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Published on: March 30, 2018
EBV-negative Aggressive NK-cell Leukemia/Lymphoma: Clinical, Pathologic, and Genetic Features
Alina Nicolae1, Karthik A Ganapathi, Trinh Hoc-Tran Pham
1*Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda ‡Department of Veteran Affairs, Maryland Healthcare System, Baltimore ∥Department of Pathology, Univerity of Maryland, St Joseph Medical Center, Towson, MD †Departments of Pathology and Dermatology, UT-MD Anderson Cancer Center, Houston, TX §Kaiser Permanente, Los Angeles, CA ¶Wayne Memorial Hospital, The Commonwealth Medical College, Scranton, PA.
Aggressive natural killer cell leukemia (ANKL) can occur without Epstein-Barr virus (EBV). This rare, aggressive cancer presents similarly to EBV-positive ANKL, affecting older adults with a poor prognosis.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Aggressive natural killer cell leukemia (ANKL) is a rare, aggressive systemic neoplasm of NK cells.
- Most ANKL cases are associated with Epstein-Barr virus (EBV), but EBV-negative cases are infrequently reported.
Purpose of the Study:
- To characterize the clinicopathologic, immunophenotypic, and molecular features of EBV-negative ANKL.
- To compare the clinical course and outcomes of EBV-negative ANKL with those of EBV-positive ANKL.
Main Methods:
- Clinicopathologic review of 7 EBV-negative ANKL cases.
- Immunohistochemistry and flow cytometry for immunophenotypic analysis.
- Mutational analysis (STAT3) and TCRG clonality assessment.
Main Results:
- EBV-negative ANKL occurred in older adults (median age 63) with an M:F ratio of 2.5:1.
- Clinical presentation included fever, cytopenias, splenomegaly, lymphadenopathy, and extranodal disease, similar to EBV-positive ANKL.
- Immunophenotype showed CD56+, CD2+, CD8+ cells, negative for EBV markers. STAT3 mutations were identified.
- Median survival was short (8 weeks), with one patient achieving remission post-allogeneic bone marrow transplant.
Conclusions:
- EBV-negative ANKL is a rare entity that clinically and pathologically resembles EBV-positive ANKL.
- It affects older adults and follows a fulminant clinical course with a poor prognosis.
- STAT3 mutations may play a role in the pathogenesis of EBV-negative ANKL.
