Efficacy and safety of SIMPLE regimen in treatment of extranodal NK/T-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

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.

Clinical analysis of seven cases of hemophagocytic lymphohistiocytosis secondary to cutaneous T-cell lymphoma / 中华皮肤科杂志

Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.

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.

Epidemiology and Spectrum of lymphoma in a single tertiary care hospital of North India

Background: Non-Hodgkin抯 Lymphoma is a common hematological malignancy. Its incidence and distribution in India are slightly different from developed nations. The study was initiated to obtain the epidemiological, clinical and histopathological spectrum of lymphoma in a single tertiary care hospital of North India. Methods: 104 eligible consecutive cases of lymphoma were retrospectively analyzed from January 2016 to March 2020. Morphology and immunohistochemistry were performed and clinical details were captured from hospital information system. Cases were reclassified according to WHO classification of Tumors of Hematopoietic and Lymphoid Tissue 2017 and also clinically as nodal and extra nodal lymphomas and analyzed. Results: Among the included patients 14.4% patients are diagnosed as Hodgkin抯 lymphoma (HL) while 85.5% belonged to non-Hodgkin抯 lymphoma (NHL). Median age for NHL is 52.5 years. Male outnumbered females in both NHL and HL with ratio of 1.87 and 1.5. Majority of NHL are mature B-cell neoplasm (83.1%), while mature T-cell and NK cell neoplasm are less (14.6%). Most common subtype found is Diffuse large B-cell lymphoma (52.8%) followed by Primary diffuse large B cell lymphoma of CNS (15.7%). Primarily nodal Vs extranodal involvement is seen in 51.9% and 48% of cases. Most common extranodal site is CNS followed by GIT and spine. Conclusion: In the present study DLBL is the most common subtype seen in 52.8% of cases in concordance with other studies but the sticking difference here is low incidence of follicular lymphoma and CLL/SLL and a much higher incidence of Primary DLBCL of CNS. There is an Inherited selection bias because the cases are collected from single institution; however, causes and reasons should be more extensively investigated.

Peritoneal lymphomatosis. A case report

ABSTRACT Introduction: Involvement of the peritoneum occurs very rarely and is exceptional as an exclusive extranodal presentation of lymphomas. In most cases lymphomas associated with this rare entity are high-grade ones. PL secondary to high-grade nodal lymphoma is more frequent than primary peritoneal lymphoma, and there are only a few cases of the latter described in the literature. Description of the case: We present the case of a patient with constitutional syndrome and imaging findings suggestive of peritoneal carcinomatosis who was finally diagnosed with a Diffuse Large B-cell Lymphoma (DLBCL) by an ultrasound-guided core needle biopsy (CNB) of peritoneum. The patient received one polychemotherapy cycle; however tumor lysis syndrome occurred with death of the patient in the following days. This case tries to show the existence of a PL without other radiological findings of lymphoma, a fact that is very exceptionally described in the literature. Discussion: The differential diagnosis between PL and others peritoneum diseases such as peritoneal carcinomatosis, malignant primary peritoneal mesotheliomas, tuberculous peritonitis, sarcomatosis, diffuse peritoneal leiomyomatosis or benign splenosis, constitutes a major problem in imaging techniques. An exhaustive analysis of the radiological characteristics as well as a clinical-analytical context allows the differential diagnosis against peritoneal carcinomatosis and the rest of the entities previously referred although the final diagnosis will always be a biopsy. Conclusion: PL usually manifests as an aggressive histological subtype of high-grade lymphomas leading to a rapid progression and deterioration of the patient. It is crucial for the radiologist and the clinician to be aware of this rare entity providing the earliest possible diagnosis and optimal treatment to prolong the patient's life.

Study of extra-nodal lymphoma with special reference to histomorphology, immunohistochemistry, and topographical distribution

Background: Primary extra-nodal lymphomas (ENLs) are rare neoplasm but can affect many organ systems of body. Proper and timely diagnosis and justified treatment of primary ENL are often affected due to variety of lymphoma types and the relative rarity of many of these tumor types. They are mainly of Non-Hodgkin lymphoma which further consists of many subtypes having variation of epidemiology and clinical presentation along with geographic distribution. Aim and Objectives: Aim and objectives of the study were to find out topographical distribution and histological patterns of ENL along with their immunohistochemical character in a tertiary care hospital of Eastern India. Materials and Methods: All the cases from April 2015 to March 2018 diagnosed as ENL by histopathological examination were included in this descriptive cross-sectional study for further immunohistochemical analysis for CD45 Life-cycle assessment (LCA), CD3 and CD 20 to identify the cell of origin (B cell vs. T cell). Results: Out of total 31 cases, 67.74% were male and the most common age group was 51–60 years. Gastrointestinal tract was the most common organ system (61.29% of cases) affected and stomach (29.03%) followed by Ileum (9.67%) were the most common sites affected by ENL. Histomorphologically diffuse large cell lymphoma was the most common pattern while immunohistochemistry study revealed all the cases were B cell type with LCA and CD 20 positive and CD3 negative. Conclusion: This study revealed the topographical pattern along with predominant histomorphological and immunohistochemical character of ENL in study population. However, further studies with meta- analysis can enlighten these characters more comprehensively.

Stage migration and treatment outcome in carcinoma tongue – A comparison of seventh and eighth AJCC pathological staging systems

Background: The eighth edition of the American Joint Committee on Cancer (AJCC) for oral cancer has incorporated additional pathological features like depth of invasion (DOI) and extranodal extension (ENE) into T and N staging. The incorporation of these two factors will impact the staging and, hence, the treatment decisions. The aim of the study was to clinically validate the new staging system in predicting the outcome in patients treated for carcinoma oral tongue. The study also examined the correlation of pathological risk factors with survival. Methods: We studied 70 patients with squamous cell carcinoma of the oral tongue who underwent primary surgical treatment at a tertiary care center in the year 2012. All these patients were restaged pathologically according to the new AJCC eighth staging system. The 5-year overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan–Meier method. Akaike information criterion and concordance index were calculated between both staging systems to identify a better predictive model. Log-rank test and univariate Cox regression analysis were conducted to find out the significance of different pathological factors on outcome. Results: Incorporation of DOI and ENE resulted in 47.2% and 12.8% stage migration, respectively. DOI less than 5 mm was associated with a 5-year OS and DFS of 100% and 92.9%, respectively, compared to 88.7% and 85.1%, respectively, when the DOI was more than 5 mm. Presence of lymph node involvement, ENE, and perineural invasion (PNI) were associated with inferior survival. The eighth edition had lower Akaike information criterion and improved concordance index values compared with the seventh edition. Conclusion: The eighth edition of AJCC allows better risk stratification. Restaging of cases based on the eighth edition AJCC staging manual resulted in significant upstaging with difference in survival.

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.

Linfoma no Hodgkin primario de vagina o cuello uterino. Un diagnóstico en ocasiones incierto: a propósito de un caso / Primary non-Hodgkin´s lymphoma of vagina or cervix. A diagnosis sometimes uncertain: about a case

Resumen ANTECEDENTES: La afectación primaria del aparato genital femenino por un linfoma no Hodgkin es excepcional, se reporta en 0.2 a 1.1% de los casos. Los órganos afectados con más frecuencia son los ovarios, seguidos del cuello uterino; el endometrio y la vagina son los menos aquejados. Debido a su baja frecuencia aún no se llega a un consenso del tratamiento más adecuado de estos linfomas; hasta ahora, por lo general, se ha individualizado para cada caso en concreto. CASO CLÍNICO: Paciente de 29 años que consultó por sangrado genital anómalo e incapacidad para la inserción de tampones vaginales. En la exploración se encontró una masa pélvica, palpable a través de la vagina, que impresionaba al infiltrar toda la luz vaginal y la parte media e izquierda de la vulva. En los estudios de imagen se objetivó una gran masa pélvica de hasta 10 centímetros que parecía depender del cuello del útero y que se extendía e infiltraba el canal vaginal, la vulva y el tercio inferior de la vejiga. El reporte anatomopatológico de la biopsia fue: infiltración de pared vaginal por un linfoma no Hodgkin B difuso de células grandes. Se le indicaron seis ciclos de quimioterapia con ciclofosfamida, vincristina, adriamicina y prednisona con los que se consiguió la remisión metabólica completa. CONCLUSIÓN: El diagnóstico del linfoma genital primario puede resultar complejo por la posibilidad de simular una neoplasia ginecológica. En casos de enfermedad avanzada, la manifestación clínica más frecuente es el sangrado genital anómalo. El esquema de tratamiento más aceptado en la actualidad es con rituximab-ciclofosfamida, vincristina, adriamicina, prednisona seguido de radioterapia de consolidación.

Abstract BACKGROUND: Primary involvement of the female genital tract by non-Hodgkin's lymphoma is exceptional, reported in 0.2 to 1.1% of cases. The most frequently affected organs are the ovaries, followed by the cervix; the endometrium and vagina are the least affected. Due to their low frequency, there is still no consensus on the most appropriate treatment of these lymphomas; until now, it has generally been individualized for each specific case. CLINICAL CASE: A 29-year-old female patient consulted for abnormal genital bleeding and inability to insert vaginal tampons. On examination a pelvic mass was found, palpable through the vagina, which impressed by infiltrating the entire vaginal lumen and the middle and left side of the vulva. Imaging studies showed a large pelvic mass of up to 10 centimeters that appeared to be dependent on the cervix and that extended and infiltrated the vaginal canal, the vulva and the lower third of the bladder. The anatomopathological report of the biopsy was: infiltration of the vaginal wall by diffuse large cell non-Hodgkin's B lymphoma. She was prescribed six cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisone with which complete metabolic remission was achieved. CONCLUSION: The diagnosis of primary genital lymphoma can be complex because of the possibility of simulating a gynecologic neoplasm. In cases of advanced disease, the most frequent clinical manifestation is abnormal genital bleeding. The most accepted treatment scheme at present is rituximab-cyclophosphamide, vincristine, adriamycin, prednisone followed by consolidation radiotherapy.

Meta analysis of the relationship between the neutrophils/lymphocytes ratio and prognosis in patients with oral squamous cell carcinoma / 口腔疾病防治

Objective@#To clarify the prognostic value of the neutrophil to lymphocyte ratio (NLR) in oral squamous cell carcinoma (OSCC) patients.@*Methods@#literature on the correlation between NLR and the prognosis and clinicopathological features of OSCC was searched in PubMed, Web of Science, Cochrane and Embase. The outcome indicators, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), tumor size, cervical lymph node metastasis, tumor stage, extracapsular lymph node invasion and peripheral nerve invasion, were analyzed by RevMan5.3 software@*Results @# In total, 6 180 patients were included in 23 studies. The analysis showed that NLR was significantly negatively correlated with OS [HR=1.62, 95%CI(1.38, 1.91), P < 0.001], DFS [HR=1.48, 95%CI(1.24, 1.77), P < 0.001] and DSS [HR=1.87, 95%CI(1.60, 2.20), P < 0.001]. In addition, higher NLR values were positively correlated with tumor size [OR=2.68, 95%CI (1.84, 3.90), P < 0.001], cervical lymph node metastasis [OR=1.59, 95%CI (1.35, 1.88), P < 0.001], tumor stage [OR=2.85, 95%CI (2.35, 3.47), P < 0.001], extralymphatic invasion [OR=1.72, 95%CI (1.23, 2.40), P=0.001], and peripheral nerve invasion [OR=1.70, 95%CI (1.29, 2.24), P < 0.001]. However, there was no significant correlation with age [OR=0.96, 95%CI (0.71, 1.29), P=0.77], sex [OR=1.08, 95%CI (0.88, 1.33), P=0.55], or degree of differentiation [OR=1.15, 95%CI (0.92, 1.43), P=0.22]@*Conclusion @#Elevated NLR was significantly associated with the prognosis and clinicopathological features of OSCC and might be an independent prognostic factor.

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.

Value of pretreatment albumin in prognostic assessment of extranodal nasal type NK/T cell lymphoma / 肿瘤研究与临床

Objective:To explore the prognostic value of pretreatment albumin in extranodal nasal type NK/T cell lymphoma (ENKTL).Methods:The clinical data of 184 ENKTL patients in Shanxi Province Cancer Hospital from January 2002 to December 2018 were retrospectively analyzed. The Contal-O'Quigley change point method was used to determine the optimal cut-off value of albumin for predicting the prognosis of patients. The propensity score matching (PSM) was used to minimize selection biases. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards model was used to determine the factors affecting survival. The time-dependent receiver operating characteristic curve, Akaike information criterion and integrated Brier score were used to evaluate the efficacy of international prognostic index (IPI), Korean prognostic index (KPI) and prognostic index of NK cell lymphoma (PINK) models incorporating albumin for predicting the prognosis of patients.Results:The optimal cut-off value of pretreatment albumin for predicting the prognosis of ENKTL patients was 37.5 g/L. The 3-year and 5-year overall survival (OS) rates in >37.5 g/L group (126 cases) were 66.2% and 60.3%, and the progression-free survival (PFS) rates were 58.8% and 49.6%; the 3-year and 5-year OS rates in ≤37.5 g/L group (58 cases) were 35.0% and 32.4%, and the PFS rates were 32.5% and 30.0%. The OS and PFS in > 37.5 g/L group were better than those in ≤37.5 g/L group (both P<0.001). After PSM, the OS and PFS in >37.5 g/L group were still better than those in ≤37.5 g/L group (both P = 0.002). Multivariate analysis showed that albumin was an independent influencing factor for OS ( RR = 0.419, 95% CI 0.266-0.660, P < 0.001) and PFS ( RR = 0.493, 95% CI 0.322-0.755, P < 0.001). After PSM, albumin was still an independent influencing factor for OS ( RR = 0.305, 95% CI 0.156-0.598, P = 0.001) and PFS ( RR = 0.341, 95% CI 0.185-0.627, P = 0.001). The prognostic prediction performance of the IPI, KPI and PINK models incorporating albumin were all improved. Conclusions:Pretreatment albumin is an important prognostic indicator for ENKTL.

Analysis of treatment results of concurrent and asynchronous radiochemotherapy for early extranodal NK/T cell lymphoma / 中华放射肿瘤学杂志

Objective:To compare the efficacy of concurrent and asynchronous radiochemotheray for early extranodal nasal natural killer/T-cell lymphoma (NKTCL).Methods:From 2007 to 2020, 278 patients with early NKTCL treated with comprehensive treatment in the Affiliated Tumor Hospital of Guizhou Medical University were recruited. According to the adjusted Nomogram-revised risk index (NRI) prognostic model, there were 49 cases in the good prognostic group without adverse prognostic factors (age>60 years old, increased serum lactate dehydrogenase (LDH), ECOG score ≥2, primary tumor invasion (PTI), Ann Arbor stage Ⅱ, and 229 cases in the poor prognostic group with any adverse prognostic factors. 145 of these cases were treated with concurrent radiochemotherapy, and 133 of them were treated with asynchronous radiochemotherapy.Results:The 5-year overall survival (OS) rate of the whole group was 71.0%, and the progression-free survival (PFS) rate was 67.6%. The 5-year OS rate in the good prognostic group was 95.6%, and 65.4% in the poor prognostic group ( P<0.001). In the poor prognostic group, the 5-year OS rates of patients with NRI=1(low-and moderate-risk group), NRI=2(moderate-and high-risk group), NRI≥3(high-risk group) were 72.1%, 61.1% and 47.7%, respectively ( P=0.007). There was no significant difference in curative effect between the concurrent and asynchronous radiochemotherapy groups. The 5-year OS rates were 70.6% and 69.8%( P=0.783), and the 5-year PFS rates were 67.6% and 65.2%( P=0.631). Further stratified analysis showed that the 5-year OS rates of patients with NRI=1 receiving concurrent and asynchronous radiochemotherapy were 73.1% and 76.5%( P=0.576), 62.6% and 69.3%( P=0.427) for those with NRI=2, and 58.1% and 42.3% for those with NRI≥3( P=0.954). Conclusions:Comprehensive treatment can significantly improve the prognosis of early NKTCL in the poor prognostic group. In the sequence of radiotherapy and chemotherapy, there is no significant difference in 5-year OS and PFS rates between concurrent and asynchronous radiochemotherapy. Sequential treatment with better tolerance can be adopted for early NKTCL with poor prognosis.

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.

Rosai-dorfman disease: a rare presentation of extranodal involvement of isolated bone. case report

ABSTRACT Introduction: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis, is a rare disorder characterized by histiocyte proliferation. Case presentation: A 33-year-old man consulted the emergency department of a tertiary care institution in Cartagena de Indias, Colombia, due to a 6-month history of progressive deformity in the frontal right side of the face, associated with pain of slow progression, without any other symptoms or dermatological involvement. There were no other major findings on physical examination and laboratory tests performed were negative. Imaging scans obtained showed extensive inflammatory involvement of the frontal bone, which led to suspect osteomyelitis as the first diagnostic possibility. A biopsy of the lesion was performed with negative cultures for bacteria, which allowed establishing a diagnosis of extranodal Rosai-Dorfman disease with isolated bone involvement. Treatment with systemic corticosteroids was indicated with poor response, so methotrexate was added, achieving an evident improvement after 2 months. Conclusions: Little is known about the manifestations of Rosai-Dorfman disease and its treatment in the adult population. The present case report contributes to expanding the literature on this topic, which can present with rare symptoms that may pose challenges for its diagnosis.

RESUMEN Introducción. La enfermedad de Rosai-Dorfman, también conocida como histiocitosis sinusal, es un trastorno poco frecuente caracterizado por la proliferación de histiocitos. Presentación del caso. Hombre de 33 años quien consultó al servicio de urgencias de una institución de tercer nivel de Cartagena de Indias, Colombia, por una deformidad de progresión lenta que apareció 6 meses atrás en el costado frontal derecho de la cara y generaba dolor. Al examen físico no hubo hallazgos mayores y los estudios paraclínicos fueron normales o negativos. Se obtuvieron imágenes que evidenciaron extenso compromiso inflamatorio/infeccioso del hueso frontal, por lo que se sospechó de osteomielitis y se realizó biopsia de la lesión que permitió establecer diagnóstico de enfermedad de Rosai-Dorfman variante extranodal con compromiso óseo aislado. El paciente recibió tratamiento con corticoide sistémico sin obtener respuesta, por lo que se adicionó metotrexato, con lo cual se logró mejoría a los 2 meses. Conclusiones. Las manifestaciones de la enfermedad de Rosai-Dorfman en población adulta son poco conocidas, además no hay mucha información sobre su tratamiento, por lo que el presente caso contribuye a ampliar la literatura sobre esta enfermedad que puede presentarse con sintomatología completamente inusual.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Linfomas extranodales de cabeza y cuello / Extranodal lymphomas of the head and neck

RESUMEN Antecedentes: los linfomas extranodales de cabeza y cuello (LECC) son neoplasias infrecuentes. El papel diagnóstico de la cirugía justifica considerar estas entidades entre los diagnósticos diferenciales de la patología quirúrgica de la región. Objetivo: describir las características clínico-patológicas, la localización y la asociación con enfermeda des sistémicas de una serie de pacientes operados con LECC. Material y métodos: se realizó una revisión retrospectiva de las historias clínicas de 5489 pacientes operados entre junio de 2009 y junio de 2019. Diecinueve de ellos (0,35%) presentaron LECC. Resultados: el promedio de edad fue de 56 años (rango 17- 84, DS 19,3), 16 fueron mujeres (84%). La localización de los LECC fue: glándula parótida en 12 casos (63%), glándula submaxilar en 3 casos (16%), glándula salival menor en 2 casos (11%), glándula lagrimal en 1 caso (5%), glándula tiroides en 1 caso (5%). Todos fueron linfomas no Hodgkin. Los tipos citológicos fueron: linfoma de tejido linfoideo asociado a mucosas (MALT) 9 (48%), linfoma folicular 4 (21%), linfoma de células B grandes 3 (16%), linfoma de células pequeñas 1 (5%), linfoma del manto 1 (5%), linfoma anaplásico 1 (5%). Cuatro pa cientes (21%) presentaron síndrome de Sjögren en el momento del diagnóstico, tres linfomas MALT y uno linfoma folicular. Diferentes procedimientos quirúrgicos permitieron llegar al diagnóstico. Conclusión: los LECC constituyen una forma singular de presentación de neoplasias oncohematológica. En la presente serie se manifestaron en un amplio rango de edad, con mayor frecuencia de mujeres y en la glándula parótida. Su diagnóstico pudo alcanzarse con la biopsia o resección de la zona afectada.

ABSTRACT Background: Extranodal lymphomas of the head and neck (ELHN) are rare neoplasms. The role of surgery for the diagnosis justifies thinking of these neoplasms among the differential diagnoses of the surgical disorders of the region. Objective: The aim of this study was to describe the clinical and pathological characteristics of ELHN, their location and association with systemic diseases in a series of patients undergoing surgery. Material and methods: The clinical records of 5489 patients undergoing surgery between June 2009 and June 2019 were retrospectively reviewed. Nineteen patients (0.35%) presented ELHN. Results: Mean age was 56 years (range: 17-84; SD 19.3) and 84% (n = 16) were women. The location of ELHN were the parotid gland (n =12, 63%), submaxillary gland (n = 3, 16%), salivary gland (n = 1, 5%), lacrimal gland (n = 1, 5%) and thyroid gland (n =1, 5%). All the tumors were non-Hodgkin lymphomas with the following subtypes: mucosa associated lymphoid tissue (MALT) lymphoma (n = 9, 48%), follicular lymphoma (n = 4, 21%), large B-cell lymphoma (n = 3, 16%), small B-cell lymphoma (n = 1, 5%), mantle cell lymphoma (n = 1, 5%), and anaplastic lymphoma (n =1, 5%). Four patients (21%) presented Sjögren syndrome at the moment of the diagnosis; three were MALT lymphomas and one patient had follicular lymphoma. The diagnosis was made with different surgical procedures. Conclusion: ELHN constitute a singular presentation of onco-hematology neoplasms. In our series, these tumors occurred within a wide age range and were more common in women. The parotid gland was more commonly affected. The diagnosis was made by surgical biopsy or resection of the area affected.

Linfoma no Hodgkin primario extranodal de musculatura masticatoria. A propósito de un caso

Resumen Entre el 25% a 40% de los linfomas no Hodgkin (LNH) surgen en ubicaciones extranodales. La afectación de los tejidos blandos por el LNH es infrecuente y el linfoma de origen primario del músculo esquelético es aún más inusual. Los músculos mayormente afectados son los de las extremidades, pelvis, región glútea y con menor frecuencia los músculos de cabeza y cuello. En este artículo se presenta nuestra experiencia sobre un caso de linfoma no Hodgkin primario extranodal del músculo masetero, que fue tratado con quimioterapia combinada tipo R-CHOP con buena respuesta. Se revisan en la literatura las características clínicas de esta patología, los criterios diagnósticos y el tratamiento en este tipo de linfoma.

Abstract Around 20% to 45% of non-Hodgkin lymphomas (NHL) develop in extranodal locations. Soft tissue involvement is rare and skeletal muscle affection is a far more unusual NHL presentation. In this singular scenario, upper and lower extremity muscles are mostly affected, especially those from the pelvic and gluteal area and less frequent of the musculature from the head and neck region. Therefore, we here in report a case of an extranodal NHL of the masseter muscle. Treatment regime was based on R-CHOP combined chemotherapy resulting in a favorable outcome. Diagnostic criteria and clinical characteristics, and treatment of this type of lymphoma are reviewed in this article.