Cutaneous Marginal Zone B-cell Lymphoma Research Articles

Large Cells With CD30 Expression and Hodgkin-like Features in Primary Cutaneous Marginal Zone B-Cell Lymphoma: A Study of 13 Cases.

The presence of CD30 cells in cutaneous lymphomas has come to prominence in recent years as a potential diagnostic and therapeutic marker. In primary cutaneous marginal zone B-cell lymphomas, the presence of large CD30 cells with Hodgkin-like features and their significance have not yet been studied. Here we describe the main clinical, histologic, immunophenotypic, and molecular characteristics of 13 cases of primary cutaneous marginal zone lymphomas featuring >10% of CD30 large cells, and analyze their relationship with histologic and clinical progression of the disease and with other morphologic and immunophenotypic features. We report 10 male and 3 female patients, 4 with early-local disease and 8 with locoregional advanced disease without extracutaneous involvement but with a high relapse rate of 69%. We describe an association between a high level of CD30 expression and disease progression, with increased clinical recurrence in cases with >15% of CD30 cells. We also discuss the differential diagnosis with other cutaneous and systemic lymphomas, especially Hodgkin lymphoma.

064 - Large cells with CD30 expression and Hodgkin-like features in primary cutaneous marginal zone B-cell lymphoma: a study of 13 cases

064 - Large cells with CD30 expression and Hodgkin-like features in primary cutaneous marginal zone B-cell lymphoma: a study of 13 cases

Advances in primary cutaneous marginal zone B-cell lymphoma

Primary cutaneous marginal zone B-cell lymphoma (pcMZL) belongs to mucosa-associated lymphoid tissue (MALT) lymphoma, and is a subtype of indolent non-Hodgkin lymphoma. Chronic antigen stimulation and gene mutations are key-players in its pathogenesis. Biopsy and immunohistochemistry are gold-standard examination for the diagnosis and staging of pcMZL. The overall prognosis of patients is excellent. This review will illustrate the advances in pathogenesis, diagnosis, therapy and prognosis of pcMZL, aimed to raise the recognition and making choice of treatments for this disease. Key words: Lymphoma, B-cell, marginal zone; Antigens; Mutation; Therapeutics

SKIN B-CELL LYMPHOMAS: 20 YEARS EXPERIENCE IN OBSERVATION AND TREATMENT

Authors observed 18 patients with cutaneous B-cell lymphomas (B-CLS): primary cutaneous follicle center lymphoma (PCFCL) (44,45%), primary diffuse large B-cell lymphoma (B-CLL) (44,45%), cutaneous marginal zone B-cell lymphoma (CMZL) (11,1%). Features of cutaneous marginal zone B-cell lymphoma are: appearance of multiple spots; identification of diagnosis in stages T2aN0M0; treatment - excision or laser destruction; frequent recurrence do not affect prognosis. Features of primary cutaneous follicle center lymphoma are: appearance of single node; identification of diagnosis in stages T1aN0M0 and T2aN0M0; treatment - excision, can be also combined with radiotherapy. Features of primary diffuse B-CLL are: appearance of multiple spots; identification of diagnosis in stages T3bN0M0, T1aN1M0 and T2bN2M0; disease is aggressive; treatment is a local radiotherapy, interferon alpha intralesional, chemotherapy according to schemes CHOP, COP and R-CHOP, photodynamic therapy is possible.

Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

Abstract In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC) classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O). The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP).

Paediatric primary cutaneous marginal zone B-cell lymphoma: does it differ from its adult counterpart?

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) has rarely been reported in patients younger than 20 years. To report our experience with PCMZL in the paediatric/adolescent age group. Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were reviewed. The study group included 11 patients (six girls; median age 16 years, range 6-19·5); 10 had generalized/multifocal (T3) and one had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in six; two had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included nonradiation modalities: one patient with localized disease received intralesional steroids; six patients with multifocal disease received the following: topical/intralesional steroids (n = 3); excision (n = 2); 'watch and wait' (n = 1). No extracutaneous progression was noted during a median follow-up of 5·5 years (mean 7·5, range 0·5-14). At present, five patients are in complete remission. Based on our data (largest series in the literature with the longest follow-up), the clinicopathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to those in adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration.

Treatment of Primary Cutaneous Marginal Zone B-Cell Lymphomas with Intralesional Rituximab

BACKGROUNDPrimary cutaneous marginal zone B-cell lymphomas (PCMZL) are low-grade lymphomas with an indolent course, but with a high rate of skin relapses. Surgical excision, local radiotherapy, or combinations of both are the first-line treatment in solitary or localized disease. Therapeutic options in cases of multifocal disease or relapse, include steroids or intravenous Rituximab in monotherapy or in combination with intravenous or oral chemotherapy. The effectiveness of intralesional Rituximab (ILR) in primary cutaneous B-cell lymphomas has been described in a small multicenter series of patients.OBJECTIVETo evaluate the effectiveness and safety of ILR in patients with PCMZL.METHODSIn our center ILR is used since 2010 as fist-line treatment for patients with PCMZL with single facial lesions, multifocal disease that cannot be irradiated or in relapsed disease. The treatment regimen consist of a course of three injections of 10 mg (days 1, 3 and 5) in a single week at monthly intervals. Oral paracetamol and dexclorfeniramine were administrated 30 minutes before the procedure. Courses of ILR were monthly repeated until response or in cases of relapse. The primary outcome measure of the study was the rate of remissions (complete and partial remissions).RESULTSTwelve patients with PCMZL have been treated so far, 50% as first-line. The relapsed-group had previously received a median of 3 previous treatments (range, 1-6) including radiotherapy in 5 cases, surgery in 1 case, intravenous chemotherapy in 2 cases, and topic steroids in 2 cases. Clinical characteristics of the 12 patients are shown in the table below.A total of 42 courses of ILR have been completed. All patients responded: a complete therapeutic response was achieved in 10 patients, whereas a partial response was observed in 2. No cases of progression or relapse in the site of ILR treatment were documented.Four patients experienced transitory mild perilesional erythema that did not require medication and resolved in less than 4 hours. No cases of significant adverse events occurred and none of the patients suffered severe bacterial or opportunistic infections.CONCLUSIONSIn our preliminary experience, ILR is an effective and safe therapeutic approach for selected PCMZL patients with single facial lesion, multifocal disease than cannot be irradiated, or in relapsed cases. To date, this is the largest experience with ILR of a single center. [Display omitted] DisclosuresGonzalez Barca:Roche: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau.

Primary Cutaneous Marginal Zone B-Cell Lymphoma Presenting as a Small Mass on Temple Area.

Primary Cutaneous Marginal Zone B-Cell Lymphoma Presenting as a Small Mass on Temple Area.

Primary Cutaneous Marginal Zone B-Cell Lymphoma Treated with Intralesional Rituximab: Experience of a Single Center

BACKGROUNDPrimary cutaneous marginal zone B-cell lymphomas (PCMZL) are low-grade lymphomas with an indolent course, but with a high rate of skin relapses. Surgical excision, local radiotherapy, or combinations of both are the first-line treatment in solitary or localized disease. Therapeutic options in cases of multifocal disease or relapse, include steroids or intravenous Rituximab in monotherapy or in combination with intravenous or oral chemotherapy. The effectiveness of intralesional Rituximab (ILR) in primary cutaneous B-cell lymphomas has been described in a small multicenter series of patients.OBJECTIVETo evaluate the effectiveness and safety of ILR in patients with PCMZL.METHODSIn our center ILR is used since 2010 as fist-line treatment for patients with PCMZL with single facial lesions, multifocal disease that cannot be irradiated or in relapsed disease. The treatment regimen consist of a course of three injections of 10 mg ( days 1, 3 and 5) in a single week at monthly intervals. Oral paracetamol and dexclofeniramire were administrated 30 minutes before the procedure. Courses of ILR were monthly repeated until response or in cases of relapse. The primary outcome measure of the study was the rate of remissions (complete and partial remissions).RESULTSEleven patients with PCMZL have been treated so far: 55% as first-line treatment and 45% in the relapse setting. The relapsed-group had previously received a median of 3 previous treatments (range, 1-6) including radiotherapy in 5 cases, surgery in 1 case, intravenous chemotherapy in 2 cases, and topic steroids in 2 cases. Clinical characteristics of the 11 patients are shown in the table below.A total of 40 courses or ILR have been completed. All patients responded, with 73% complete responses, without evidence of progression or relapse in the site of ILR treatment.Four patients experienced transitory mild perilesional erythema that did not require medication and resolved in less than 4 hours. No systemic toxicities or infections were observed; the tolerance was excellent in all cases.CONCLUSIONSIn our preliminary experience, ILR is an effective and safe therapeutic approach for selected PCMZL patients with single facial lesion, multifocal disease than cannot be irradiated or in relapsed cases. Further controlled studies are needed to confirm these findings. [Display omitted] DisclosuresSureda:Takeda: Consultancy, Speakers Bureau.

Cutaneous primary B-cell lymphomas: from diagnosis to treatment.

Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. The most indolent forms comprise the primary cutaneous marginal zone and follicle center B-cell lymphomas that despite the excellent prognosis have cutaneous recurrences very commonly. The most aggressive forms include the primary cutaneous large B-cell lymphomas, consisting in two major groups: the leg type, with poor prognosis, and others, the latter representing a heterogeneous group of lymphomas from which specific entities are supposed to be individualized over time, such as intravascular large B-cell lymphomas. Treatment may include surgical excision, radiotherapy, antibiotics, corticosteroids, interferon, monoclonal antibodies and chemotherapy, depending on the type of lymphoma and on the type and location of the skin lesions. In subtypes with good prognosis is contraindicated overtreatment and in those associated with a worse prognosis the recommended therapy relies on CHOP-like regimens associated with rituximab, assisted or not with local radiotherapy. We review the primary cutaneous B-cell lymphomas, remembering the diagnostic criteria, differential diagnosis, classification, and prognostic factors and presenting the available therapies.

Primary Cutaneous B-Cell Lymphoma: Management and Patterns of Recurrence at the Multimodality Cutaneous Lymphoma Clinic of The Ohio State University.

The increasing incidence of primary cutaneous B-cell lymphomas (PCBCLs) presents new challenges for clinicians. Despite advances in the clinical and pathologic characterization of PCBCL, the significance of the current staging approach as a risk profiling tool and the effect of various treatments on outcome remain unclear. We retrospectively reviewed patients who presented with a diagnosis of PCBCL seen at The Ohio State University between 1998 and 2012. We reviewed the initial presentation and treatment modality. We then assessed whether the treatment modality (conservative skin-directed vs. definitive radiation with or without systemic therapy), stage (T1 or ≥T2), or histologic subtype (primary cutaneous follicle center lymphoma [PCFCL] vs. primary cutaneous marginal zone B-cell lymphoma [PCMZL]) affected the risk of recurrence. We identified 67 patients referred with an initial diagnosis of PCBCL. After imaging, 12 did not meet the criteria for PCBCL and were classified as having systemic B-cell lymphoma with cutaneous involvement. The remaining 55 patients included 25 with PCMZL, 24 with PCFCL, 2 with primary cutaneous large B-cell lymphoma leg type, and 4 with unclassifiable disease. According to the International Society of Cutaneous Lymphoma-European Organization for Research and Treatment of Cancer staging, 30 cases were T1 (55%), 14 T2 (25%), and 11 T3 (20%). Comparing the time to first recurrence (TFR) by indolent PCBCL subtypes, we found no difference in the recurrence risk for either stage (T1, p = .51 vs. T2/T3, p = .30). Comparing TFR by treatment modality, we found no difference in TFR within T1 patients (p = .34) or T2/T3 patients (p = .44). Our limited analysis highlights the importance of complete staging at diagnosis and suggests that the treatment modality does not affect the risk of recurrence in T1 indolent PCBCL.

Cutaneous marginal zone B-cell lymphoma with a biclonal population of B-lymphocytes

Cutaneous marginal zone B-cell lymphoma with a biclonal population of B-lymphocytes

シェーグレン症候群を合併した皮膚原発marginal zone B-cell lymphom of MALT typeの1例

シェーグレン症候群を合併した皮膚原発marginal zone B-cell lymphom of MALT typeの1例

Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma.

High Incidence of Gastrointestinal Tract Disorders and Autoimmunity in Primary Cutaneous Marginal Zone B-Cell Lymphomas

To our knowledge, this is the first comprehensive study addressing comorbidities associated with primary cutaneous marginal zone B-cell lymphomas (PCMZLs). To determine if patients with PCMZL were at risk for other medical conditions. Case-control study at a cutaneous lymphoma clinic and a dermatopathologic consultation service at a single academic institution using an extensive questionnaire of illnesses, symptoms, and environmental exposures for 80 sequential patients with PCMZL and 80 matched controls. The frequency of several morbidities was obtained in both groups from data gathered from the questionnaire and corroborated by reviewing medical records when available. We found a high incidence of past or present gastrointestinal tract problems in 49 patients (61.2%) with PCMZL compared with 30 participants (37.5%) in the control group (CG) (P = .003). Gastroesophageal reflux was reported in 50.0% (40 vs 27 in the CG, P = .04) and gastric ulcers in 10.0% (8 vs 3 in the CG, P = .13); 20.0% of the cohort had positive Helicobacter pylori serology (16 vs 2 in the CG, P = .003). Colon disorders, including irritable bowel syndrome and inflammatory bowel disease, were more common in the PCMZL cohort (20 vs 7 in the CG, P = .01). Autoimmunity was reported in 20.0% of participants (16 vs 6 in the CG, P = .03). Eight patients had a history of Hashimoto thyroiditis. Three patients had a positive antinuclear antibody. Two had a diagnosis of lupus erythematosus and 1 had Sjögren syndrome. Sicca syndrome was noted in 12.5% (10 vs 3 in the CG, P = .052). A history of noncutaneous malignant neoplasms was observed in 21.3% of the patients (17 vs 8 in the CG, P = .050). Other notable morbidities did not reach statistical significance. Our results indicate a high incidence of systemic conditions in patients with PCMZL, especially involving the gastrointestinal tract, but also autoimmunity and cancer.

A case of coexistent cutaneous marginal zone B-cell lymphoma and peripheral T-cell lymphoma

A case of coexistent cutaneous marginal zone B-cell lymphoma and peripheral T-cell lymphoma

Recent advances in primary cutaneous B-cell lymphomas

In the last decade, there has been considerable debate regarding the classification and terminology of the group of primary cutaneous B-cell lymphomas (CBCLs). With the introduction of the WHO-EORTC classification for cutaneous lymphomas, three main types of CBCLs are recognized: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCLBCL, LT). Epidemiological studies performed on different patient cohorts showed that the CBCL entities described in the WHO-EORTC classification and the 4th WHO classification of tumours of haematopoietic and lymphoid tissues are reproducible worldwide and are clinically relevant, thereby illustrating the clinical usefulness of the WHO-EORTC classification. Furthermore, collaborative studies between the ISCL and EORTC lymphoma group resulted in recommended staging procedures and consensus treatment recommendations for different CBCL subtypes. The advances in the classification, staging procedures and treatment of CBCLs have led to a major improvement in clinical care. The progress in CBCL classification enables molecular studies on well defined groups of patients and facilitates comparison of treatment results between different centres. Recent studies found that intralesional/intravenous rituximab has a therapeutic value in PCFCL and PCMZL with widespread cutaneous lesions and suggest that therapies targeting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway could be helpful in DLBCL, LT.

Cutaneous marginal zone B-cell lymphoma with high IgA expression and IgA+ dutcher bodies: a case report

Cutaneous marginal zone B-cell lymphoma (cuMZL) is an indolent lymphoma with dermal nodular or diffuse lymphoid infiltrate consisting of small B cells varying from centrocyte-like, mono-cytoid, lymphoplasmacytoid and plasma cells. The Dutcher bodies (DB) were found in 20%. 1 Immunohistochemistry (IHC) or in situ hybridization (ISH) detected light chain restriction in 78% and IGH PCR detected clonality in 46%. 2 Distinguishing cutaneous reactive from neoplastic B-cell lymphoid infiltrate can be difficult. The elderly male presented with violaceous to hyperpigmented plaques at back and cheek which had progressed over five years. Skin biopsies from both sites showed nodular small lymphoid infiltrates with prominent plasma cells and rare DB. The small lymphoid cells were mixture of lymphoplasmacytoid and few monocytoid cells. They were positive for CD20 and CD79a, and negative for CD5, CD10, CD23 and cyclin D1. Plasma cells expressed polytypic light chain immunoglobulin (kappa:lambda = 3:1 by IHC and 2:1 by ISH) with increased IgA expression (IgG:IgA:IgM=8:5:

In-Depth miRNA Profiling Of Germinal Center Derived B-Cell Lymphomas By Next Generation Sequencing: A Report From The German Icgc-Mmml-Seq Project

The discovery of microRNAs (miRNAs), a group of small non-coding regulatory RNAs, revolutionized the field of posttranscriptional gene regulation. Mature miRNAs are single-stranded RNA molecules of 20- to 23-nucleotide length that control gene expression. They typically reduce the translation and stability of mRNAs important in tumorigenesis mediating processes such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion.Germinal center (GC) derived B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), are the most frequent malignant lymphomas. Although clear distinctions on histologic and genetic grounds exist, there is also a large number of cases with intermediate features, not unequivocally attributable to one of these entities.Recently, a signature of 38 miRNAs containing MYC regulated and nuclear factor-kB pathway-associated miRNAs was published, which differentiated BL from DLBCL. However, available data is preliminary as published profiles are not derived from large sample collections and also originate mostly from PCR-based approaches and microarrays. Yet, only sequencing-based approaches allow for an unbiased analysis and the discovery of novel miRNAs and small RNA classes.The ICGC (International Cancer Genome Consortium)-MMML-Seq (Molecular Mechanisms in Malignant Lymphoma by Sequencing) Consortium aims at fully characterizing a total of 250 GC derived B-cell lymphomas over a period of five years. We here report the miRNA analysis of the first 49 patient samples including BL, DLBCL and FL using Illumina technology. We are recording the classical miRNA fraction (18-35 nucleotides) as well as a larger size fraction (35-90 nucleotides).Initial differential expression analyses comparing BL against non-BL showed eight miRNAs to be differentially expressed. This comprises hsa-miR-150, which has been ascribed a role in the adaptive immune response and which was shown to be upregulated in cutaneous marginal zone B-cell lymphomas. Further differentially expressed miRNAs include e.g. hsa-miR-211, hsa-miR-548ac and hsa-miR-1244-1/3, which represent novel targets in lymphomagenesis.Among the many bioinformatically predicted novel miRNAs, we have been able to validate four candidates by Northern Blot experiments and are currently performing functional studies.Mutational analysis is ongoing, but so far has yielded two miRNAs with mutations in the mature sequences (hsa-miR-4537, hsa-miR-758).In conclusion, our initial series of 49 cases from the ICGC-MMML-Seq cohort has already given exciting insights into the role of miRNAs in GC derived B-cell lymphomas. (Supported by BMBF through 01KU1002A-J) Disclosures:No relevant conflicts of interest to declare.

Is Bone Marrow Biopsy Always Indicated in Patients With Primary Cutaneous Marginal Zone B-Cell Lymphoma?

Bone marrow involvement at the time of diagnosis is uncommon in patients with primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these patients such involvement is rarely found in isolation on diagnosis. Typically the few patients with PCMZL who have early bone marrow involvement also present secondary nodal or visceral involvement, which is detected by other staging studies (usually computed tomography). In recent years, this has given rise to some debate about whether a bone marrow biopsy should be routinely performed in patients diagnosed with PCMZL in view of the good prognosis and low incidence of bone marrow infiltration and/or extracutaneous involvement in this type of lymphoma.