+). Considering cellular atypia, the GCB-type DLBCL likely progressed to non-GCB-type DLBCL. Case 2 was a 34-year-old man who underwent ileocecal resection, with four lesions observed in the ileum. All four lesions indicated centroblastic morphology. Three lesions showed a GCB phenotype (CD10+, BCL6+, and MUM1+), while the other showed a non-GCB phenotype (CD10-, BCL6+, and MUM1+). These tumors were clonally related. BCL2 expression and MYC rearrangement were not related to changes in the cell of origin (COO) in either case. In conclusion, changes in the COO in DLBCL may not be uncommon. Therefore, investigation of the COO in other sites or at relapse may be needed if new drugs with different indications for each COO are developed.

Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation.

Patients with recurrent peripheral T-cell lymphoma (PTCL) after allogeneic hematopoietic cell transplantation (HCT) have dismal outcomes. Nodal PTCL with the T follicular helper phenotype (PTCL-TFH) is uniquely sensitive to histone deacetylase inhibitors compared to non-TFH phenotypes. We report the case of a 19-year-old man who experienced recurrence of PTCL-TFH shortly after allogeneic HCT and subsequently achieved durable remission with romidepsin. Before HCT, the patient had refractory disease after CHOP and ESHAP chemotherapies but achieved a partial response after two cycles of romidepsin as salvage treatment. HLA-haploidentical peripheral blood stem cell transplantation was performed using conditioning with fludarabine 180 mg/sqm, melphalan 80 mg/sqm, and total body irradiation 2 Gy, and graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide. One month after HCT, disease progression was observed in the lung. Romidepsin was readministered every 2 weeks at a reduced dose of 12 mg/sqm. After two cycles of romidepsin, the patient achieved a complete metabolic response without severe GVHD or other non-hematological toxicities. Romidepsin was discontinued after seven treatment cycles due to prolonged lymphopenia. The patient remains in complete remission 30 months after the last dose of romidepsin. Our experience suggests that romidepsin could be safely administered soon after allogeneic transplantation.

Diagnostic clues of BCL2-negative, faint, or controversial follicular lymphomas: a study of 103 cases.

BCL2 positivity by immunohistochemistry is helpful for the diagnosis of follicular lymphoma (FL); however, a minority of FL cases are BCL2-negative, and the diagnosis is thus challenging. We retrospectively analyzed the incidence, morphology, immunophenotype, and genetic status of BCL21+ (weakly/focally positive by clone 124), BCL20 (negative), and BCL2controversial FLs compared with BCL22+ (strongly positive) FLs to clarify diagnostic clues. In 1068 FL cases, 103 (10%) with BCL21+ (37 cases, 4%), BCL20 (61 cases, 6%), or BCL2controversial (5 cases, 0.5%) were included in the final analysis. BCL21+ and BCL20 FLs tended to have limited stage disease, nodal disease, and grades 3A/3B histology and showed a higher complete response rate than BCL22+ FLs. Among 103 BCL20, BCL21+, or BCL2controversial FL cases, 34 (33%) had a diffuse area composed of CD20-positive small-to medium-sized lymphoid cells, a feature of low-grade B-cell lymphoma. Interfollicular dense CD20-positive cells and interfollicular clusters of CD10-positive cells were observed in 59% and 37% of cases, respectively. In remaining 13/40 cases (33%), BCL2 was converted to BCL22+ by other clones E17/SP66. CD23 and MUM1 were positive in 10/40 (25%) and 1/40 (3%) cases, respectively. IGH/BCL2 fusion and clonality were detected in 6/37 (16%) and 31/34 (91%) cases, respectively. In conclusion, morphological examination of the distribution of CD20-and/or CD10-positive cells and the presence of diffuse area could be used to diagnose FL in most cases. The majority of the remaining FL cases could be diagnosed using other BCL2 clones and clonality analyses.