Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion:A case report

BACKGROUND Intestinal natural killer/T-cell lymphoma(NKTCL)is a rare and aggressive non-Hodgkin’s lymphoma,and its occurrence is closely related to Epstein-Barr virus infection.In addition,the clinical symptoms of NKTCL are not obvious,and the specific pathogenesis is still uncertain.While NKTCL may occur in any segment of the intestinal tract,its distinct location in the periampullary region,which leads clinicians to consider mimics of a pancreatic head mass,should also be addressed.Therefore,there remain huge challenges in the diagnosis and treatment of intestinal NKTCL.CASE SUMMARY In this case,we introduce a male who presented to the clinic with edema of both lower limbs,accompanied by diarrhea,and abdominal pain.Endoscopic ultrasound(EUS)showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas.Under the guidance of EUS-fine needle biopsy(FNB)with 19 gauge or 22 gauge needles,combined with multicolor flow cytometry immunophenotyping(MFCI)helped us diagnose NKTCL.During treatments,the patient was prescribed the steroid(dexamethasone),methotrexate,ifosfamide,L-asparaginase,and etoposide chemotherapy regimen.Unfortunately,he died of leukopenia and severe septic shock in a local hospital.CONCLUSION Clinicians should enhance their understanding of NKTCL.Some key factors,including EUS characteristics,the right choice of FNB needle,and combination with MFCI,are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Synchronous adenocarcinoma and extranodal natural killer/T-cell lymphoma of the colon:A case report and literature review

Extranodal natural killer/T-cell lymphoma(ENKTL) is a distinct subtype of non-Hodgkin's lymphoma and is rare in the colon.Synchronous adenocarcinoma and ENKTL of the colon has not been reported in the literature.In the present study,we report a 63-year-old male who suffered from intermittent bloody stools for 2 mo.He did not have fever,body weight loss or night sweat.Endoscopic and imaging studies revealed a 4.5-cm ulcerative mass in the ascending colon and a 3.0-cm polypoid,easy bleeding mass in the sigmoid colon,respectively.Thought to have double carcinoma of the colon,he received simultaneous right hemicolectomy and sigmoidectomy.The pathological diagnosis was a synchronous ENKTL(ascending colon) and adenocarcinoma(sigmoid colon).The literature on synchronous adenocarcinoma and malignant lymphoma of the colon was also reviewed.

Extranodal natural killer/T-cell lymphoma(nasal type) presenting as a perianal abscess: A case report

BACKGROUND Extranodal natural killer(NK) T-cell lymphoma(ENKTL), nasal type is a rare subtype of extranodal non-Hodgkin lymphoma characterized by vascular damage and necrosis. The lesions usually present in the nasal cavity and adjacent tissues, however, the disease originates from the gastrointestinal or genitourinary tract in 25% of cases. Since rectal involvement in ENKTL is rare, rectal symptoms in the course of ENKTL are often misdiagnosed and considered to be related to benign diseases such as rectal fistula or perianal abscess.CASE SUMMARY We report the case of a 24-year-old Han Chinese female who initially presented with a perianal abscess that was subsequently diagnosed as nasal type ENKTL.Due to typical perianal pain, perianal abscess was diagnosed and surgical incision and drainage were performed. After recurrent, severe anal hemorrhages leading to hypovolemic shock and multiple surgeries, a diagnosis of ENKTL was made. The patient's condition gradually deteriorated, and she died shortly after initiation of chemotherapy.CONCLUSION Systemic and neoplastic diseases should be included in the differential diagnosis of any potentially benign perianal abscess complicated with recurrent hemorrhages.

Outcomes of patients treated with SVILE vs.P-GemOx for extranodal natural killer/T-cell lymphoma,nasal type:a prospective,randomized controlled study

Objective:To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma,nasal type(ND-ENKTL).Methods:From April 2015 to July 2018,103 patients with ND-ENKTL were randomly assigned to SVILE(experimental group)or P-GemOx(control group)chemotherapy followed by radiotherapy and consolidation chemotherapy.The primary endpoint was the overall response rate after 3 cycles of chemotherapy,and secondary study endpoints were complete response(CR),progression-free survival(PFS),and overall survival(OS).Safety was also evaluated.Results:There were no significant differences in baseline characteristics in the experimentalvs.control groups.In experimental and control groups,respectively,the overall response rates were 91.7%vs.97.0%for stageI/II and 75.0%vs.72.2%for stage III/IV.The CR rates were 83.4%vs.97.0%for stage I/II and 68.8%vs.61.1%for stage III/IV.None of those differences were significant.There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV.The 3-year PFS and OS in stage I/II were 88.3%vs.93.3%and 88.8%vs.97.0%,respectively.The 3-year PFS and OS in stage III/IV were 46.2%vs.65.7%and 68.8%vs.72.2%,respectively.The common adverse events were hematological toxicity,hepatotoxicity,and coagulation abnormalities,which were found to be reversible with supportive therapy.Conclusions:The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated.SVILE is a therapeutic option for ND-ENKTL.

Natural killer/T-cell lymphoma with concomitant syndrome of inappropriate antidiuretic hormone secretion: A case report and review of literature

We report a case of natural killer(NK)/T-cell lymphoma with concomitant syndrome of inappropriate antidiuretic hormone secretion(SIADH).The patient was a 64-yearold woman with a history of nasopharyngeal carcinoma of over 30 years.She was admitted with a chief complaint of intermittent fever for 2 mo.Palpation after admission indicated a swollen lymph node below the left jaw.Multiple imaging examinations on admission indicated multiple enlarged lymph nodes throughout the body.We performed a left submandibular lymph node biopsy,and the results revealed NK/T-cell lymphoma.A biochemical examination indicated Epstein-Barr virus positivity.At the same time,the patient developed hyponatremia.Based on her laboratory examination and clinical manifestation,decreased plasma osmolality,urine osmolality greater than plasma osmolality,lack of skin swelling,normal blood pressure,normal renal function,no adrenal function detected on serology,and no abnormalities in imaging examination of the adrenal glands,the likelihood of SIADH in the patient was high.After fluid restriction and administration of sodium chloride,the patient’s blood sodium level gradually increased.Subsequently,the immune function of the patient declined,there were severe symptoms of infection,and she died of respiratory failure.NK/T-cell lymphoma associated with SIADH has not,to our knowledge,been previously reported in PubMed.This case emphasizes the importance of monitoring serum ion levels,especially serum sodium,in patients with NK/T-cell lymphoma.

Natural killer/T-cell lymphoma with intracranial infiltration and Epstein-Barr virus infection: A case report

BACKGROUND Because of atypical clinical symptoms,lymphoma is easily confused with infectious diseases.Extranodal nasal-type natural killer/T-cell lymphoma(NKTL)is more common,and there are few cases of eyelid site onset and intracranial infiltration,which increases the difficulty of diagnosis.This disease usually has a very poor prognosis and there are few reports of recovery.CASE SUMMARY A 3-year-old boy was admitted to our hospital due to an initial misdiagnosis of"eyelid cellulitis"and failed antibiotic treatment.He was characterized by fever,right eyeball bulging,convulsions,and abnormal liver function.His blood Epstein-Barr virus(EBV)DNA was positive(8.798×10^4 copies/mL),and remained positive for about half a year.The cranial imaging examination suggested a space-occupying lesion in the right eyelid,with the right temporal lobe and meninges involved.The boy underwent ocular mass resection.The pathological diagnosis was NKTL.He was diagnosed as having NKTL with intracranial infiltration,combined with chronic active EBV infection(CAEBV).Then he underwent systemic chemotherapy and intrathecal injection.The boy suffered from abnormal blood coagulation,oral mucositis,diarrhea,liver damage,and severe bone marrow suppression but survived.Finally,the tumor was completely relieved and his blood EBV-DNA level turned negative.The current follow-up has been more than 2 years and his condition is stable.CONCLUSION This case suggests that chemotherapy combined with intrathecal injection may have a good effect on intracranial infiltrating lymphoma and CAEBV,which deserves further study and discussion.

Combination of atezolizumab and chidamide to maintain long-term remission in refractory metastatic extranodal natural killer/T-cell lymphoma:A case report

BACKGROUND The prognosis of refractory extranodal natural killer/T-cell lymphoma(ENKTL)is poor.Recent data have indicated that immune checkpoint blockade with a programmed cell death protein-1(PD-1)antibody in combination with administration of histone deacetylase inhibitors represents a potentially effective treatment strategy.Compared with PD-1 antibodies,programmed death-ligand 1 antibodies have fewer side effects.Here,we present a rare case of a patient with refractory metastatic ENKTL who achieved sustained remission of approximately 10 mo with minor adverse effects after combination therapy with atezolizumab,chidamide,and radiotherapy.CASE SUMMARY A 56-year-old woman underwent resection of a tumour in her left nasal cavity and was diagnosed with ENKTL(nasal type).Medical examination revealed tumours observed in the bilateral nasal mucosa,the subcutaneous soft tissue of the inner side of the left eye,the soft tissue of the nasopharynx,the bilateral tonsils,and the left preauricular,right hilar,bilateral neck lymph nodes and bone marrow.However,tomography/computed tomography showed increased metabolism of the bilateral nasal mucosa and subcutaneous soft tissue of the inner side of the left eye and newly increased metabolism of the left cervical lymph node after chemotherapy.Therefore,combination therapy with chidamide,atezolizumab,and radiotherapy was performed.Fortunately,the patient achieved a complete response following 10 mo of combination therapy.CONCLUSION The outcome in this case suggests that the combination of atezolizumab,chidamide,and radiotherapy is a promising regimen for treating refractory metastatic ENKTL following chemotherapy treatment failure.

Primary intestinal extranodal natural killer/T-cell lymphoma, nasal type: A case report

BACKGROUND Primary intestinal extranodal natural killer/T-cell lymphoma,nasal type(PIENKTCL)is a rare non-Hodgkin’s lymphoma(NHL)subtype,and its prognosis is extremely poor.Clinical characteristics of the disease are not obvious and easily misdiagnosed.In this case report,we describe a patient with PI-ENKTCL who presented with intermittent hematochezia.The advantages of positron emission tomography/computed tomography(PET-CT)as a useful diagnostic tool and the role of surgery as an important therapy are highlighted.CASE SUMMARY A 45-year-old man,hospitalized due to intermittent hematochezia,underwent gastroscopy,colonoscopy,biopsy and CT,but no cause was found.Hence,we carried out a multidisciplinary team(MDT)discussion on the causes and treatment of this patient,and it was decided to perform PET-CT imaging with a MDT discussion of the results.PET-CT demonstrated a diagnosis of lymphoma and it was decided to surgically resect the lesion,and a R0 resection was successfully performed.Postoperative pathology showed negative resection margins,and examination of the lesion confirmed the diagnosis of PI-ENKTCL.After surgery,the patient underwent a follow-up period of 6 mo and received 6 cycles of gemcitabine,oxaliplatin and L-asparaginase.No recurrence or metastasis occurred.CONCLUSION PI-ENKTCL is rare,and MDT discussion is required during diagnosis.PET-CT can be performed for imaging diagnosis.Treatment is based on surgical resection,and the best treatment regimen is determined according to postoperative pathological results to improve prognosis and to extend survival in patients.

Primary site and regional lymph nodeinvolvement are independent prognosticfactors for early？stage extranodal nasal？typenatural killer/T cell lymphoma

Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement.The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.Methods:To develop a nomogram,we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011.The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index(C-index) and calibration curve.Results:The 5-year overall survival(OS) and progression-free survival(PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL(OS:68.2%vs.46.0%,P = 0.030;PFS:53.4%vs.26.6%,P = 0.010).The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage HE ENKTCL(OS:66.3%vs.59.2%,P = 0.003;PFS:51.4%vs.40.3%,P = 0.009).Multivariate analysis showed that age >60 years,ECOG performance status score >2,elevated lactate dehydrogenase(LDH) level,extranasal primary site,and regional lymph node involvement were significantly associated with lower 5-year OS rate;age >60 years,elevated LDH level,extra-nasal primary site,and regional lymph node involvement were significantly associated with lower 5-year PFS rate.The nomogram included the primary site and regional lymph node involvement based on multivariate analysis.The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates,and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634,respectively.Conclusions:The primary site and regional lymph node involvement are independent prognostic factors for earlystage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma,nasal type:a triple.center study

Background:The prognostic significance of ABO blood type for lymphoma is largely unknown.We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer(NK)/T-cell lymphoma(ENKTL).Methods:We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers.The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models.The prognostic values of the International Prognostic Index(IPI) and the Korean Prognostic Index(KPI)were also evaluated.Results:Compared with patients with blood type O,those with blood type non-O tended to display elevated baseline serum C-reactive protein levels(P=0.038),lower rate of complete remission(P=0.005),shorter progression-free survival(PFS,P<0.001),and shorter overall survival(OS,P=0.001).Patients with blood type O/AB had longer PFS(P<0.001) and OS(P=0.001) compared with those with blood type A/B.Multivariate analysis demonstrated that age >60 years(P<0.001),mass ≥5 cm(P=0.001),stage Ⅲ/Ⅳ(P<0.001),elevated serum lactate dehydrogenase(LDH) levels(P=0.001),and blood type non-O were independent adverse predictors of OS(P=0.001).ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low-and high-to-intermediate-risk groups.Conclusions:ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

Primary duodenal NK/T-cell lymphoma with massive bleeding: A case report

Primary natural killer/T-cell(NK/T-cell) lymphoma of the gastrointestinal tract is a very rare disease with a poor prognosis, and the duodenum is quite extraordinary as a primary lesion site. Here, we describe a unique case of a primary duodenal NK/T-cell lymphoma in a 26-year-old man who presented with abdominal painand weight loss. Abdominal computed tomography scan demonstrated a hypodense tumor in the duodenum. Because of massive upper gastrointestinal tract bleeding during hospitalization, the patient was examined by emergency upper gastrointestinal endoscopy. Under endoscopy, an irregular ulcer with mucosal edema, destruction, necrosis, a hyperplastic nodule and active bleeding was observed on the duodenal posterior wall. Following endoscopic hemostasis, a biopsy was obtained for pathological evaluation. The lesion was subsequently confirmed to be a duodenal NK/T-cell lymphoma. The presenting symptoms of primary duodenal NK-/T-cell lymphoma in this patient were abdominal pain and gastrointestinal bleeding, and endoscopy was important for diagnosis. Despite aggressive treatments, the prognosis was very poor.

IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma

Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and survival.In the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell lines.Methods:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6.Lentiviral vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 cells.The biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were analyzed.Results:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 cells.Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and asparaginase.These effects were reversed by an anti-IL-2Rαantibody.Conclusions:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rαexpression.IL-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.

Natural killer T-cell lymphoma originating from the orbit

Natural killer T-cell lymphoma （NKTL） is a malignant neoplasm which usually involves the nasal cavity or paranasal sinuses, while an orbit origin is extremely rare. Here we report the clinical, radiological and histopathologic features of a patient with NKTL originating from the orbit. We analyzed the clinical and radiologic records in the whole course of the disease. We also reviewed the morphology and immunohistochemistry of the neoplasm biopsy, including the presence of CD56, CD3 and cytotoxic molecules. This case demonstrated that nasal-type NKTL with a poor prognosis can originate from the orbit.

NK/T细胞淋巴瘤

目的 了解和认识NK /T细胞淋巴瘤的临床病理和免疫学特点。方法 选用NK细胞特异性抗体CD 5 6、T细胞特异性抗体CD3ε ,对 117例T细胞淋巴瘤进行标记。结果 117例T细胞淋巴瘤中 2 6例CD5 6( +)、CD3ε( +) ,阳性表达率为2 2 .2 % ;2 6例中结外淋巴瘤 16例 ( 61.5 % ) ,其中 15例位于鼻部 ;淋巴结内 10例 ( 38.5 % ) ;2 6例中 18例 ( 69.2 % )表现为细胞的多形性特点 ,12例 ( 46.2 % )有凝固性坏死。结论 NK /T细胞淋巴瘤免疫学特点是CD 5 6与CD3ε共同表达。NK /T细胞淋巴瘤多发生在结外 ,以发生于鼻部者为多 ,少数发生在结内 ,肿瘤细胞的多形性和肿瘤组织的凝固性坏死是主要的病理学特点。

Raji细胞逃逸NK细胞免疫杀伤机制的初步探讨

目的探讨人B细胞淋巴瘤Raji细胞逃逸NK细胞免疫杀伤的机制。方法以K562细胞作为对照，应用LDH释放法检测不同效靶比时同种异体NK细胞杀伤Rail细胞的活性。并分别用PCR方法和流式细胞仪检测K562和Raji细胞MICA／B、ULBP1～3、HLA基因型和分子的表达情况。效靶比20：1时用单抗分别阻断K562和Raji细胞表面MICA、MICB、ULBP1、ULBP2、ULBP3和HLA-Ⅰ类分子，观察NK细胞对其杀伤活性的变化。结果不同效靶比时NK细胞杀伤Raji细胞的活性明显低于杀伤K562细胞的活性，二者之间差异有统计学意义（P〈0．05）。K562细胞表达MICA／B和ULBP1～3基因和分子，不表达HLA—Ⅰ类分子，Raji细胞表达ULBP1～3基因和HLA-Ⅰ类分子，不表达MICA／B和ULBP1～3分子。Rail细胞HLA基因型为A＊3、3，B＊71、71，Cw3、4。用单抗封闭MICA／B和ULBP1-3分子后，NK细胞对K562细胞的杀伤活性明显降低，对Raji细胞的杀伤活性无明显改变。结论Raji细胞逃逸NK细胞免疫杀伤机制和Raji细胞高表达HLA-Ⅰ类分子，不表达NKG2D的配体MICA／B和ULBP1～3有关。

57例鼻腔NK/T细胞淋巴瘤临床分析

目的:探讨鼻腔NK/T细胞淋巴瘤的临床表现、放疗和化疗的近期疗效以及不同的治疗方法对生存率的影响。方法:收集我院1994年2月～2002年12月收治的57例经病理形态学诊断为鼻腔NK/T细胞淋巴瘤患者的临床资料,主要表现为鼻塞、涕血、恶臭。采用单纯放疗或放疗后化疗35例,化疗后放疗22例,观察及治疗效果。结果:近期疗效:35例经单纯放疗或放疗后化疗,放疗后完全缓解(CR)率为74%,其余22例为化疗后放疗,化疗后CR率仅23%,单纯放疗或放疗后化疗的CR率明显高于化疗后放疗的CR率(P<0.01),全组患者中先放疗组、化疗后放疗组患者的5年生存率分别为60%和55%(P>0.05)。结论:鼻腔NK/T细胞淋巴瘤的临床表现不典型,单纯放疗或放疗后化疗的近期疗效显著优于常规化疗,化疗加入放疗并未改善生存率。

头颈部鼻型结外NK/T细胞淋巴瘤误诊分析及文献复习

目的分析头颈部鼻型结外NK/T细胞淋巴瘤(extranodal NK/T-cell lymphoma,nasal type,ENKTCL)误诊病例,提高认识以避免误诊。方法回顾分析8例存在多次误诊误治头颈部ENKTCL的诊治经过。同时在数据库上查找同期关于头颈部ENKTCL误诊病例报道文献一并进行分析。结果本研究8例病例误诊次数 3~4次,误诊疾病有鼻窦炎、鼻出血、上呼吸道感染等。查到符合条件的文献共21篇,误诊疾病有鼻窦炎、面部蜂窝织炎、鼻炎等。导致误诊的原因有早期临床表现缺乏特异性、影像学表现缺乏明显特征和病理学特征的复杂性。结论 ENKTCL早期容易发生误诊,加强对其临床、影像和病理特征的认识,有助于及早识别ENKTCL,及时准确取病理才能尽可能避免误诊误治。

结外鼻型NK/T细胞淋巴瘤的流行病学调查(英文)

Extranodal natural killer(NK)/T-cell lymphoma,nasal type(ENKTCL) is a rarely kind of non-Hodgkin lymphoma(NHL).It is much more frequent in Asian and Latin American countries than other part of the world.It typically affects nasal cavity.In China,one of its endemically places,ENKTCL accounts for 74%-96% of nasal NHL.Patients with ENKTCL usually show a highly aggressive clinical course,and its etiology is unclear.However,it is already proved that ENKTCL is associated with Epstein-Barr virus(EBV) infection,regardless patients',ethnicity and areas.Some studies show that the risk will increase among several occupations,such as farmer,who are frequently exposure to pesticides and chemical solvent and risk can be cut down if taking some protective measures.

Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natura-killer/T-cell lymphoma: a single-center retrospective analysis

Background:Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage Ⅰ/Ⅱ ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. Methods: We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients5 overall survival (OS). Results: Of the 86 patients, 71(82.6%) experienced invasion of AS, 22(25.6%) of soft tissue, and 26(30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank X^2 = 1.177, P = 0.278);however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank x^2 = 4.105, P = 0.043) or brain involvement (Log rank x^2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank x^2 = 10.390, P = 0.001) or bones (Log rank x^2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [Cl]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% Cl: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. Conclusions: Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

Immunotherapy of Cancer—A Historical Note

We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells: killer T (TK), natural killer (NK), lymphokine activated killer (LAK) cells. Both TX and TO inhibited the growth of tumors that express estrogen receptors. Thus these antiestrogens inhibited tumor growth and stimulated killer cells for cytotoxicty on such tumors. Therefore these agents were presumed to stimulate tumor immunity. We tested the P815 mouse mastcytoma with TK, LK, and TX or TO. A therapeutic effect was observed in both experiments. The SL2-5 murine lymphoma was tested with NK and TX cells or TO cells and successful immunotherapy was observed.?We digested human breast carcinomas and lung tumors with collagenase. The killer cells were separated from tumor cells on Ficoll gradients. TX and TO enhanced the cytotoxic effect of autologous killer cells on the corresponding tumor cells. This experiment indicates that the results obtained in animals are also valid for human malignant disease.