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 (SUV_max) 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 SUV_max 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 SUV_max of patients with local lymph nodes involvement was significantly higher than those without local lymph nodes involvement (P=0.007). The SUV_max 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 SUV_max 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 SUV_max is potential for prognosis evaluation since it is correlated with prognostic factors.
Fluorodeoxyglucose F18 ; Humans ; Lymphoma, Extranodal NK-T-Cell/radiotherapy* ; Positron Emission Tomography Computed Tomography/methods* ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies

PURPOSE: To evaluate radiotherapy (RT) and chemotherapy (CT) treatments of early-stage extranodal natural killer/T-cell lymphoma (ENKTL). MATERIALS AND METHODS: Fifty-five patients with stage I or II ENKTL [n=39 (71%) and 16 (29%) patients, respectively] who were treated with RT between 1999 and 2013 were analyzed retrospectively. The median age was 54 years (range, 24-81). Patients were grouped by treatment modality as RT alone [n=19 (35%)], upfront CT plus RT [CT+RT, n=16 (29%)], and concurrent chemoradiotherapy [CCRT, n=20 (36%)]. The median RT dose was 48 Gy. Patient characteristics between each treatment group were well balanced. Patterns of failure and survival were analyzed. RESULTS: The overall response rate after RT was 94.6%. Ten patients experienced distant failure, and seven experienced local failure comprising five in-field and two out-field failures. The local and distant failure rates in the RT-alone group were the same (16%). In the CT+RT group, the most common failure sites were local (19%). In the CCRT group, the most common failures were distant (25%). At a median follow-up of 56 months (range, 1-178 months), the 5-year overall survival (OS) and progression-free survival rates were 66% and 54%, respectively. The 5-year OS rate for the RT-alone and CT+RT groups were 76% and 69%, respectively, and the 2-year OS rate for the CCRT group was 62% (p=0.388). CONCLUSION: In the era of multimodal treatment for ENKTL, RT alone using advanced techniques should be considered for local disease control, whereas maintenance CT regimens should be considered for distant disease control.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Chemoradiotherapy ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Extranodal NK-T-Cell/*drug therapy/mortality/*radiotherapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

A 68-year-old Chinese man presented with an eight-month history of pyrexia of unknown origin and chronic sinusitis despite multiple courses of antibiotics. He underwent extensive investigations, including workups for infections, chronic granulomatous diseases and malignancy. Nasal biopsies were performed twice under local anaesthesia, but did not show any evidence of malignancy. Eventually, the patient was diagnosed with natural killer (NK)/T-cell lymphoma, nasal variant, based on histopathological findings from harvested deep tissue obtained via functional endoscopic sinus surgery. This study highlights that, for patients presenting with pyrexia of unknown origin and nasal symptoms, NK/T-cell lymphoma must be considered as a differential diagnosis. Generous amounts of tissue should be harvested under general anaesthesia rather than limited tissue under local anaesthesia, in order to facilitate and ensure a definitive diagnosis.
Aged ; Anti-Bacterial Agents ; chemistry ; Biopsy ; China ; Humans ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; diagnostic imaging ; pathology ; Male ; Nasal Cavity ; pathology ; Nose Neoplasms ; complications ; diagnosis ; radiotherapy ; Prognosis ; Radiography ; Radiotherapy ; Sinusitis ; complications ; diagnosis ; Treatment Outcome

OBJECTIVE: To explore the curative effect of nasal type extranodal NK/T-cell lymphoma by sequential chemotherapy combined radiotherapy compared with chemtherapy. METHOD: Fifty-seven cases of nasal type extranodal NK/T-cell lymphoma confirmed by pathological morphology and immuno-histochemistry were divided into chemotherapy combined radiotherapy group (34 cases) or chemotherapy group (23 cases). Twenty-three patients in the chemotherapy group alternately applied CHOP, VDLP and MEOP regimen after each two treatments into the clinical observation; Chemotherapy combined radiotherapy group of 34 patients, in addition to the above chemotherapy, applied three-dimensional conformal radiation therapy of the primary site by linear accelerators. Then all of patients were ceased treatment and followed up 3-5 years. RESULT: (1) After treatment, effective rate of two groups was 91.2% and 87.0%, there was no obvious difference (P > 0.05); After follow up about 1 year, effective rate of two groups was 76.5% and 73.9%, there was no obvious difference (P > 0.05); (3) After follow up about 3 years and 5 years, disease free survival (DFS) of two groups was 61.3%, 47.6% and 43.5%, 21.4%, there was obvious difference (P < 0.05). (4) Long-term survival is closely related to treatment mode. (5) B symptoms, advanced (III, IV) stage, the International Prognostic Index (IPI), KPS scores were correlated with prognosis, and were independent prognostic factors. CONCLUSION Treatment with chemotherapy and radiotherapy for nasal type extranodal NK/T-cell lymphoma had obvious curative effect and may improve long-term survival efficiently compared with chemotherapy alone.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Combined Modality Therapy ; Female ; Humans ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; radiotherapy ; therapy ; Male ; Middle Aged ; Radiotherapy ; methods ; Treatment Outcome ; Young Adult

Extranodal NK/T-cell lymphoma is a rare pathological type, incidence of which is 2% - 10% of the primary NHL cases, showing a broad morphologic spectrum with frequent necrosis. Extranodal NK/T-cell lymphoma occurs more frequently in Asian population, especially in Southern China and Southeast Asian population. It is reported that the incidence of ENKL among lymphomas (1314 cases) in Asian countries was 4 times as much as the Western countries (22% vs. 5%) by the International Peripheral T-cell Lymphoma Project. Nasal NK/T-cell lymphoma most commonly occurred in the nasal cavity or other parts of the upper aerodigestive tract, and is highly associated with EBV (Epstein-Barr virus) infection, which is highly aggressive and its prognosis generally is poor. The mean survival time is about 12-38 months. It is important to accurately assess the patients prognosis for an optimal treatment. Localized disease (stage I and II) often has a relatively good prognosis through local radiation or combined therapy. There is a paucity of data to guide therapy in advanced disease. Generally, combining therapy is the most commonly selected approach for advanced disease. The conditions of the patients with advanced, relapsed or refractory diseases have been improved by high-intensity chemotherapy combined with radiation, and a regimen containing L-asparaginase L-Asp. Recently some studies have demonstrated promising outcomes in the selected cases by high-dose chemotherapy supplemented with auto-or allo-HSCT. Targeting therapy is also developing quickly. This current review mainly focuses on the advance of treatment for extranodal NK/T-cell lymphoma.
Antineoplastic Combined Chemotherapy Protocols ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; radiotherapy ; therapy

BACKGROUND AND OBJECTIVEExpression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma.

METHODSThe clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections.

RESULTSAmong the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma.

CONCLUSIONHigh expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase ; blood ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; metabolism ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; Remission Induction ; S-Phase Kinase-Associated Proteins ; metabolism ; Survival Rate ; Young Adult

OBJECTIVETo evaluate the expression and prognostic significance of T-bet and its cofactors EOMES, ETS-1 and MEF [which are transcription factors and responsible for development of natural killer (NK) cells] in the extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT).

METHODSThe expression status of T-bet, EOMES, ETS-1 and MEF in 40 cases of EN-NK/T-NT occurring in Chinese population was studied by immunohistochemistry and in-situ hybridization (ISH). The clinical relevance was also evaluated. The control cases included 18 cases of peripheral T-cell lymphoma, 10 cases of B-cell lymphoma, 5 cases of normal spleen, 5 cases of normal thymus and 10 cases of nasal mucosal tissues affected by chronic inflammation.

RESULTSThe expression levels of T-bet mRNA and protein were high in EN-NK/T-NT (82.5% and 100%, respectively) and in peripheral T cell lymphoma (17/18 and 72.2%, respectively). There was no expression in B-cell lymphoma. The expression of EOMES (80.0% by ISH), ETS-1 (82.5% by ISH) and MEF (62.5% by ISH) was high in EN-NK/T-NT, but not in the control group. The frequency of co-expression of T-bet and EOMES (75%, 30/40) was significantly higher than that of the other genes. Follow-up study showed that the mean and median survival of the 19 cases of EN-NK/ T-NT was 33 months and 10 months, respectively. The five-year survival rate was 10.5%. Statistical analysis showed that only treatment modalities significantly affected the patients' overall survival; and none of the four transcription factors had significant impact on survival. The expression rates of T-bet, EOMES, ETS-1 or MEF had no significant difference between the 9 alive and the 10 dead cases.

CONCLUSIONSThe expression of T-bet correlates with the lymphoma types. It is mainly expressed in peripheral NK and T-cell lymphomas. The important functional gene engaged in NK cells development is highly expressed in EN-NK/T-NT. They may play a crucial role in pathogenesis and aggressive biologic behavior.

Adolescent ; Adult ; Aged ; China ; epidemiology ; DNA-Binding Proteins ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Extranodal NK-T-Cell ; Lymphoma, T-Cell, Peripheral ; metabolism ; Male ; Middle Aged ; Nose Neoplasms ; drug therapy ; metabolism ; pathology ; radiotherapy ; Proto-Oncogene Protein c-ets-1 ; metabolism ; RNA, Messenger ; metabolism ; Survival Rate ; T-Box Domain Proteins ; genetics ; metabolism ; Transcription Factors ; metabolism ; Young Adult

OBJECTIVETo investigate the expression of murine double minute 2 (mdm2), p53, p21 and latent membrane protein 1 (LMP-1) in nasal NK/T-cell lymphoma (NKTL) and analyze their relationship with the clinical stage and prognosis.

METHODSThe clinicopathological and follow-up data of 62 patients with NKTL proven by pathology were collected. Paraffin-embedded tissue sections were examined for mdm2, p53, p21 and LMP-1 proteins by tissue microarray technique and immunohistochemistry. In situ hybridization was used to detect EBER1/2.

RESULTSThe positive expression rates of mdm2, p53, p21 and LMP-1 proteins in NKTL were 61.3%, 79.0%, 58.1% and 48.4%, respectively, and EBER1/2 was 90.3%. The positive expression rates of mdm2 in Ann Arbor stage I, II, III and IV NKTL were 43.5%, 62.5%, 73.3% and 87.5%, respectively; p53 were 69.6%, 75.0%, 86.7% and 100.0%; p21 were 47.8%, 56.3%, 60.0% and 87.5%; while those of LMP-1 were 60.9%, 50.0%, 26.7% and 50.0%, respectively. With the progression of tumor, the positive expression rates of mdm2, p53 and p21 proteins gradually increased. There were statistically significant differences between them (P<0.05). There were statistically positive correlations among those three genes (P<0.05). The prognosis of the positive expression group of these three genes was worse than that of negative expression group (P<0.05). No statistically significant difference was observed between the expression of LMP-1 protein and the clinical stage or prognosis (P>0.05). The expression of p53 protein was an independent prognostic factor.

CONCLUSIONThe expression of mdm2, p53 and p21 proteins is closely related with the pathogenesis and progression of NKTL. They are good markers for judgement of the biological behavior of NKTL. The expression of p53 protein is an independent prognostic factor. Though no significant relationship was found between the expression of LMP-1 protein and the clinical stage or prognosis, it may play some role in tumor progression.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; metabolism ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; Nose Neoplasms ; drug therapy ; metabolism ; pathology ; radiotherapy ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-mdm2 ; metabolism ; RNA, Viral ; metabolism ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism ; Vincristine ; therapeutic use ; Viral Matrix Proteins ; metabolism ; Young Adult

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD56 Antigen ; metabolism ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Esophageal Neoplasms ; drug therapy ; metabolism ; pathology ; radiotherapy ; Follow-Up Studies ; Humans ; Leukocyte Common Antigens ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; metabolism ; pathology ; radiotherapy ; Male ; Middle Aged ; Poly(A)-Binding Proteins ; metabolism ; Prednisone ; therapeutic use ; T-Cell Intracellular Antigen-1 ; Treatment Outcome ; Vincristine ; therapeutic use

A nasal NK/T cell lymphoma is a very aggressive form of lymphoma. Patterns of relapse after treatment have not been systematically evaluated, and mediastinal nodal relapse at a primary site has never been documented. We describe here a 40-year old man who presented with a nasal obstruction caused by a protruding mass that was identified as a nasal NK/T cell lymphoma. The initial work-up, including chest and abdominopelvic computed tomography (CT) and positron emission tomography (PET), showed no regional or distant metastasis. A CT scan performed following three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) showed that the mass had nearly disappeared. Radiation therapy undertaken following chemotherapy was given to the primary site. However, PET performed following radiotherapy revealed a single mediastinal lymphadenopathy, with no evidence of residual tumor in the nasal cavity. A biopsy using video-assisted thoracoscopy (VATS) showed the presence of a recurrent NK/T cell lymphoma with an immunophenotype identical to that of the primary nasal lymphoma. An additional three cycles of CHOP chemotherapy were administered, and the patient remains alive, with no evidence of disease 30 months after the initial relapse. These findings indicate that early detection with PET and prompt surgical excision with the use of VATS can lead to successful treatment of a relapsed nasal NK/T cell lymphoma.
Adult ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Humans ; Lymphatic Metastasis ; Lymphoma, Extranodal NK-T-Cell/*diagnosis/*therapy ; Male ; Nose Neoplasms/*diagnosis/*therapy ; Positron-Emission Tomography ; Prednisolone/administration & dosage ; Radiotherapy, Adjuvant ; Tomography, X-Ray Computed ; Vincristine/administration & dosage