Abstract
Diffuse large B-cell lymphoma (DLBCL) is a curable, highly aggressive subtype of non-Hodgkin's lymphoma (NHL). It typically manifests as a rapidly-growing mass in a lymph node or extranodal distribution. Outcomes in this disease have improved significantly with the incorporation of anti-CD20 monoclonal antibodies in addition to combination chemotherapy. Further characterization of molecular and pathologic subtypes of DLBCL is currently the subject of intensive investigation, and optimal therapy for specific subtypes of DLBCL remains to be determined.
We report the case of a 66-year-old woman who presented to the Emergency Department with a diffuse, non-pruritic, purple rash of her bilateral lower extremities of one week duration. The rash was accompanied by one episode of subjective fever and lower back pain. The patient did not endorse night sweats or weight loss prior to presentation. Physical examination revealed a healthy-appearing woman with systemic pallor, non-blanching, pink/purple papules over both lower extremities, and one indurated, pink/brown, firm plaque over the left medial malleolus (Image 1-3). Laboratory studies revealed a leukocytosis with a total white blood cell count of 46.6x109/L (28% polymorphonuclear cells, 13% band forms, 16% lymphocytes, and 34% atypical lymphoid cells), lactate dehydrogenase >3600 IU/L, uric acid 15.2 mg/dL. Radiographic studies of the chest, abdomen, and pelvis revealed only minimally-prominent mesenteric lymph nodes, which were not reported as pathologically enlarged, with no other mass or potential primary lesion identified.
Flow cytometry of peripheral blood identified 44% neoplastic B-lymphoid cells expressing CD19, CD20, CD10, and CD38. The hypercellular bone marrow had 80-90% blast-like, surface IgG positive B-lymphoid cells, positive for MUM1, CD10 and bcl2 and in a small subset (10%) positive for c-myc. They were cyclin D1, CD34 and TdT negative. FISH studies detected the presence of t(14;18), IGH-BCL2 fusion, and deletion of both CDKN2A and MLL; a c-myc rearrangement was not detected. A punch biopsy of the right medial malleolus showed dense infiltration of the subcutaneous fat and dermis by CD20, CD10, MUM-1, CD31positive B- lymphoid cells in a subset also bcl6 positive. Together, these findings were interpreted to be most consistent with a leukemic-phase DLBCL.
Given previous reports that DLBCL with CDKN2A deletions have poor outcomes with standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)1, treatment was initiated with dose-adjusted rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone (DA-R-EPOCH). The patient subsequently transferred care to another institution and continued treatment with R-CHOP and methotrexate (MTX). The patient's rash and leukocytosis resolved after the first cycle of DA-R-EPOCH. After the third cycle of R-CHOP and MTX, the patient presented to the Emergency Department with febrile neutropenia and mucositis, and was found to have a methotrexate level of 0.19 µMol/L. She ultimately died due to complications from severe sepsis.
In summary, we present a patient with a rare presentation of leukemic-phase DLBCL, with the first reported case of skin infiltration from this entity. Further studies are necessary to determine treatment with optimal outcomes and minimal toxicity for this and other rare subtypes of DLBCL.
Reference:
1. Jardin, F., et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 116(7): 1092-1104. 2010
Figure 1 Left ankle Figure 1. Left ankle Figure 2 Right Calf Figure 2. Right Calf Figure 3 Right leg Figure 3. Right leg
Disclosures
No relevant conflicts of interest to declare.
MYC-Positive Diffuse Large B-Cell Lymphoma in Leukemic Phase at Presentation: A Diagnostic and Therapeutic Challenge