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Barbati ZR, Charli-Joseph Y. Unveiling Primary Cutaneous B-Cell Lymphomas: New Insights into Diagnosis and Treatment Strategies. Cancers (Basel) 2025; 17:1202. [PMID: 40227781 PMCID: PMC11987940 DOI: 10.3390/cancers17071202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/23/2025] [Accepted: 03/26/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND/OBJECTIVES Primary cutaneous B-cell lymphomas (PCBCL) are a rare and heterogeneous group of non-Hodgkin lymphomas that are confined to the skin at diagnosis and exhibit a tendency for cutaneous recurrence. The 5th edition of the World Health Organization and the 2022 International Consensus Classification recognize three main subtypes: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma/lymphoproliferative disorder (PCMZL/LPD), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT). These subtypes differ in clinical behavior, histopathologic features, immunophenotype, and molecular alterations. Diagnosis and management remain challenging for clinicians. This review aims to provide a comprehensive overview of the defining features and current treatment strategies for PCBCL. METHODS This narrative review synthesizes current literature on the clinical, morphologic, immunohistochemical, and molecular characteristics of PCBCL. It also evaluates the diagnostic utility of immunohistochemistry, gene expression profiling, and molecular assays, particularly in distinguishing primary cutaneous disease from secondary cutaneous involvement by systemic lymphomas. RESULTS PCFCL arises from germinal center B-cells and must be differentiated from nodal follicular lymphoma. PCMZL/LPD is derived from post-germinal center B-cells and is often linked to chronic antigenic stimulation. Both PCFCL and PCMZL/LPD are indolent and associated with favorable outcomes. By contrast, PCDLBCL,LT is an aggressive lymphoma characterized by genetic alterations activating the NF-κB pathway, commonly including mutations to MYD88 and CD79B. Treatment strategies vary by subtype, ranging from localized therapies for indolent lymphomas to systemic chemoimmunotherapy for aggressive PCBCL. Emerging therapies, such as Bruton tyrosine kinase inhibitors and immunoregulatory agents, are being investigated for relapsed/refractory disease. CONCLUSIONS PCBCL encompass distinct clinicopathologic entities with subtype-specific diagnostic and therapeutic considerations. While current management is guided by clinical behavior, significant knowledge gaps remain regarding the molecular mechanisms underlying skin tropism, immune evasion, and disease progression. Future research could focus on improving molecular characterization and developing personalized and immune-based therapies to enhance outcomes. This review consolidates current knowledge and highlights innovations aimed at advancing the diagnosis and treatment of PCBCL in clinical practice.
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Affiliation(s)
- Zachary R. Barbati
- Department of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, CA 94107, USA;
| | - Yann Charli-Joseph
- Dermatology and Dermatopathology Private Practice, Mexico City 01090, Mexico
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2
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Villasenor-Park J, Chung J, Kim EJ. Cutaneous B-Cell Lymphomas. Hematol Oncol Clin North Am 2024; 38:1111-1131. [PMID: 39048407 DOI: 10.1016/j.hoc.2024.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
Primary cutaneous B-cell lymphomas represent a type of non-Hodgkin's lymphoma of the skin without evidence of extracutaneous involvement at the time of diagnosis. According to the 2018 World Health Organization-the European Organization for Research and Treatment of Cancer classification, primary cutaneous B-cell lymphomas include primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, intravascular large B-cell lymphoma, and Epstein-Barr virus+ mucocutaneous ulcer (provisional). Herein, we provide a comprehensive review of the updated literature on these entities, including clinical presentation, histopathology, immunophenotype, molecular genetics, prognosis, and treatment.
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Affiliation(s)
- Jennifer Villasenor-Park
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Jina Chung
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, 2 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA
| | - Ellen J Kim
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard, Room 721, 7th floor, Philadelphia, PA 19104, USA.
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3
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Fattah YH, Liu SS, Susa J, Hanly A, Russo J, Karai LJ. Spindle Cell Lipoma With Florid Primary Follicular Lymphocytic Hyperplasia: A Novel Association With Potential Diagnostic Pitfalls. Am J Dermatopathol 2023; 45:563-566. [PMID: 37462206 DOI: 10.1097/dad.0000000000002483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
ABSTRACT Spindle cell lipoma (SCL) is a benign subcutaneous lipomatous neoplasm with a heterogeneous histologic appearance that varies greatly depending on the amount of fat, collagen, and myxoid stroma, which define the multiple subtypes of SCL, such as fat poor SCL, pseudoangiomatous SCL, and dendritic fibromyxolipoma. Cutaneous lymphoid hyperplasia is a spectrum of benign conditions characterized by reactive B-cell and T-cell cutaneous lymphocytic infiltrates. Cutaneous B-cell lymphoid hyperplasia is a heterogeneous group of non-neoplastic conditions that can be observed as reactive phenomena to infections, medications, allergens, or neoplasms and must be distinguished from cutaneous B-cell lymphomas. Here, we report a novel case of spindle cell lipoma, associated with B-cell primary lymphoid follicular hyperplasia, mixed within the tumor in a peculiar pattern, while discussing potential diagnostic pitfalls with low-grade B-cell lymphomas. This is the first report of such association in the literature.
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Affiliation(s)
- Yasmin H Fattah
- Department of Dermatology, Larkin Community Hospital, South Miami, FL
| | - Shuo S Liu
- Department of Dermatology, Larkin Community Hospital, South Miami, FL
| | - Joseph Susa
- Pro Path, Sonic Health Care USA, Dallas, TX; and
| | - Andrew Hanly
- Global Pathology, Sonic Health Care USA, Miami Lakes, FL
| | | | - Laszlo J Karai
- Global Pathology, Sonic Health Care USA, Miami Lakes, FL
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4
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Miyashiro D, Sanches JA. Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management. Front Oncol 2023; 13:1141108. [PMID: 37124514 PMCID: PMC10140754 DOI: 10.3389/fonc.2023.1141108] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic Alibert-Bazin MF, folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin, each with characteristic clinical presentation, histopathological findings, and distinct clinical behaviors. SS is an aggressive leukemic variant of cutaneous lymphoma, and it is characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by malignant cells. There is a wide range of dermatological manifestations of MF/SS, and prompt recognition is essential for early diagnosis. Skin biopsy for histopathology and immunohistochemical analysis is imperative to confirm the diagnosis of MF/SS. Histopathology may also provide information that may influence prognosis and treatment. Staging follows the TNMB system. Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase. Treatment is divided into skin-directed therapies (topical treatments, phototherapy, radiotherapy), and systemic therapies (biological response modifiers, targeted therapies, chemotherapy). Allogeneic bone marrow transplantation and extracorporeal photopheresis are other treatment modalities used in selected cases. This review discusses the main clinical characteristics, the histopathological/immunohistochemical findings, the staging system, and the therapeutic management of MF/SS.
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5
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Elmore SA, Rehg JE, Schoeb TR, Everitt JI, Bolon B. Pathologists' perspective on the study design, analysis, and interpretation of proliferative lesions in lifetime and prenatal rodent carcinogenicity bioassays of aspartame. Food Chem Toxicol 2022; 171:113504. [PMID: 36414169 DOI: 10.1016/j.fct.2022.113504] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/21/2022] [Accepted: 10/27/2022] [Indexed: 11/21/2022]
Abstract
Aspartame, an artificial sweetener commonly used as a sugar substitute, is currently authorized for use in more than 100 countries. Hundreds of studies, conducted in various countries dating back to the 1970s, have shown that aspartame is safe at real-world exposure levels. Furthermore, multiple human epidemiology studies have provided no indication that consumption of aspartame induces cancer. Given the continued controversy surrounding the Ramazzini Institute's (RI) studies suggesting that aspartame is a carcinogenic hazard in rodents and evaluation by the International Agency for Research on Cancer, this report aims to provide the perspective of experienced pathologists on publicly available pathology data regarding purported proliferative lesions in liver, lung, lymphoid organs, and mammary gland as well as their implications for human risk assessment as reported for three lifetime rodent carcinogenicity bioassays of aspartame conducted at the RI. In the authors' view, flaws in the design, methodology and reporting of the RI aspartame studies limit the utility of the data sets as evidence that this agent represents a carcinogenic hazard. Therefore, all three RI studies, and particularly the accuracy of their pathology diagnoses and interpretations, should be rigorously reviewed by qualified and experienced veterinary toxicologic pathologists in assessing aspartame's carcinogenic risk.
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Affiliation(s)
| | - Jerold E Rehg
- Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Trenton R Schoeb
- Department of Genetics and Animal Resources Program, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jeffrey I Everitt
- Department of Pathology, Duke University School of Medicine, Durham, NC, USA
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Craddock AP, Kane WJ, Raghavan SS, Williams ES, Gru AA, Gradecki SE. 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. Am J Surg Pathol 2022; 46:956-962. [PMID: 35067516 DOI: 10.1097/pas.0000000000001868] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
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.
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7
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Nakagawa Y, Hamada T, Takahashi T, Miyake T, Hirai Y, Iwatsuki K, Morizane S. Analysis of clonality in cutaneous B-cell lymphoma and B-cell pseudolymphoma using skin flow cytometry: Comparison of immunophenotyping and gene rearrangement studies. J Dermatol 2021; 49:246-252. [PMID: 34263482 DOI: 10.1111/1346-8138.16057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 06/18/2021] [Accepted: 06/19/2021] [Indexed: 01/13/2023]
Abstract
To identify clonal neoplastic cells in skin affected by B-cell lymphoma using skin flow cytometry (FCM) techniques, we investigated light-chain restriction using skin FCM with clonality assessed by polymerase chain reaction and light-chain restriction by in situ hybridization (ISH). We retrospectively analyzed 16 cases of B-cell lymphoma with cutaneous involvement: primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) (n = 7), DLBCL-not otherwise specified (DLBCL-NOS) (n = 6), primary cutaneous follicle center lymphoma (pcFCL) (n = 1), and follicular lymphoma (n = 2), as well as cutaneous B-cell pseudolymphoma (n = 9). Results of skin FCM light-chain restriction analyses were compared with immunoglobulin H (IgH) gene rearrangement and κ/λ ISH findings. Skin FCM detected light-chain restriction in 11 of 14 B-cell lymphoma patients but none of the B-cell pseudolymphoma patients. The sensitivity of skin FCM for distinguishing B-cell lymphoma and B-cell pseudolymphoma was 79%, and the specificity was 100%. Eleven of 13 B-cell lymphoma patients exhibited gene rearrangement (sensitivity 85%), whereas six of seven pseudolymphoma patients were negative (specificity 86%). ISH was positive in three of 16 B-cell lymphoma cases (sensitivity 19%) but none of the B-cell pseudolymphoma cases (specificity 100%). ISH sensitivity was 29% for pcDLBCL-LT, 17% for DLBCL-NOS, and 0% for pcFCL and follicular lymphoma. Skin FCM therefore appears to be more sensitive than ISH in detecting light-chain restriction in DLBCL and follicular lymphoma, and as sensitive as IgH gene rearrangement analysis in detecting clonality. Skin FCM is thus a promising diagnostic tool for identifying monoclonal neoplastic B-cell populations.
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Affiliation(s)
- Yuki Nakagawa
- Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Toshihisa Hamada
- Department of Dermatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Takahide Takahashi
- Division of Medical Support, Okayama University Hospital, Okayama, Japan
| | - Tomoko Miyake
- Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yoji Hirai
- Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Keiji Iwatsuki
- Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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8
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Hristov AC, Comfere NI, Vidal CI, Sundram U. Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates. J Cutan Pathol 2020; 47:1103-1110. [PMID: 32870521 DOI: 10.1111/cup.13858] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 08/04/2020] [Accepted: 08/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Atypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda immunohistochemistry (IHC) and in situ hybridization (ISH) in the evaluation of atypical cutaneous or mucosal lymphoid infiltrates. METHODS Relevant articles from 1967 to 2018 in the English language were identified and summarized. In the absence of larger studies, case series of n ≥ 3 were included. RESULTS Sixty-three articles assessing kappa and lambda IHC and/or ISH were identified. Most focused on marginal zone lymphomas. Other lymphomas included follicle center lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS). Non-neoplastic lesions included reactive lymphoid hyperplasia, cutaneous plasmacytosis, connective tissue disease, IgG4-related disease, acrodermatitis chronic atrophicans, Zoon balanitis, dermatitides, and infiltrates around epithelial dysplasias/neoplasias. CONCLUSION Kappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B-cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light-chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B-cell lymphoma with plasmacytic differentiation.
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Affiliation(s)
- Alexandra C Hristov
- Departments of Pathology and Dermatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Nneka I Comfere
- Department of Dermatology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Claudia I Vidal
- Dermatology Center of Southern Indiana, Bloomington, Indiana, USA
| | - Uma Sundram
- Department of Pathology, Oakland University William Beaumont School of Medicine and Beaumont Health Systems, Royal Oak, Michigan, USA
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9
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Ronchi A, Zito Marino F, Vitiello P, Caccavale S, Argenziano G, Crisci S, Franco R, Sica A. A case of primary cutaneous B-cell lymphoma with immature features in an old man. Diffuse large B-cell lymphoma with immature features or B-cell lymphoblastic lymphoma? J Cutan Pathol 2020; 48:535-540. [PMID: 32623764 DOI: 10.1111/cup.13795] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 06/24/2020] [Accepted: 07/01/2020] [Indexed: 12/22/2022]
Abstract
Primary cutaneous B-cell lymphomas are a heterogeneous group of lymphoid neoplasms primarily occurring in the skin. Although most cases are represented by primary cutaneous follicle center cell lymphoma, primary cutaneous marginal zone lymphoma and leg-type diffuse large B-cell lymphoma, other diffuse large B-cell lymphomas and B-cell lymphoblastic lymphoma may rarely present primarily in the skin. In this setting, the presence of histopathologic and immunohistochemical features of cellular immaturity is exceedingly rare and may represent a diagnostic challenge. We present the first case of a primary cutaneous diffuse large B-cell lymphoma characterized by diminished expression of CD45, expression of TdT and rearrangement of MYC gene. The differential diagnosis mainly included B-cell lymphoblastic lymphoma, and required the genetic analysis of heavy chain (IGH) gene rearrangements.
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Affiliation(s)
- Andrea Ronchi
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Federica Zito Marino
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Paola Vitiello
- Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Stefano Caccavale
- Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppe Argenziano
- Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Stefania Crisci
- Hematology-Oncology and Stem Cell Transplantation Unit, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Antonello Sica
- Oncology and Hematology Unit, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
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10
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Fratoni S, Zanelli M, Zizzo M, Sanguedolce F, Aimola V, Cerrone G, Ricci L, Filosa A, Martino G, Fara AM, Annessi V, Soriano A, Ascani S. The broad landscape of follicular lymphoma: Part II. Pathologica 2020; 112:79-92. [PMID: 32202535 PMCID: PMC7931560 DOI: 10.32074/1591-951x-6-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 01/16/2020] [Indexed: 12/15/2022] Open
Abstract
Follicular lymphoma is a neoplasm derived from follicle center B cells, typically both centrocytes and centroblasts, in variable proportions according to the lymphoma grading. The pattern of growth may be entirely follicular, follicular and diffuse and rarely completely diffuse. It represents the second most common non-Hodgkin lymphoma, after diffuse large B-cell lymphoma and it is the most common low-grade mature B-cell lymphoma in Western countries. In the majority of cases, follicular lymphoma is a nodal tumor, occurring in adults and is frequently associated with the translocation t(14;18)(q32;q21)/IGH-BCL2. However, in recent years the spectrum of follicular lymphoma has expanded and small subsets of follicular lymphoma, which differ from common follicular lymphoma, have been identified and included in the current 2017 WHO classification. The aim of our review is to describe the broad spectrum of follicular lymphoma, pointing out that the identification of distinct clinicopathological variants of follicular lymphoma is relevant for the patient outcomes and treatment.
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Affiliation(s)
- Stefano Fratoni
- Department of Anatomic Pathology, St. Eugenio Hospital of Rome, Rome, Italy
| | - Magda Zanelli
- Pathology Unit, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Maurizio Zizzo
- Surgical Oncology Unit, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy.,Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesca Sanguedolce
- Pathology Unit, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Foggia, Foggia, Italy
| | | | | | - Linda Ricci
- Pathology Unit, University of Siena, Siena, Italy
| | | | - Giovanni Martino
- Hematology Unit, CREO, Azienda Ospedaliera di Perugia, University of Perugia, Perugia, Italy
| | - Antonella Maria Fara
- Pathology Unit, Department of Medical, Surgical and Experimental Surgery, University of Sassari, Italy
| | - Valerio Annessi
- General Surgery Unit, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Guastalla, Reggio Emilia, Italy
| | - Alessandra Soriano
- Gastroenterology Unit, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Stefano Ascani
- Pathology Unit, Azienda Ospedaliera Santa Maria Terni, University of Perugia, Terni, Italy
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Abstract
CONTEXT.— Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma that is limited to the skin at diagnosis. It has a differential diagnosis that includes systemic/nodal follicular lymphoma secondarily involving the skin; primary cutaneous diffuse large B-cell lymphoma leg type; reactive lymphoid hyperplasia; and primary cutaneous marginal zone lymphoma. OBJECTIVE.— To review the clinical, morphologic, immunophenotypic, and genetic features of primary cutaneous follicle center lymphoma; its differential diagnosis; and the evidence that supports use of immunohistochemistry and genetic testing in the diagnosis and prognosis of this entity. DATA SOURCES.— Pertinent literature regarding cutaneous B-cell lymphomas is summarized and University of Michigan cases are used to highlight characteristics of primary cutaneous follicle center lymphoma. CONCLUSIONS.— Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma with distinctive features, although some cases may have elements that overlap with other lymphomas, complicating interpretation.
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Affiliation(s)
| | | | - Alexandra C Hristov
- From the Department of Pathology, University of Michigan Medical Center, Ann Arbor (Drs Skala and A. C. Hristov); the Department of Internal Medicine, Section of Radiation Oncology, Wright Patterson Air Force Base (Dr B. Hristov); and the Department of Dermatology, University of Michigan Medical Center (Dr A. C. Hristov)
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12
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13
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Abstract
B-cell lymphomas represent approximately 20% to 25% of primary cutaneous lymphomas. Within this group, most cases (>99%) are encompassed by 3 diagnostic entities: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type. In this article, the authors present clinical, histopathologic, immunophenotypic, and molecular features of each of these entities and briefly discuss the rarer intravascular large B-cell lymphoma.
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Affiliation(s)
- Charity B Hope
- Department of Pathology, UCSF Dermatopathology Section, University of California, San Francisco, 1701 Divisidero Street, Room 280, San Francisco, CA 94115, USA
| | - Laura B Pincus
- Department of Pathology, UCSF Dermatopathology Section, University of California, San Francisco, 1701 Divisidero Street, Room 280, San Francisco, CA 94115, USA; Department of Dermatology, UCSF Dermatopathology Section, University of California, San Francisco, 1701 Divisidero Street, Room 280, San Francisco, CA 94115, USA.
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14
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Comfere N, Sundram U, Hurley MY, Swick B. Views of dermatopathologists about clonality assays in the diagnosis of cutaneous T-cell and B-cell lymphoproliferative disorders. J Cutan Pathol 2017; 45:39-47. [DOI: 10.1111/cup.13072] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 09/01/2017] [Accepted: 10/26/2017] [Indexed: 12/11/2022]
Affiliation(s)
- Nneka Comfere
- Department of Dermatology and Laboratory Medicine and Pathology; Mayo Clinic; Rochester Minnesota
| | - Uma Sundram
- Department of Pathology; Oakland University William Beaumont School of Medicine and Beaumont Health Systems; Royal Oak Michigan
| | | | - Brian Swick
- Department of Dermatology; University of Iowa; Iowa City Iowa
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15
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Jeon YK, Yoon SO, Paik JH, Kim YA, Shin BK, Kim HJ, Cha HJ, Kim JE, Huh J, Ko YH, The Hematopathology Study Group of the Korean Society of Pathologists, The Molecular Pathology Study Group of Korean Society of Pathologists. Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives. J Pathol Transl Med 2017; 51:224-241. [PMID: 28535584 PMCID: PMC5445208 DOI: 10.4132/jptm.2017.04.09] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 04/09/2017] [Indexed: 12/13/2022] Open
Abstract
Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.
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Affiliation(s)
- Yoon Kyung Jeon
- Corresponding Author Yoon Kyung Jeon, MD, PhD Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-1347 Fax: +82-2-743-5530 E-mail:
| | - Sun Och Yoon
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Ho Paik
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young A Kim
- Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Bong Kyung Shin
- Department of Pathology, Korea University Guro Hospital, Korea University School of Medicine, Seoul, Korea
| | - Hyun-Jung Kim
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Hee Jeong Cha
- Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Ji Eun Kim
- Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Jooryung Huh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Hyeh Ko
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - The Hematopathology Study Group of the Korean Society of Pathologists
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Korea University Guro Hospital, Korea University School of Medicine, Seoul, Korea
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
- Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - The Molecular Pathology Study Group of Korean Society of Pathologists
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Korea University Guro Hospital, Korea University School of Medicine, Seoul, Korea
- Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea
- Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
Some cutaneous inflammatory disorders are typified by a predominant or exclusive localization in the dermis. They can be further subdivided by the principal cell types into lymphocytic, neutrophilic, and eosinophilic infiltrates, and mixtures of them are also seen in a proportion of cases. This review considers such conditions. Included among the lymphoid lesions are viral exanthems, pigmented purpuras, gyrate erythemas, polymorphous light eruption, lupus tumidus, and cutaneous lymphoid hyperplasia. Neutrophilic infiltrates are represented by infections, Sweet syndrome, pyoderma gangrenosum, and hidradenitis suppurativa, as well as a group of so-called "autoinflammatory" dermatitides comprising polymorphonuclear leukocytes. Eosinophil-dominated lesions include arthropod bite reactions, cutaneous parasitic infestations, the urticarial phase of bullous pemphigoid, Wells syndrome (eosinophilic cellulitis), hypereosinophilic syndrome, and Churg-Strauss disease. In other conditions, eosinophils are admixed with neutrophils in the corium, with or without small-vessel vasculitis. Exemplary disorders with those patterns include drug eruptions, chronic idiopathic urticaria, urticarial vasculitis, granuloma faciale, and Schnitzler syndrome (chronic urticarial with a monoclonal gammopathy).
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Affiliation(s)
- Mark R Wick
- Section of Dermatopathology, Division of Surgical Pathology & Cytopathology, University of Virginia Medical Center, Room 3020 University of Virginia Hospital, 1215 Lee Street, Charlottesville, VA 22908-0214, USA.
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17
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Application of Immunohistochemistry in Toxicologic Pathology of the Hematolymphoid System. IMMUNOPATHOLOGY IN TOXICOLOGY AND DRUG DEVELOPMENT 2017. [DOI: 10.1007/978-3-319-47377-2_10] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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18
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Hope CB, Pincus LB. Primary cutaneous B-cell lymphomas with large cell predominance-primary cutaneous follicle center lymphoma, diffuse large B-cell lymphoma, leg type and intravascular large B-cell lymphoma. Semin Diagn Pathol 2016; 34:85-98. [PMID: 28065463 DOI: 10.1053/j.semdp.2016.11.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In this review, we present clinical features and detailed histopathologic, immunologic, and molecular information regarding primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type which together represent two of the three most common types of primary cutaneous B-cell lymphoma recognized in the current WHO classification system.1,2 Overall, B-cell lymphomas represent 19-27% of primary cutaneous lymphomas in most large European and American studies3-6 and together, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type account for approximately 2/3 to ¾ of these cases.5,7-11 Both subtypes can contain a high content of large B-lymphocytes, although most cases of primary cutaneous follicle center lymphomas exhibit a range in cell size and cytology. Intravascular large B-cell lymphoma, a less commonly-encountered EBV-negative primary cutaneous B-cell lymphoma composed of large cells, will be more briefly discussed in this report as well.
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Affiliation(s)
- Charity B Hope
- Department of Pathology, University of California San Francisco, USA
| | - Laura B Pincus
- Department of Pathology, University of California San Francisco, USA; Department of Dermatology, University of California San Francisco, USA.
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19
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Charli-Joseph YV, Gatica-Torres M, Pincus LB. Approach to Cutaneous Lymphoid Infiltrates: When to Consider Lymphoma? Indian J Dermatol 2016; 61:351-74. [PMID: 27512181 PMCID: PMC4966394 DOI: 10.4103/0019-5154.185698] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cutaneous lymphoid infiltrates (CLIs) are common in routine dermatopathology. However, differentiating a reactive CLI from a malignant lymphocytic infiltrate is often a significant challenge since many inflammatory dermatoses can clinically and/or histopathologically mimic cutaneous lymphomas, coined pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs and the most common differential imitators of lymphoma is discussed herein based on six predominant morphologic and immunophenotypic, histopathologic patterns: (1) Superficial dermal T-cell infiltrates (2) superficial and deep dermal perivascular and/or nodular natural killer/T-cell infiltrates (3) pan-dermal diffuse T-cell infiltrates (4) panniculitic T-cell infiltrates (5) small cell predominant B-cell infiltrates, and (6) large-cell predominant B-cell infiltrates. Since no single histopathological feature is sufficient to discern between a benign and a malignant CLI, the overall balance of clinical, histopathological, immunophenotypic, and molecular features should be considered carefully to establish a diagnosis. Despite advances in ancillary studies such as immunohistochemistry and molecular clonality, these studies often display specificity and sensitivity limitations. Therefore, proper clinicopathological correlation still remains the gold standard for the precise diagnosis of CLIs.
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Affiliation(s)
- Yann Vincent Charli-Joseph
- Cutaneous Hematopathology Clinic, Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Michelle Gatica-Torres
- Cutaneous Hematopathology Clinic, Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Laura Beth Pincus
- Department of Dermatology and Pathology, University of California, San Francisco, United States of America
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20
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Lima M. Cutaneous primary B-cell lymphomas: from diagnosis to treatment. An Bras Dermatol 2016; 90:687-706. [PMID: 26560215 PMCID: PMC4631235 DOI: 10.1590/abd1806-4841.20153638] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2014] [Accepted: 06/05/2014] [Indexed: 12/19/2022] Open
Abstract
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.
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Affiliation(s)
- Margarida Lima
- Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal
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21
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Yilmaz F, Soyer N, Vural F. Primary cutaneous B cell lymphoma: Clinical features, diagnosis and treatment. World J Dermatol 2015; 4:50-56. [DOI: 10.5314/wjd.v4.i1.50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Revised: 12/18/2014] [Accepted: 01/12/2015] [Indexed: 02/06/2023] Open
Abstract
Primary cutaneous B cell lymphoma (PCBCL) is defined as B cell lymphomas that presents in the skin without any evidence of extra-cutaneous involvement at diagnosis. They are the second most common type of primary cutaneous lymphomas accounting for 25%-30%. Since the prognosis and treatment differ from systemic lymphomas involving the skin, differential diagnosis is very important. PCBCL is a heterogeneous group of disease comprising different B cell lymphomas with distinct treatment and prognosis. PCBCL is divided into 5 subclasses according to World Health Organization and European Organization of Research and Treatment of Cancer classification. Primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma are indolent forms and often confined to skin at presentation and during the course of the disease. But primary cutaneous diffuse large B cell lymphoma, leg type and intravascular large B cell lymphoma are more aggressive forms that may disseminate to extra-cutaneous tissues. There is not a treatment consensus since they are rare entities. Local therapies like radiotherapy, surgery or intralesional steroids are options for localized disease in indolent forms. More disseminated disease may be treated with a systemic therapy like single agent rituximab. However combination chemotherapies which are used in systemic lymphomas are also required for aggressive PCBCL. Although indolent forms have relatively better prognosis, early relapses and disseminated diseases are mostly observed in aggressive form with a consequent poor prognosis.
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