Cutaneous B-cell Lymphoma Research Articles

No evidence of Borrelia in cutaneous infiltrates of B-cell lymphomas with a highly sensitive, semi-nested real-time polymerase chain reaction targeting the 5S-23S intergenic spacer region.

The role of Borrelia in the development of skin lymphomas has been under discussion for decades. A similar association has been shown for Helicobacter pylori and gastric lymphomas (MALT type). Nevertheless, few molecular studies investigated Borrelia in skin lymphomas and the results are controversial. We analysed 46 formalin-fixed, paraffin-embedded skin specimens of clincopathologically confirmed B-cell lymphomas (15 marginal zone lymphomas; 20 follicular lymphomas; three diffuse large B-cell lymphomas; eight secondary cutaneous infiltrates) taken from 36 patients from Northern Germany, an endemic area for Borrelia. Fifteen pseudolymphomatous lesions of cutaneous Borreliosis served as the control. Both groups were examined with a real-time (rt) PCR and a semi-nested PCR targeting the 5S-23S intergenic spacer region (IGS). A multiplex PCR was used to investigate B-cell clonality in all lymphomatous infiltrates (Biomed Primers). With both assays no Borrelia burgdorferi-specific DNA was identified in any of the B-cell lymphomas, while all 15 Borreliosis specimens gave a positive PCR result in the semi-nested PCR protocol, 12 were also positive in the rt PCR (P < 0.01). All B-cell lymphomas showed monoclonal IgH-Rearrangement. Analysis of cutaneous B-cell lymphomas from available studies including ours (n = 334) reveals an odds ratio <1. While some previous studies suggested an association between B. burgdorferi and the development of cutaneous B-cell lymphomas in endemic areas, we were unable to confirm this in our patients, despite a highly sensitive Borrelia PCR assay. Our results including meta-analysis of previous studies question the need for antibiotic therapy in patients with cutaneous B-cell lymphomas.

Primary cutaneous lymphoma: the 2018 update of the WHO-EORTC classification

Primary cutaneous lymphomas are a heterogeneous group of cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL) that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. In the last decade the 2005 WHO-EORTC consensus classification has served as a golden standard for the diagnosis and classification of these conditions. Recently, an updated version of the WHO-EORTC was published. This classification contains several new entities, including primary cutaneous acral CD8+ T-cell lymphoma and EBV-positive mucocutaneous ulcer, while other conditions were slightly modified. Herein, the characteristic features of the different types of CTCL and CBCL are presented, differences with previous classification schemes discussed and the results of more recent molecular studies with clinical implications for these conditions reviewed. In addition, an update of the frequency and survival of the different types of primary cutaneous lymphomas is provided.

A Rare Case of Primary Cutaneous Follicle Center Lymphoma Mimicking Leprosy

Cutaneous B-Cell Lymphoma is a rare type of cutaneous lymphoma with a plethora of clinical manifestations ranging from macules, papules, nodules, or plaques. The lesions are often painless and certain subtypes such as the primary cutaneous follicle center lymphoma (PCFCL) are indolent. The disease is often misdiagnosed with other dermatoses including bacterial and fungal infections. Here we report a 55-year-old female patient with clinical manifestations resembling multibacillary leprosy that was then confirmed to be PCFCL through aid of dermoscopy and histopathology. The patient then undergone chemotherapy using the R-CHOP regiment which resulted in significant clinical improvement and no signs of metastases or extracutaneous involvement upon follow-up.

Immunohistochemical algorithms and gene expression profiling in primary cutaneous B-cell lymphoma

Objectiveto assess whether immunohistochemical (IHC) algorithms used to classify the cell of origin (COO) of nodal Diffuse Large B-cell lymphoma (nDLBCL) in Germinal Center type (GCB) and non-GCB subtypes may be applied to Primary Cutaneous B-cell lymphoma (PCBCL) too, and which of these algorithms performs better on PCBCL. DesignRetrospective case control study. SettingPathology Department of the University Hospital “San Giovanni di Dio e Ruggi d′Aragona” Salerno, Italy. ParticipantsFourteen PCBCL, including Primary Cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous diffuse large B-cell lymphoma, Leg type (PCDLBCL-LT) and 14 nDLBCL were evaluated for 7-year period (January 2011 to December 2017). Primary cutaneous marginal zone cell lymphoma (PCMZL) cases were not included in the present study. InterventionEvaluation of immunohistochemical CD10, BCL6, MUM1/IRF4, BCL2, MYC and Ki-67 expression and classification according to three different algorithms. Gene expression profiling (GEP) was performed on the same series using Lymph2Cx assay (Nanostring). The data obtained were compared and analysed. ResultsAll the IHC algorithms showed 13 GCB and 15 non-GCB. GEP showed 12 GCB, 12 activated B cell–type and 4 unclassified. ConclusionsThe PCBCL were classifiable as GCB and non-GCB like the nDLBCL as IHC algorithms were concordant to GEP and produced the same results.

Pediatric Cutaneous Hematologic Disorders: Cutaneous Lymphoma and Leukemia Cutis-Experience of a Tertiary-Care Pediatric Institution and Review of the Literature.

Cutaneous hematologic malignancies are rare in children, and the literature about them is still sparse. The purpose of our study was to report our experience with pediatric cases of cutaneous hematologic disorders and describe their clinical and histological features. Data were retrospectively collected from the histopathologic database of the CHU Sainte-Justine, University of Montreal, Montreal, Canada. All patients up to 18 years of age with a diagnosis of a primary cutaneous lymphoma (including lymphomatoid papulosis), secondary cutaneous lymphoma or cutaneous manifestations of leukemia, followed from 1980 to 2019 at our center were reviewed. Thirty-six patients were included. Age at presentation ranged from birth to 18 years of age (mean 7.83 ± 5.16; median 7.0). Ten different hematologic disorders were identified according to the WHO-EORTC classifications: lymphomatoid papulosis (10 cases), mycosis fungoides (6 cases), anaplastic large cell lymphoma (4 cases), pre-B acute lymphoid leukemia (5 cases), primary cutaneous marginal zone B-cell lymphoma (4 cases), primary cutaneous CD4+medium T-cell lymphoproliferative disorder (1 case), extranodal NK/T-cell lymphoma (1 case), hydroa vacciniforme-like lymphoproliferative disorder (1 case), B-cell lymphoblastic lymphoma (1 case) and acute myeloid leukemia (3 cases). The most common subtype of cutaneous hematologic disease in our single institution study was lymphomatoid papulosis (type A and type C), followed by mycosis fungoides. Recognition of this large clinical and histological spectrum by dermatologists is important because diagnosis is often established by biopsy of skin lesions, even in secondary cutaneous cases. Moreover, the clinicopathological correlation is of utmost importance for the final diagnosis of those pathologies.

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.

Yellow Plugs: An Additional Dermoscopic Criterion in the Diagnosis of Primary Cutaneous B-Cell Lymphoma.

Citation: Conforti C, Giuffrida R, Dri A, Zalaudek I, Di Meo N. Yellow plugs: an additional dermoscopic criterion in the diagnosis of primary cutaneous b-cell lymphoma. Dermatol Pract Concept. 2022;12(1):e2022006. DOI: https://doi.org/10.5826/dpc.1201a06

Use of Ultrasensitive RNA In Situ Hybridization for Determining Clonality in Cutaneous B-Cell Lymphomas and Lymphoid Hyperplasia Decreases Subsequent Use of Molecular Testing and Is Cost-effective.

Primary cutaneous B-cell lymphomas (PCBCLs) are diagnostically challenging entities due to significant overlap in clinical and morphologic features with reactive lymphoid proliferations. Traditional methods for evaluating clonality such as immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) are limited by low sensitivity, which leads to additional costly and time-consuming molecular clonality assays. More recent technology has introduced ultrasensitive bright-field RNA in situ hybridization (BRISH) to the field, which can detect single molecules of light-chain mRNA. The current study evaluated 274 cases of PCBCL in addition to atypical and reactive lymphoid infiltrates, with CISH or BRISH performed on 180 (65.7%). CISH was performed on 105 (58.3%), and BRISH was performed on 75 (41.7%). Significantly fewer immunoglobulin heavy-chain (IGH) rearrangement studies were performed on cases that were evaluated with BRISH as compared with CISH (P=0.02). Subgroup analysis demonstrated that cases with restriction by BRISH were significantly less likely to have subsequent IGH studies performed (P=0.01). The expected costs of cases using CISH versus BRISH were $1053.89 versus $810.32 to the patient and $245.63 versus $225.23 to the laboratory. The use of ultrasensitive BRISH to evaluate clonality in PCBCL reduced the use of IGH rearrangement studies when compared with CISH. In particular, cases with light-chain restriction by BRISH did not result in confirmatory molecular testing. Despite slightly higher costs to the laboratory to perform BRISH, routine use of this methodology can result in cost savings to both the patient and laboratory by decreasing the use of expensive molecular methods.

Asymptomatic, reddish-brown papules and plaques in an elderly Japanese woman

Asymptomatic, reddish-brown papules and plaques in an elderly Japanese woman

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.

Cutaneous B-cell lymphomas: Update on diagnosis, risk-stratification, and management

PCBCLs are a group of Non-Hodgkin's B-cell lymphomas originating in and usually confined to the skin, representing approximately one fourth of primary cutaneous lymphomas (PCL). Their current classification system has been the result of the joint World Health Organization (WHO) - European Organization for Research and Treatment of Cancer (EORTC) consensus in 2018. To date, several types of PCBCLs have been described in the scientific literature, with different clinical presentation and prognosis. Primary cutaneous follicle-center lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) are the most common forms, with a typical indolent course. On the contrary, primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is less common, yet more aggressive, with a reported 5-year overall survival of approximatively 50%. In this review, we outline the PCBCLs defining diagnostic criteria, report the features of the less common subtypes and summarize the noteworthy therapeutical options currently available in this field.

Prognostic significance of Bcl-2 expression in primary cutaneous B-cell lymphoma: a reappraisal.

Bcl-2 family protein plays an important role in apoptosis and its overexpression is protects neoplastic cell from apoptotic stimuli. Cutaneous B-cell lymphoma are rare non-Hodgkin lymphomas and can be classified in primary forms, featuring an exclusive skin-involvement at diagnosis, and cutaneous spread of a nodal disease. Such a distinction is not trivial, owing to different prognosis (indolent vs. aggressive) and therapeutic management. Bcl-2 expression at immunohistochemistry can be crucial in differential diagnosis between cutaneous and systemic disease, as well as between the different primary cutaneous forms. In the last few years, an animated debate on the prognostic role of Bcl-2 overexpression at molecular analysis have been developed in cutaneous B-cell lymphoma. To conclude, Bcl-2 expression have a diagnostic role more than prognostic in primary cutaneous B-cell lymphomas.

Clinicopathological Spectrum of Cutaneous Lymphomas and Distinction of Early Mycosis Fungoides from its Mimics-A Retro-Prospective Descriptive Study from Southern India.

Cutaneous lymphomas (CLs) could be either primary (PCL) or secondary; the former comprises cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs). Mycosis fungoides (MF) is the most common PCL. Diagnosis of early MF and distinguishing it from benign inflammatory mimics is challenging. This study aims to assess the clinicopathological spectrum of CL and to characterize early MF from its mimics using clinical characteristics, histopathological features, and ancillary techniques. This retro-prospective descriptive study was conducted in a tertiary-care institute, for over 5 years. Clinically as well as histopathologically suspected and biopsy-proven CL and their mimics were included. Cases were reviewed and subgrouped based on clinical and histopathological parameters and immunohistochemistry (IHC). Data were analyzed using descriptive statistics and a Chi-square test at a 5% level of significance. Among PCL, CTCL comprised 84% (21/25) and CBCL was 16% (4/25); the most common CTCL was MF at 81% (17/21). Histologically, atypia of dermal infiltrate (100%), epidermotropism (91.7%), basal alignment of lymphocytes (91.7%), clear haloed cells (91.7%), wiry collagen (66.7%), grandiosity sign (50%), eccrine infiltration (66.7%), and follicular infiltration (50%) were significantly associated with early MF. Spongiosis (84.6%), pigment incontinence (84.6%), exocytosis (76.9%), and parakeratosis (76.9%) were significantly associated with inflammatory mimics. There was no significant difference in the downregulation pattern of CD7 (P = 0.206) between early MF and its mimics. The four cases of CBCL in our study were plasmablastic lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and lymphoblastic lymphoma. MF was the most common PCL. Histological parameters showed a significant difference, whereas IHC did not show any significant difference between early MF and its mimics.

Hardbound indurated plaque and nodules with “m band”: A report of secondary cutaneous diffuse large b-cell lymphoma

Hardbound indurated plaque and nodules with “m band”: A report of secondary cutaneous diffuse large b-cell lymphoma

Exclusive surgical treatment of a primary cutaneous marginal zone lymphoma: a case report

Primary cutaneous B-cell lymphomas are non-Hodgkin lymphomas presenting only in the skin and represent 25% of all primary cutaneous lymphomas. Based on their clinical behavior, they are classified into indolent and intermediate forms. Treatment of indolent forms includes surgery, radiotherapy, and, in extensive disease, rituximab. We report a case of a 57-year-old woman with a single nodule in the left arm treated with surgical excision with 5-mm security margins, without relapse after 36 months. Surgery is a therapeutic option in these lymphomas without compromising disease-free survival.

Non-Hodgkin’s Lymphoma: A Case Report

Introduction: Hodgkin's and non-lymphomas Hodgkin's are malignant tumours of lymphoid tissue. Non-lymphomas Hodgkin's are a type of lymphoid tissue cancers that arise from T or B cells or their progenitors, and can be indolent or aggressive. B-cell lymphomas account for around 80% of all cases in the United States. Chronic lymphocytic leukaemia or small lymphocytic lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and primary cutaneous B-cell lymphoma are all examples of Non-Hodgkin's Lymphoma. Non-Lymphoma Hodgkin's is the sixth most prevalent malignancy in the United States, with incidence rates nearly doubling in the last 35 years. With each decade of life, the incidence rises; the median age upon diagnosis is 66. In India, the incidence rates in urban regions are many times higher than in rural areas, with the incidence being higher in metropolitan cities and among Indian immigrants, implying that urban lifestyles and economic advancement may boost cancer incidence. In 2010, NHL was projected to have caused roughly 0.36 million new cases and 0.19 million deaths.&#x0D; Case Presentation: A male patient of Two and half years from Shiwangaon MO, was admitted to Paediatric Ward, AVBRH on 31st May, 2021 with a known case of Non-Hodgkin Lymphoma which was diagnosed itself at AVBRH on 31st May,2021. My patient was brought with a chief complain of swelling in the testicular region for 6 days. As narrated by the patient’s father, my patient was apparently alright 6 months back and then patient develop swelling in temporal region suddenly, associated with pain on touch, as the swelling develops more and uncomfortable, patient was brought immediately to AVBRH and was admitted in Paediatric Ward for further investigation.

Differential survival of systemic B-cell lymphomas initially diagnosed in the skin: a population-based study of 883 patients.

Although the majority of lymphomas are diagnosed in lymph nodes, bone marrow, or other viscera, initial diagnosis of systemic lymphomas in the skin is a rare but important occurrence in dermatology. This study seeks to quantify the incidence of initial skin presentation in patients with systemic B-cell lymphomas (BCL) via examination of data in the Surveillance, Epidemiology, and End Results (SEER)-18 database; cases of primary cutaneous B-cell lymphoma were excluded. We found that aninitial diagnosis of lymphoma in the skin is a very rare occurrence for systemic B-cell lymphomas, comprising < 0.3% of cases overall. Follicular lymphoma was the most likely to be diagnosed in the skin (1.47%), followed by marginal zone lymphoma (MZL, 0.5%), mantle cell lymphoma (0.4%), diffuse large B-cell lymphoma (DLBCL, 0.23%), Burkitt lymphoma (0.23%), Hodgkin lymphoma (0.04%), and chronic lymphocytic leukemia (0.006%). While indolent systemic lymphomas (MZL and FL) presenting initially in the skin have a better prognosis than those presenting at other sites, the more aggressive systemic DLBCL presenting in the skin does not demonstrate improved prognosis.

Clinical Outcomes and CNS Relapse Risk in Patients with Primary Cutaneous DLBCL, Leg Type Treated in the Rituximab Era: Long-Term Follow-up of a Single-Center Experience

Clinical Outcomes and CNS Relapse Risk in Patients with Primary Cutaneous DLBCL, Leg Type Treated in the Rituximab Era: Long-Term Follow-up of a Single-Center Experience

Diffuse Large B-cell Lymphoma in Bilateral Lower Extremities

Diffuse large B-cell lymphoma, leg type, is a rare variant of primary cutaneous B-cell lymphomas. It typically presents as rapidly enlarging solitary or multiple violaceous nodules on the lower extremities. Even with adequate treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, recurrence and systemic spread is common. Timely treatment is necessary as this malignancy is associated with a more aggressive course than other variants of primary cutaneous B-cell lymphomas and overall prognosis is poor.

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

Introduction/BackgroundCutaneous 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 MethodsA 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. ResultspcMZL 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. ConclusionsAll 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.