EBV Viral Load in Tumor Tissue Is an Important Prognostic Indicator for Lym
We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (<1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.
Nasal NK/T-cell lymphoma (NNTCL), defined as extra-nodal NK/T-cell lymphoma, nasal type, occurring in nasal areas, is a rare lymphoma in the United States and Europe but is relatively common in Asia and Latin America. Although most sinonasal lymphomas in the Western population are diffuse large B-cell lymphomas, 40% to 74% of sinonasal lymphomas are NNTCL in Asia. NNTCLs usually occur in middle-aged patients, and their presenting features are characterized by localized disease in the majority of patients, frequent adjacent tissue invasion, a high frequency of B symptoms, and rare bone marrow involvement. Pathologically, NNTCL has a broad cytologic spectrum varying from small, medium, and large cells to anaplastic cells. The tumor cells have been characterized positively for CD2, cytoplasmic CD3 (CD3ε), CD56, and T-cell intracellular antigen-1 (TIA-1) by immunophenotyping and positively for Epstein-Barr virus–encoded RNA (EBER) by in situ hybridization.
Because NNTCL is relatively a newly recognized, distinctive clinicopathologic entity in the World Health Organization (WHO) classification, prognostic factors have not been fully defined. Although validated in many types of lymphomas ranging from low to high grades, the prognostic impact of the International Prognostic Index has been controversial in NNTCL, with some studies yielding a positive correlation and some a negative correlation. Similarly, the Ann Arbor Staging System has only limited value in predicting prognosis. Patients with nasal stage IIIE/IVE had been reported to exhibit more aggressive tumor behavior and poorer prognosis than patients with nasal stage IE/IIE NNTCL. However, the Ann Arbor stage failed to predict the survival difference between stage IE and stage IIE, which included most of the cases (82%) at presentation.
A few studies have evaluated the relationship between patient survival and disease extent, histologic subtype, or plasma EBV viral load. A recent study suggested that local tumor invasiveness is more predictive of patient survival than the International Prognostic Index in stage IE/IIE NNTCL. Kuo et al noted no statistical difference in patient survival by histologic subtype. Lei et al stated that patients with high baseline plasma Epstein-Barr virus (EBV) DNA levels (≥600 copies/mL) demonstrated a significantly inferior survival to patients with low baseline plasma EBV DNA levels (<600 copies/mL) in extranodal NK/T-cell lymphoma.
The lack of prognostic markers has created significant challenges in treatment selection for the very heterogeneous clinical behavior of NNTCL—particularly for patients with stage IE/IIE disease (ie, paranasal extension, bone destruction, skin or regional lymph node involvement). The goal of the present study was to identify prognostic markers for NNTCL by comprehensively evaluating the prognostic significance of the following factors: extent of lesion, histologic subtypes, age, CD56 expression, stage, necrosis, angiocentric and angiodestructive growth patterns, and EBV viral load in tumor tissue. To the best of our knowledge, the last 2 factors have never been well studied in NNTCL.
We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (<1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.
Nasal NK/T-cell lymphoma (NNTCL), defined as extra-nodal NK/T-cell lymphoma, nasal type, occurring in nasal areas, is a rare lymphoma in the United States and Europe but is relatively common in Asia and Latin America. Although most sinonasal lymphomas in the Western population are diffuse large B-cell lymphomas, 40% to 74% of sinonasal lymphomas are NNTCL in Asia. NNTCLs usually occur in middle-aged patients, and their presenting features are characterized by localized disease in the majority of patients, frequent adjacent tissue invasion, a high frequency of B symptoms, and rare bone marrow involvement. Pathologically, NNTCL has a broad cytologic spectrum varying from small, medium, and large cells to anaplastic cells. The tumor cells have been characterized positively for CD2, cytoplasmic CD3 (CD3ε), CD56, and T-cell intracellular antigen-1 (TIA-1) by immunophenotyping and positively for Epstein-Barr virus–encoded RNA (EBER) by in situ hybridization.
Because NNTCL is relatively a newly recognized, distinctive clinicopathologic entity in the World Health Organization (WHO) classification, prognostic factors have not been fully defined. Although validated in many types of lymphomas ranging from low to high grades, the prognostic impact of the International Prognostic Index has been controversial in NNTCL, with some studies yielding a positive correlation and some a negative correlation. Similarly, the Ann Arbor Staging System has only limited value in predicting prognosis. Patients with nasal stage IIIE/IVE had been reported to exhibit more aggressive tumor behavior and poorer prognosis than patients with nasal stage IE/IIE NNTCL. However, the Ann Arbor stage failed to predict the survival difference between stage IE and stage IIE, which included most of the cases (82%) at presentation.
A few studies have evaluated the relationship between patient survival and disease extent, histologic subtype, or plasma EBV viral load. A recent study suggested that local tumor invasiveness is more predictive of patient survival than the International Prognostic Index in stage IE/IIE NNTCL. Kuo et al noted no statistical difference in patient survival by histologic subtype. Lei et al stated that patients with high baseline plasma Epstein-Barr virus (EBV) DNA levels (≥600 copies/mL) demonstrated a significantly inferior survival to patients with low baseline plasma EBV DNA levels (<600 copies/mL) in extranodal NK/T-cell lymphoma.
The lack of prognostic markers has created significant challenges in treatment selection for the very heterogeneous clinical behavior of NNTCL—particularly for patients with stage IE/IIE disease (ie, paranasal extension, bone destruction, skin or regional lymph node involvement). The goal of the present study was to identify prognostic markers for NNTCL by comprehensively evaluating the prognostic significance of the following factors: extent of lesion, histologic subtypes, age, CD56 expression, stage, necrosis, angiocentric and angiodestructive growth patterns, and EBV viral load in tumor tissue. To the best of our knowledge, the last 2 factors have never been well studied in NNTCL.
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