TY - JOUR
T1 - EBV-negative aggressive NK-cell leukemia/ lymphoma
T2 - A clinical and pathological study from a single institution
AU - Gao, Juehua
AU - Behdad, Amir
AU - Ji, Peng
AU - Wolniak, Kristy L.
AU - Frankfurt, Olga
AU - Chen, Yi Hua
N1 - Publisher Copyright:
© 2017 USCAP, Inc All rights reserved.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Aggressive natural killer (NK)-cell leukemia/lymphoma is a systemic NK-cell neoplasm that preferentially affects Asians with a fulminant clinical course and is almost always associated with Epstein-Barr virus (EBV). The data on EBV-negative aggressive NK-cell leukemia/lymphoma are limited. Here we report a series of three patients (two Caucasians, one African-American) with EBV-negative aggressive NK-cell leukemia/lymphoma from a single institution, including a case diagnosed on post-mortem examination. Similar to EBV-positive aggressive NK-cell leukemia/lymphoma, our patients presented with constitutional symptoms and hepatosplenomegaly, and followed a highly aggressive clinical course. The disease involved peripheral blood, bone marrow, liver, spleen, and lymph node, and the neoplastic cells were pleomorphic with prominent azurophilic granules and demonstrated an atypical NK-cell phenotype. Lack of blood lymphocytosis (3 of 3), bone marrow interstitial infiltration (2 of 3), EBER negativity (3 of 3), and atypical phenotype including CD3 negativity by immunohistochemistry make an early recognition of the disease difficult. Ancillary studies revealed a complex karyotype (1 of 2), overexpression (3 of 3), and amplification (1 of 1) of c-MYC. The polycomb repressive complex 2 pathwayassociated proteins EZH2 and H3K27me3 and immune checkpoint protein PD-L1 were overexpressed in three of three and two of three cases, respectively. Our findings indicate that the EBV-negative aggressive NK-cell leukemia/lymphoma shares similar clinicopathological features to the EBV-positive counterpart except for the high prevalence of Asian seen in EBV-positive cases. Overexpression of polycomb repressive complex 2 pathway-associated proteins and PD-L1 suggest potential therapeutic targets for this aggressive disease. Nextgeneration sequencing on two of three cases identified multiple genetic alterations but were negative for JAK- STAT pathway-associated gene mutations previously reported in EBV-positive NK/T-cell lymphoma, suggesting alternative molecular pathogenic mechanisms for EBV-negative aggressive NK-cell leukemia/lymphoma.
AB - Aggressive natural killer (NK)-cell leukemia/lymphoma is a systemic NK-cell neoplasm that preferentially affects Asians with a fulminant clinical course and is almost always associated with Epstein-Barr virus (EBV). The data on EBV-negative aggressive NK-cell leukemia/lymphoma are limited. Here we report a series of three patients (two Caucasians, one African-American) with EBV-negative aggressive NK-cell leukemia/lymphoma from a single institution, including a case diagnosed on post-mortem examination. Similar to EBV-positive aggressive NK-cell leukemia/lymphoma, our patients presented with constitutional symptoms and hepatosplenomegaly, and followed a highly aggressive clinical course. The disease involved peripheral blood, bone marrow, liver, spleen, and lymph node, and the neoplastic cells were pleomorphic with prominent azurophilic granules and demonstrated an atypical NK-cell phenotype. Lack of blood lymphocytosis (3 of 3), bone marrow interstitial infiltration (2 of 3), EBER negativity (3 of 3), and atypical phenotype including CD3 negativity by immunohistochemistry make an early recognition of the disease difficult. Ancillary studies revealed a complex karyotype (1 of 2), overexpression (3 of 3), and amplification (1 of 1) of c-MYC. The polycomb repressive complex 2 pathwayassociated proteins EZH2 and H3K27me3 and immune checkpoint protein PD-L1 were overexpressed in three of three and two of three cases, respectively. Our findings indicate that the EBV-negative aggressive NK-cell leukemia/lymphoma shares similar clinicopathological features to the EBV-positive counterpart except for the high prevalence of Asian seen in EBV-positive cases. Overexpression of polycomb repressive complex 2 pathway-associated proteins and PD-L1 suggest potential therapeutic targets for this aggressive disease. Nextgeneration sequencing on two of three cases identified multiple genetic alterations but were negative for JAK- STAT pathway-associated gene mutations previously reported in EBV-positive NK/T-cell lymphoma, suggesting alternative molecular pathogenic mechanisms for EBV-negative aggressive NK-cell leukemia/lymphoma.
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U2 - 10.1038/modpathol.2017.37
DO - 10.1038/modpathol.2017.37
M3 - Article
C2 - 28548121
AN - SCOPUS:85026547693
SN - 0893-3952
VL - 30
SP - 1100
EP - 1115
JO - Modern Pathology
JF - Modern Pathology
IS - 8
ER -