EBV+ nodal T/NK-cell lymphoma associated with clonal hematopoiesis and structural variations of the viral genome.

ABSTRACT: Epstein-Barr virus (EBV)-positive (EBV+) nodal T- and natural killer (NK)-cell lymphoma is a peripheral T-cell lymphoma (EBV+ nPTCL) that presents as a primary nodal disease with T-cell phenotype and EBV-harboring tumor cells. To date, the genetic aspect of EBV+ nPTCL has not been fully investigated. In this study, whole-exome and/or whole-genome sequencing was performed on 22 cases of EBV+ nPTCL. TET2 (68%) and DNMT3A (32%) were observed to be the most frequently mutated genes whose presence was associated with poor overall survival (P = .004). The RHOA p.Gly17Val mutation was identified in 2 patients who had TET2 and/or DNMT3A mutations. In 4 patients with TET2/DNMT3A alterations, blood cell-rich tissues (the bone marrow [BM] or spleen) were available as paired normal samples. Of 4 cases, 3 had at least 1 identical TET2/DNMT3A mutation in the BM or spleen. Additionally, the whole part of the EBV genome was sequenced and structural variations (SVs) were found frequent among the EBV genomes (63%). The most frequently identified type of SV was deletion. In 1 patient, 4 pieces of human chromosome 9, including programmed death-ligand 1 gene (PD-L1) were identified to be tandemly incorporated into the EBV genome. The 3' untranslated region of PD-L1 was truncated, causing a high-level of PD-L1 protein expression. Overall, the frequent TET2 and DNMT3A mutations in EBV+ nPTCL seem to be closely associated with clonal hematopoiesis and, together with the EBV genome deletions, may contribute to the pathogenesis of this intractable lymphoma.

Estimating the global burden of Epstein-Barr virus-related cancers.

BACKGROUND: More than 90% of the adult population globally is chronically infected by the Epstein-Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers. METHOD: We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein. CONCLUSION: We estimated that EBV-related cases from these six cancers accounted for 239,700-357,900 new cases and 137,900-208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.

Secondary parenchymal CNS involvement by lymphoma including rare types: Follicular and EBV-positive NK/T cell lymphoma, nasal type.

BACKGROUND: Secondary CNS involvement by systemic lymphomas (SCNSL) is uncommon, but when it occurs, is usually due to diffuse large B cell lymphoma (DLBCL). Three recent unusual cases serve to highlight diagnostic challenges. OBJECTIVE: To report SCNSL from DLBCL and two unusual lymphoma types: follicular lymphoma with high-grade transformation to DLBCL and NK/T cell lymphoma, nasal type (ENKL), nasal type. RESULTS: SCNSL in the DLBCL case occurred at 7-year interval from primary in a 54-year-old woman who presented with stroke-like symptoms and a right postcentral gyrus 2.6 × 2.9 × 2.6 cm. mass. The follicular lymphoma occurred at 6-month interval in a 69-year-old woman with 1 month of diplopia and 2 weeks of cognitive decline; multifocal lesions involved temporal lobe, subependymal periventricular areas, brainstem, cerebellum, hypothalamus, corpus callosum and gyrus rectus. The ENKL occurred at 25-month interval from nasal biopsy in a 45-year-old man with 1 week of altered mental status; multifocal cerebral and brainstem lesions were identified. Histological features in cases 1 and 3 were identical to the primary lymphoma, with high-grade transformation to DLBCL in the follicular lymphoma. CONCLUSION: Unusual features in our series include longer interval from primary to relapse in case 1 with DLBCL (usually <2 years of diagnosis), and SCNSL occurring from either follicular lymphoma or EKNL, nasal type (<6% of cases). Pathologists play an important role in excluding infectious, especially in cases with parenchymal lesions and characterizing the lymphoma type in SCNSL.

Combination of Gemcitabine and Thymosin alpha 1 exhibit a better anti-tumor effect on nasal natural killer/T-cell lymphoma.

BACKGROUND: Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive and poor prognostic malignant tumor along with high-level infection of Epstein-Barr virus (EBV). Gemcitabine (Gem) and Thymosin alpha 1 (Tα1) exert an anti-tumor effect in various cancers. However, the effect of the combination of Gem and Tα1 in NNKTL remains unknown. METHODS: SNK6 cells were treated with Gem, Tα1 and Gem plus Tα1 for 48 h. The expression levels of EBV and inflammatory factors were measured by qRT-PCR assay. The effect of Gem and Tα1 on cell viability, proliferation, apoptosis, autophagy was detected by CCK-8, colony formation, flow cytometry, autophagic flux measurement, respectively. Western blot was used to evaluate the expression of proteins related to epithelial-mesenchymal transition (EMT), apoptosis and autophagy. In vivo xenograft models were used to further verify the roles of Gem and Tα1. Tumors were removed for weight measurement, H&E and IHC staining. RESULTS: We identified that the half maximal inhibitory concentration (IC50) of Gem and Tα1 was 116.5 µmol/ml and 1.334 µmol/ml. Alone or combined administration of Gem and Tα1 dramatically attenuated the EBV viral load and promoted inflammatory factors expression in SNK6 cells, among which the combination of Gem and Tα1 treatment showed the most significant effect. Besides, combination treatment with Gem and Tα1 markedly inhibited cell growth and EMT progress, and enhanced apoptosis and autophagy. Similarly, Gem combined with Tα1 suppressed tumor growth, promoted apoptosis and autophagy in vivo. Additionally, combination treatment with Gem and Tα1 inhibited PI3K/AKT/mTOR pathway. CONCLUSION: In summary, combination administration of Gem and Tα1 suppressed the progression of NNKTL in vivo and in vitro. Our study provided an effective therapeutic strategy potentially for the clinical treatment of NNKTL.

Updating targets for natural killer/T-cell lymphoma immunotherapy.

Natural killer/T-cell lymphoma (NKTCL) is a highly invasive subtype of non-Hodgkin lymphoma, typically positive for cytoplasmic CD3, CD56, cytotoxic markers, including granzyme B and TIA1, and Epstein-Barr virus (EBV). The current treatment methods for NKTCL are associated with several drawbacks. For example, chemotherapy can lead to drug resistance, while treatment with radiotherapy alone is inadequate and results in frequent relapses. Moreover, hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts. In recent years, immunotherapy has shown good clinical results and has become a hot spot in cancer research. Clinical activity of targeted antibodies, such as daratumumab (anti-CD38 antibody) and brentuximab vedotin (anti-CD30 antibody), have been reported in NKTCL. Additionally, dacetuzumab and Campath-1H have demonstrated promising results. Further encouraging data have been obtained using checkpoint inhibitors. The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL. Furthermore, anti-CCR4 monoclonal antibodies (mAbs) exert cytotoxic actions on both CCR4+ tumor cells and regulatory T cells. Depletion of these cells and the long half-life of anti-CCR4 mAbs result in enhanced induction of antitumor effector T cells. The role of IL10 in NKTCL has also been investigated. It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies. Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission. Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease. The present review outlines the known immunotherapy targets for the treatment of NKTCL.

Analysis of latent T-cell epitopes in Epstein-Barr virus isolated from extranodal nasal-type natural killer/T-cell lymphoma in Taiwanese population.

Extranodal nasal-type natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive lymphoma that is prevalent among East Asian and South American populations. Although Epstein-Barr virus (EBV) is commonly detected in NKTCL, there are limited studies that have analyzed the EBV genomic variations in NKTCL. In this study, 8 EBV latent genes were analyzed using targeted gene sequencing in 23 formalin-fixed paraffin-embedded tissues derived from 18 patients with NKTCL. Five cases with paired samples were comparatively analyzed. The consistency of EBV sequencing data between tissue samples was high (96.3%-98.7%), whereas that of variant calling among the tissue samples and plasma samples (74.3%-79.2%) was low. The highest densities of non-synonymous variants were detected in the EBNA3B gene. Among the 74 known T-cell epitopes, 363 non-synonymous variants were identified in 32 (43.2%) epitopes. Additionally, the AVFDRKSDAK (A1S/P and V2F/M/L) and YHLIVDTDSL (I4L and L10R/V/G/H) epitopes were associated with 5 patterns of amino acid changes in EBNA3B and EBNA-2, respectively. The frequency of variation in the human leukocyte antigen (HLA)-restricted epitopes with corresponding HLA types common among Taiwanese population was significantly low (P = 0.011), whereas that in anchor residues was significantly high (P = 0.012). In conclusion, this study demonstrated the genomic diversity of EBV in NKTCL and its correlation with the HLA-restricted epitope variations in Taiwanese population. The findings of this study provide useful insights for the development of novel therapeutic strategies for NKTCL.

Nodal EBV+ cytotoxic T-cell lymphoma: A literature review based on the 2017 WHO classification.

Nodal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (CTL) is a primary nodal peripheral T-cell lymphoma (PTCL) characterized by a cytotoxic phenotype and EBV on the tumor cells. This disease reportedly accounts for 21% of PTCL not otherwise specified (NOS). However, few nodal EBV+ lymphomas have been documented in detail. Nodal EBV+ CTL and nasal-type NK/T-cell lymphoma (NKTL) both exhibit cytotoxic molecule expression and EBV positivity on the tumor cells; however, nodal EBV+ CTL is characterized as a systemic disease without nasopharyngeal involvement, and exhibits a CD8+/CD56- phenotype distinct from NKTL. The clinicopathological uniqueness of nodal EBV+ CTL is further supported by its T-cell origin in most reported cases. In the 2008 WHO classification, it was unclear whether nodal EBV+ CTL should be classified as PTCL or NKTL. However, based on additional data, the 2017 revision classifies nodal EBV+ CTL as PTCL. In the present review, we focus on the clinicopathological characteristics of nodal EBV+ CTL, discuss the relationship between chronic active EBV infection and nodal EBV+ lymphoma, and highlight future perspectives regarding the treatment of this disease.

Extranodal NK/T-Cell Lymphomas: The Role of Natural Killer Cells and EBV in Lymphomagenesis.

Keywords: NK cells, extranodal NK/T-cell lymphoma, EBV.

Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America.

Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV) associated lymphoma, prevalent in Asia and Latin America. Studies in Asian cohorts have identified some recurrent gene mutations in ENKTL; however, the mutational landscape of ENKTL in Latin America is unknown. In this study, we investigated the mutational profile and EBV strains of 71 ENKTL cases from Latin America (42 from Mexico, 17 from Peru, and 12 from Argentina) and compared it with Asian cohorts. The mutational analysis was performed by next generation sequencing (NGS) using an Ion AmpliSeq™ custom panel covering for the most frequently mutated genes identified in ENKTL. STAT3 was the most frequent mutated gene (16 cases: 23%), followed by MSN (10 cases; 14%), BCOR (9 cases; 13%), DDX3X (6 cases; 8%), TP53 (6 cases; 8%), MGA (3 cases; 4%), JAK3 (2 cases; 3%), and STAT5B (1 case; 1%). Mutations in STAT3, BCOR, and DDX3X were nearly mutually exclusive, suggesting different molecular pathways involved in the pathogenesis of ENKTL; whereas mutations in MGA, MSN, and TP53 were concomitant with other mutations. Most cases (75%) carried Type A EBV without the 30-bp LMP1 gene deletion. The overall survival was significantly associated with serum LDH level, Eastern Cooperative Oncology Group (ECOG) performance status, International Prognostic Index (IPI) score, and therapy (p < 0.05), but not associated with any mutation, EBV strain or deletion in EBV LMP1 gene. In conclusion, mutational analysis of ENKTL from Latin America reveals frequent gene mutations leading to activation of the JAK-STAT pathway (25%), mostly STAT3. Compared to Asian cohorts, BCOR, DDX3X and TP53 mutations were also identified but with different frequencies. None of these mutations were associated with prognosis.

Linfoma Extranodal de Células T/NK en Cavidad Oral. Reporte de un Caso en Chile / Extranodal Lymphoma of T / NK Cells in Oral Cavity. Case Report in Chile

RESUMEN: El linfoma extranodal de células T/NK es una neoplasia maligna agresiva que se caracteriza por una destrucción de estructuras de la línea media de la cara como paladar y fosa nasal. Presentamos el caso de un paciente de sexo masculino, 48 años de edad, consumidor de cocaína, que consulta en la Facultad de Odontología de la Universidad de Chile en Septiembre del 2015 por síntomas de disfagia, rinorrea y que presenta al examen clínico un tumor ulcerado que compromete paladar duro y blando, de un mes de evolución. Se confirma diagnóstico de linfoma de células T/NK con una batería de pruebas inmunohistoquímicas. Esta patología, aunque infrecuente, siempre debe ser considerada dentro los diagnósticos diferenciales en tumores ulcerados en esta localización.

ABSTRACT: Extranodal T / NK cell lymphoma is an aggressive malignant neoplasm characterized by destruction of midline structures of the face such as the palate and nasal fossa. We present the case of a male patient, 48 years old, cocaine user, who consults at the Faculty of Dentistry of the Universidad de Chile in September of 2015 due to symptoms of dysphagia, rhinorrhea and presenting to the clinical examination an ulcerated tumor which compromises hard and soft palate, a month of evolution. Diagnosis of T / NK cell lymphoma is confirmed with a battery of immunohistochemical tests. This pathology, although infrequent, should always be considered within the differential diagnoses in ulcerated tumors of this location.

Expression and clinical significance of neuropilin-1 in Epstein-Barr virus-associated lymphomas.

BACKGROUND: The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated. METHODS: The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia. RESULTS: In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas (P= 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma (P= 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin's lymphoma (NHL). CONCLUSIONS: NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL.

Intravascular NK/T-cell lymphoma: clinicopathological and integrated molecular analysis of two cases provides a clue to disease pathogenesis.

AIMS: To elucidate the clinicopathological and molecular features of intravascular NK/T-cell lymphoma (IVNKTCL). METHODS: Two cases of IVNKTCL were retrieved from a single-centre cohort composed of 25 intravascular lymphomas. Whole-exome and RNA sequencing and immunohistochemistry were performed. RESULTS: We identified somatic mutations in the following epigenetic regulators: four histone genes (HIST1H2AN, HIST1H2BE, HIST1H2BN and H3F3A), histone deacetylase (HDAC5), two helicases (WRN and DDX3X), two methylation-related enzymes (TET2 and DNMT1) and the SNI/SWF pathway (ARID1A). Copy number analysis identified driver gene alterations comprising the loss of ARID1B, HACE1 and SMAD4, and the gain of SOX2 and histone clusters. RNA sequencing analysis did not indicate the presence of any fusion gene. Both cases were positive for Epstein-Barr virus (EBV) and showed strong expression of programmed death-ligand 1 (PD-L1). CONCLUSIONS: This study raises the possibility that, at least for some patients, IVNKTCL may be considered an epigenetic disease with EBV infection-associated aetiopathogenesis.

Laryngeal Extranodal Nasal-type Natural Killer/T-cell Lymphoma: A Clinicopathologic Study of 31 Cases in China.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL-N) initially presented in larynx is a rare condition without distinctive clinicopathologic features, with a challenging pathologic diagnosis. This study aimed to evaluate the clinicopathologic features and diagnosis of laryngeal ENKTL-N and spread awareness regarding ENKTL-N. A series of 31 cases of laryngeal ENKTL in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 50 years (range, 13 to 77 y) with a male/female ratio of 5.2:1 (26/5). All patients initially presented with hoarseness and/or laryngalgia, and 10 patients (32.3%) experienced B symptoms. The supraglottic region was the most common site of occurrence (58.1%), the glottic area being the rarest site (6.5%). The mucosal squamous epithelium was detected in 26 specimens and pseudoepitheliomatous hyperplasia was observed in 8 cases (8/26, 30.8%). "Keratin-pearls" and a "pseudoinvasive" pattern were observed in 2 cases. Follow-up data were available for 26 patients (83.9%), the median survival duration was 9 months, and the overall survival rate at 5 years was 29.6%. Univariate analysis revealed that patients experiencing B symptoms (P=0.019) and age above 60 years had a significantly low survival (P=0.049) and that combined radiotherapy and chemotherapy prolongs overall survival (P<0.001). Laryngeal ENKTL-N is a rare entity with high aggressiveness and a poor prognosis. Multiple biopsies are usually required owing to secondary infection and massive necrosis. Laryngeal EKTL-N may mimic inflammatory lesions or well-differentiated squamous cell carcinoma. Therefore, clinical vigilance is essential to prevent misdiagnosis or a delayed diagnosis.

Genome-Wide Analysis of Epstein-Barr Virus Isolated from Extranodal NK/T-Cell Lymphoma, Nasal Type.

BACKGROUND: Extranodal natural killer (NK) cell/T-cell lymphoma (NKTCL), a rare type of non-Hodgkin's lymphoma, has strongly been associated with Epstein-Barr virus (EBV) infection. However, there are no EBV genomes isolated from NKTCL, and the roles the variations of EBV strains play in the pathogenesis of NKTCL are still unclear. MATERIALS AND METHODS: In this study, whole EBV genomes from eight primary NKTCL biopsy specimens were obtained using next-generation sequencing, designated NKTCL-EBV1 to NKTCL-EBV8. RESULTS: Compared with the six mostly referenced EBV strains, NKTCL-EBVs closely resemble the GD1 strain but still harbor 2,072 variations, including 1,938 substitutions, 58 insertions, and 76 deletions. The majority of nonsynonymous mutations were located in latent and tegument genes. Moreover, the results from phylogenetic analysis of whole NKTCL genomes and specific genes demonstrated that all the NKTCL-EBVs were related to Asian EBV strains. Based on the amino acid changes in certain residues of latent membrane protein 1 (LMP1) and EBV-determined nuclear antigen 1 (EBNA1), all the NKTCL-EBVs were sorted to China 1 and V-val subtype, respectively. Furthermore, changes in CD4+ and CD8+ T-cell epitopes of EBNA1 and LMP1 may affect the efficacy for a cytotoxic T lymphocyte (CTL)-based therapy. CONCLUSION: This is the first large study to our knowledge to obtain EBV genomes isolated from NKTCL and show the diversity of EBV genomes in a whole genome level by phylogenetic analysis. IMPLICATIONS FOR PRACTICE: In this study, the full-length sequence of Epstein-Barr virus (EBV) isolated from eight patients with nasal natural killer/T-cell lymphoma (NKTCL) was determined and further compared with the sequences previously reported isolated from other malignancies. Phylogenetic analysis showed that NKTCL-EBV strains are close to other Asian subtypes instead of non-Asian ones, leading to the conclusion that EBV infections are more likely affected by different geographic regions rather than particular EBV-associated malignancies. Therefore, these data have implications for the development of effective prophylactic and therapeutic vaccine approaches targeting the personalized or geographic-specific EBV antigens in these aggressive diseases.

Angiocentric Centrofacial Lymphoma as a Challenging Diagnosis in an Elderly Man.

BACKGROUND Angiocentric centrofacial lymphomas, now known as nasal-type extranodal natural killer T-cell lymphomas, are neoplasms of highly destructive characteristics that mainly affect the nasal cavity and palate. The most frequent clinical presentation includes fever, weight loss, nasal obstruction, epistaxis, nasal or facial edema, as well as necrotic ulcers in the nasal cavity, gums, and palate. It has been found to have an important association with the Epstein-Barr virus. Diagnostic pathology could be difficult due to the typical widespread tissue necrosis. CASE REPORT A 72-year-old Caucasian male sought medical attention with a chief complaint of nasal obstruction for the past 3 years, which only responded partially to unspecific treatment. He also presented with intermittent fever and nocturnal hyperhidrosis. Physical examination with rhinoscopy demonstrated a deviated septum, congestive turbines, and fragile and pale mucous membrane with yellowish, thick mucus. The pathology report described an angiocentric centrofacial lymphoma and a positive serology for Epstein-Barr virus. CONCLUSIONS The objective of this case report was to show that this illness represents a diagnostic challenge for the treating physician. It may be concluded that despite the poor prognosis of the disease, this particular case showed slower evolution and the patient remained stable despite multiple consecutive complications.

The impact of early diagnosis on the prognosis of extranodal NK/T-cell lymphoma with massive lung involvement: a case report.

BACKGROUND: Pulmonary non-Hodgkin lymphoma (NHL) is rare. The most frequent subtype of pulmonary NHL is low-grade B-cell lymphoma, such as lymphoma of mucosa-associated lymphoma tissue. Extranodal natural killer cell/T-cell lymphoma, nasal type (ENKL) is characterized by predominant extranodal involvement and association with Epstein-Barr virus (EBV). ENKL with massive lung involvement has been infrequently reported, and its prognosis is extremely poor. CASE PRESENTATION: A 20-year-old Japanese man presented with intermittent fever lasting for 2 months. Radiological imaging demonstrated multiple nodules of uneven shape and size in both lungs. Video-assisted thoracic surgical lung biopsy showed abnormal lymphocyte infiltration, which was positive for CD3, CD56, and perforin. In situ hybridization for EBV-encoded RNA was positive. From these findings, he was diagnosed with ENKL with lung involvement. The patient was successfully treated with intensive combinational chemotherapy followed by allogeneic cord blood transplantation. He has been alive with continuous complete remission for 1 year after diagnosis. CONCLUSIONS: Although ENKL involving the lung has been reported to have dismal outcomes, our patient showed long-term survival after intensive chemotherapy and up-front allogeneic hematopoietic transplantation. The present case highlights the importance of early diagnosis as well as allogeneic transplantation.

The factors associated with the early diagnosis of nasal NK/T-cell lymphoma with prominent ocular symptoms and general nasal NKTL.

AIM: This study explored the clinical features of nasal natural killer/T-cell lymphoma (NKTL) in patients with prominent ocular symptoms and those with general nasal NKTL to improve the early diagnosis of nasal NKTL. METHOD: A retrospective cohort study was performed with 278 patients with nasal NKTL admitted to the First Affiliated Hospital of Zhengzhou University between January 2011 and December 2017. Of these cases, 56 presented with nasal NKTL and prominent ocular symptoms, and 222 presented with general nasal NKTL. RESULTS: No significant differences in gender and age distribution were found between patients with general nasal NKTL and those with nasal NKTL and prominent ocular symptoms (p > 0.05). Cases of nasal NKTL and prominent ocular symptoms were usually complicated with B symptoms(48.2% vs 32.9%, p < 0.05). Patients with nasal NKTL and prominent ocular symptoms were more likely to progress to stage III disease (p < 0.01). The median time from first onset to diagnosis was 2.5 months. Most patients with general nasal NKTL had a longer history (69.6% vs 45.0%, p < 0.01). The misdiagnosis rate of the first visit of patients with general nasal NKTL was 29.3%, and that of patients with prominent ocular symptoms was 51.8%; this difference was significant (p < 0.01). Patients with nasal NKTL and prominent ocular symptoms showed a higher positive rate of EBV DNA (p < 0.01), which was significantly associated with staging (p < 0.01). CONCLUSIONS: Compared with patients with general nasal NKTL, the early diagnosis of patients with prominent ocular symptoms is difficult and easy to misdiagnose. Patients with nasal NKTL and prominent ocular symptoms mostly present with advanced disease stages, and most patients have B symptoms and a high positive rate of EBV DNA.