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Martínez-Banaclocha N, Martínez-Madueño F, Caballé B, Badia J, Blanes M, Bujanda DA, Calvo V, Gómez Codina J, Blanco CQ, Espinosa P, Lavernia J, Arroyo FRG, Risueño MG, Llorca C, Cumeras R, Pulla MP, Gumà J. A Descriptive Study of 103 Primary Cutaneous B-Cell Lymphomas: Clinical and Pathological Characteristics and Treatment from the Spanish Lymphoma Oncology Group (GOTEL). Cancers (Basel) 2024; 16:1034. [PMID: 38473391 PMCID: PMC10931196 DOI: 10.3390/cancers16051034] [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: 02/12/2024] [Revised: 02/29/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024] Open
Abstract
Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.
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Affiliation(s)
- Natividad Martínez-Banaclocha
- Medical Oncology Department, Hospital General Universitario Dr. Balmis, Institute for Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain
| | - Francisca Martínez-Madueño
- Southern Catalonia Institute of Oncology, Hospital Universitari Sant Joan de Reus, IISPV-URV-CERCA, 43204 Reus, Spain; (F.M.-M.); (B.C.); (J.B.); (R.C.); (J.G.)
| | - Berta Caballé
- Southern Catalonia Institute of Oncology, Hospital Universitari Sant Joan de Reus, IISPV-URV-CERCA, 43204 Reus, Spain; (F.M.-M.); (B.C.); (J.B.); (R.C.); (J.G.)
| | - Joan Badia
- Southern Catalonia Institute of Oncology, Hospital Universitari Sant Joan de Reus, IISPV-URV-CERCA, 43204 Reus, Spain; (F.M.-M.); (B.C.); (J.B.); (R.C.); (J.G.)
| | - Mar Blanes
- Dermatology Department, Hospital General Universitario Dr. Balmis, Institute for Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain;
| | - David Aguiar Bujanda
- Medical Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrin, 35010 Las Palmas de Gran Canaria, Spain;
| | - Virginia Calvo
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain; (V.C.); (M.P.P.)
| | - Jose Gómez Codina
- Medical Oncology Department, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain;
| | - Cristina Quero Blanco
- Medical Oncology Department, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain;
| | - Pablo Espinosa
- Dermatology Department, Hospital Infanta Cristina, 28981 Parla, Spain;
| | - Javier Lavernia
- Medical Oncology Department, Fundación Instituto Valenciano de Oncología (I.V.O.), 46009 Valencia, Spain;
| | | | - María Guirado Risueño
- Medical Oncology Department, Hospital General Universitario de Elche, 03203 Alicante, Spain;
| | - Cristina Llorca
- Medical Oncology Department, Hospital General Universitario de Elda, 03600 Alicante, Spain;
| | - Raquel Cumeras
- Southern Catalonia Institute of Oncology, Hospital Universitari Sant Joan de Reus, IISPV-URV-CERCA, 43204 Reus, Spain; (F.M.-M.); (B.C.); (J.B.); (R.C.); (J.G.)
| | - Mariano Provencio Pulla
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain; (V.C.); (M.P.P.)
| | - Josep Gumà
- Southern Catalonia Institute of Oncology, Hospital Universitari Sant Joan de Reus, IISPV-URV-CERCA, 43204 Reus, Spain; (F.M.-M.); (B.C.); (J.B.); (R.C.); (J.G.)
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Gómez Arias PJ, Vázquez Díaz S, Rothenberg Lausell C, Sanz Zorrilla A, Baleato Gómez B. Clinical Features, Epidemiology, Management and Prognosis of Patients With Primary Cutaneous Marginal Zone Lymphoma: An Observational Study. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:T106-T109. [PMID: 37838228 DOI: 10.1016/j.ad.2022.10.056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/28/2022] [Accepted: 10/09/2022] [Indexed: 10/16/2023] Open
Affiliation(s)
- P J Gómez Arias
- UGC de Dermatología y Venereología, Hospital Universitario Reina Sofía, Córdoba, España.
| | - S Vázquez Díaz
- UGC de Hematología y Hemoterapia, Hospital Universitario Juan Ramón Jiménez, Huelva, España
| | | | - A Sanz Zorrilla
- UGC de Anatomía Patológica, Hospital Universitario Reina Sofía, Córdoba, España
| | - B Baleato Gómez
- UGC de Dermatología y Venereología, Hospital Universitario Reina Sofía, Córdoba, España
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3
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Gómez Arias PJ, Vázquez Díaz S, Rothenberg Lausell C, Sanz Zorrilla A, Baleato Gómez B. Clinical Features, Epidemiology, Management and Prognosis of Patients With Primary Cutaneous Marginal Zone Lymphoma: An Observational Study. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:106-109. [PMID: 37683801 DOI: 10.1016/j.ad.2022.10.054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/28/2022] [Accepted: 10/09/2022] [Indexed: 09/10/2023] Open
Affiliation(s)
- P J Gómez Arias
- Dermatology & Venereology Department, Reina Sofía Universitary Hospital, Córdoba, Spain.
| | - S Vázquez Díaz
- Hematology & Hemotherapy Department, Juan Ramón Jiménez Universitary Hospital, Huelva, Spain
| | | | - A Sanz Zorrilla
- Pathologist Pathology Department, Reina Sofía Universitary Hospital, Córdoba, Spain
| | - B Baleato Gómez
- Dermatology & Venereology Department, Reina Sofía Universitary Hospital, Córdoba, Spain
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4
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Hristov AC, Tejasvi T, Wilcox RA. Cutaneous B-cell lymphomas: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol 2023; 98:1326-1332. [PMID: 37434388 DOI: 10.1002/ajh.26968] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 07/13/2023]
Abstract
DISEASE OVERVIEW Approximately one-fourth of primary cutaneous lymphomas are B-cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). DIAGNOSIS Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B-cell lymphomas from systemic B-cell lymphomas with secondary skin involvement. RISK-STRATIFICATION Disease histopathology remains the most important prognostic determinant in primary cutaneous B-cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5-year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis. RISK-ADAPTED THERAPY PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
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Affiliation(s)
- Alexandra C Hristov
- Departments of Pathology and Dermatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Trilokraj Tejasvi
- Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ryan A Wilcox
- Division of Hematology/Oncology, University of Michigan Cancer Center, Ann Arbor, Michigan, USA
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Treatment of Indolent Cutaneous B-Cell Lymphoma with Intralesional or Intravenous Rituximab. Cancers (Basel) 2022; 14:cancers14194787. [PMID: 36230709 PMCID: PMC9564090 DOI: 10.3390/cancers14194787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Cutaneous B-cell lymphomas (CBCL) are a heterogeneous group of mature B-cells neoplasms that present in the skin without evidence of nodal or systemic involvement. Despite being indolent in nature, they tend to recur in a third of patients after treatment. As repetitive treatments may be necessary for patients with CBCL, there is a need for gentle non-invasive therapy. Rituximab is a medication that targets CD20, a receptor regularly expressed on CBCL, and thereby destroys the cancerous cells. This medication can be given as an infusion into the vein or as an injection directly into the skin tumors. In this study, we found that rituximab injections have a similar efficacy compared to infusions for patients with limited CBCL lesions. Abstract Indolent cutaneous B-cell lymphomas (CBCL) are a rare disease for which the therapeutic recommendations are based on clinical reports. Recommendations for solitary lesions include surgery or irradiation. However, the high relapse rates may require less invasive repeatable therapy. This study seeks to retrospectively assess the efficacy of intralesional rituximab (ILR) for indolent CBCL when compared with intravenous rituximab (IVR). Patients treated for indolent CBCL with ILR or IVR at the Division of DermatoOncology of the University Hospital Heidelberg were eligible for this study. Characteristics of lymphoma, treatment response, and adverse events were assessed. Twenty-one patients, 67% male at a median age of 52 (range 17–80), were included. Nineteen (90%) had only localized lymphoma (stage T1 and T2). Complete response was achieved in 92% (11/12) of ILR after a median of one cycle (three injections) and 78% (7/8) of IVR patients after a median of six cycles. Half of ILR patients and 78% of IVR patients showed relapse after a median of 15 and 23 months, respectively. Adverse reactions were usually mild and were limited to the first injection of ILR. One patient with IVR contracted a pulmonary infection. ILR may be an alternative to the intravenous administration of rituximab for localized indolent CBCL.
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6
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Krenitsky A, Klager S, Hatch L, Sarriera-Lazaro C, Chen PL, Seminario-Vidal L. Update in Diagnosis and Management of Primary Cutaneous B-Cell Lymphomas. Am J Clin Dermatol 2022; 23:689-706. [PMID: 35854102 DOI: 10.1007/s40257-022-00704-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2022] [Indexed: 02/05/2023]
Abstract
Primary cutaneous lymphomas are a rare group of diseases, with an estimated incidence of 0.5-1 case per 100,000 people per year. Primary cutaneous B-cell lymphomas (pCBCLs) represent 25-30% of all primary cutaneous lymphomas. There are three main subtypes of pCBCL: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type. Cutaneous B-cell lymphomas have a broad spectrum of clinical presentations, which makes diagnostic and therapeutic strategies challenging. To date, treatment recommendations for cutaneous B-cell lymphomas have been largely based on small retrospective studies and institutional experience. Recently, the pharmacotherapeutic landscape has expanded to include drugs that may modify the underlying disease pathology of pCBCLs, representing new therapeutic modalities for this rare group of diseases. Novel therapies used for other systemic B-cell lymphomas show promise for the treatment of pCBCLs and are being increasingly considered. These new therapies are divided into five main groups: monoclonal antibodies, immune checkpoint inhibitors, small-molecule inhibitors, bispecific T-cell engaging, and chimeric antigen receptor T cell. In this review, we discuss the clinical, histopathological, molecular, and cytogenetic features of the most common pCBCL subtypes with a focus on current and innovative therapeutic developments in their management. These emerging treatment strategies for B-cell lymphomas and cutaneous B-cell lymphomas may represent novel first-line options for the management of these rare diseases.
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Affiliation(s)
- Amanda Krenitsky
- Department of Dermatology and Cutaneous Surgery, University of South Florida, 13320 USF Laurel Drive, Tampa, FL, 33612, USA.
| | - Skylar Klager
- Department of Dermatology and Cutaneous Surgery, University of South Florida, 13320 USF Laurel Drive, Tampa, FL, 33612, USA
| | - Leigh Hatch
- Department of Dermatology and Cutaneous Surgery, University of South Florida, 13320 USF Laurel Drive, Tampa, FL, 33612, USA
- Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | | | - Pei Ling Chen
- Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
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Sakhiya J, Sakhiya D, Kaklotar J, Hirapara B, Purohit M, Bhalala K, Daruwala F, Dudhatra N. Intralesional Agents in Dermatology: Pros and Cons. J Cutan Aesthet Surg 2021; 14:285-295. [PMID: 34908770 PMCID: PMC8611707 DOI: 10.4103/jcas.jcas_109_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Since introduced in 1961, intralesional (IL) agent has become an essential part of the dermatological practice. The term IL referred to the direct delivery of agent percutaneously into skin lesions. This therapeutic approach is relatively safe, easy to perform and applicable for a broad range of dermatological conditions. On the other hand, immediate side effects, including pain during administration, bleeding, high risk of infection and allergic reaction, and subsequent side effects involving skin changes such as atrophy, telangiectasia, pigmentary changes, and striae are usually associated with this modality. This review paper highlights the pros and cons of IL agents in modern dermatology practice.
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Affiliation(s)
- Jagdish Sakhiya
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
| | - Dhruv Sakhiya
- B.J. Medical College, New Civil Hospital Asarwa, Ahmedabad, Gujarat, India
| | - Jitesh Kaklotar
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
| | - Bansi Hirapara
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
| | - Madhav Purohit
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
| | - Krishna Bhalala
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
| | - Feral Daruwala
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
| | - Nimish Dudhatra
- Sakhiya Skin Clinic, 2nd Floor, Ayush Doctor House, Station-Lal Darwaja Road, Surat, Gujarat, India
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8
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Lee SY, Kim WH, Choi JH, Kim KS, Hwang JH. Early diagnosis and surgical treatment of primary cutaneous marginal zone B-cell lymphomas of the face in an Asian patient. Arch Craniofac Surg 2021; 22:280-284. [PMID: 34732041 PMCID: PMC8568496 DOI: 10.7181/acfs.2021.00472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 10/17/2021] [Indexed: 12/04/2022] Open
Abstract
Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is an uncommon type of malignant lymphoma that mainly occurs in the trunk and upper extremity, with less frequent incidence observed on the head. Herein, we report the early diagnosis and treatment of a rare case of facial PCMZL in an Asian patient. A 51-year-old man presented with masses on the forehead and nose tip, which he had incidentally discovered 2 months previously. The masses appeared as a papule on the forehead and a patch on the nose. There were no signs of infection or bleeding, and the patient reported no other symptoms. After complete surgical excision, PCMZL was diagnosed based on the permanent biopsy. The histopathological findings revealed lymphoid aggregations with multifocal granulomas. Further treatment and follow-up were conducted at the hematology and oncology department. Despite its rarity in Asian populations, cutaneous lymphoma should be included in the differential diagnosis of facial masses. Early diagnosis and treatment based on a physical examination, imaging study, and excisional biopsy are important for a favorable prognosis.
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Affiliation(s)
- Sam Yong Lee
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Woo Hyeong Kim
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Jun Ho Choi
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Kwang Seog Kim
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Jae Ha Hwang
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
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Sarriugarte Aldecoa-Otalora J, Mitxelena Eceiza J, Córdoba Iturriagagoitia A, Viguria Alegría MC. Reddish Papules in the Center of the Face. ACTAS DERMO-SIFILIOGRAFICAS 2021:S1578-2190(21)00175-X. [PMID: 34059452 DOI: 10.1016/j.adengl.2021.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
| | - J Mitxelena Eceiza
- Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, Spain
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10
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Ronchi A, Sica A, Vitiello P, Franco R. Dermatological Considerations in the Diagnosis and Treatment of Marginal Zone Lymphomas. Clin Cosmet Investig Dermatol 2021; 14:231-239. [PMID: 33727844 PMCID: PMC7954031 DOI: 10.2147/ccid.s277667] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/23/2021] [Indexed: 12/16/2022]
Abstract
Primary cutaneous marginal zone lymphoma (PC-MZL) is a B-cell lymphoma arising in the skin. Although it is a rare disease, PC-MZL accounts for 20-40% of all primary cutaneous B-cell lymphoma in Western Countries. The aetiology and the pathogenesis of PC-MZL are poorly understood, as it generally lacks the chromosomal translocations most typically present in marginal zone lymphomas of other sites. The diagnosis of PC-MZL may be challenging, due to the rarity of the disease, and needs the competence of different professional figures, including the dermatologist and the pathologist. Furthermore, the management of the patient after the diagnosis is complex and involves the dermatologist, the haematologist, the surgeon, the radiotherapist and the radiologist. The aim of this review is to describe the clinical and histological findings for the diagnosis of PC-MZL, and the state of art for the management of the patient.
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Affiliation(s)
- Andrea Ronchi
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, 80138, Italy
| | - Antonello Sica
- Oncology and Haematology Unit, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, 80131, Italy
| | - Paola Vitiello
- Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, 80131, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, 80138, Italy
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11
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Cutaneous Lymphomas — Part II: Other Cutaneous Lymphomas. ACTAS DERMO-SIFILIOGRAFICAS 2021. [DOI: 10.1016/j.adengl.2020.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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12
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Sarriugarte Aldecoa-Otalora J, Mitxelena Eceiza J, Córdoba Iturriagagoitia A, Viguria Alegría MC. Reddish Papules in the Center of the Face. ACTAS DERMO-SIFILIOGRAFICAS 2020; 112:S0001-7310(20)30530-5. [PMID: 33307010 DOI: 10.1016/j.ad.2019.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 11/04/2019] [Accepted: 11/26/2019] [Indexed: 11/30/2022] Open
Affiliation(s)
| | - J Mitxelena Eceiza
- Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, España
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13
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Ohtsuka M, Hamada T, Miyagaki T, Shimauchi T, Yonekura K, Kiyohara E, Fujita H, Izutsu K, Okuma K, Kawai K, Koga H, Sugaya M. Outlines of the Japanese guidelines for the management of primary cutaneous lymphomas 2020. J Dermatol 2020; 48:e49-e71. [PMID: 33245165 DOI: 10.1111/1346-8138.15707] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 10/31/2020] [Indexed: 01/06/2023]
Abstract
Since the publication of the Japanese "Guidelines for the management of cutaneous lymphomas" in 2011, the World Health Organization (WHO) classification of hematolymphoid neoplasms and the WHO-European Organisation for Research and Treatment of Cancer classification for primary cutaneous lymphomas were updated and a number of novel systemic drugs for cutaneous T-cell lymphoma had been approved in Japan. In 2020, we revised the Japanese guidelines for the management of cutaneous lymphomas with consideration of the recent advances in the understanding of the pathophysiology and classification of cutaneous lymphomas together with the update of treatment strategies reflecting the advent of novel drugs. In addition to a brief explanation of epidemiology, diagnosis, staging system, prognosis and management of each subtype of cutaneous lymphomas, the recommendations for nine clinical questions regarding treatment options that can vary even among experts are also described. A systematic review process and determination of recommendations in answer to each clinical question have been performed in accordance with the Grading of Recommendations, Assessment, Development and Evaluation scheme by a multidisciplinary expert panel consisting of dermatologists, a hematologist and a radiation oncologist. In this article, we present the outlines of the revised Japanese "Guidelines for the management of cutaneous lymphomas".
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Affiliation(s)
- Mikio Ohtsuka
- Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Toshihisa Hamada
- Department of Dermatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Tomomitsu Miyagaki
- Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Takatoshi Shimauchi
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kentaro Yonekura
- Department of Dermatology, Imamura General Hospital, Kagoshima, Japan
| | - Eiji Kiyohara
- Department of Dermatology, Osaka University School of Medicine, Suita, Japan
| | - Hideki Fujita
- Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Koji Izutsu
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Kae Okuma
- Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuhiro Kawai
- Department of Dermatology, Kido Hospital, Niigata, Japan
| | - Hiroshi Koga
- Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Makoto Sugaya
- Department of Dermatology, International University of Health and Welfare, Narita, Japan
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14
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Mazloom E, Daneshpazhooh M, Shokouhi Shoormasti R, Balighi K, Mahmoudi H, Moradi Ketisari M, Eslami Faresani V, Ghandi N. Intralesional injection of biosimilar rituximab in recalcitrant mucocutaneous lesions of patients with pemphigus vulgaris: A pilot study. Dermatol Ther 2020; 33:e14407. [PMID: 33051954 DOI: 10.1111/dth.14407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 09/27/2020] [Accepted: 10/04/2020] [Indexed: 11/30/2022]
Abstract
The efficacy of intravenous rituximab (RTX) in patients with pemphigus have been shown in the previous studies. The study aimed to investigate the effectiveness of intralesional injection of RTX in the healing of pemphigus lesions, with lower doses and probable better safety profile than intravenous RTX. Eleven Pemphigus patients with recalcitrant lesions received two intralesional injections of biosimilar RTX, 5 mg/cm2 . During 6 months follow-up, Pemphigus Disease Area Index, the patients' satisfaction, quality of life, the disease activity, the number and size of lesions, the anti-desmoglein (Dsg) 1 and 3 antibodies and the count of CD4+ and CD19+ cells were assessed. All patients were in partial remission on therapy. The absolute count of CD19+ B cells showed a statistically significant decline (P = .006). The percentage of CD4 + T lymphocytes increased 2 weeks after injection and decreased 2 weeks later (P = .01). The average number and size of lesions decreased. The concentration of anti-Dsg 3 antibody decreased insignificantly during the study. The severe pain during the injection was considered as the main complication. At the end of the study, two patients were in complete remission on therapy, and the other nine remained in partial remission on therapy. Few side effects resulting from intralesional injection of RTX and enhanced quality of life of the patients were considered as the valuable achievements of this study. The results showed that although a low dose of RTX leads to a significant decrease of CD19+ B lymphocytes, it did not show parallel clinical effectiveness.
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Affiliation(s)
- Ebrahim Mazloom
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Maryam Daneshpazhooh
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.,Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Kamran Balighi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.,Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Mahmoudi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.,Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Moradi Ketisari
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Vahid Eslami Faresani
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Narges Ghandi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
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15
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Cutaneous Lymphomas -Part II: Other Cutaneous Lymphomas. ACTAS DERMO-SIFILIOGRAFICAS 2020; 112:24-31. [PMID: 33045210 DOI: 10.1016/j.ad.2020.09.005] [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: 05/19/2020] [Revised: 09/22/2020] [Accepted: 09/26/2020] [Indexed: 11/20/2022] Open
Abstract
Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30+ disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish-violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.
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16
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Hristov AC, Tejasvi T, Wilcox RA. Cutaneous B-cell lymphomas: 2021 update on diagnosis, risk-stratification, and management. Am J Hematol 2020; 95:1209-1213. [PMID: 32815650 DOI: 10.1002/ajh.25970] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 08/15/2020] [Indexed: 11/12/2022]
Abstract
DISEASE OVERVIEW Approximately one-fourth of primary cutaneous lymphomas are B-cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). DIAGNOSIS Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B-cell lymphomas from systemic B-cell lymphomas with secondary skin involvement. RISK-STRATIFICATION Disease histopathology remains the most important prognostic determinant in primary cutaneous B-cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5-year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis. RISK-ADAPTED THERAPY Both PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multi-agent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
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Affiliation(s)
- Alexandra C Hristov
- Departments of Pathology and Dermatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Trilokraj Tejasvi
- Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ryan A Wilcox
- Departments of Pathology and Dermatology, University of Michigan, Ann Arbor, Michigan, USA
- Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, USA
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17
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Chirico A, Henderson Berg MH, Roberge D, Pehr K. Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphoma. Br J Dermatol 2020; 184:354-356. [PMID: 32798319 DOI: 10.1111/bjd.19490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 11/30/2022]
Affiliation(s)
- A Chirico
- Division of Dermatology, McGill University, Montreal, QC, Canada
| | | | - D Roberge
- Division of Radiation Oncology, CHUM-Hôtel-Dieu de Montréal, Montreal, QC, Canada
| | - K Pehr
- Division of Dermatology, McGill University, Montreal, QC, Canada
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18
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Dumont M, Battistella M, Ram-Wolff C, Bagot M, de Masson A. Diagnosis and Treatment of Primary Cutaneous B-Cell Lymphomas: State of the Art and Perspectives. Cancers (Basel) 2020; 12:cancers12061497. [PMID: 32521744 PMCID: PMC7352758 DOI: 10.3390/cancers12061497] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 05/30/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022] Open
Abstract
Primary cutaneous B-cell lymphomas are rare entities that develop primarily in the skin. They constitute a heterogeneous group that represents around a quarter of primary cutaneous lymphomas. The 2018 update of the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification differentiates primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma with an indolent course from primary cutaneous diffuse large B-cell lymphoma, leg type with an aggressive behavior. The broad spectrum of clinical presentations and the disease course marked by frequent relapses are diagnostic and therapeutic challenges. The classification of these diseases has been refined in recent years, which allows to better define their immunopathogenesis and specific management. In the present article, we review the main clinico-biological characteristics and the current therapeutic options of these three main subsets. Based on the recent therapeutic advances in nodal B-cell lymphomas, we focus on the development of novel treatment options applicable to primary cutaneous B-cell lymphomas, including targeted therapies, combination treatments and immunotherapeutic approaches, and cover basic, translational and clinical aspects aiming to improve the treatment of cutaneous B-cell lymphomas.
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Affiliation(s)
- Maëlle Dumont
- Department of Dermatology, APHP, Saint-Louis Hospital, F-75010 Paris, France; (M.D.); (C.R.-W.); (A.d.M.)
- INSERM U976, Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, F-75010 Paris, France;
- Faculty of Medicine, Université de Paris (Paris University), F-75010 Paris, France
| | - Maxime Battistella
- INSERM U976, Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, F-75010 Paris, France;
- Faculty of Medicine, Université de Paris (Paris University), F-75010 Paris, France
- Pathology, APHP, Saint-Louis Hospital, F-75010 Paris, France
| | - Caroline Ram-Wolff
- Department of Dermatology, APHP, Saint-Louis Hospital, F-75010 Paris, France; (M.D.); (C.R.-W.); (A.d.M.)
| | - Martine Bagot
- Department of Dermatology, APHP, Saint-Louis Hospital, F-75010 Paris, France; (M.D.); (C.R.-W.); (A.d.M.)
- INSERM U976, Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, F-75010 Paris, France;
- Faculty of Medicine, Université de Paris (Paris University), F-75010 Paris, France
- Correspondence: ; Tel.: +33-1-53-72-20-93; Fax: +33-1-42-49-40-38
| | - Adèle de Masson
- Department of Dermatology, APHP, Saint-Louis Hospital, F-75010 Paris, France; (M.D.); (C.R.-W.); (A.d.M.)
- INSERM U976, Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, F-75010 Paris, France;
- Faculty of Medicine, Université de Paris (Paris University), F-75010 Paris, France
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19
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20
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Vitiello P, Sica A, Ronchi A, Caccavale S, Franco R, Argenziano G. Primary Cutaneous B-Cell Lymphomas: An Update. Front Oncol 2020; 10:651. [PMID: 32528871 PMCID: PMC7266949 DOI: 10.3389/fonc.2020.00651] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 04/07/2020] [Indexed: 12/13/2022] Open
Abstract
Primary cutaneous B-cell lymphomas (PCBCLs) comprise a group of extranodal B-cell non-Hodgkin lymphomas B-cell derived, which primarily involve the skin without evidence of extracutaneous disease at the time of diagnosis. They include ~25% of all cutaneous lymphomas and are classified in three major subgroups (World Health Organization (WHO) 2017): primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center cell lymphoma (PCFCL), and diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). This classification also includes some less common entities such as intravascular large B-cell lymphoma. Recently, WHO-EORTC added Epstein-Barr virus positive (EBV+) mucocutaneous ulcer, as a new provisional distinct entity, to cutaneous B-cell lymphomas. PCBCLs are classically characterized by patches, plaques, or nodules showing great variability for color, shape, and location. Diagnosis requires histological examination with immunohistochemical staining. In general, therapeutic options depend on the exact histological and immunohistochemical classification, disease presentation, and risk assessment. PCMZL and PCFCL are considered indolent lymphomas with a good prognosis and are associated with 5-year disease-specific survival ≥ 95%. In contrast, PCDLBCL, LT is considered an aggressive lymphoma with a survival rate in 5 years of lower than 60%. Patients with a solitary lesion or limited lesions in a single anatomical site require different treatments as compared to patients with generalized lesions or refractory disease or extracutaneous involvement. Therapeutic choice includes observation, local, or systemic therapy based on histology and disease extension. Patient management is multidisciplinary, including dermatologists, pathologists, hemato-oncologists, and radiation oncologists.
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Affiliation(s)
- Paola Vitiello
- Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonello Sica
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
- *Correspondence: Antonello Sica
| | - Andrea Ronchi
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Stefano Caccavale
- Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
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21
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Gupta A, Sharma YK, Bhawalkar JS, Kothari P, Kharat R, Patil A. Intralesional rituximab salvages refractory scalp lesions in a case of pemphigus vulgaris. Dermatol Ther 2019; 33:e13154. [DOI: 10.1111/dth.13154] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 10/31/2019] [Accepted: 11/01/2019] [Indexed: 01/20/2023]
Affiliation(s)
- Aayush Gupta
- Department of DermatologyDr. D.Y. Patil Medical College and Hospital Pimpri Pune India
| | - Yugal K Sharma
- Department of DermatologyDr. D.Y. Patil Medical College and Hospital Pimpri Pune India
| | - Jitendra S. Bhawalkar
- Department of Community MedicineDr. D.Y. Patil Medical College and Hospital Pimpri Pune India
| | - Preeti Kothari
- Department of DermatologyDr. D.Y. Patil Medical College and Hospital Pimpri Pune India
| | - Rajeshri Kharat
- Department of DermatologyDr. D.Y. Patil Medical College and Hospital Pimpri Pune India
| | - Aishwarya Patil
- Department of DermatologyDr. D.Y. Patil Medical College and Hospital Pimpri Pune India
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22
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Bobrowicz M, Zagozdzon R, Domagala J, Vasconcelos-Berg R, Guenova E, Winiarska M. Monoclonal Antibodies in Dermatooncology-State of the Art and Future Perspectives. Cancers (Basel) 2019; 11:E1420. [PMID: 31554169 PMCID: PMC6826541 DOI: 10.3390/cancers11101420] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/08/2019] [Accepted: 09/17/2019] [Indexed: 12/21/2022] Open
Abstract
Monoclonal antibodies (mAbs) targeting specific proteins are currently the most popular form of immunotherapy used in the treatment of cancer and other non-malignant diseases. Since the first approval of anti-CD20 mAb rituximab in 1997 for the treatment of B-cell malignancies, the market is continuously booming and the clinically used mAbs have undergone a remarkable evolution. Novel molecular targets are constantly emerging and the development of genetic engineering have facilitated the introduction of modified mAbs with improved safety and increased capabilities to activate the effector mechanisms of the immune system. Next to their remarkable success in hematooncology, mAbs have also an already established role in the treatment of solid malignancies. The recent development of mAbs targeting the immune checkpoints has opened new avenues for the use of this form of immunotherapy, also in the immune-rich milieu of the skin. In this review we aim at presenting a comprehensive view of mAbs' application in the modern treatment of skin cancer. We present the characteristics and efficacy of mAbs currently used in dermatooncology and summarize the recent clinical trials in the field. We discuss the side effects and strategies for their managing.
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Affiliation(s)
| | - Radoslaw Zagozdzon
- Department of Clinical Immunology, Medical University of Warsaw, 02-006 Warsaw, Poland.
- Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, 02-006 Warsaw, Poland.
| | - Joanna Domagala
- Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland.
- Postgraduate School of Molecular Medicine, 02-091 Warsaw, Poland.
| | - Roberta Vasconcelos-Berg
- Department of Dermatology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
| | - Emmanuella Guenova
- Department of Dermatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
- Department of Dermatology, University of Lausanne, 1011 Lausanne, Switzerland.
| | - Magdalena Winiarska
- Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland.
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23
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Abstract
Primary cutaneous lymphomas are the second most common form of extra-nodal lymphomas. They have special characteristics compared with other lymphomas. They are most frequently of T-cell origin and they generally have a much more indolent course than lymphomas of similar histology in other locations. Mycosis fungoides is the most common type of cutaneous lymphoma. Primary cutaneous lymphomas remain confined to the skin for a long time. Skin-directed therapies are the main treatments; systemic treatments are not very effective for the skin lesions. Skin-directed therapies used for the early and thin lesions are topical corticosteroids, phototherapy and topical retinoids and, for the more widespread or thick lesions, topical nitrogen mustard and radiation. Radiation therapy is highly effective and is indicated in virtually all cases of localised disease. Radiation therapy may be given to the whole skin surface, so-called total skin electron beam therapy. However, if the disease spreads to other organs, systemic treatments are indicated, often combined with skin-directed therapies. Conventional cytotoxic therapy is less effective in cutaneous lymphomas. The commonly used therapies, such as interferon, enhanced anti-tumour immunity and the recent advances in immune therapies may improve our treatments for cutaneous lymphomas.
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24
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Comparison between the efficacy of intralesional rituximab versus intralesional triamcinolone in the treatment refractory Pemphigus Vulgaris lesions: A randomized clinical trial. Int Immunopharmacol 2019; 73:94-97. [DOI: 10.1016/j.intimp.2019.04.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/14/2019] [Accepted: 04/15/2019] [Indexed: 12/13/2022]
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25
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Malachowski SJ, Sun J, Chen PL, Seminario-Vidal L. Diagnosis and Management of Cutaneous B-Cell Lymphomas. Dermatol Clin 2019; 37:443-454. [PMID: 31466585 DOI: 10.1016/j.det.2019.05.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Primary cutaneous B-cell lymphomas are a group of diseases with indolent and aggressive behavior. The goal of the initial workup is to evaluate for systemic involvement, provide adequate staging, and guide therapy. Histopathological studies are a critical part of the workup for classification of these lymphomas because they are similar to their nodal counterparts. There are limited data for treatment guidelines, and thus, therapy differs among institutions. Overall, localized therapies are preferred for indolent types and chemotherapy or immunotherapy for the aggressive forms.
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Affiliation(s)
- Stephen J Malachowski
- Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL 33612, USA
| | - James Sun
- Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Drive, Tampa, FL 33612, USA
| | - Pei-Ling Chen
- Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Drive, Tampa, FL 33612, USA
| | - Lucia Seminario-Vidal
- Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL 33612, USA; Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Drive, Tampa, FL 33612, USA.
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26
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Russo I, Sernicola A, Alaibac M. Recent advances in localized immunotherapy of skin cancers. Immunotherapy 2019; 11:443-456. [PMID: 30786845 DOI: 10.2217/imt-2018-0139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Skin cancer is the most frequent malignancy in humans. The immune system has long been known to have an important role in defeating cancer. Immunotherapy, which includes various strategies to enhance tumor immunity, currently represents an exciting option for the treatment of skin cancers. Local immunotherapy is a promising therapeutic approach and may improve response rates without inducing systemic toxicity. Here, we review the main localized immunotherapies for the management of skin cancer with a special focus on advanced melanoma, nonmelanoma skin cancer and primary cutaneous lymphoma.
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Affiliation(s)
- Irene Russo
- Unit of Dermatology, University of Padua, Via Gallucci 4, Padova 35128, Italy
| | - Alvise Sernicola
- Unit of Dermatology, University of Padua, Via Gallucci 4, Padova 35128, Italy
| | - Mauro Alaibac
- Unit of Dermatology, University of Padua, Via Gallucci 4, Padova 35128, Italy
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27
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Gilson D, Whittaker S, Child F, Scarisbrick J, Illidge T, Parry E, Mohd Mustapa M, Exton L, Kanfer E, Rezvani K, Dearden C, Morris S, McHenry P, Leslie T, Wakelin S, Hunasehally R, Cork M, Johnston G, Chiang N, Worsnop F, Salim A, Buckley D, Petrof G, Callachand N, Flavell T, Salad A. British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous lymphomas 2018. Br J Dermatol 2018; 180:496-526. [DOI: 10.1111/bjd.17240] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2018] [Indexed: 02/07/2023]
Affiliation(s)
- D. Gilson
- Leeds Cancer Centre St James's University Hospital Leeds LS9 7TF U.K
| | - S.J. Whittaker
- St John's Institute of Dermatology Guy's and St Thomas NHS Foundation Trust St Thomas’ Hospital London SE1 7EH U.K
| | - F.J. Child
- St John's Institute of Dermatology Guy's and St Thomas NHS Foundation Trust St Thomas’ Hospital London SE1 7EH U.K
| | - J.J. Scarisbrick
- Queen Elizabeth Hospital University Hospital Birmingham Birmingham B15 2TH U.K
| | - T.M. Illidge
- Institute of Cancer Sciences University of Manchester The Christie NHS Foundation Trust Manchester M20 4BX U.K
| | - E.J. Parry
- Tameside Hospital Integrated Care NHS Foundation Trust Ashton‐under‐Lyne OL6 9RW U.K
| | - M.F. Mohd Mustapa
- British Association of Dermatologists Willan House, 4 Fitzroy Square London W1T 5HQ U.K
| | - L.S. Exton
- British Association of Dermatologists Willan House, 4 Fitzroy Square London W1T 5HQ U.K
| | - E. Kanfer
- Haematology Department Hammersmith Hospital Du Cane Road London W12 0HS U.K
| | - K. Rezvani
- The University of Texas MD Anderson Cancer Centre Houston TX U.S.A
| | - C.E. Dearden
- Chronic Lymphocytic Leukaemia (CLL) Unit The Royal Marsden NHS Foundation Trust Sutton SW3 6JJ U.K
| | - S.L. Morris
- Guy's and St Thomas’ NHS Foundation Trust Guy's Hospital London SE1 9RT U.K
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28
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Wilcox RA. Cutaneous B-cell lymphomas: 2019 update on diagnosis, risk stratification, and management. Am J Hematol 2018; 93:1427-1430. [PMID: 30039522 DOI: 10.1002/ajh.25224] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 07/16/2018] [Indexed: 11/06/2022]
Abstract
DISEASE OVERVIEW Approximately one-fourth of cutaneous lymphomas are B-cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). DIAGNOSIS Diagnosis and disease classification are based on histologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B-cell lymphomas from systemic B-cell lymphomas with secondary skin involvement. RISK STRATIFICATION Disease histology remains the most important prognostic determinant. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5-year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis. RISK-ADAPTED THERAPY PCFCL and PCMZL patients with solitary or relatively few skin lesions may be affectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
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Affiliation(s)
- Ryan A. Wilcox
- Division of Hematology/Oncology; University of Michigan, Rogel Cancer Center; Ann Arbor Michigan
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29
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The First Year of the AEVD Primary Cutaneous Lymphoma Registry. ACTAS DERMO-SIFILIOGRAFICAS 2018. [DOI: 10.1016/j.adengl.2018.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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30
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Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento. ACTAS DERMO-SIFILIOGRAFICAS 2018; 109:610-616. [DOI: 10.1016/j.ad.2018.03.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 02/19/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023] Open
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31
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Nicolay JP, Wobser M. Cutaneous B-cell lymphomas - pathogenesis, diagnostic workup, and therapy. J Dtsch Dermatol Ges 2018; 14:1207-1224. [PMID: 27992127 DOI: 10.1111/ddg.13164] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 10/07/2016] [Indexed: 12/31/2022]
Abstract
Cutaneous B-cell lymphomas (CBCLs) comprise a group of mature lymphoproliferative B-cell disorders that primarily affect the skin. Characterized by great biological and clinical variability among its various subtypes, CBCLs fundamentally differ from primary nodal or systemic B-cell lymphomas. Given their uncomplicated course and excellent prognosis, lymphoma classifications rank primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) as indolent CBCLs. By contrast, diffuse large B-cell lymphoma, leg type (DLBCL-LT) in particular, represent more aggressive lymphoma variants associated with a poorer prognosis. Therapeutic decisions and diagnostic procedures are based on the exact histological and immunohistochemical classification as well as the exclusion of systemic involvement and thus differentiation from nodal and systemic lymphomas. In this context, the diagnostic workup should also include molecular biology methods. Primary therapeutic options for indolent CBCL lesions include surgery and radiation therapy, as well as systemic treatment with rituximab (anti-CD20 antibody) in case of dissemination. More aggressive CBCLs usually require a combination of rituximab and polychemotherapy, primarily the CHOP regimen or modifications thereof. Given that the pathogenesis and biology of CBCLs has not been conclusively elucidated, and given the limited therapeutic armamentarium available, there is great need for comprehensive research, especially with respect to DLBCL-LT.
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Affiliation(s)
- Jan P Nicolay
- Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany
| | - Marion Wobser
- Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Germany
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Grandi V, Alberti Violetti S, La Selva R, Cicchelli S, Delfino C, Fava P, Fierro MT, Pileri A, Pimpinelli N, Quaglino P, Berti E. Primary cutaneous B-cell lymphoma: narrative review of the literature. GIORN ITAL DERMAT V 2017; 154:466-479. [PMID: 29144099 DOI: 10.23736/s0392-0488.17.05670-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Primary cutaneous B-cell lymphomas comprehend a group of lymphoproliferative disorders characterized by being monoclonal proliferations of B-cell primarily involving the skin. Despite being recognized as autonomous and distinct clinico-pathologic entities since the late 80s, their classification is still an ongoing matter of debate. At the moment, WHO classification recognizes three disorders: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large b-cell lymphoma (leg type). Primary cutaneous diffuse large b-cell lymphoma (other) has been used to define rare cases which show histologically an infiltrate with diffuse pattern composed by large b-cell, but not fitting with criteria for follicle center lymphoma nor for primary cutaneous diffuse large b-cell lymphoma (leg type). Aim of this review was to briefly describe all recognized and provisional entities included in the primary cutaneous b-cell lymphomas and to discuss recent acquisitions that may influence their future classifications.
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Affiliation(s)
- Vieri Grandi
- Unit of Dermatology, Department of Surgery and Translational Medicine, University of Florence Medical School, Florence, Italy -
| | | | - Roberta La Selva
- Clinic of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Stefano Cicchelli
- Clinic of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Chiara Delfino
- Unit of Dermatology, Department of Surgery and Translational Medicine, University of Florence Medical School, Florence, Italy
| | - Paolo Fava
- Clinic of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Maria T Fierro
- Clinic of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Alessandro Pileri
- Unit of Dermatology, Department of Surgery and Translational Medicine, University of Florence Medical School, Florence, Italy.,Unit of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Nicola Pimpinelli
- Unit of Dermatology, Department of Surgery and Translational Medicine, University of Florence Medical School, Florence, Italy
| | - Pietro Quaglino
- Clinic of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Emilio Berti
- Unit of Dermatology, IRCCS Ca' Granda, Maggiore Policlinico Hospital, Milan, Italy
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Abstract
Primary cutaneous B‑cell lymphomas are rarely encountered and represent 25% of all cutaneous lymphomas. Follicular B‑cell lymphoma and marginal zone lymphoma belong to indolent subtypes which as a rule have no systemic dissemination and, thus, a mostly unchanged life expectancy. Therefore, skin-directed treatment options such as excision or radiotherapy are usually sufficient to control the disease. In contrast, cutaneous diffuse large B‑cell lymphoma and EBV-associated B‑cell lymphomas of the skin belong to more aggressive entities which demand a systemic first-line upfront therapy with R‑CHOP. Nevertheless, mortality is still high and comparable to that of systemic/nodal large B‑cell lymphomas so that the identification of pathogenetic driver mutations or novel therapeutic targets may pave the way to better target-oriented therapies.
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Eberle FC, Holstein J, Scheu A, Fend F, Yazdi AS. Intraläsionale Therapie niedrig maligner primär kutaner B-Zell-Lymphome mit Anti-CD20-Antikörper: Nebenwirkungen korrelieren mit gutem klinischen Ansprechen. J Dtsch Dermatol Ges 2017; 15:319-324. [DOI: 10.1111/ddg.13188_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 07/21/2016] [Indexed: 11/28/2022]
Affiliation(s)
| | - Julia Holstein
- Universitäts-Hautklinik; Eberhard Karls Universität; Tübingen
| | - Alexander Scheu
- Universitäts-Hautklinik; Eberhard Karls Universität; Tübingen
| | - Falko Fend
- Institut für Pathologie und Neuropathologie; Eberhard Karls Universität; Tübingen
| | - Amir S. Yazdi
- Universitäts-Hautklinik; Eberhard Karls Universität; Tübingen
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35
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Eberle FC, Holstein J, Scheu A, Fend F, Yazdi AS. Intralesional anti-CD20 antibody for low-grade primary cutaneous B-cell lymphoma: Adverse reactions correlate with favorable clinical outcome. J Dtsch Dermatol Ges 2017; 15:319-323. [DOI: 10.1111/ddg.13188] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 07/21/2016] [Indexed: 11/27/2022]
Affiliation(s)
| | - Julia Holstein
- Department of Dermatology; Eberhard Karls University; Tübingen Germany
| | - Alexander Scheu
- Department of Dermatology; Eberhard Karls University; Tübingen Germany
| | - Falko Fend
- Institute of Pathology and Neuropathology; Eberhard Karls University; Tübingen Germany
| | - Amir S. Yazdi
- Department of Dermatology; Eberhard Karls University; Tübingen Germany
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36
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Selva RL, Violetti SA, Delfino C, Grandi V, Cicchelli S, Tomasini C, Fierro MT, Berti E, Pimpinelli N, Quaglino P. A Literature Revision in Primary Cutaneous B-cell Lymphoma. Indian J Dermatol 2017; 62:146-157. [PMID: 28400634 PMCID: PMC5363138 DOI: 10.4103/ijd.ijd_74_17] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The term “Primary Cutaneous B-Cell Lymphoma” (PCBCL) comprehends a variety of lymphoproliferative disorders characterized by a clonal proliferation of B-cells primarily involving the skin. The absence of evident extra-cutaneous disease must be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's lymphoma (NHL) with secondary cutaneous involvement, which may have a completely different clinical behavior and prognosis. In this article, we have summarized the clinico-pathological features of main types of PCBCL and we outline the guidelines for management based on a review of the available literature.
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Affiliation(s)
- R La Selva
- Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy
| | - S Alberti Violetti
- UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - C Delfino
- Department of Surgery and Translational Medicine, Section of Dermatology and Venereology, University of Florence Medical School, Florence, Italy
| | - V Grandi
- Department of Surgery and Translational Medicine, Section of Dermatology and Venereology, University of Florence Medical School, Florence, Italy
| | - S Cicchelli
- Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy
| | - C Tomasini
- Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy
| | - M T Fierro
- Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy
| | - E Berti
- University of Milano-Bicocca, Milan, Italy
| | - N Pimpinelli
- Department of Surgery and Translational Medicine, Section of Dermatology and Venereology, University of Florence Medical School, Florence, Italy
| | - P Quaglino
- Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy
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Nicolay JP, Wobser M. B-Zell-Lymphome der Haut - Pathogenese, Diagnostik und Therapie. J Dtsch Dermatol Ges 2016; 14:1207-1225. [PMID: 27992139 DOI: 10.1111/ddg.13164_g] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 10/07/2016] [Indexed: 12/14/2022]
Abstract
Primär kutane B-Zell-Lymphome (PCBCL) beschreiben reifzellige lymphoproliferative Erkrankungen der B-Zell-Reihe, die primär die Haut betreffen. Die Biologie und der klinische Verlauf der einzelnen PCBCL-Subtypen variieren untereinander stark und unterscheiden sich grundsätzlich von primär nodalen und systemischen B-Zell-Lymphomen. Primär kutane Marginalzonenlymphome (PCMZL) und primäre kutane follikuläre Keimzentrumslymphome (PCFCL) werden auf Grund ihres unkomplizierten Verlaufs und ihrer exzellenten Prognose zu den indolenten PCBCL gezählt. Demgegenüber stellen die diffus großzelligen B-Zell-Lymphome, hauptsächlich vom Beintyp (DLBCL, LT) die aggressiveren PCBCL-Varianten mit schlechterer Prognose dar. Für die Ausbreitungsdiagnostik und die Therapieentscheidung sind eine genaue histologische und immunhistochemische Klassifizierung sowie der Ausschluss einer systemischen Beteiligung in Abgrenzung zu nodalen oder systemischen Lymphomen notwendig. Die Diagnostik sollte dabei durch molekularbiologische Untersuchungen unterstützt werden. Therapeutisch stehen für die indolenten PCBCL primär operative und radioonkologische Maßnahmen im Vordergrund sowie eine Systemtherapie mit dem CD20-Antikörper Rituximab bei disseminiertem Befall. Die aggressiveren Varianten sollten in erster Linie mit Kombinationen aus Rituximab und Polychemotherapieschemata wie z. B. dem CHOP-Schema oder Modifikationen davon behandelt werden. Auf Grund der in allen seinen Einzelheiten noch nicht vollständig verstandenen Pathogenese und Biologie sowie des begrenzten Therapiespektrums der PCBCL besteht hier, speziell beim DLBCL, LT, noch erheblicher Forschungsbedarf.
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Affiliation(s)
- Jan P Nicolay
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin und Medizinische Fakultät Mannheim der Ruprecht-Karls-Universität Heidelberg, Mannheim
| | - Marion Wobser
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg
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Rubio-Gonzalez B, Zain J, Rosen ST, Querfeld C. Clinical manifestations and pathogenesis of cutaneous lymphomas: current status and future directions. Br J Haematol 2016; 176:16-36. [PMID: 27782301 DOI: 10.1111/bjh.14402] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The primary cutaneous lymphomas are a heterogeneous group of T-, Natural Killer- and B- cell neoplasms with a wide range of clinical and pathological presentations, and with very different prognoses compared to systemic lymphomas. Recent studies have shown that the skin microenvironment, which is composed of various immune cell subsets as well as their spatial distribution and T-cell interactions through different chemokines and cytokines, has an important role in the development and pathogenesis of cutaneous lymphomas and has assisted in the development of novel and more effective immunotherapies. The following review will focus on the major subtypes of primary cutaneous lymphomas, including the clinical and histological patterns, molecular hallmarks, and current and future treatment strategies.
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Affiliation(s)
| | - Jasmine Zain
- Department of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA
| | - Steven T Rosen
- Department of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA
| | - Christiane Querfeld
- Department of Pathology, City of Hope, Duarte, CA, USA.,Department of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.,Division of Dermatology, City of Hope, Duarte, CA, USA
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39
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Maillet-Lebel N, Thibeault MM. Intralesional rituximab for cutaneous manifestations of systemic B-cell lymphoma. JAAD Case Rep 2016; 2:334-6. [PMID: 27570817 PMCID: PMC4992004 DOI: 10.1016/j.jdcr.2016.07.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
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40
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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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41
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Bellodi-Schmidt F, Shah KN. Beyond Psoriasis: Novel Uses for Biologic Response Modifiers in Pediatric Dermatology. Pediatr Dermatol 2016; 33:18-27. [PMID: 26607958 DOI: 10.1111/pde.12707] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Dermatologists have witnessed the increasing availability of novel biologic response modifiers for the treatment of inflammatory and autoimmune diseases in recent years. The most common dermatologic indication for the use of biologic response modifiers in adults is psoriasis, but the U.S. Food and Drug Administration has not approved any of these agents for use in any dermatologic disease in children with the exception of omalizumab, and as such, use in this population is considered off-label. In this review, we focus on the use of these agents in children to treat inflammatory skin diseases other than psoriasis, including atopic dermatitis, hidradenitis suppurativa, pemphigus vulgaris, bullous pemphigoid, and toxic epidermal necrolysis, with an emphasis on the use of etanercept, infliximab, rituximab, omalizumab, and ustekinumab. By highlighting novel uses of these agents, particularly for the treatment of dermatologic conditions for which optimal therapies are yet to be established, we hope to raise awareness of the potential use of this class of medications to treat inflammatory skin diseases in children.
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Affiliation(s)
- Fernanda Bellodi-Schmidt
- Division of Dermatology, Cincinnati Children's Hospital, Cincinnati, Ohio
- Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Kara N Shah
- Division of Dermatology, Cincinnati Children's Hospital, Cincinnati, Ohio
- Department of Dermatology, College of Medicine, University of Cincinnati, Cincinnati, Ohio
- Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio
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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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Abstract
PURPOSE OF REVIEW 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). RECENT FINDINGS 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. SUMMARY 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.
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Abstract
Rituximab is a monoclonal therapeutic anti-CD20 antibody that has been approved for use in lymphoma and rheumatoid arthritis. Over the past decade several reports based on case series and observational studies have recorded the benefits of rituximab in particular groups of dermatological patients. Off-label use of rituximab in many dermatological indications is not uncommon in many countries in the world. This article reviews the available data that may be of use to the practicing dermatologist. Because of its potential complications, paucity of clinical data, and cost considerations, rituximab is favoured only when standard systemic therapies fail or corticosteroids are absolutely contraindicated. Further research is required in this field.
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Affiliation(s)
- Prasan R Bhandari
- Department of Pharmacology, S.D.M. College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
| | - Varadraj V Pai
- Department of Dermatology, S.D.M. College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
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45
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Beck K, Paul J, Sawardekar S, Harvey V. Secondary cutaneous marginal zone B-cell lymphoma presenting as lipoatrophy in a patient with hepatitis C. J Dermatol Case Rep 2014; 8:46-9. [PMID: 25024777 PMCID: PMC4094737 DOI: 10.3315/jdcr.2014.1171] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C viral infection is a significant public health problem; 170 million persons are infected worldwide and the prevalence in the southern part of the United States exceeds two percent. Extrahepatic manifestations of hepatitis C viral infection are common; notably, 15-20% of patients will develop cutaneous manifestations of their disease. There are numerous dermatologic diseases associated with hepatitis C infection, including lichen planus, leukocytoclasticvasculitis, and porphyria cutaneatarda. MAIN OBSERVATION Recently, epidemiological studies have also demonstrated an association between hepatitis C infection and the development of non-Hodgkin lymphoma, especially marginal zone B-cell lymphoma. Herein we report the unusual case of a systemic marginal zone lymphoma in a patient with hepatitis C infection presenting clinically as localized lipoatrophy. CONCLUSIONS Lipoatrophy can be a rare and diagnostically challenging presentation of secondary cutaneous marginal zone B-cell lymphoma. The importance of early recognition and detection cannot be over emphasized, as new and effective anti-viral treatments can lead to lymphoma regression in up to 75% of patients. To our knowledge, this is the first case of hepatitis C viral infection associated marginal zone lymphoma to present as localized lipoatrophy.
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Affiliation(s)
- Kristyn Beck
- Eastern Virginia Medical School, Department of Internal Medicine, 700 West Olney Road, Norfolk, VA, 23507, USA
| | - Joan Paul
- Dartmouth Hitchcock Medical Center, Section of Dermatology, 18 Old Etna Road, Lebanon, NH, 03756, USA
| | - Shilpa Sawardekar
- Eastern Virginia Medical School, Department of Dermatology, 721 Fairfax Avenue, Suite 200, Norfolk, VA, 23507, USA
| | - Valerie Harvey
- Eastern Virginia Medical School, Department of Dermatology, 721 Fairfax Avenue, Suite 200, Norfolk, VA, 23507, USA
- Hampton University Skin of Color Research Institute, Hampton University, Hampton, VA, USA
- Corresponding author: Valerie M. Harvey, 1) Hampton University Skin of Color Research Institute, 27 East Tyler Street
Hampton, VA, 23668, USA. 2) Eastern Virginia Medical School, Department of Dermatology, 721 Fairfax Avenue, Suite 200, Norfolk, VA, 23507, USA. E-mail:
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Fernández-Guarino M, Ortiz-Romero P, Fernández-Misa R, Montalbán C. Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review. ACTAS DERMO-SIFILIOGRAFICAS 2014. [DOI: 10.1016/j.adengl.2014.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Savino G, Battendieri R, Gari M, Caputo CG, Laurenti L, Blasi MA. Long-term outcomes of primary ocular adnexal lymphoma treatment with intraorbital rituximab injections. J Cancer Res Clin Oncol 2013; 139:1251-5. [PMID: 23625184 DOI: 10.1007/s00432-013-1438-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 04/15/2013] [Indexed: 12/21/2022]
Abstract
PURPOSE We recently reported on the efficacy of intralesional rituximab for treating primary ocular adnexal lymphoma in a pilot study. After treatment, a complete response was observed in two of five patients, a partial response in one patient, and lesion recurrence in two patients. In this study, we evaluate the long-term follow-up of the five previously treated patients as well as the response of two new patients to an augmented dose of rituximab. METHODS We followed up the five patients who were treated with rituximab during the initial pilot study. Two additional patients were also enrolled and treated with four intraorbital injections of 10 mg rituximab once a week for 1 month (total dose of 40 mg). Median follow-up period was 4 years for the first five patients and 1 year for the last two patients. RESULTS Lymphoma did not relapse in the two patients who originally responded immediately to treatment. Of the initial partial responders, one became disease-free after additional rituximab treatment, and one experienced a standardized uptake value reduction, as measured with positron emission tomography-CT. One patient who experienced abdominal and pulmonary localization 7 months later showed no local recurrence. The two newly enrolled patients had complete remission after the first cycle of treatment and no disease recurrence eight and 11 months later, respectively. CONCLUSIONS This study suggests that intralesional administration of rituximab for treating localized ocular adnexal CD20+ lymphomas could be an effective front-line therapeutic option with negligible side effects and a good response rate and duration.
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Affiliation(s)
- Gustavo Savino
- Institute of Ophthalmology, Catholic University of Sacred Heart, Largo F Vito 1, 00168 Rome, Italy.
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Servitje O, Muniesa C, Benavente Y, Monsálvez V, Garcia-Muret MP, Gallardo F, Domingo-Domenech E, Lucas A, Climent F, Rodriguez-Peralto JL, Ortiz-Romero PL, Sandoval J, Pujol RM, Estrach MT. Primary cutaneous marginal zone B-cell lymphoma: response to treatment and disease-free survival in a series of 137 patients. J Am Acad Dermatol 2013; 69:357-65. [PMID: 23796549 DOI: 10.1016/j.jaad.2013.04.047] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 04/23/2013] [Accepted: 04/25/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. OBJECTIVE We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. METHODS Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. RESULTS Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. LIMITATIONS This was a case series retrospective study. CONCLUSION Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.
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Affiliation(s)
- Octavio Servitje
- Department of Dermatology, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
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Fernández-Guarino M, Ortiz-Romero PL, Fernández-Misa R, Montalbán C. Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review. ACTAS DERMO-SIFILIOGRAFICAS 2013; 105:438-45. [PMID: 23540593 DOI: 10.1016/j.ad.2012.10.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2012] [Revised: 10/24/2012] [Accepted: 10/25/2012] [Indexed: 11/16/2022] Open
Abstract
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.
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Affiliation(s)
- M Fernández-Guarino
- Servicio de Dermatología, Hospital Central de la Cruz Roja, Universidad Alfonso X El Sabio, Madrid, España.
| | - P L Ortiz-Romero
- Facultad de Medicina, Universidad Complutense, Instituto i+12, Hospital Universitario 12 de Octubre, Madrid, España
| | - R Fernández-Misa
- Servicio de Dermatología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España
| | - C Montalbán
- Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Madrid, España
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Ghatalia P, Porter J, Wroblewski D, Carlson JA. Primary cutaneous marginal zone lymphoma associated with juxta-articular fibrotic nodules in a teenager. J Cutan Pathol 2013; 40:477-84. [DOI: 10.1111/cup.12102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Revised: 01/16/2013] [Accepted: 01/18/2013] [Indexed: 11/27/2022]
Affiliation(s)
- Pooja Ghatalia
- Department of Pediatric Hematology/Oncology; Albany Medical College; Albany; NY; 12208; USA
| | - Joanne Porter
- Department of Pediatric Hematology/Oncology; Albany Medical College; Albany; NY; 12208; USA
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