Primary cutaneous marginal zone lymphoma
- 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 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, leg type
●Primary cutaneous marginal zone lymphoma (PCMZL); this subtype is included in the broader category of extranodal marginal zone B cell lymphoma (see "Clinical manifestations, pathologic features, and diagnosis of extranodal (MALT) and nodal marginal zone lymphomas")
These three subtypes appear to be unique entities with differing clinical presentation, pathologic features, and prognosis. They also require slightly different treatment approaches. This topic review will discuss PCMZL. Before 2008 some cases of PCMZL may have been classified as primary cutaneous immunocytoma or cutaneous plasmacytoma.
- 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.
- 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.
- Park JH, Shin HT, Lee DY, et al. World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphoma in Korea: a retrospective study at a single tertiary institution. J Am Acad Dermatol 2012; 67:1200.
- Fujita A, Hamada T, Iwatsuki K. Retrospective analysis of 133 patients with cutaneous lymphomas from a single Japanese medical center between 1995 and 2008. J Dermatol 2011; 38:524.
- 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.
- Gerami P, Wickless SC, Querfeld C, et al. Cutaneous involvement with marginal zone lymphoma. J Am Acad Dermatol 2010; 63:142.
- Servitje O, Muniesa C, Benavente Y, et al. 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.
- Rijlaarsdam U, Bakels V, van Oostveen JW, et al. Demonstration of clonal immunoglobulin gene rearrangements in cutaneous B-cell lymphomas and pseudo-B-cell lymphomas: differential diagnostic and pathogenetic aspects. J Invest Dermatol 1992; 99:749.
- Anthonissen FM, De Kesel M, Hoet PP, Bigaignon GH. Evidence for the involvement of different genospecies of Borrelia in the clinical outcome of Lyme disease in Belgium. Res Microbiol 1994; 145:327.
- Jelić S, Filipović-Ljesković I. Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding? Hematol Oncol 1999; 17:107.
- Li C, Inagaki H, Kuo TT, et al. Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathologic study of 24 asian cases. Am J Surg Pathol 2003; 27:1061.
- Wood GS, Kamath NV, Guitart J, et al. Absence of Borrelia burgdorferi DNA in cutaneous B-cell lymphomas from the United States. J Cutan Pathol 2001; 28:502.
- Balmelli T, Piffaretti JC. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato. Res Microbiol 1995; 146:329.
- Goodlad JR, Davidson MM, Hollowood K, et al. Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland. Am J Surg Pathol 2000; 24:1279.
- Slater DN. Borrelia burgdorferi-associated primary cutaneous B-cell lymphoma. Histopathology 2001; 38:73.
- Beylot-Barry M, Vergier B, Masquelier B, et al. The Spectrum of Cutaneous Lymphomas in HIV infection: a study of 21 cases. Am J Surg Pathol 1999; 23:1208.
- McGregor JM, Yu CC, Lu QL, et al. Posttransplant cutaneous lymphoma. J Am Acad Dermatol 1993; 29:549.
- Watabe H, Kawakami T, Soma Y, et al. Primary cutaneous T-cell-rich B-cell lymphoma in a zosteriform distribution associated with Epstein-Barr virus infection. J Dermatol 2002; 29:748.
- Nagore E, Ledesma E, Collado C, et al. Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas. Br J Dermatol 2000; 143:320.
- Peris K, Niedermeyer H, Cerroni L, et al. Detection of Epstein-Barr virus genome in primary cutaneous T and B cell lymphomas and pseudolymphomas. Arch Dermatol Res 1994; 286:364.
- Viguier M, Rivet J, Agbalika F, et al. B-cell lymphomas involving the skin associated with hepatitis C virus infection. Int J Dermatol 2002; 41:577.
- Hermine O, Lefrère F, Bronowicki JP, et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002; 347:89.
- Rijlaarsdam JU, van der Putte SC, Berti E, et al. Cutaneous immunocytomas: a clinicopathologic study of 26 cases. Histopathology 1993; 23:117.
- Cunningham-Rundles C, Cooper DL, Duffy TP, Strauchen J. Lymphomas of mucosal-associated lymphoid tissue in common variable immunodeficiency. Am J Hematol 2002; 69:171.
- Pereira FO, Graf H, Nomura LM, et al. Concomitant presentation of Hashimoto's thyroiditis and maltoma of the thyroid in a twenty-year-old man with a rapidly growing mass in the neck. Thyroid 2000; 10:833.
- Hoefnagel JJ, Vermeer MH, Jansen PM, et al. Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic features in 50 cases. Arch Dermatol 2005; 141:1139.
- 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.
- Connors JM, Hsi ED, Foss FM. Lymphoma of the skin. Hematology Am Soc Hematol Educ Program 2002; :263.
- Zinzani PL, Magagnoli M, Galieni P, et al. Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients. J Clin Oncol 1999; 17:1254.
- Streubel B, Lamprecht A, Dierlamm J, et al. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 2003; 101:2335.
- Schreuder MI, Hoefnagel JJ, Jansen PM, et al. FISH analysis of MALT lymphoma-specific translocations and aneuploidy in primary cutaneous marginal zone lymphoma. J Pathol 2005; 205:302.
- Streubel B, Simonitsch-Klupp I, Müllauer L, et al. Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites. Leukemia 2004; 18:1722.
- 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.
- Streubel B, Vinatzer U, Lamprecht A, et al. T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia 2005; 19:652.
- Swerdlow SH, Quintanilla-Martinez L, Willemze R, Kinney MC. Cutaneous B-cell lymphoproliferative disorders: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol 2013; 139:515.
- Sarantopoulos GP, Palla B, Said J, et al. Mimics of cutaneous lymphoma: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol 2013; 139:536.
- Magro C, Crowson AN, Porcu P, Nuovo GJ. Automated kappa and lambda light chain mRNA expression for the assessment of B-cell clonality in cutaneous B-cell infiltrates: its utility and diagnostic application. J Cutan Pathol 2003; 30:504.
- van Maldegem F, van Dijk R, Wormhoudt TA, et al. The majority of cutaneous marginal zone B-cell lymphomas expresses class-switched immunoglobulins and develops in a T-helper type 2 inflammatory environment. Blood 2008; 112:3355.
- Kazakov DV, Belousova IE, Müller B, et al. Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature. J Cutan Pathol 2002; 29:244.
- Green T, Grant J, Pye R, Marcus R. Multiple primary cutaneous plasmacytomas. Arch Dermatol 1992; 128:962.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Golling P, Cozzio A, Dummer R, et al. Primary cutaneous B-cell lymphomas - clinicopathological, prognostic and therapeutic characterisation of 54 cases according to the WHO-EORTC classification and the ISCL/EORTC TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome. Leuk Lymphoma 2008; 49:1094.
- Chang YT, Wong CK. Primary cutaneous plasmacytomas. Clin Exp Dermatol 1994; 19:177.
- Senff NJ, Kluin-Nelemans HC, Willemze R. Results of bone marrow examination in 275 patients with histological features that suggest an indolent type of cutaneous B-cell lymphoma. Br J Haematol 2008; 142:52.
- Kim YH, Willemze R, Pimpinelli N, et al. TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007; 110:479.
- 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.
- 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.
- http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf (Accessed on September 24, 2013).
- 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.
- Hamilton SN, Wai ES, Tan K, et al. Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience. Int J Radiat Oncol Biol Phys 2013; 87:719.
- Neelis KJ, Schimmel EC, Vermeer MH, et al. Low-dose palliative radiotherapy for cutaneous B- and T-cell lymphomas. Int J Radiat Oncol Biol Phys 2009; 74:154.
- Perry A, Vincent BJ, Parker SR. Intralesional corticosteroid therapy for primary cutaneous B-cell lymphoma. Br J Dermatol 2010; 163:223.
- Amitay-Laish I, Feinmesser M, Ben-Amitai D, et al. Juvenile onset of primary low-grade cutaneous B-cell lymphoma. Br J Dermatol 2009; 161:140.
- Peñate Y, Hernández-Machín B, Pérez-Méndez LI, et al. Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphomas: an epidemiological observational multicentre study. The Spanish Working Group on Cutaneous Lymphoma. Br J Dermatol 2012; 167:174.
- Terhorst D, Mestel DS, Humme D, et al. Evaluation of different methods in the follow-up of patients with indolent types of primary cutaneous lymphomas. Br J Dermatol 2012; 166:1295.
- Gerami P, Wickless SC, Rosen S, et al. Applying the new TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome in primary cutaneous marginal zone lymphoma. J Am Acad Dermatol 2008; 59:245.
- 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.
- Zinzani PL, Quaglino P, Pimpinelli N, et al. Prognostic factors in primary cutaneous B-cell lymphoma: the Italian Study Group for Cutaneous Lymphomas. J Clin Oncol 2006; 24:1376.
- Infectious etiology
- - Borrelia burgdorferi
- - Viral etiologies
- Autoimmune disorders
- CLINICAL FEATURES
- PATHOLOGIC FEATURES
- DIFFERENTIAL DIAGNOSIS
- Reactive infiltrate
- Systemic lymphoma
- - Marginal zone lymphoma
- - Other systemic lymphomas
- Other cutaneous lymphomas
- - Primary cutaneous diffuse large B cell lymphoma, leg type
- - Primary cutaneous follicle center lymphoma
- - Cutaneous T cell lymphoma
- - Intravascular lymphoma
- Extramedullary plasmacytoma
- ASSESSING DISEASE RESPONSE
- TREATMENT AT RELAPSE
- SUMMARY AND RECOMMENDATIONS