To the Editor:
A 73-year-old man was admitted to the hospital with progressive abdominal and hip pain of several weeks’ duration that was accompanied by unilateral swelling of the left leg. He had a medical history of hypertension, hyperlipidemia, and prediabetes. Computed tomography (CT) showed extensive intra-abdominal, retroperitoneal, and pelvic lymphadenopathy in addition to poorly defined hepatic lesions.
A CT-guided core biopsy of a left inguinal lymph node showed Burkitt lymphoma. Fluorescence in situ hybridization was positive for oncogene c-MYC rearrangement on chromosome 8q24 and negative for B-cell lymphoma 2 (BCL2) and B-cell lymphoma 6 (BCL6) gene rearrangements. Flow cytometry demonstrated an aberrant population of κ light chain-restricted CD5−CD10+ B lymphocytes.
The patient’s overall disease burden was consistent with stage IV Burkitt lymphoma. R-miniCHOP chemotherapy—rituximab plus a reduced dose of cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone—was initiated. Approximately 2 weeks after chemotherapy was initiated, the patient developed a firm erythematous eruption on the left hip (Figure 1A). His regimen was then switched to R-EPOCH—rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin—at the time of discharge, and he was referred to dermatology due to an initial concern of an adverse reaction to R-EPOCH chemotherapy. The patient denied any pain, pruritus, or irritation. Physical examination showed multifocal, subcutaneous, indurated, erythematous and violaceous nodules without epidermal changes. Some nodules on the lateral aspect of the hip coalesced to form firm plaques.
FIGURE 1. A, Erythematous and violaceous indurated nodules and plaques on the left lower abdomen and left hip that were later diagnosed as cutaneous Burkitt lymphoma. B, Regression of lesions was noted after the second round of R-EPOCH chemotherapy— rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin.
A punch biopsy specimen showed markedly atypical lymphocytes with enlarged nuclei and scant cytoplasm present throughout the dermis (Figures 2A and 2B). Numerous apoptotic cells and cellular debris were seen. Immunohistochemical staining demonstrated that the lymphocytic infiltrate comprised CD79a+ B cells that were positive for Bcl-6 and CD10 and negative for Bcl-2 (Figures 2C and 2D). There also was diminished focal expression of CD20. Ki-67 protein staining was intensely positive and demonstrated a very high proliferative index.
FIGURE 2. A and B, A punch biopsy specimen showed markedly atypical lymphocytes present throughout the dermis (H&E, original magnifications ×4 and ×40). Lymphocytes have enlarged nuclei and scant cytoplasm. Numerous apoptotic cells with cellular debris were present. C and D, Immunohistochemical staining demonstrated that the infiltrate was comprised of CD79a+ B cells that were Bcl-6 positive (original magnifications ×20), respectively.
Taken together, these findings were consistent with a diagnosis of cutaneous metastasis of Burkitt lymphoma. The patient’s cutaneous lesions improved after continued aggressive chemotherapy. At follow-up 2 weeks after biopsy, he was receiving his second round of R-EPOCH chemotherapy with appreciable regression of skin lesions (Figure 1B). However, he then developed right-side double vision, ptosis, and right-side facial paresthesia. Although magnetic resonance imaging of the brain and lumbar puncture did not show evidence of central nervous system involvement, the chemotherapy regimen was switched to dose-adjusted CVAD-R—hypercyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone plus rituximab—for empiric treatment of central nervous system disease. Although treatment was complicated by sepsis with extended-spectrum β-lactamase-producing Enterobacter cloacae, Burkitt lymphoma was found to be in remission after 3 cycles of CVAD-R and 5 months of chemotherapy.
Burkitt lymphoma is a B-cell non-Hodgkin malignancy caused by translocation of chromosome 8 and chromosome 14, leading to overexpression of c-MYC and subsequent hyperproliferation of B lymphocytes.1,2 The disease is divided into 3 major categories: sporadic, endemic, and immunodeficiency related.3 The endemic variant is the most prevalent subtype in Africa and is associated with Plasmodium falciparum malaria; the sporadic variant is the most common subtype in the rest of the world.4
Burkitt lymphoma is highly aggressive and is characterized by unusually high rates of mitosis and apoptosis that result in abundant cellular debris and a distinctive starry-sky pattern on histopathology.5,6 Extranodal metastasis is common,7 but cutaneous involvement is exceedingly rare, with only a few cases having been reported.8-14 Cutaneous metastasis of Burkitt lymphoma often is associated with a high overall disease burden and poor prognosis.8,11