Primary Cutaneous Diffuse Large B-cell Lymphoma Successfully Treated With R-CHOP Chemotherapy.

Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) represent approximately 10%-20% of primary cutaneous B-cell lymphomas. They present as nodules in the skin or as rapidly growing aggressive behavior tumors with a poor prognosis. In this article, we report a case of PCDLBCL presented with an aggressively enlarging skin lesion on the right cheek. This case was diagnosed based on clinicopathological features and characteristic immunohistochemical expression. During the 11-month follow-up period, the patient showed significant clinical improvement after undergoing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, abbreviated as R-CHOP chemotherapy, without evidence of extracutaneous dissemination or disease relapse.

Prolonged Complete Response with Lenalidomide in a Relapsed Diffuse Large B-Cell Lymphoma, Leg-Type: A Case Report.

INTRODUCTION: For primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT), there are no uniform recommendations for second-line treatment in case of relapse. CASE PRESENTATION: Here, we present the case of an elderly relapsed/refractory PCDLBCL-LT patient who obtained a prolonged clinical complete remission with lenalidomide. CONCLUSION: Lenalidomide as single agent led to an unexpected long complete response with manageable toxicity.

Primary Cutaneous B-Cell Lymphoma in a Young Female.

Primary cutaneous lymphomas are a group of lymphomas that originate in the skin at the time of diagnosis. We report a case of a 45-year-old female who presented with cutaneous lesions that were unresponsive to conservative management. A biopsy was performed, which was consistent with primary cutaneous B-cell lymphoma. She received four cycles of chemotherapy and her end-of-treatment positron emission tomography (PET)-computed tomography (CT) scan showed a complete metabolic response.

F-18 FDG PET/CT in staging and response assessment of primary cutaneous diffuse large B-cell lymphoma (leg type).

Primary cutaneous Diffuse Large B-Cell Lymphoma-leg type (PCDLBCL-LT) is a rare subtype of cutaneous lymphomas, with high frequency of extra-cutaneous relapse and poor prognosis. We report a case of 70-year-old lady who was diagnosed with PCDLBCL-LT on biopsy and underwent a baseline F-18 FDG PET/CT, followed by interim and post-treatment PET/CTs. With this case report, we highlight the findings of F-18 FDG PET/CT in the staging of this cutaneous lymphoma, and also emphasize on its role in the response assessment.

Case report: Cryoablation as a novel bridging strategy prior to CAR-T cell therapy for B cell malignancies with bulky disease.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a powerful immunotherapy in relapsed/refractory (R/R) hematological malignancies, especially in R/R B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). To prevent disease progression and reduce tumor burden during CAR-T cell manufacturing, bridging therapies prior to CAR-T cell infusion are crucial. At present, it has been demonstrated that targeted therapy, radiotherapy and autologous stem cell transplantation (ASCT) could serve as effective bridging strategies. However, whether cryoablation could serve as a novel bridging strategy is unknown. In this paper, we report 2 cases of R/R B cell malignancies with bulky disease that were successfully treated with a combination of cryoablation and CAR-T cell therapy. Patient 1 was a 65-year-old female who was diagnosed with R/R MM with extramedullary disease (EMD). She was enrolled in the anti-BCMA CAR-T cell clinical trial. Patient 2 was a 70-year-old man who presented with a subcutaneous mass in the right anterior thigh and was diagnosed with primary cutaneous diffuse large B cell lymphoma, leg type (PCLBCL-LT) 1 year ago. He failed multiline chemotherapies as well as radiotherapy. Thus, he requested anti-CD19 CAR-T cell therapy. Unfortunately, they all experienced local progression during CAR-T cell manufacturing. To rapidly achieve local tumor control and reduce tumor burden, they both received cryoablation as a bridging therapy. Patient 1 achieved a very good partial response (VGPR) 1 month after CAR-T cell infusion, and patient 2 achieved a partial response (PR) 1 month after CAR-T cell infusion. In addition, adverse effects were tolerable and manageable. Our study demonstrated the favorable safety and efficacy of combination therapy with cryoablation and CAR-T cell therapy for the first time, and it also indicates that cryoablation could serve as a novel therapeutic strategy for local tumor control in B cell malignancies.

A Practical Review of the Presentation, Diagnosis, and Management of Cutaneous B-Cell Lymphomas.

This review of cutaneous B-cell lymphoma (CBCL) is focused on the clinical presentation, treatment, and workup of each type of lymphoma. Part 1 is an overview of each of the CBCLs, including clinical presentation, recent advances in the pathobiology, and evidence regarding treatment strategies. Part 2 is a detailed guide to the steps in diagnosis and workup of a newly diagnosed CBCL according to the International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer and NCCN guidelines.

Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients.

Primary cutaneous diffuse large B-cell lymphoma after total knee arthroplasty: a case study and a systematic review of its cutaneous manifestations and treatment options.

Introduction: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) after total knee arthroplasty (TKA) is rare. Aim: The literature that analyses the cutaneous manifestations of PCDLBCL and assesses the effect and the outcome of treatment is scarce. Material and methods: We described a case of PCDLBCL after TKA, whose cutaneous mass develops around surgical sites, mimicking a prosthetic joint infection. In addition, we conducted a systematic review of 29 reported cases with PCDLBCL. Primary endpoint for the review was main cutaneous manifestations of PCDLBCL. Secondary endpoint included treatment options of PCDLBCL and optimal therapeutic method. Results: We found that the main cutaneous manifestations include infiltrative cutaneous lesions such as macules, papules or nodules, some of them presented as ulcerations or formation of vesicles, subcutaneous nodules or both. The treatment options include excision, radiotherapy, chemotherapy, and even "watchful waiting" as spontaneous regression was noted in some cases. Systemic chemotherapy is the most frequent initial treatment approach chosen, of which rituximab is often combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy and patients who received systemic rituximab tend to have a better overall survival (OS) time than those who did not. Conclusions: PCDLBCL is a rare disease after TKA, however, an early recognition and distinguishing from infection is still needed. Patients with PCDLBCL may profit from rituximab-based chemotherapy, increasing the survival rate, despite the high relapse rate and limited OS time in some cases.

Germinal Centre-Related Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type: Report of a Remission Case.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LTs) is a rare and the most aggressive type of the cutaneous B-cell lymphoma with poor prognosis and low therapeutic response. It mostly affects elderly women, with a 5-year survival rate of 50% if not efficiently treated. We present a 28-year-old male patient with indolent PCDLBCL-LT who reached nearly 100% clearance after six rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy sessions.

Radiotherapy as a Treatment Option for Local Disease Control in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is an aggressive lymphoma variant. Anthracycline-based chemotherapy with rituximab is recommended as first-line treatment. Radiotherapy (RT) has been considered as a therapeutic option for local disease control in patients with solitary or localized lesions. METHODS: We report the results of a retrospective analysis of PCDLBC, LT patients treated either with RT alone or with physician's decision as first-line treatment, aiming to assess disease progression and/or first recurrence in these treatment groups. RESULTS: We retrospectively analyzed 20 patients treated either with RT alone (n = 8) or with investigator's choice treatment (n = 12), which included chemotherapy alone or combined with local therapy (RT and wide local excision). Complete response (CR) was achieved in 8 patients from the first group and 9 patients from the second group, with 1 treatment failure. Six patients treated with RT alone progressed with a median time to progression (TTP) of 12.5 months. In the second group, 5 patients progressed with a median TTP of 5.2 months. RT showed good local disease control in both groups without any skin relapses during the follow-up period. CONCLUSION: RT as first-line monotherapy followed by watchful waiting did not significantly improve the overall risk of disease progression but resulted in good local disease control. After progression, RT could still easily be combined with systemic treatment. The strength of this analysis needs to be evaluated in a larger patient cohort.

Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

Characterization of Primary and Secondary Cutaneous B-Cell Lymphomas: A Population-Based Study of 4758 Patients.

INTRODUCTION/BACKGROUND: Cutaneous B-cell lymphomas are a heterogeneous group of rare malignancies whose specific site tropisms and site-specific survival have not been well documented. In this study, we seek to investigate the frequency and survival for primary and secondary cutaneous MZL (pcMZL and scMZL), primary and secondary cutaneous FCL (pcFCL and scFCL), and primary and secondary cutaneous DLBCL (pcDLBCL and scDLBCL) to better understanding their prognosis and natural history. MATERIALS AND METHODS: A total of 4758 cases of CBCL diagnosed between 1975 and 2016 were identified in the SEER-18 database. Statistical analysis was performed to identify the frequency of location and survival. RESULTS: pcMZL was disproportionately likely to present on the face and upper limb while those of scMZL approximated the expected ratios based on body surface area. pcFCL and scFCL were more likely to present on the face and scalp/neck. pcDLBCL and scDLBCL were more likely to present on the face, scalp/neck, and lower limb. Patients with systemic MZL or FCL, but not DLBCL, had significantly better survival than those diagnosed in the skin than at other sites. CONCLUSIONS: All of these lymphomas demonstrate site-specific tropisms and survival. Molecular characterization of cutaneous lymphomas with analyses of tumor microenvironment are the next steps in understanding disease biology.

Double expressor and double/triple hit status among primary cutaneous diffuse large B-cell lymphoma: a comparison between leg type and not otherwise specified subtypes.

Primary cutaneous diffuse large B-cell lymphomas (pcDLBCLs) are rare hematological neoplasms. The pcDLBCL category includes primary cutaneous large B-cell lymphoma leg type (pcDLBCL-LT), characterized by a particularly unfavorable outcome, and primary cutaneous large B-cell lymphoma not otherwise specified (pcDLBCL-NOS), a widely debated subentity with a more indolent course. The negative prognostic impact of double expressor status (DE status, given by coexpression of MYC and BCL2) and double hit/triple hit status (DH/TH status, given by translocations of MYC and BCL2 and/or BCL6) in nodal DLBCL is well known; however, no unanimous conclusions regarding relevance of DE and DH/TH status have been reached in pcDLBCL. Therefore, our purpose has been to investigate the presence and prognostic relevance of DE and DH/TH status among a retrospective multicentric cohort of 16 cases of pcDLBCL-LT and 17 cases of pcDLBCL-NOS. All cases were thoroughly reevaluated, both on a morphological and immunohistochemical level, and tested by means of fluorescence in situ hybridization for MYC, BCL2 and BCL6 rearrangements. DE status was observed in 69% of pcDLBCL-LT cases and in 24% of pcDLBCL-NOS cases; however, it did not impact prognosis in any of the groups examined. Combining molecular results, we highlighted a relevant fraction of DH pcDLBCL cases (three pcDLBCL-LT cases and one pcDLBCL-NOS case) and the very first case of TH pcDLBCL-LT reported to date. All DH cases were characterized by MYC and BCL6 rearrangements. Overall, DH/TH cases represented 15% (5/33) of all pcDLBCLs and were mostly pcDLBCL-LT. DH/TH status and DH status alone were associated with poorer overall survival and disease-specific survival (both p < 0.05) among all pcDLBCLs, without reaching statistical significance in the pcDLBCL-LT and pcDLBCL-NOS groups. In conclusion, MYC, BCL2, and BCL6 cytogenetical testing could be useful in identifying a putative subset of more aggressive pcDLBCLs, although this observation has to be confirmed by further studies.

Primary cutaneous diffuse large B-cell lymphoma, leg type, in a patient with rheumatoid arthritis undergoing etanercept therapy.

An 84-year-old woman, who was diagnosed with rheumatoid arthritis (RA) and was treated with methotrexate and, subsequently, etanercept (ETN) for 6 years, presented with rapidly progressing painful cutaneous mass on the right medial malleolus. The patient was eventually diagnosed with primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT). ETN therapy was promptly discontinued expecting spontaneous regression of the lymphoma, which was thought to have developed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders. However, no tumour regression was noted. Chemoimmunotherapy was subsequently initiated, which resulted in partial remission. PCLBCL-LT rarely occurs in patients with RA. Here, we report the first case of PCLBCL-LT that developed in a patient with RA receiving ETN therapy.

Effectiveness of lenalidomide in relapsed primary cutaneous diffuse large B-cell lymphoma, leg type.

The primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) has a poor prognosis. R-CHOP with or without radiotherapy is the available recommendations for first-line treatment. Relapses/refractory cases are frequent with no standardized therapeutic guidelines. Lenalidomide seems to be an excellent therapeutic option as a second-line treatment of relapsed PCDLBCL-LT.

Primary cutaneous large B-cell lymphomas: relevance of the 2017 World Health Organization classification: clinicopathological and molecular analyses of 64 cases.

AIMS: We applied the 2017 World Health Organization (WHO) classification criteria to categorise a series of 64 primary cutaneous large B-cell lymphomas (PCLBCLs), containing a majority (≥80%) of large cells and a proliferative rate of ≥40%, raising the problem of the differential diagnosis between PCLBCL, leg type (PCLBCL-LT) and primary cutaneous follicle centre lymphoma, large cell (PCFCL-LC). The aims were to determine the reproducibility and prognostic relevance of the 2017 WHO criteria. METHODS AND RESULTS: Morphology and phenotype identified 32 PCLBCLs-LT and 25 PCFCLs-LC; seven cases (11%) remained unclassified. Morphology was less reproducible than immunophenotype. Pertinent markers for the differential diagnosis were MUM1, FOXP1, CD10, and IgM. bcl-2 and bcl-6 were expressed by both PCFCLs-LC and PCLBCLs-LT at substantial levels. Neither Ki67 expression nor p63 expression was of diagnostic value. MYD88 was found to be mutated only in PCLBCLs-LT (n = 22, 69%). According to Hans/Hans modified algorithms, 23 of 25 PCFCLs-LC had germinal centre (GC) status, and the 32 PCLBCLs-LT had non-GC status. Overall survival was poorer for PCLBCLs-LT than PCFCLs-LC (P = 0.0002). Non-GC cases had poorer overall survival than GC cases (P = 0.0007). In PCLBCLs-LT, MYC expression was associated with cutaneous relapses (P = 0.014). When GC/non-GC status was applied to unclassified cases, only a single case remained discordant. CONCLUSIONS: Our results support the 2017 WHO classification criteria for PCLBCL diagnosis. The Hans modified algorithm using CD10 and MUM1 distinguished PCFCLs-LC from PCLBCLs-LT with optimal diagnostic value without requiring bcl-6 immunolabelling (poorly reproducible). Rare unclassified cases may constitute a provisionally heterogeneous subgroup for which GC/non-GC status (relevant for prognosis) may guide therapeutic decisions.