Answer: B

Primary cutaneous B-cell lymphoma is a non-Hodgkin lymphoma, the primary site of which is the skin. These lymphomas have no evidence of extracutaneous involvement at the time of the initial staging evaluation. Historically, cutaneous B-cell lymphomas were always considered to be secondary to dissemination from a lymph node or other extracutaneous source. It was not until the 1980s that cutaneous B-cell lymphomas were first recognized as a separate entity.10

Cutaneous B-cell lymphomas make up approximately 25% of primary cutaneous lymphomas, with T-cell lymphomas comprising the other 75%.11 There are 3 main classes of primary cutaneous B-cell lymphoma: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone B-cell lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type.12

Primary cutaneous lymphoma affects one person per 100,000 to 200,000 people in Western countries annually. The incidence of primary cutaneous B-cell lymphoma differs by region. An epidemiologic study in the United States demonstrated that only 4.5% of primary cutaneous lymphomas were classified as B cell in origin; however, in some European countries, cutaneous B-cell lymphomas comprised 22.5% of primary cutaneous lymphomas.13 Primary cutaneous B-cell lymphoma affects adults (median age, 51 years), with a male-to-female ratio of 1.5:1. Unlike mycosis fungoides (T-cell lymphoma), which has a high prevalence in black patients, primary cutaneous B-cell lymphoma almost exclusively affects non-Hispanic white patients.14

The pathogenesis of primary cutaneous B-cell lymphoma is unknown, and there are no known risk factors for the disease. It has been hypothesized that chronic exposure to antigens stimulates cutaneous B-cell lymphoma development. Some studies and case reports suggest an association between primary cutaneous B-cell lymphoma and Borrelia burgdorferi or certain viruses; these studies have been unsubstantiated to date.15

The presentation and histology of cutaneous B-cell lymphoma differ by subtype. PCFCL is defined as a neoplastic proliferation of germinal center cells in the skin. It presents as singular or clustered pink-to-purple papules, plaques, or nodules. A peripheral ring of erythema often surrounds these lesions. PCFCL lesions favor the head, neck, and trunk. PCFCL is a slow-growing, indolent neoplasm. Skin lesions may be present for decades, with a period of gradual growth and a latent phase, before diagnosis. Systemic “B” symptoms are extremely rare in PCFCL.16 These tumors rarely metastasize and prognosis is favorable.15 On histologic examination, PCFCL demonstrates a follicular and/or diffuse growth pattern of centrocytes and centroblasts in the dermis and subcutaneous tissue. The tumor is positive for CD20, CD79a, and Bcl-6 on immunohistochemical staining. Unlike other follicular lymphomas, PCFCL is rarely associated with the Bcl-2 t(14;18) translocation.14

PCMZL presents as red-violet papules, plaques, or nodules most commonly located on the trunk, upper extremity, or head. PCMZL is a neoplasm of marginal-zone B-cells. It carries an excellent prognosis, with a 5-year survival rate of nearly 100%. Cutaneous relapse after resolution may occur. On histologic examination, a nodular, patchy, or diffuse infiltrate of marginal-zone B-cells (small cells with irregular nuclei and pale cytoplasm) joined by various other immune cells can be visualized in the dermis and subcutaneous tissue. On immunohistochemical staining, the neoplasm is positive for CD20, CD43, and Bcl-2, but negative for CD5, CD10, and Bcl-6.14

Primary cutaneous DLBCLLT most commonly presents in elderly female patients as single or grouped red-to-brown nodules on a lower extremity. The nodules may be admixed with smaller papules, and ulceration of the lesions may occur. Although this subtype is designated “leg type,” these tumors present elsewhere on the body in approximately 20% of patients.15 The prognosis for DLBCLLT is poor, with a 5-year disease-specific survival rate of only 40% to 50%. Histologic examination demonstrates diffuse proliferation of large centroblasts and immunoblasts that are twice the size of normal lymphocytes. Many cells contain prominent nucleoli and mitotic figures. The infiltrate occupies the dermis in sheets. The neoplastic cells stain positive for CD20, CD79a, Bcl-2, FOX-P1, and MUM1, with variable expression of Bcl-6 and negative expression of CD10.14,17

All of the primary cutaneous B-cell lymphomas must be distinguished from each other and from other cutaneous lymphomas. Examination of histopathologic morphology and performance of immunohistochemical staining allows differentiation between the various subtypes of primary cutaneous lymphomas. It is especially critical to differentiate PCFCL from DLBCLLT, as both present with large B-cell infiltrates, but the latter has a more aggressive course with poor prognosis. This can be accomplished via immunophenotyping. Cutaneous T-cell lymphomas such as mycosis fungoides are distinguished by their positive expression of T-cell markers, including CD3.15

Primary cutaneous B-cell lymphomas must also be differentiated from other inflammatory processes, such as infection or arthropod bites, which may have a similar clinical appearance and histopathology. The cutaneous follicular hyperplasia of an inflammatory process, however, will have clearly defined follicles, mantle zones, and the presence of tingible body macrophages.18

Diagnosis is based on histopathology of the skin biopsy, evaluating for cell morphology, pattern of growth, and immunohistochemical properties. The biopsy must include the reticular dermis and fat, and excisional biopsies are often preferred.14 Complete staging must be performed to rule out secondary cutaneous involvement from an extracutaneous source, most commonly a lymph node. Staging includes complete blood count, peripheral blood flow cytometry, and computed tomographic and positron emission tomographic imaging. Measurement of lactate dehydrogenase can also be used to rule out nodal lymphoma, as the level should fall within normal limits in primary cutaneous lymphomas.15

Patients with PCFCL and PCMZL who have few lesions have several treatment options: direct radiotherapy of the lesion, surgical excision, or surgical excision followed by radiotherapy. For select indolent lesions, “watchful waiting” with close clinical follow-up may be the best option. Intralesional rituximab is another potential therapy for indolent, localized lesions.15 Patients with disseminated B-cell lymphomas or DLBCLLT usually require systemic chemotherapy plus intravenous rituximab.17 After completion of therapy, patients should be monitored closely and assessed for relapse.

As for the patient in our case, an excisional biopsy demonstrated PCFCL. She elected to receive radiotherapy to her lesion, and she is currently undergoing treatment.

Talia Noorily, BS, is a medical student; Joan Fernandez, BS, is a medical student; and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.  

References

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