Case Reports

Primary Cutaneous Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma: A Rare and Aggressive Cutaneous Lymphoma

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Cutaneous B-cell lymphomas represent a group of lymphomas derived from B lymphocytes in various stages of differentiation. The skin can be the site of primary or secondary involvement of any of the B-cell lymphomas. The classification of primary cutaneous B-cell lymphomas has evolved as the use of immunohistochemical and molecular genetic techniques have become more widespread. Primary cutaneous Epstein-Barr virus (EBV)–positive diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive cutaneous neoplasm with a more aggressive clinical course and poorer prognosis than most of the primary cutaneous B-cell lymphoma subtypes. Further research is needed to establish optimal treatment regimens for this aggressive cutaneous lymphoma. Although rare, EBV-positive DLBCL is an important entity to consider when evaluating a patient with a suspected primary cutaneous lymphoma.

Practice Points

  • Primary cutaneous lymphomas are malignant lymphomas confined to the skin.
  • Complete staging workup is necessary to rule out secondary involvement of the skin from a nodal lymphoma.
  • Epstein-Barr virus-positive diffuse large B-cell lymphoma is a rare and aggressive primary cutaneous lymphoma.


 

References

Cutaneous B-cell lymphomas represent a group of lymphomas derived from B lymphocytes in various stages of differentiation. The skin can be the site of primary or secondary involvement of any of the B-cell lymphomas. Primary cutaneous B-cell lymphomas present in the skin without evidence of extracutaneous disease at the time of diagnosis.1 The World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues recognizes 5 distinct primary cutaneous B-cell lymphoma subtypes: primary cutaneous follicle center lymphoma; primary cutaneous marginal zone lymphoma; primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type; DLBCL, not otherwise specified; and intravascular DLBCL.1-3 The DLBCL, not otherwise specified, category includes less common provisional entities with insufficient evidence to be recognized as distinct diseases. Epstein-Barr virus (EBV)–positive DLBCL is a rare subtype in this group.4

This article reviews the different clinicopathologic subtypes of primary cutaneous B-cell lymphoma. It also serves to help dermatologists recognize primary cutaneous EBV-positive DLBCL as a rare and aggressive form of this disease.

Case Report

An 84-year-old white man presented with a pruritic eruption on the arms, legs, back, neck, and face of 5 months’ duration. His medical history was notable for prostate cancer that was successfully treated with radiation therapy 6 years prior. The patient denied any constitutional symptoms such as fever, chills, night sweats, or weight loss, and review of systems was negative. The patient was taking prednisone, which alleviated the pruritus, but the lesions persisted.

Physical examination revealed multiple pink to erythematous papules and subcutaneous nodules involving the face, neck, back, arms, and legs (Figure 1). No scale, crust, or ulceration was present. Palpation of the cervical, supraclavicular, axillary, and inguinal lymph nodes was negative for lymphadenopathy.

Figure1

Figure 1. Primary cutaneous Epstein-Barr virus–positive diffuse large B-cell lymphoma presenting as erythematous subcutaneous nodules on the back (A) and pink and flesh-colored subcutaneous nodules on the right upper arm (B).

Punch biopsies of representative lesions on the upper back and right arm revealed diffuse and nodular infiltrates of large atypical lymphoid cells with scattered centroblasts and immunoblasts (Figures 2 and 3). Immunohistochemical staining demonstrated CD79, MUM-1, and EBV-encoded RNA positivity among the neoplastic cells. The Ki-67 proliferative index was greater than 90%. The neoplastic cells were negative for CD5, CD10, CD20, CD21, CD30, CD56, CD123, CD138, PAX5, C-MYC, BCL-2, BCL-6, cyclin D1, TCL-1A, and terminal deoxynucleotidyl transferase. Polymerase chain reaction showed a clonal B-cell population.

Figure2

Figure 2. A diffuse and nodular infiltrate of atypical lymphocytes in the dermis that extended into the subcutaneous tissue (H&E, original magnification ×4).

Figure3

Figure 3. A field composed of centrocytes with a few scattered centroblasts (H&E, original magnification ×40).

A peripheral blood smear did not show evidence of a B-cell lymphoproliferative process. A bone marrow biopsy was performed and did not show evidence of B-cell lymphoid neoplasia but did show reactive lymphoid aggregates composed of CD4+ and CD10+ T cells. Peripheral blood T-cell rearrangement and JAK2 were negative.

Based on clinical and histologic findings, the patient was diagnosed with primary cutaneous EBV-positive DLBCL. The patient was started on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for treatment of this aggressive cutaneous lymphoma, which initially resulted in clinical improvement of the lesions and complete involution of the subcutaneous nodules. After the sixth cycle of CHOP, he developed faintly erythematous indurated papules on the upper arms, chest, and back. Biopsy confirmed recurrence of the EBV-positive cutaneous lymphoma, and he started salvage chemotherapy with gemcitabine, oxaliplatin, and rituximab every 2 weeks; however, 4 months later (9 months after the initial presentation) he died from complications of the disease.

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