There have been several attempts to improve treatment and outcome of patients with primary mediastinal B-cell lymphoma (PMBL) and Burkitt's lymphoma (BL). In recent years, chemotherapy dose intensification and the addition of rituximab have led to a remarkable progress and have developed into integral parts of treatment for both entities of lymphoma [1][2][3][4]. Here, we report our monocenter results of a highdose methotrexate based alternating regimen with rituximab (B-ALL/ NHL 2002 protocol) in 15 patients with PMBL and 28 patients with sporadic BL. Since the early 1980s, protocols of GMALL have been continuously adapted and in the meantime they have become reference treatment for BL and B-ALL in Germany. The latest changes comprised the additional use of rituximab, standardized G-CSF support, implementation of high-dose cytarabine, intrathecal triple therapy, and age-adjusted stratification. Furthermore, we additionally amended supportive care with palifermin as it reduced severity and prevalence of mucositis [5].Almost all patients responded to chemotherapy, leading to an overall response rate of 98% (PMBL 100%, 95% confidence interval (CI) 1.0-1.0; BL 96.4%, 95%CI 0.68-1.0). Complete remission (CR) was achieved in 83.8% (PMBL 80%, BL 85.7%), and the rate of partial remission (PR) was 14% (20% PMBL, BL 10.7%). On average, the individual best response to chemotherapy was achieved after 3.68 courses.After initial response, three patients (two BL, one PMBL) experienced a progression or relapse within 3, 5, and 10 months, respectively. Thus, 5-year progression-free survival (PFS) was 93.3% (95%CI 0.74-1.0) for patients with PMBL and 82.1% (95%CI 0.67-0.96) for BL. Five-year overall survival (OS) was 100% for PMBL and 94.1% (95%CI 0.83-1.0) for BL in the younger group, and 100% and 63.6% (95%CI 0.35-0.92), respectively, in patients >55 years (Fig. 1a,b). Regarding the BL group, two patients died from treatment-related sepsis, a 74-year-old woman discontinued therapy, and two progressed during salvage therapy.Postchemotherapy consolidation radiotherapy was performed in 66.7% in PMBL and in 10.7% in BL. A total of 93% of patients with PMBL and 100% of patients with BL received prophylactic intrathecal therapy.Overall response and survival rate of 100% of all patients in the PMBL subgroup was observed. Fietz et al. [6] already reported a CR rate of 73% and an OS of 80% at 8.6 years in a cohort of 15 patients with PMBL treated according a prior B-ALL protocol of the GMALL (without rituximab). Improved OS in our cohort may be explained by recent changes such as the additional use of rituximab or high-dose cytarabine. Additional use of rituximab had predominantly shown benefit in nonmethotrexate but not in methotrexate-containing regimens [3,4,[7][8][9]. Preliminary results of a current protocol by Hoelzer et al. [10] with 42 patients with PMBL showed an inferior CR rate of 69%, but a comparable 3-year OS of 90% in patients younger than 55 years and of 67% in the elderly group (>55 years). However, this difference c...
In situ follicular lymphoma (FL) has been acknowledged as a pathological and biological entity [1,2]. In situ FL might represent an early stage in the development of overt FL carrying the t(14;18) translocation [3]. The criteria to make a diagnosis of in situ FL include: normal follicle size with well defined mantle zones and no evidence of interfollicular infiltration. BCL2 and CD10 are required for the diagnosis. The expression of these two markers should be very strong (stronger than the mantle zone and reactive T-cells), and confined to the germinal centers (GCs) [3,4]. We here describe a case of an extranodal diffuse large B-cell lymphoma (DLBCL) clonally related to a synchronous in situ lymphoma, displaying immunophenotypic and genotypic features of FL [1,2,5].A 51-year-old man, admitted to Pordenone Hospital, presented with a 11-cm sized mass of the left iliac fossa, detected by CT studies, without lymphadenopathies. Multiple biopsies of the mass, of parietal peritoneum, and omentum showed a DLBCL with a GC B-cell-like phenotype (CD201, CD101, BCL61, MUM12, BCL21, CD32, CD52, Ki671 [90%]) (Fig. 1A). Staging procedures, including bone marrow biopsies, were negative. However, endoscopy biopsies of slightly elevated mucosal zones of the ileum revealed a lymphoma characterized by a B-cell population with immunoarchitectural features of in situ FL (CD201, CD101 strong, BCL61, MUM12, BCL21 strong, CD32, CD52, Ki671 [15%]). Morphologically, the lymphoma was exclusively localized to GCs of abnormal lymphoid follicles (Fig. 1B). The patient was then referred to CRO-Aviano, where previous histopathologic diagnoses were confirmed. After surgery, ab-extrinsic involvement of the colonic wall by DLBCL was found and Stage IVB disease was established. The patient is under treatment with rituximab-cyclophosphamide doxorubicin vincristine prednisone (R-CHOP) regimen.Molecular studies were performed in bioptic samples from ileal lymphoma and in bioptic and surgically removed samples from extranodal DLBCL mass. Polymerase chain reaction for immunoglobulin heavy chain (PCR IGH) clonality analysis showed identical monoclonal peaks in both lymphomas (Fig. 1C). BCL2 PCR analysis showed identical peaks for mcr region (Fig. 1C). Fluorescence in situ hybridization (FISH) analysis using split signal probes (Dakocytomation, Copenhagen, Denmark) confirmed the presence of BCL2 rearrangement in both lymphomas and revealed a minor clone [6] with BCL6 rearrangement in ileal lymphoma or in extranodal DLBCL, accounting for 4% and 14% of rearranged nuclei. No MYC rearrangement was observed. The chromosome assessment evaluated using BCL2 (Fig. 1D) and BCL6 regions was trisomic in both lymphomas.There are quite a few reports on in situ FL with associated FL and even DLBCL [7,8]. Recently, Bonzheim et al. reported the first description of an in situ FL clonally related to a synchronous overt FL where secondary genetic alterations were demonstrated, probably representing clonal evolution as sign of disease progression [9]. We report on a uniqu...
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