Primary cutaneous large B cell lymphoma, leg type
- Eric Jacobsen, MD
Eric Jacobsen, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Rein Willemze, MD
Rein Willemze, MD
- Professor and Chairman, Department of Dermatology
- Leiden University Medical Center
- Section Editors
- Timothy M Kuzel, MD, FACP
Timothy M Kuzel, MD, FACP
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine, Rush University Medical Center
- Chief, Division of Hematology/Oncology/Cell Therapy
- John A Zic, MD
John A Zic, MD
- Section Editor — Cutaneous Lymphoma
- Associate Professor of Medicine/Dermatology
- Vanderbilt University School of Medicine
Primary cutaneous B cell lymphoma (PCBCL) refers to those cases of B cell lymphoma that present in the skin when there is no evidence of extracutaneous disease at the time of diagnosis and after the completion of an initial staging evaluation. There are three main subtypes of PCBCL:
●Primary cutaneous follicle center lymphoma (PCFCL)
●Primary cutaneous large B cell lymphoma (PCLBCL), leg type
●Primary cutaneous marginal zone lymphoma (PCMZL), included in the broader category of extranodal marginal zone B cell lymphoma
These appear to be unique entities with differing clinical presentation, pathologic features, prognosis, and treatment approach. This topic review will discuss primary cutaneous large B cell lymphoma; leg type.
- Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997; 90:354.
- Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues, IARC Press, Lyon 2008.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Burg G, Kerl H, Przybilla B, Braun-Falco O. Some statistical data, diagnosis, and staging of cutaneous B-cell lymphomas. J Dermatol Surg Oncol 1984; 10:256.
- Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105:3768.
- Dores GM, Anderson WF, Devesa SS. Cutaneous lymphomas reported to the National Cancer Institute's surveillance, epidemiology, and end results program: applying the new WHO-European Organisation for Research and Treatment of Cancer classification system. J Clin Oncol 2005; 23:7246.
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
- Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood 2009; 113:5064.
- Grange F, Beylot-Barry M, Courville P, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol 2007; 143:1144.
- Paulli M, Viglio A, Vivenza D, et al. Primary cutaneous large B-cell lymphoma of the leg: histogenetic analysis of a controversial clinicopathologic entity. Hum Pathol 2002; 33:937.
- Senff NJ, Hoefnagel JJ, Jansen PM, et al. Reclassification of 300 primary cutaneous B-Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers. J Clin Oncol 2007; 25:1581.
- Vermeer MH, Geelen FA, van Haselen CW, et al. Primary cutaneous large B-cell lymphomas of the legs. A distinct type of cutaneous B-cell lymphoma with an intermediate prognosis. Dutch Cutaneous Lymphoma Working Group. Arch Dermatol 1996; 132:1304.
- Hallermann C, Kaune KM, Gesk S, et al. Molecular cytogenetic analysis of chromosomal breakpoints in the IGH, MYC, BCL6, and MALT1 gene loci in primary cutaneous B-cell lymphomas. J Invest Dermatol 2004; 123:213.
- Dijkman R, Tensen CP, Jordanova ES, et al. Array-based comparative genomic hybridization analysis reveals recurrent chromosomal alterations and prognostic parameters in primary cutaneous large B-cell lymphoma. J Clin Oncol 2006; 24:296.
- Senff NJ, Zoutman WH, Vermeer MH, et al. Fine-mapping chromosomal loss at 9p21: correlation with prognosis in primary cutaneous diffuse large B-cell lymphoma, leg type. J Invest Dermatol 2009; 129:1149.
- Hoefnagel JJ, Dijkman R, Basso K, et al. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling. Blood 2005; 105:3671.
- Pham-Ledard A, Cappellen D, Martinez F, et al. MYD88 somatic mutation is a genetic feature of primary cutaneous diffuse large B-cell lymphoma, leg type. J Invest Dermatol 2012; 132:2118.
- Pham-Ledard A, Prochazkova-Carlotti M, Andrique L, et al. Multiple genetic alterations in primary cutaneous large B-cell lymphoma, leg type support a common lymphomagenesis with activated B-cell-like diffuse large B-cell lymphoma. Mod Pathol 2014; 27:402.
- Pham-Ledard A, Beylot-Barry M, Barbe C, et al. High frequency and clinical prognostic value of MYD88 L265P mutation in primary cutaneous diffuse large B-cell lymphoma, leg-type. JAMA Dermatol 2014; 150:1173.
- Koens L, Zoutman WH, Ngarmlertsirichai P, et al. Nuclear factor-κB pathway-activating gene aberrancies in primary cutaneous large B-cell lymphoma, leg type. J Invest Dermatol 2014; 134:290.
- Grange F, Hedelin G, Joly P, et al. Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome. The French Study Group on Cutaneous Lymphomas. Blood 1999; 93:3637.
- Koens L, Vermeer MH, Willemze R, Jansen PM. IgM expression on paraffin sections distinguishes primary cutaneous large B-cell lymphoma, leg type from primary cutaneous follicle center lymphoma. Am J Surg Pathol 2010; 34:1043.
- Demirkesen C, Tüzüner N, Esen T, et al. The expression of IgM is helpful in the differentiation of primary cutaneous diffuse large B cell lymphoma and follicle center lymphoma. Leuk Res 2011; 35:1269.
- Grange F, Petrella T, Beylot-Barry M, et al. Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas. Blood 2004; 103:3662.
- Hallermann C, Niermann C, Fischer RJ, Schulze HJ. New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas. J Am Acad Dermatol 2007; 56:588.
- Geelen FA, Vermeer MH, Meijer CJ, et al. bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related. J Clin Oncol 1998; 16:2080.
- Koens L, Senff NJ, Vermeer MH, et al. Methotrexate-associated B-cell lymphoproliferative disorders presenting in the skin: A clinicopathologic and immunophenotypical study of 10 cases. Am J Surg Pathol 2014; 38:999.
- Sterry W, Krüger GR, Steigleder GK. Skin involvement of malignant B-cell lymphomas. J Dermatol Surg Oncol 1984; 10:276.
- Muniesa C, Pujol RM, Estrach MT, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type and secondary cutaneous involvement by testicular B-cell lymphoma share identical clinicopathological and immunophenotypical features. J Am Acad Dermatol 2012; 66:650.
- Fink-Puches R, Zenahlik P, Bäck B, et al. Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients. Blood 2002; 99:800.
- Pandolfino TL, Siegel RS, Kuzel TM, et al. Primary cutaneous B-cell lymphoma: review and current concepts. J Clin Oncol 2000; 18:2152.
- Rijlaarsdam JU, Toonstra J, Meijer OW, et al. Treatment of primary cutaneous B-cell lymphomas of follicle center cell origin: a clinical follow-up study of 55 patients treated with radiotherapy or polychemotherapy. J Clin Oncol 1996; 14:549.
- Grange F, Joly P, Barbe C, et al. Improvement of survival in patients with primary cutaneous diffuse large B-cell lymphoma, leg type, in France. JAMA Dermatol 2014; 150:535.
- Senff NJ, Noordijk EM, Kim YH, et al. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood 2008; 112:1600.
- Suárez AL, Querfeld C, Horwitz S, et al. Primary cutaneous B-cell lymphomas: part II. Therapy and future directions. J Am Acad Dermatol 2013; 69:343.e1.
- Specht L, Dabaja B, Illidge T, et al. Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 2015; 92:32.
- http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf (Accessed on July 23, 2015).
- Kodama K, Massone C, Chott A, et al. Primary cutaneous large B-cell lymphomas: clinicopathologic features, classification, and prognostic factors in a large series of patients. Blood 2005; 106:2491.
- Senff NJ, Willemze R. The applicability and prognostic value of the new TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: results on a large cohort of primary cutaneous B-cell lymphomas and comparison with the system used by the Dutch Cutaneous Lymphoma Group. Br J Dermatol 2007; 157:1205.
- CLINICAL FEATURES
- PATHOLOGIC FEATURES
- DIFFERENTIAL DIAGNOSIS
- Systemic lymphoma
- Primary cutaneous follicle center lymphoma
- Primary cutaneous marginal zone lymphoma
- Cutaneous T cell lymphoma
- Intravascular lymphoma
- Iatrogenic immunodeficiency-associated lymphoproliferative disorders
- ASSESSING DISEASE RESPONSE
- TREATMENT AT RELAPSE
- SUMMARY AND RECOMMENDATIONS