Suguru Fukuhara

Bulky disease has an impact on outcomes in primary diffuse large B-cell lymphoma of the breast: A retrospective analysis at a single institution

Objectives: Primary breast lymphoma (PBL) is rare, and its clinical behavior and standard initial treatment are not yet established. Methods: We retrospectively analyzed the clinicopathological features and treatment outcomes of 14 patients with primary breast diffuse large B‐cell lymphoma. Results: There were nine patients with stage IE and five with stage IIE disease. The median largest tumor diameter was 4.5 cm, and five patients had bulky disease >5 cm. The complete response rate was 94%. However, the 5‐year progression‐free survival rate was 52% with a median follow‐up of 5.2 years. Patients with bulky disease had an unfavorable prognosis. All five patients with bulky disease progressed or relapsed. Of the four patients that recurred in the central nervous system (CNS), three had bulky disease although some received rituximab. There were no CNS recurrences in the three patients who received CNS prophylaxis. All eight patients who responded to radiotherapy (RT) did not have recurrences in the ipsilateral breast, although one patient with bulky disease relapsed in the adjacent regional lymph nodes within the RT field despite immunochemotherapy. Conclusions: Patients with bulky disease had a poorer prognosis and recurred frequently in the CNS. CNS prophylaxis might yield better outcomes, but a larger, prospective trial is needed to elucidate the optimal initial treatment of PBL in the rituximab era.

Bcl-2, Bcl-6, and the International Prognostic Index are prognostic indicators in patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy.

This study aimed to clarify the clinicopathological prognostic parameters of de novo diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. We examined the correlation of 22 clinicopathological parameters with progression‐free survival (PFS), overall survival (OS), and primary refractory disease in 285 DLBCL patients treated with rituximab‐containing chemotherapy. Complete response rate was 87%, overall response rate was 91%, 5‐year PFS rate was 72%, and 5‐year OS rate was 91%. By log–rank test, higher International Prognostic Index (IPI) (P < 0.0001), Bcl‐2 positivity (P = 0.0013), Bcl‐6 negativity (P = 0.0112), and no irradiation (P = 0.0371) were significantly correlated with shorter PFS; higher IPI (P = 0.0107), starry sky pattern (P = 0.0466), and no irradiation (P = 0.0264) correlated with shorter OS. In multivariate analyses, higher IPI (P = 0.0006), Bcl‐2 positivity (P = 0.0015), and Bcl‐6 negativity (P = 0.04) were significantly correlated with shorter PFS; higher IPI (P = 0.0045) correlated with shorter OS. Bcl‐2 (P = 0.0029), Bcl‐6 (P = 0.002), and IPI (P < 0.0001) were significantly correlated with primary refractory disease. In conclusion, Bcl‐2 positivity, Bcl‐6 negativity, and higher IPI were indicators of shorter PFS and OS plus primary refractory disease in patients with DLBCL in the rituximab era.

Follow-up data of 10 patients with B-cell non-Hodgkin lymphoma with a CD20-negative phenotypic change after rituximab-containing therapy.

Recently, a CD20-negative phenotypic change in CD20-positive B-cell non-Hodgkin lymphoma (B-NHL) after rituximab therapy was described. We report the follow-up data of 10 B-NHL patients showing this change after rituximab therapy. Ten patients (4 men and 6 women; median age, 57 y) with B-NHL who were initially CD20 positive and became CD20 negative after rituximab therapy were analyzed. Clinicopathologic features, including clinical course, CD20 expression, and histopathology, were examined. CD20 expression in lymphoma cells was evaluated using immunohistochemistry and/or flow cytometry. Histopathologically, diagnosis at initial presentation was follicular lymphoma (FL) in 7 patients; diffuse large B-cell lymphoma in 1; and chronic lymphocytic leukemia in 2. Six patients (60%, 3 FL, 1 diffuse large B-cell lymphoma, and 2 chronic lymphocytic leukemia patients) showed continuous CD20 negativity until 24 months after the phenotypic change. Three patients (30%) with FL regained CD20 expression within 1 to 7 months after detection of the CD20 change. Two patients (20%) with FL, including 1 who regained CD20 expression, showed heterogenous CD20 expression with a CD20-negative low-grade component and a CD20-positive large cell component. The overall response rate to therapy before the CD20-negative change was 70%. We reported the follow-up data of 10 B-NHL patients with a CD20-negative phenotypic change associated with rituximab-containing therapy. The most common histologic phenotypes were continuous CD20 negativity, recovery of CD20 expression within 7 months, and heterogenous CD20 expression. As the changes in morphology and CD20 expression after rituximab therapy vary widely, careful follow-up and rebiopsy are recommended.

Prognostic implications of histologic grade and intensity of Bcl-2 expression in follicular lymphomas undergoing rituximab-containing therapy ☆

This study aimed to determine the correlations of 7 histopathologic prognostic indicators of follicular lymphoma (follicular lymphoma grade, CD10 expression, Bcl-2 expression, IGH/BCL2 fusion, diffuse area, fibrosis, and marginal zone differentiation) with progression-free survival, overall survival, and follicular lymphoma histologic grade in 255 follicular lymphoma patients who were treated with rituximab-containing therapy. The complete response, overall response, 6-year progression-free survival, and 6-year overall survival rates were 83%, 96%, 56%, and 97%, respectively. Patients with follicular lymphoma grades 3a and 3b showed 100% 6-year and 10-year overall survival, and progression-free survival did not significantly differ between patients with follicular lymphoma grade 3 and those with follicular lymphoma grades 1 and 2. The absence or presence of Bcl-2 expression and intensity of Bcl-2 expression were not significant prognostic indicators of progression-free survival and overall survival. Likewise, the presence of IGH/BCL2 fusion, diffuse area, fibrosis, and marginal zone differentiation were not significantly correlated with progression-free survival and overall survival. Follicular lymphoma grade 3 was correlated with nodal disease and negative or lower intensity of Bcl-2 expression, but not with age, stage, or IGH/BCL2 status. In the prerituximab era, grade 3 disease was reported to be associated with a poor prognosis; however, the opposite was true for patients treated with rituximab-containing therapy, regardless of their age or disease stage. Bcl-2 expression and marginal zone differentiation were not prognostic indicators in follicular lymphoma patients treated with rituximab-containing therapy.

Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma

Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma

Clinicopathological characteristics of follicular lymphoma with peripheral blood involvement.

Abstract This study aimed to indicate patient outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement (p = 0.021), but the overall survival was not different (p = 0.804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) (p = 0.004 and p = 0.0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out.

Clinicopathological features of histological transformation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue to diffuse large B-cell lymphoma: an analysis of 467 patients

This study analysed incidence, patient outcome, immunophenotype and prognostic factors of histological transformation (HT) from extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) to diffuse large B‐cell lymphoma (DLBCL) in 467 patients (median age, 61 years). The primary sites of MALT lymphoma were the stomach (43%), ocular adnexa (25%), lung (8%), systemic (8%) and other tissues (16%). HT occurred in 8% of MALT lymphomas. Risk of HT by 15 years was 5%: 4% in limited‐stage diseases (n = 385) and 16% in advanced‐stage diseases (n = 56) (P = 0·02). The median time to HT was 48 months (range, 4–139). Five‐year progression‐free survival (PFS) and overall survival (OS) rates after HT were 80% and 94%, respectively. Immunohistochemical results of DLBCL were as follows: germinal centre B‐cell (GCB)/non‐GCB, 37%/63%; CD10, 9%; BCL6, 59%; MUM1, 38%; MYC, 42%; BCL2, 35%; Ki67 ≥ 90%, 23%; and CD5, 3%. The majority (75%, 9/12) of GCB‐type DLBCLs exhibited CD10−, BCL6+ and MUM1− immunophenotypes; the remainder had CD10+ immunophenotypes. Multivariate analysis revealed that only advanced stage at HT was a significant adverse factor for PFS (P = 0·037). Thus, overall risk of HT was low and prognosis after HT was favourable; however, in advanced‐stage cases, risk of HT was relatively high and prognosis was unfavourable.

Histopathological Characteristics of Lymphomas in the Upper Aerodigestive Tract. A Single-Institute Study in Japan.

We analyzed the histopathological characteristics of lymphomas biopsied from the upper aerodigestive tract between 2000 and 2014 at the National Cancer Center Hospital in Japan. Of a total of 309 consecutive cases, the following incidences were observed: mature B-cell neoplasms, 77% (n = 239); mature T- and NK-cell neoplasms, 20% (n = 63); classical Hodgkin lymphomas, 0.7% (n = 2); and lymphoblastic lymphomas, 2% (n = 5). Lymphomas were most frequently (57%) detected in the oropharynx. The majority of cases (89%) were mature B-cell neoplasms (diffuse large B-cell lymphoma, 60%; follicular lymphoma, 10%), and 10% of cases were mature T-cell neoplasms. Six cases of plasma cell neoplasm (4 primary and 2 secondary involvement) and 2 cases of plasmablastic lymphoma in the upper aerodigestive tract were observed. Two out of 3 cases of extraosseous plasmacytoma with available biopsy material were positive for EBER1. All 3 patients received irradiation and achieved complete response; 1 had not relapsed after 17 months and the remaining 2 relapsed as plasma cell myeloma and solitary plasmacytoma of the bone. Of 47 extranodal NK/T-cell lymphoma, nasal-type cases in the upper aerodigestive tract, 38 (81%) were present in the sinonasal region and the remaining 9 (19%) were in the oropharynx (n = 4), nasopharynx (n = 3), and oral cavity (n = 2). In conclusion, since both primary lymphoma and secondary involvement of lymphoma are often diagnosed using biopsied materials from the upper aerodigestive tract, pathologists and hematologists should recognize the characteristics of lymphoma in this tissue.

Clinicopathological features of classical Hodgkin lymphoma in patients ≥40 years old, with special reference to composite cases

OBJECTIVE Classical Hodgkin lymphoma shows a peak incidence at 15-35 years, and a second peak in elderly patients; however, pathological characteristics of elderly patients with classical Hodgkin lymphoma have not been analyzed enough. METHODS In a total of 154 patients with classical Hodgkin lymphoma, we analyzed the clinicopathological characteristics of classical Hodgkin lymphoma patients aged ≥ 40 years old, with special reference to the incidence, histopathology and outcome of patients with composite classical Hodgkin lymphoma. RESULTS Of 154 patients with classical Hodgkin lymphoma, 50 (32%) were ≥ 40 years old. The 5-year progression-free and overall survival rates were 59 and 86%, respectively. Thirty-eight patients (76%) had non-composite classical Hodgkin lymphoma, 10 patients (20%) had composite (6 simultaneous and 4 consecutive) classical Hodgkin lymphoma and B-cell non-Hodgkin lymphoma and 2 patients (4%) had methotrexate-associated classical Hodgkin lymphoma. Of 10 patients with composite classical Hodgkin lymphoma, composite lymphomas were detected throughout the staging procedure of the upper gastrointestinal tract or bone marrow in 4 patients. Fluorescence in situ hybridization revealed that the composite lymphomas of 4, 1 and 5 patients were related, unrelated and of unknown correlation status, respectively. The treatments after the diagnosis of a classical Hodgkin lymphoma component varied, and three patients died of lymphoma. CONCLUSIONS We found that the incidence of composite classical Hodgkin lymphoma in patients ≥ 40 years old was 20%. Correct diagnosis and optimal treatment for patients with composite classical Hodgkin lymphoma and B-cell non-Hodgkin lymphoma is highly important in this patient population.

Expression pattern of PD-L1 and PD-L2 in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and gray zone lymphoma

We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B‐cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network.