Linfoma de células T/natural killer extranodal de tipo nasal enmascarado en una sinusopatia

Introducción: El linfoma de células T citotóxico/natural killer extranodal de tipo nasal es poco frecuente, pero con alta tasa de mortalidad. Las manifestaciones clínicas de la enfermedad pueden simular una infección de senos paranasales. Objetivo: Presentar las manifestaciones clínicas de un paciente de 34 años de edad con diagnóstico de linfoma de células T citotóxico/natural killer extranodal de tipo nasal. Caso clínico: Se presenta un paciente masculino de 34 años de edad con rinorrea verdosa fétida recurrente y obstrucción en fosa nasal derecha. En la evaluación inicial sugiere sinusitis crónica, sin embargo, debido al empeoramiento de las manifestaciones clínicas se realiza una tomografía computarizada que muestra lesiones sugestivas de infiltración neoplásica, una biopsia de la lesión confirma el diagnóstico de linfoma de células T/natural killer extranodal de tipo nasal. Conclusiones: Los linfomas de células T citotóxico/natural killer extranodal de tipo nasal son considerados neoplasias poco frecuentes, caracterizadas por el patrón rápidamente progresivo con afectación ósea; en su etapa inicial presenta manifestaciones clínicas similares a una sinusitis. La tomografía computarizada y la histopatología, son indispensables en el diagnóstico de la enfermedad.

Introduction: Nasal-type extranodal natural killer/cytotoxic T-cell lymphoma is rare but has a high mortality rate. The clinical manifestations of the disease can mimic a paranasal sinus infection. Objective: To present the clinical manifestations of a 34-year-old patient diagnosed with nasal-type extranodal natural killer/cytotoxic T-cell lymphoma. Clinical case: A 34-year-old male patient with recurrent greenish fetid rhinorrhea and obstruction in the right nostril is presented. In the initial evaluation, it suggests chronic sinusitis, however, due to the worsening of the clinical manifestations, a computed tomography is performed that shows lesions suggestive of neoplastic infiltration, a biopsy of the lesion confirms the diagnosis of T-cell lymphoma/extranodal natural killer. Conclusions: Nasal-type extranodal natural killer/cytotoxic T-cell lymphomas are considered rare neoplasms characterized by a rapidly progressive pattern with bone involvement; in its initial stage it presents clinical manifestations similar to sinusitis. Computed tomography and histopathology are essential in the diagnosis of the disease.

Linfoma de células T/NK primario de testículo. Caso clínico y revisión de la literatura

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Regulation of Baicalin on Growth of Extranodal NK/T Cell Lymphoma Cells through FOXO3/CCL22 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism.@*METHODS@#Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation.@*RESULTS@#In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001).@*CONCLUSION@#Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.

Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS.@*RESULTS@#The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL.@*CONCLUSION@#Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging / 中华放射肿瘤学杂志

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Relato de caso: linfoma de células t/nk extranodal tipo nasal / Case Report: Extranodal Nk/T-Cell Lymphoma, N a s a l Ty p e / Reporte de caso: linfoma extranodal de células t/nk de tipo nasal

Introdução: O linfoma não-Hodgkin é dividido em linfomas de células B e linfomas de células T, e o linfoma extranodal de células T / NK do tipo nasal está dentro do último grupo.Relato de caso: Paciente do sexo masculino de 30 anos, relata que há 6 meses, de forma progressiva e de início insidioso, apresenta tumor cervical à direita de crescimento progressivo, pelo qual foi encaminhado ao ambulatório de cabeça e pescoço onde apresentou seus principais sinais e sintomas adenopatia cervical direita, sintoma B e tumoração ao nível da nasofaringe, envolvendo o teto, parede posterior e face lateral; se movimenta com auxílio, com extenso conglomerado linfonodal supraclavicular direito, eritematoso, com calor local, além de áreas de ulceração e secreção serosa.Conclusão: O diagnóstico e tratamento precoces desta doença são as únicas ferramentas para melhorar o mau prognóstico e o grave impacto na qualidade de vida dos pacientes que a padecem

Introduction: Non-Hodgkin's lymphomas are divided into B-cell lymphomas and T-cell lymphomas, and extranodal NK/T-cell lymphoma, nasal type, is in the latter group.Case report: A 30-year-old male patient, for six months, progressively and with an insidious onset, has had a right-sided cervical tumor with progressive growth. He came to a head and neck outpatient clinic where the main signs and symptoms detected were right cervical lymphadenopathy, B-symptoms, and a tumor in the nasopharynx affecting the roof, posterior wall, and lateral wall. The patient moves with assistance and has an enlarged, erythematous warm right supraclavicular lymph node conglomerate. In addition, he has some ulcerated areas with serous drainage.Conclusion: Early diagnosis and treatment of this disease are the only tools to improve these patients' poor prognosis and severely deteriorated quality of life.

Introducción:El linfoma no Hodgkin se divide en linfomas de células B y linfomas de células T; y en este último grupo se encuentra el linfoma extraganglionar de células T / NK de tipo nasal.Caso clínico: Un paciente masculino de 30 años refiere que durante 6 meses de forma progresiva, y con un início insidioso, presenta una tumoración cervical en el lado derecho de crecimiento progresivo, por lo que acude a la consulta externa de cabeza y cuello, donde los signos y síntomas principales fueron adenopatía cervical derecha, síntoma B, y una tumoración a nivel de nasofaringe, que afecta el techo, la pared posterior y la cara lateral. Se moviliza con ayuda, con un extenso conglomerado ganglionar supraclavicular derecho, eritematoso, con calor local. Además, también muestra algunas áreas de ulceración y secreción serosa. Conclusión: El diagnóstico y tratamiento precoz de esta enfermedad son las únicas herramientas para mejorar el mal pronóstico y el deterioro severo en la calidad de vida de los pacientes que la padecen

Quality of life in patients with early-stage extra-nodal NK/T cell lymphoma of nasal type after definitive radiation therapy / 中华放射肿瘤学杂志

Objective:To investigate the quality of life in patients with early-stage extra-nodal NK/T cell lymphoma of nasal type (ENKTL) arising from the upper aerodigestive tract, who had remained progression-free survival (PFS) for over 3 months after definitive intensity-modulated radiation therapy (IMRT), and to analyze the factors related to main adverse symptoms.Methods:276 patients who received IMRT from March, 2012 to June, 2021 were included. There were 201 males and 75 females with a median age of 41.5 years (range: 13-81 years) upon diagnosis. Consistent target delineation schemes and similar dose gradients were adopted for IMRT, with a median prescribed dose of 54.6 Gy/26F. Cross-sectional investigation was performed with a modified EORTC QLQ-H&N35 questionnaire, the incidence and severity of adverse symptoms, severity of disease and their influencing factors at each time-point during their survival were statistically analyzed.Results:The median age of patients at the investigation was 46.2 years, and the median PFS after IMRT was 47.2 months (range: 3.1-115.7 months). The most common adverse symptoms included nasal symptoms (incidence rate 63.8%), dry mouth (50%), tooth diseases (47.1%), smell and taste alteration, and sexual apathy, etc. Most symptoms were mild (the average standardized score was 5.50, the full score of 100 indicating the most severe), and could be relieved remarkably over survival time, but some symptoms, such as tooth diseases and sexual apathy, were more obvious and recurred for several years. Age and anti-PD-1 immune therapy influenced the symptom scores, and tooth diseases were closely correlated with dry mouth. Conclusion:The quality of life in patients with early-stage ENKTL after definitive IMRT is high, and the most significant symptoms include nasal symptoms, tooth diseases, and sexual apathy, etc. , which need to be mitigated with more studies.

Association of plasma EBV-DNA copy number and cytokines with B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type / 中华放射肿瘤学杂志

Objective:To investigate the association of plasma EBV-DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators.Methods:Clinical data of 173 newly-diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I-II and 47 cases of stage Ⅲ-IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra-upper aerodigestive tract (extra-UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV-DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10 4 copies/ml, n=73) and high load group (≥10 4 copies/ml, n=64). Serum cytokines including IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α were detected. Correlation analysis was performed by Cochran-Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan-Meier survival analysis. Results:The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV-DNA copy levels. In addition, serum levels of IFN-γ, IL-6 and IL-10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN-γ, IL-6, and IL-10 levels were also positively correlated with plasma EBV-DNA copy number. The occurrence of B symptoms was associated with high-risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre-treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV-DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression-free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion:This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV-DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.

Pretreatment evaluation of 18F-FDG PET-CT in extranodal NK/T-cell lymphoma / 中华肿瘤杂志

Objective: To investigate the clinical value of pretreatment 18F-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET-CT) in extranodal NK/T-cell lymphoma. Methods: Eighty-one patients with pathologically confirmed extranodal NK/T-cell lymphoma and pretreatment with PET-CT scan in Cancer Hospital, Chinese Academy of Medical Sciences from August 2006 to December 2017 were enrolled in the study. The clinical, follow-up and imaging data were analyzed retrospectively. The relationship between maximum standard uptake value (SUVmax) and prognosis were evaluated by Mann-Whitney U test and Spearman rank correlation analysis. Results: Among the 81 patients, 98.8% (80/81) were upper aerodigestive tract (UAT) involved. Lesions at extra-UAT sites were detected in 7 cases, involving parotid gland (n=1), breast (n=1), spleen (n=1), pancreas (n=1), skin and subcutaneous soft tissue (n=1), muscle (n=1), lung (n=2) and bone (n=3). Lymph node involvement were demonstrated in 33 cases. All of the lesions had increased uptake of PET, the median SUVmax was 8.6. PET-CT changed staging in 15 cases, and 12 cases were adjusted treatment methods. 21 cases were changed radiotherapy target because of PET-CT. The 1-, 2-year progression-free survival (PFS) rates were 88.7% and 80.3% while 1-, 2-year overall survival (OS) rates were 97.2% and 94.4% respectively. The median SUVmax of patients with local lymph nodes involvement was significantly higher than those without local lymph nodes involvement (P=0.007). The SUVmax was positively associated with Ann Arbor stage (r=0.366, P=0.001), lactate dehydrogenase (r=0.308, P=0.005) and Ki-67 level (r=0.270, P=0.017). The SUVmax was inversely associated with lymphocyte count (r=-0.324, P=0.003) and hemoglobin content (r=-0.225, P=0.043). Conclusions: Extranodal NK/T-cell lymphoma predominantly occurs in extra-nodal organs, mainly in the upper respiratory and gastrointestinal tracts, with marked FDG-addiction. Compared with conventional imaging, 18F-FDG PET-CT is sensitive and comprehensive in detecting extra-nodal NK/T-cell lymphoma involvement, assisting in accurate clinical staging and treatment planning. Pretreatment SUVmax is potential for prognosis evaluation since it is correlated with prognostic factors.

Safety and efficacy of upfront autologous transplantation as a consolidation therapy for progressive nasal type extranodal NK/T-cell lymphoma / 中华器官移植杂志

Objective:To evaluate the efficacy and safety of upfront autologous hematopoietic stem cell transplantation(auto-HSCT)as a consolidation therapy of progressive nasal type extranodal NK/T-cell lymphoma, (ENKL).Methods:From January 2012 to June 2021, clinical data were retrospectively reviewed for 28 patients with advanced-stage ENKL on chemotherapy of asparaginase-containing regimen followed by upfront auto-HSCT as a consolidation therapy.The median age at transplantation was 34.5(14-61)years.There were 19 males and 9 females.Clinical types were nasal(n=22)and non-nasal(n=6). Clinical stages were Ann Arbor III(n=15)and IV(n=13). Clinical risks were intermediate(n=8)and high(n=20)according to the Prognostic Index for Natural-Killer cell lymphoma-Epstein-Barr virus(PINK-E).Results:Hematopoietic reconstruction was performed.Median time of neutrophil engraftment was 10(8-17)days and 13(10-22)days for platelet.Median follow-up time was 59.5 months and 5-year OS/PFS 70.0%(95% CI: 50.60%-89.40%)and 59.1%(95% CI: 39.11%-79.10%). And 5-year cumulative recurrence and non-recurrence mortality rates were 35.42%(95% CI: 19.11%-59.39%)and 4.2%(95% CI: 2.16%-29.87%). Conclusions:Asparaginase-based chemotherapy followed by auto-HSCT is both safe and efficacious for progressive ENKTL.

Relation Between EB Virus Infection and Curative Effect, Prognosis of Patients with Early-stage Extranodal Nasal-type NK/T-cell Lymphoma / 肿瘤防治研究

Objective To explore the correlation of pretreatment EBV DNA load, EBV EA-IgA and VCA-IgA antibodies levels with the clinical characteristics, curative effect and prognosis of the patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL). Methods We analyzed the clinical features and prognostic factors of 78 ENKTCL patients. Results Positive rates of pretreatment EBV DNA, VCA-IgA and EA-IgA were 43.6%, 20.5% and 14.1%, respectively. EBV DNA was significantly associated with Ann Arbor stage, primary site, PTI and non-CR (all P < 0.05). VCA-IgA and EA-IgA were related to positive EBV DNA and non-CR (all P < 0.05). Multivariate analysis showed that age, EBV DNA and non-CR were independent prognostic factors for OS (all P < 0.05); age, EBV DNA, primary site and non-CR were independent prognostic factors for PFS (all P < 0.05). Conclusion The pretreatment positive EBV DNA is related to advanced Ann Arbor stage, PTI, primary extra-nasal subtypes of upper aerodigestive tract and poor response to treatment. The elevated levels of EA-IgA and VCA-IgA are related to positive EBV DNA and poor response to treatment. Pretreatment EBV DNA could be used for risk stratification and prognosis prediction of ENKTCL, while EA-IgA and VCA-IgA play limited role in guiding the prognosis of ENKTCL.

Efficacy and toxicities of chemoradiotherapy in the treatment of early stage extranodal nasal-type NK/T-cell lymphoma / 中华放射医学与防护杂志

Objective:To assess the efficacy and toxicity of chemoradiotherapy in the treatment of early stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL).Methods:Retrospective review was conducted for 174 patients with pathological proved early stage ENKTCL who were treated in the Department of Radiation Oncology, Peking University Cancer Hospital & Institute. The Kaplan-Meier survival analysis was adopted to calculate the local-regional control (LRC), overall survival (OS), and progression free survival (PFS), and the Log-rank test COX regression model were applied to univariate and multivariate analyses.Results:The patients in this study included 102 and 72 patients diagnosed with Ann Arbor stage-Ⅰ and stage-Ⅱ, respectively. Among them, two patients received radiotherapy alone and 172 patients were treated with combined chemoradiotherapy. The overall response rate of all the patients was 94.2%, with a complete response (CR) rate of 87.9% (153). Furthermore, the rates of 5-year OS, PFS, and LRC were 87.3%, 83.1%, and 91.9%, respectively. The most common toxicities during the chemotherapy and radiotherapy included myelosuppression and oral mucositis, with grade ≥ 3 myelosuppression and grade ≥ 3 oral mucositis accounting for 62.1% and 10.9% of all patients, respectively. As shown by multivariate analysis, the adverse prognostic factors for OS included age > 60, B symptoms, and stage Ⅱ, while the adverse prognostic factors for PFS included age > 60 and stage Ⅱ. Meanwhile, the PFS rate was significantly improved by increasing the radiation dose (≥ 50 Gy vs.<50 Gy), and the 5-year PFS rates of the two groups were 83.5% and 76.5%, respectively [hazard ratio ( HR) 0.374; 95% CI, 0.169-0.826; P=0.015]. Conclusions:A good therapeutic effect can be achieved for early stage NK/T-cell lymphoma and the toxicities after combined chemoradiotherapy can be tolerated.

Linfoma de células T/NK extranasal primario en íleon / Natural Killer/T cell primary extranasal ileum lymphoma

RESUMEN El linfoma extranodal de células T/NK extranasal (NKTL) primario del tracto gastrointestinal es poco frecuente y tiene carácter agresivo. Presentamos el caso de un paciente inmunocompetente de 51 años que ingresa por dolor abdominal de dos meses de evolución. En la colonoscopía, se hallaron ulceraciones ileales, por lo que se le realizaron estudios para descartar enfermedad de Crohn y tuberculosis intestinal, posteriormente presentó obstrucción intestinal. En la laparotomía exploratoria, se encontró un conglomerado ganglionar en mesenterio. La anatomía patológica confirmó el diagnóstico de NKTL primario en íleon. Se inició quimioterapia y el paciente pidió alta voluntaria dada su precaria condición. Dos meses después del alta el paciente fallece. Este linfoma ha sido reportado principalmente en Asia y posiblemente sea el primer caso reportado en Perú. Tiene un pronóstico funesto con una supervivencia global de ocho meses. Por ello, es necesario un diagnóstico precoz e iniciar la terapia oportunamente.

ABSTRACT Primary extranodal Natural Killer / T cell lymphoma (NKTL) on gastrointestinal tract is an uncommon and aggressive neoplasm. We present the case of a 51-year-old immunocompetent patient with a 2-month history of abdominal pain. Colonoscopy findings showed ileal ulcerations, so studies were carried out to rule out Crohn's disease and intestinal tuberculosis. Later, he developed intestinal obstruction. Exploratory laparotomy found a nodal conglomerate in the mesentery. Anatomical pathology confirmed the diagnosis of primary NKTL on the ileum. Chemotherapy was initiated but the patient asked for voluntary discharge because of his precarious condition. Two months after discharge the patient died. This lymphoma has been reported mainly in Asia and is possibly the first case in Peru. It has a dismal prognosis with overall survival of 8 months. Therefore, it is necessary to get an early diagnosis and begin therapy in a timely manner.

Clinical analyses of 24 patients with primary pulmonary NK/T-cell lymphoma / 中华血液学杂志

Objective@#To explore the clinical characteristics, the best treatment and prognostic factors of primary pulmonary NK/T-cell lymphoma.@*Methods@#A total of 24 cases with primary pulmonary NK/T-cell lymphoma from April 2011 to May 2019 were analyzed retrospectively. Survival analysis was performed using the Kaplan-Meier method and groups were compared using the log-rank test. Multivariate analysis using Cox proportional hazard regression model was conducted to confirm independent prognostic factors for overall survival (OS) and progression-free survival (PFS) .@*Results@#①The cohort of 24 patients included 16 male and 8 female with a median age of 49 years (range, 4-76 years) old. ②Most patients initially presented with a fever (66.7%) , cough and dyspnea. Chest imaging manifestations were primarily unilateral (45.8%) or bilateral (54.2%) pulmonary consolidation, nodules or mass. ③20 patients received chemotherapy, radiotherapy or hematopoietic stem cell transplantation, the rest 4 cases palliative treatment. Median OS was 9.5 months (range, 0.1-26.0 months) . The estimated 1-year OS rate was 45.8%. Overall response rate of patients treated with asparaginase-based regimen was 88.2%. ④In univariate survival analysis, age≤60 was prognostic for longer OS and PFS, compared with age>60 (P=0.002 and 0.004, respectively) ; ECOG≤2 was prognostic for longer OS and PFS, compared with ECOG>2 (P=0.042 and 0.004, respectively) . In multivariate survival analysis, age>60 and ECOG>2 were significantly correlated with inferior OS and PFS (OS: P=0.024 and 0.024, respectively; PFS: P=0.035 and 0.024, respectively) .@*Conclusions@#Primary pulmonary NK/T-cell lymphoma was a rare disease with poor prognosis. Asparaginase-based regimens appeared to be effective. Age and ECOG served as independent prognostic factors for primary pulmonary NK/T-cell lymphoma patients.

Cytological findings of NK/T-cell lymphoma in pericardial effusion: A case report with a review of the literature

Extranodal Natural Killer/T-cell lymphoma (ENKL) is an aggressive NK or cytotoxic T-cell neoplasm. The cytological features of NK/T-cell lymphoma have been rarely described, mainly focusing on the fine needle aspiration cytology from lymph nodes or soft tissue, except for a few cases focused on body fluid. A 46-year-old man visited the hospital due to generalized weakness and weight loss. Three months prior, computed tomographic scan revealed mesenteric panniculitis and reactive lymph nodal enlargement, as well as a mildly thickened left adrenal gland, suggesting an inflammatory condition. About 100 days later, marked enlargement of both adrenal glands with pericardial effusion was noted. The pericardial effusion contained medium-sized atypical lymphocytes, suspicious for malignant lymphoma, and the left adrenal mass was histologically confirmed as ENKL on biopsied specimen. Herein, we describe the cytological features of NK/T-cell lymphoma in body fluid cytology along with a review of the literature.

Circulating Low Absolute CD4⁺ T Cell Counts May Predict Poor Prognosis in Extranodal NK/T-Cell Lymphoma Patients Treating with Pegaspargase-Based Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. MATERIALS AND METHODS: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens. Comparison of ACD4Cs as a continuous parameter in different groups was calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: Stage III/IV, B symptoms, elevated lactate dehydrogenase, monocytopenia, high-intermediate and high risk International Prognostic Index (IPI) and Korean Prognostic Index (KPI), high risk Prognostic Index of Natural Killer Lymphoma (PINK), and lower lymphocytes were significantly associated with low ACD4C at diagnosis. With a median follow-up time of 32 months, patients who had an ACD4C < 0.30×109/L had a worse OS. Median OS was 11 months and median PFS was 5 months in the low ACD4C cohort. There were significant differences in both OS and PFS between the two cohorts. Moreover, multivariate Cox analysis identified ACD4Cs as an independent predictor for OS and PFS. CONCLUSION: Low ACD4Cs were associated with poorer survival and could act as a negative predictor for ENKTL patients treated with asparaginase-based regimens.

Extranodal NK/T-cell lymphoma mimicking Crohn’s colitis

@#Introduction: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract. Case Report: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn’s colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn’s disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made. Discussion: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.

Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. MATERIALS AND METHODS: From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCLpatients (87.8%). RESULTS: NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. CONCLUSION: NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.

Effect of miR-218-2-3P on proliferation and apoptosis of NK/T-cell lymphoma by targeting SIN3A / 上海交通大学学报（医学版）

Objective • To investigate the expression of miR-218-2-3P in NK/T-cell lymphoma, and the effect of miR-218-2-3P on the proliferation, apoptosis and cycle of NK/T-cell lymphoma by targeting SIN3A. Methods • Quantitative real-time PCR (qPCR) was used to detect the expressions of miR-218-2-3P in normal NK cells and NK/T-cell lymphoma cells NK92MI and NKYS. Lipofectamine 3000 was used to transfect the inhibitor containing nonsense sequences (inhibitors NC), miR-218-2-3P inhibitor and the same dose of transfection reagent without any fragment into NK92MI cells, which were divided into three groups. qPCR and Western blotting were used to detect the expression levels of miR-218-2-3P and SIN3A protein in the inhibitor NC group, the miR-218-2-3P inhibitor group and the blank control group, respectively. The cell proliferation activities of the three group were measured by CCK8 method. The apoptosis rates and cell cycles of the three group were determined by flow cytometry. The double luciferase reporter gene assay was performed to detect whether SIN3A was a target gene of miR-218-2-3P. NK92MI cells were transfected with miR-218-2-3P inhibitor+SIN3A small interfering RNA (si-SIN3A) and miR-218-2-3P inhibitor+nonsense sequences small interfering RNA (si-NC), respectively, which were divided into two groups. The cell proliferation activities of the two groups were detected by CCK8 method. Results • Compared with the normal NK cells, the expressions of miR-218-2-3P in NK92MI and NKYS cells significantly increased (both P<0.05). Compared with the blank control group and the inhibitor NC group, the proliferation activity of NK92MI cells in the miR-218-2-3P inhibitor group decreased (both P<0.05), the apoptosis rate increased (both P<0.05) and cell cycle arrest occurred in G0/G1 phase (both P<0.05). The double luciferase reporter gene assay showed that SIN3A was the target gene of miR-218-2- 3P. Compared with the blank control group and the inhibitor NC group, the SIN3A protein expression of the miR-218-2-3P inhibitor group was increased (both P<0.05). The down-regulation of SIN3A expression could restore the proliferation activity of cells weakened by miR-218-2-3P inhibitor (both P<0.05). Conclusion • miR-218-2-3P is highly expressed in the NK92MI and NKYS cell lines. miR-218-2-3P may affect the proliferation, apoptosis and cycle of NK/T-cell lymphoma through targeted regulation of SIN3A.

Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL). MATERIALS AND METHODS: A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups. RESULTS: The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067). CONCLUSION: IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.