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Recurrent localized primary cutaneous marginal-zone B-cell lymphoma

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Recurrent localized primary cutaneous marginal-zone B cell lymphoma
Shoshana Marmon MD PhD, Julie Chu MD, Rishi Patel MD, Shane Meehan MD, Miriam Keltz Pomeranz MD
Dermatology Online Journal 17 (10): 27

Department of Dermatology, New York University, New York, New York


A 36-year-old man with a prior diagnosis of primary cutaneous marginal-zone B cell lymphoma presented with newly-developed, small, erythematous papules and nodules on his upper left arm and pink-to-skin-colored, clustered papules on his left forearm. A biopsy specimen and immunohistochemical analysis of the left arm lesions showed a lymphocytic infiltrate which stained positively for CD20 and Bcl-2 and negatively for CD10. A PET-CT scan was negative for any extra-cutaneous manifestations of disease. These clinicopathologic findings are indicative of recurrent localized primary cutaneous marginal-zone B cell lymphoma.


A 36-year-old man was referred to the Charles C. Harris Skin and Cancer Pavilion with new, erythematous papules on his left arm. The patient initially had presented five years prior to an another institution with a long history of raised, erythematous papules on his left arm. Multiple biopsies were performed. Polymerase chain reaction (PCR) of the initial biopsy specimens showed clonal rearrangement of immunoglobulin heavy chains. In situ hybridization for lambda and kappa chains showed a lambda-restricted monotypic process. PCR for Borrelia burgdorferi was negative. Immunohistochemical analysis showed a lymphocytic infiltrate with strong expression of CD20, Bcl-2, and the proliferative marker Ki-67. A number of similar lesions on the left arm were excised. A positron emission tomography/computed tomography (PET-CT) scan performed at the time of diagnosis was negative for lymphadenopathy or hepatosplenomegaly. The patient also was treated with topical bexarotene and electron-beam radiation therapy.

Physical examination

Figure 1Figure 2

Two, 3 mm to 4 mm, erythematous papules and nodules were noted on the upper left arm, and multiple, fine, 1 mm to 2 mm, pink-to-skin-colored papules were clustered on the left forearm.

Laboratory data

A complete blood count and comprehensive metabolic panel were normal. No paraproteins were noted in the serum or urine. No evidence of a clonal B or T cell process was detected in peripheral blood. Repeat PET-CT scan was normal.


Figure 3

Within the dermis, there is a perivascular and nodular proliferation of lymphocytes, which are reactive for CD20 and Bcl-2. Plasma cells are reactive for kappa and lambda light chains at a ratio of approximately 1:3.


Primary cutaneous B cell lymphomas are comprised of a heterogeneous group of diseases with various clinical, histopathologic, and immunophenotypic properties. The current classification of primary cutaneous lymphomas is based on guidelines developed by consensus between the European Organization for Research and Treatment of Cancer and the World Health Organization in 2005 [1]. B cell lymphomas are divided into four distinct subtypes: primary cutaneous marginal zone B cell lymphoma (PCMZL), primary cutaneous follicular center lymphoma, primary cutaneous diffuse large B cell lymphoma, leg type, and primary cutaneous diffuse large B cell lymphoma [1,2].

PCMZLs encompass entities previously designated as immunocytomas and plasmacytomas. These entities currently fall under the umbrella of extranodal marginal zone B cell lymphomas, which usually involve mucosal sites and are known as MALT (mucosa-associated lymphoid tissue) lymphomas [2]. Clinically, PCMZL presents as a few, multiple, pink, red-to-violaceous papules, plaques, or nodules that most often involve the trunk or extremities, especially the arms [3]. Although recurrence is not uncommon, extracutaneous dissemination is exceedingly rare and results in an excellent prognosis, with a five-year survival rate that approaches 100 percent [4].

Histopathologic features of PCMZLs include localized, nodular, or diffuse infiltrates of marginal-zone centrocyte-like cells with relative sparing of the epidermis. Plasma cells localized at the periphery of the infiltrate are a common feature as is the presence of reactive germinal centers, which may resemble a pseudolymphoma [1, 4].

The immunophenotype of the marginal-zone B lymphocytes in PCMZL is distinguished by the presence of CD20, CD79a, and Bcl-2 and the absence of CD5 and CD10 [1, 4]. Distinct genetic abnormalities and clonal rearrangements of immunoglobulin heavy chain genes also have been associated with PCMZLs. The presence of a translocation that involves the IGH and the MLT genes as well as the IGH and FOXP1 genes has been demonstrated in a percentage of PCMZLs [5, 6].

Although the pathogenesis of PCMZL remains unclear, an infectious agent that leads to chronic antigenic stimulation has been purported as potentially causative. An association between infection with Borrelia burgdorferi and the development of PCMZL evolved from studies in regions of Europe where Lyme borreliosis is endemic, and a greater prevalence of the spirochete was noted in patients with PCMZL. However, no such link has been identified in American or Asian cases of PCMZL. Furthermore, a recent study that involved 60 cases of PCMZL from Asia, Germany, and the United States, specifically examined this association. Cases of PCMZL were examined for the presence of Borrelia DNA by PCR analysis, and all were negative, which illustrated that the underlying pathogenesis of this lymphoma remains ambiguous [7].

Alterations in mechanisms inherent to B cell maturation may be central to the pathogenesis of PCMZL. In secondary lymphoid organs, B cells are selected which will produce antibody with the greatest affinity for the encountered antigen. This process, which is known as affinity maturation, involves somatic hypermutation and clonal selection which results in the survival of B cells that will drive a productive immune response and the elimination of ineffectual or potentially harmful cells. The pathogenesis of most non-Hodgkin B cell lymphomas has been thought to be in some way associated with genetic errors, such as chromosomal translocations or aberrant somatic hypermutation (ASHM), which occur during this selection process [8]. An analysis of this phenomena in tissue from PCMZL patients found ASHM in the regulatory and coding regions in a number of proto-oncogenes in nearly all of the PCMZL samples that were evaluated [8]. This observation suggests that aberrant mutation events coupled with a breakdown in the protective repair mechanisms in germinal center B cells also may underlie the genesis of more indolent lymphomas such as PCMZL. It is as yet unclear as to why this type of lymphoma remains largely confined to the skin.

As PCMZL rarely has been shown to exhibit extra-cutaneous manifestations, the treatment options are variable and include surgical excision, topical or intralesional glucocorticoids, interferon-α, chemotherapy, expectant management, and the anti-CD20 monoclonal antibody rituximab [9]. Reports have demonstrated partial-to-complete remission with the use of rituximab as a treatment for primary cutaneous lymphomas using either intravenous or intralesional forms of the agent [10]. A nearly complete regression has been reported in two patients with PCMZL without systemic involvement, who were treated with intralesional rituximab for eighteen weeks [9]. Because of the indolent nature of PCMZL, the course of treatment also may be influenced by the involved site, age and health of the patient, number of lesions, and presence or absence of recurrence.


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