American journal of clinical pathology · 2026
TP53 genetic alterations are highly recurrent in Epstein-Barr virus-negative aggressive NK-cell leukemia: insights from an institutional experience and comprehensive literature review.
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Gonzalez Mancera Miguel, Wilk Aaron J, Oak Jean, Natkunam Yasodha, Silva Oscar
Аннотация
OBJECTIVE: The differences between EBV-positive and EBV-negative aggressive NK-cell leukemia (ANKL) remain po orly understood. Herein, we sought to investigate the clinicopathologic and molecular differences between EBV-positive and EBV-negative ANKL.
METHODS: We retrospectively analyzed 14 ANKL cases (9 EBV-positive, 5 EBV-negative), assessing clinicopathologic, cytogenetic, and mutational features. In addition, we searched the published literature to further analyze the distribution of genetic variation between EBV-positive (n=116) and EBV-negative-ANKL (n=14). Lastly, we assessed the utility of p53 immunohistochemistry to screen for EBV-negative-ANKL.
RESULTS: Demographically, EBV-negative-ANKL patients were older (median age 64 vs. 37 years) and showed longer survival (median 13 vs. 1 month) than EBV-positive counterparts. Morphologic and immunophenotypic features were similar between groups. All EBV-negative cases assessed in our cohort harbored TP53 mutations (3/3). Combining our data with all reported ANKL cases with comprehensive mutational assessment of TP53, JAK/STAT and epigenetic modifier genes in the literature we find TP53 mutations or copy number alterations present in 82% of EBV-negative-ANKL (14/17) but in only 25% (29/116) of EBV-positive cases. In contrast, EBV-negative-ANKL showed less JAK/STAT and epigenetic modifier gene mutations compared to EBV-positive ANKL. Given the high frequency of TP53 genetic alteration, we show that p53 immunohistochemistry overexpression is present in all but one EBV-negative-ANKL case assessed thus far.
CONCLUSIONS: Our findings suggest that EBV-negative-ANKL is a distinct subtype of ANKL, highly enriched for TP53 genetic alterations and showing different epidemiologic and prognostic features compared to EBV-positive-ANKL. In addition, p53 immunohistochemistry may serve as a screening tool for EBV-negative-ANKL.
METHODS: We retrospectively analyzed 14 ANKL cases (9 EBV-positive, 5 EBV-negative), assessing clinicopathologic, cytogenetic, and mutational features. In addition, we searched the published literature to further analyze the distribution of genetic variation between EBV-positive (n=116) and EBV-negative-ANKL (n=14). Lastly, we assessed the utility of p53 immunohistochemistry to screen for EBV-negative-ANKL.
RESULTS: Demographically, EBV-negative-ANKL patients were older (median age 64 vs. 37 years) and showed longer survival (median 13 vs. 1 month) than EBV-positive counterparts. Morphologic and immunophenotypic features were similar between groups. All EBV-negative cases assessed in our cohort harbored TP53 mutations (3/3). Combining our data with all reported ANKL cases with comprehensive mutational assessment of TP53, JAK/STAT and epigenetic modifier genes in the literature we find TP53 mutations or copy number alterations present in 82% of EBV-negative-ANKL (14/17) but in only 25% (29/116) of EBV-positive cases. In contrast, EBV-negative-ANKL showed less JAK/STAT and epigenetic modifier gene mutations compared to EBV-positive ANKL. Given the high frequency of TP53 genetic alteration, we show that p53 immunohistochemistry overexpression is present in all but one EBV-negative-ANKL case assessed thus far.
CONCLUSIONS: Our findings suggest that EBV-negative-ANKL is a distinct subtype of ANKL, highly enriched for TP53 genetic alterations and showing different epidemiologic and prognostic features compared to EBV-positive-ANKL. In addition, p53 immunohistochemistry may serve as a screening tool for EBV-negative-ANKL.