Nasal-type Lymphoma Research Articles

Clinical characteristics and prognostic analysis of primary extranodal non-Hodgkin lymphoma of the head and neck.

Primary extranodal non-Hodgkin's lymphoma (PE-NHL) of the head and neck is the second common site of extranodal lymphoma, accounting for approximately one-third of all extranodal non-Hodgkin's lymphoma (E-NHL). However, in recent years, large-scale PE-NHL case studies in China and worldwide are rare and not comprehensive enough. This work analyzed the clinical manifestations, pathological features, immunophenotypes and diagnosis of PE-NHL, as well as the factors affecting the treatment and prognosis. A retrospective study was performed on 74 patients who were diagnosed with head and neck PE-NHL and treated for the first time. The clinical manifestations, pathological features, and immunophenotypes were summarized, and the factors related to the treatment and prognosis were analyzed. The most common site of this disease was the Waldeyer's ring, followed by the nasal cavity. Diffuse large B-cell lymphoma was the most common type, followed by extranodal NK T-cell lymphoma nasal type. The 1-year, 2-year, and 5-year progression-free survival (PFS) rates were 76.4%, 67.9%, and 59.3%. The 1-year, 2-year, and 5-year overall survival (OS) rates were 89.4%, 85.6%, and 63.2%. ECOG score ≥ 2, Ann Arbor stage III or IV and IPI risk stratification identifying patients as the high-risk group were independent risk factors affecting the OS of patients with PE-NHL of the head and neck. The most common site of PE-NHL in these Chinese patients was the Waldeyer's ring, but the incidence in the nasal cavity was higher than that reported in Western countries. Radiotherapy combined with chemotherapy had better efficacy than chemotherapy alone, and the prognosis depended on the ECOG score and clinical stage. IPI had a better prognostic value in patients in the high-risk group of head and neck PE-NHL.

A Case of Acute Extensive Viral Sinusitis Secondary to Acute Epstein Barr Virus.

Infectious mononucleosis (IM) can present with various atypical presentations. Consideration of IM should not be limited to people presenting with a triad of fever, lymphadenopathy and sore throat. Lymphocytosis with atypical symptoms should raise suspicion of infectious mononucleosis.No case has been reported of EBV as a causal organism for acute sinusitis. Association with EBV infection and chronic sinusitis or nasal polyp or extranodal NK/T cell lymphoma has been demonstrated but pathogenesis is poorly understood.Studies should be done on whether acute sinusitis secondary to EBV poses a risk for nasal type lymphoma.

Laryngeal NK/T Cell Lymphoma, Nasal Type: Case Report and Literature Review

Extranodal Natural Killer T-cell lymphoma, nasal type represent a rare and aggressive entity of the non-Hodgkin's lymphomas. Laryngeal localization is rare and has a poor prognosis. We report the case of a 66-year-old patient who consulted for dyspnea, dysphonia and dysphagia. Endoscopic examination revealed an endo-laryngeal lesion. Anatomopathological study with immunohistochemistry concluded to a peripheral T NK/T-cell lymphoma nasal type. The extension workup was without abnormalities. Induction chemotherapy without anthracyclines was administered followed by conformal radiotherapy with intensity modulation in arctotherapy. Significant advances have been made over the past decade including better clarification of clinical heterogeneity, more accurate classification using imaging modalities, establishment of new prognostic models, and sequential use of anthracycline-free radiotherapy and chemotherapy in early stages and risk-adapted first-line treatment strategies in advanced stages.

National population-based analysis of demographics and outcomes of patients diagnosed with extranodal NK/T-cell nasal type lymphoma in the US: Does ethnicity play a role?

e18772 Background: Extranodal Natural Killer/T-cell Lymphoma Nasal Type (ENKTL-NT) in an uncommon malignancy with rising incidence in the United States (US) despite previously being described only in Asia and Latin America (J Oral Maxillofac Pathol PMC3125667 Crit Rev Oncol Hematol PMID33493634). Although primarily occupying the nasal cavity, other locations may be affected, which makes its presentation ambiguous. Diagnosis is important as omitting radiation has been associated with detrimental survival (J Oncol Pract PMID31600462). This is the first national population-based analysis evaluating ethnic differences for Hispanics (HI) diagnosed with ENKTL-NT. Methods: Data were analyzed on ENKTL-NT patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) database between 2000-2018. Demographic, clinical and survival patterns were analyzed. Kaplan-Meier and Cox regression analyses were used when appropriate. Multivariate analysis and propensity score matching were performed with adjustment for age, stage and B-symptoms. Results: 1,205 patients (HI=409, Non HI (NH)=796) were diagnosed with ENKTL-NT. Male sex predominated in both. HI were diagnosed at younger median age, 43 years (y) vs 59y in NH [p <0.001]. Most of HI and NH were whites 98% vs 58%; however, for NH other races were noted. Most of the patients were diagnosed between 2010-2014. For both, the presence of B symptoms was predominantly unknown. At diagnosis stage I was mainly for HI while unknown stage was most likely noted for NH [p = 0.013]. HI were less likely than NH to receive radiation as part of their treatment, 47% vs 57% respectively [p = 0.003]. Median survival for HI was 1.7y vs 1.2y for NH; survival probability at 2, 5 and 10y for HI corresponded to 0.467, 0.413 and 0.355, while for NH it was 0.444, 0.352 and 0.292, respectively. OS probability at 10y had no statistically significant difference [p = 0.06]. On multivariate analysis, those who were older than 80y and between 60-80y, had worse OS compared to those younger than 60y (HR 2.3 - 95% CI: 1.7 – 3 and 1.2 - 95% CI: 1 – 1.5). Regarding stage, those who were at stage III/IV had worse OS than those at early stage I/II (HR 2.4 -95% CI: 1.7 - 3.2 and HR 3.4 -95% CI: 2.7 - 4.30). Conclusions: This national population-based study identified statistical differences in HI diagnosed with ENKTL-NT. Interestingly, HI were less likely to receive radiation therapy which is the mainstay treatment and key determinant for survival. The fact that there was no statistical difference in survival for HI and NH may underrepresent the improved survival from HI as they are not optimally treated and still living as longer as the NH. Additional research with biological variables should be carried out to better understand this oncological outcome and potentially offer improved targeted treatments for this ethnic minority.

Clinical Impact of the Intensity of Induction Regimens Prior to Consolidation in Treatment-Naïve Patients with Peripheral T-Cell Lymphoma (PTCL)

Introduction: Frontline treatment of peripheral T-cell lymphoma (PTCL) remains a challenge because, despite good overall response rate (ORR 60-70%) to chemotherapy, more than 50% of patients (pts) relapse quickly and die of their disease. (Mehta-Shah, ASH 2019). Two prospective clinical trials (D'Amore, JCO 2012 - non-randomized study- and Horwitz, Lancet 2019 - randomized) demonstrated improved outcomes by adding Brentuximab Vedotin (BV-CHP) or etoposide (CHOEP) to the cyclophosphamide-vincristine-adriamycine-prednisone (CHOP) backbone in selected PTCL populations. Intensive induction chemotherapy (IIC) regimens commonly used in high grade B-cell malignancies (i.e. HyperCVAD) have also been used in PTCL based on phase I-II trial data (Abramson, Ann Oncol 2014). However, IIC regimens have not been compared to CHOP or CHOP+ (CHOEP/BV-CHP) in prospective studies. Methods: Naïve PTCL treated at Roswell Park Comprehensive Cancer Center between 1997 to 2020 were identified. Pts were divided in three groups based on front-line therapy: CHOP vs. CHOP+ (CHOEP/BV-CHP) vs. IIC (HyperCVAD, ICE). We retrospectively analyzed pre-treatment characteristics, clinical outcomes (overall and complete response rate (ORR, CR), incidence rate ratio of relapse or death within 2 years of treatment (IRR), progression free (PFS), and overall survival (OS) at 5 years) and gross toxicity indices (treatment interruptions unrelated to progression of disease (POD), and causes of death). We used the chi square test and logistic regression to compare categorical variables, the Poisson distribution to compare IRR, log rank to compare time to event curves (PFS/OS). Analysis and graphs were done with SAS and STATA software programs. Results: We identified 151 newly diagnosed PTCL treated at RPCCC. Twenty pts who received palliative therapy or comfort care were excluded from the study. We excluded 6 NK/T-cell lymphoma nasal type (NKTL), 5 hepatosplenic gamma delta TCL (HSTCL) and 1 Adult T-cell leukemia/lymphoma (ATLL) for which CHOP-like regimens are not standard of care. In addition, we also excluded 18 ALK+ Anaplastic large cell lymphoma (ALCL) from the analysis as this good prognosis group exclusively received CHOP or CHOP+, potentially confounding the analysis. A total of 101 pts were included in the analysis representing the following subtypes: angioimmunoblastic T cell lymphoma (AITL) (N=22, 21.8%), PTCL-not otherwise specified (NOS) (N=36, 35.6%), PTCL-with T follicular helper phenotype (TFH) (N=2, 2.0%) or ALK- ALCL (N=41, 35.6%). CHOP was used in 54 pts, 27 received CHOP+ (18 CHOEP, 8 BV-CHP, 1 EPOCH), and 20 received IIC chemo (17 HyperCVAD, 3 ICE). Consolidation with HDC-ASCT was performed in 7 pts after CHOP (14%), 5 pts after CHOP+ (18%) and 8 pts after IIC treatment (40%). Baseline characteristics including sex, age, comorbidities, performance status (ECOG), international prognostic index (IPI) and histology were balanced in the CHOP, CHOP+ and IIC chemo treatment groups, after we excluded ALK+ ALCL as described above (all p values > 0.4). ORR was 69% (61% CR), 86% (81% CR) and 80% (80% CR) in the CHOP, CHOP+ and IIC groups (p=0.3). A multivariate analysis including treatment type, ECOG performance status, Charlson comorbidity score and age did not show any significant correlation with ORR (lowest p value was 0.07 for the Charlson comorbidity score). Incidence rate ratio of progression or death was 3.1, 3.4 and 4.6 per 100-person months respectively for CHOP, CHOP+ and IIC chemo (proportions: 46%, 44%, 60% respectively). PFS and OS did not show significant differences among treatment groups (Log Rank test p = 0.90 for PFS and p = 0.79 for OS). The proportion of treatment interruptions without evidence of POD was 23% in the CHOP, 28% in the CHOP+ and 40% in the IIC group (p=0.31). Of all death events per group, POD was the cause of 43%, 41% and 36% deaths respectively in the CHOP, CHOP+ and IIC groups (p=0.92), death for treatment related toxicity occurred in 21% (CHOP), 41% (CHOP+) and 45% (ICC chemo) of all deaths per group, p=0.19. Conclusions: In our population, the intensity of front-line chemotherapy does not seem to impact on IRR PFS or OS. CHOP+ and IIC might have a tendency towards better ORR and CR rates vs CHOP. However, IIC have a tendency (non-statistically significant) of an increase in adverse events leading to treatment interruptions unrelated to POD and deaths for toxicity. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 4098: Comparison of frontline therapeutic modalities in stages I/IE extranodal NK/T-cell lymphoma-nasal type (ENKTL-N): A network meta-analysis

Abstract Introduction: Despite many studies reporting on the optimal therapies for early stage ENKTL-N in the front-line setting, this area continues to be subject to significant controversy regarding single modalities versus combination or sequential approaches. All these comparative studies were small non-randomized studies that combined stages I & II. The results were often inconclusive and occasionally conflicting. In the absence of direct head-to-head randomized controlled trials in this clinical setting, a network meta-analysis was conducted to compare these therapeutic approaches and their respective impact on 5-year survival in stage I/IE ENKTL-N. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of stage I/IE ENKTL-N, treatment with chemotherapy (CT), radiation (RT), sequential CT and RT (SEQ), and chemoradiotherapy (CRT), comparative studies that reported predominantly I/IE 5-year survival and disease-free survival rates. Studies that reported on mixed samples of early and advanced ENKTL were excluded. A frequentist network meta-analysis was conducted using the netmeta package and random-effects model. Results: Seven studies comprising a total of 377 participants were included. Our network meta-analysis revealed that upfront RT tended to have better 5-year OS and DFS than CRT and SEQ, though it did not reach statistical significance. However, RT demonstrated significant 5-year OS and DFS when compare to CT alone in the frontline setting. Based on the pairwise and network meta-analyses, RT was ranked as the most effective first-line treatment approach followed by CRT, SEQ, and CT in decreasing order. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates. Conclusions: This is the first network meta-analysis to compare all commonly utilized upfront treatment modalities in stages I/IE ENKTL-N. It indicates that upfront RT alone may be sufficient as there was no signal that chemotherapy added any OS or DFS advantages. Adequately powered randomized trials are warranted. Citation Format: Philip A. Haddad, Kevin Gallagher, Dalia Hammoud. Comparison of frontline therapeutic modalities in stages I/IE extranodal NK/T-cell lymphoma-nasal type (ENKTL-N): A network meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4098.

Nasal-type extranodal NK/T cell lymphoma in association with hemophagocytic syndrome: a case report and literature review*

Abstract We present a rare case of nasal-type CD56-negative NK/T-cell lymphoma. The patient developed hemophagocytic syndrome during diagnosis and treatment. The patient presented to our hospital (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) with “nasal congestion for 3 months and scattered erythema, nodules, and ulcers all over the body for 1 month.” We analyzed clinical manifestations, skin histopathology, immunohistochemistry, and in situ hybridization results. Histopathology of the skin revealed a moderate amount of atypical lymphocyte infiltration between the entire dermis and collagen bundles. Immunohistochemistry showed the following: CD30 (+), TIA-1 (+), CD3(2GV6) (+), CD5 part (+), CD8 part (+), CD43 (+), CD56 (-), CD4 (-), CD20 (-), PAX5 (-), PCK (-), P63 (-), P40 (-), EGFR (-), Ki-67 (the hot spot LI is approximately 80%), and in situ hybridization EBER-ROCH (+). The diagnosis made was “NK/T cell lymphoma nasal type”. This type of lymphoma is aggressive, progresses quickly, and has a poor prognosis. Early clinical manifestations are extremely atypical, especially in the absence of rash. Analysis of the skin manifestations of the disease has a positive effect on its early diagnosis, early treatment, and prognosis.

Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas.

Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16–101 months.

EBV associated T- and NK-cell lymphoproliferative diseases: A comprehensive overview of clinical manifestations and novel therapeutic insights.

EBV is a ubiquitous virus that infects nearly all people around the world. Most infected people are asymptomatic and do not show serious sequelae, while others may develop Epstein-Barr virus (EBV)-positive T and NK-cell lymphoproliferations characterised by EBV-infected T or NK cells. These disorders are more common in Asian and Latin American people, suggesting genetic predisposition as a contributing factor. The revised WHO classification classifies the lymphoproliferative diseases as: extranodal NK/T-cell lymphoma nasal type (ENKTL), aggressive NK-cell leukemia (ANKL), primary EBV-positive nodal T or NK cell lymphoma (NNKTL), systemic EBV-positive T-cell lymphoproliferative disease of childhood (STCLC), systemic chronic active EBV infection (sys CAEBV), hydroa-vacciniforme (HV) andsevere mosquito bite allergy (SMBA). Recent advances in the molecular pathogenesis of these diseases have led to the development of new therapeutic strategies. Due to the infrequency of the diseases and broad clinicopathological overlap, the diagnosis and classification are challenging for both clinicians and pathologists. In this article, we aim to review the recent pathological findings which can be helpful for designing new drugs, clinical presentations and differential diagnoses, and suggested therapeutic interventions to provide a better understanding of these rare disorders.

Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas.

Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16-101 months.

Extranodal NK/T cell lymphoma nasal type: A case report and literature review

Extranodal NK/T cell lymphoma nasal type: A case report and literature review

Review on natural killer/T-cell lymphoma.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is strongly associated with Epstein-Barr virus (EBV) and has a high prevalence in Asian and in Central and South America. About 85% of ENKTLs derive from NK cells and 15% from T-cells. Various factors have been implicated in the development of ENKTL. Molecular pathogenesis of NK/T-cell lymphomas include mutations of genes, involving in the Janus Kinase/signal transducer and activator of transcription pathway, RNA helicase family, epigenetic regulation, and tumor suppression. The relationship between ENKTL and human leukocyte antigen has been demonstrated. Radiotherapy plays a key role in the first-line treatment of early-stage. In stage III/IV diseases, non-anthracycline-regimens-containing L-asparaginase are recommended. Although clinical remission after L-asparaginase-based combination therapy has been achieved in the majority of patients with advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma-nasal type, the long-term overall survival is still poor. Recently, immunotherapy and new therapeutic targets have gained much attention. In this article, we discuss the pathogenesis, diagnosis, prognostic models and management options of ENKTL.

Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches.

Simple SummaryIt is challenging for pathologists to diagnose primary gastrointestinal T-cell neoplasms. Besides the rarity of the diseases, the small biopsy material makes it more difficult to differentiate between non-neoplastic inflammation and secondary involvement of extra gastrointestinal lymphoma. Since this group of diseases ranges from aggressive ones with a very poor prognosis to indolent ones that require caution to avoid overtreatment, the impact of the diagnosis on the patient is enormous. Although early treatment of aggressive lymphoma is essential, the treatment strategy is not well established, which is a problem for clinicians. This review provides a cross-sectional comparison of histological findings. Unlike previous reviews, we summarized up-to-date clinically relevant information including the treatment strategies as well as practical differential diagnosis based on thorough literature review.Primary gastrointestinal (GI) T-cell neoplasms are extremely rare heterogeneous disease entities with distinct clinicopathologic features. Given the different prognoses of various disease subtypes, clinicians and pathologists must be aware of the key characteristics of these neoplasms, despite their rarity. The two most common aggressive primary GI T-cell lymphomas are enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. In addition, extranodal natural killer (NK)/T-cell lymphoma of the nasal type and anaplastic large cell lymphoma may also occur in the GI tract or involve it secondarily. In the revised 4th World Health Organization classification, indolent T-cell lymphoproliferative disorder of the GI tract has been incorporated as a provisional entity. In this review, we summarize up-to-date clinicopathological features of these disease entities, including the molecular characteristics of primary GI T-cell lymphomas and indolent lymphoproliferative disorders. We focus on the latest treatment approaches, which have not been summarized in existing reviews. Further, we provide a comprehensive review of available literature to address the following questions: How can pathologists discriminate subtypes with different clinical prognoses? How can primary GI neoplasms be distinguished from secondary involvement? How can these neoplasms be distinguished from non-specific inflammatory changes at an early stage?

Extranodal natural killer/T-cell lymphoma nasal type with extensive ocular tissue involvement: a case report

BackgroundTo report a rare case of extranodal natural killer/T-cell lymphoma (ENKTL), nasal type related to extensive ocular tissue, including conjunctiva, ciliary body, vitreous and retina.Case presentationA 52-year-old woman who had been treated by radiotherapy for ENKTL, nasal type in the right nasal cavity presented with a dramatic deterioration of vision in right eye. Physical and accessory examination showed extensive ocular tissue related, including conjunctiva, ciliary body, vitreous and retina. Vitreous specimen and conjunctiva biopsy revealed the presence of ENKTL, nasal type in the right eye. She was treated with systemic and ophthalmic chemotherapy, her ocular symptoms significantly improved, and systemic condition remained stable 7 months after the diagnosis.ConclusionsExtranodal natural killer/T-cell lymphoma, nasal type is an aggressive disease and may relate extensive ocular tissue and course dramatic vision deterioration. It is important to observe ocular related and begin aggressive combined therapy as early as possible after diagnosis.

The optimal timing of radiotherapy in the combination treatment of limited-stage extranodal natural killer/T-cell lymphoma, nasal type: an updated meta-analysis.

This study was designed to explore the relative efficacy and toxicity of upfront radiotherapy (RT) and late RT in combination treatments for patients with limited-stage extranodal natural killer/T-cell lymphoma nasal type (LS-ENKTL). We searched for clinical trials in the PubMed database that compared upfront RT with late RT in the combined treatment of patients with LS-ENKTL. We systematically evaluated the differences in survival, treatment response, and treatment-related adverse events (AEs) between these two groups. Ten retrospective studies with a total of 1752 patients were included. Upfront RT significantly prolonged the overall survival (OS) and progression-free survival (PFS) of patients compared to late RT in combination with chemotherapy (CT) (HR = 0.72, 95% CI 0.59-0.88, P = 0.001 for OS; HR = 0.57, 95% CI 0.41-0.79, P = 0.0007 for PFS). The complete remission (CR) rate in the upfront RT group was superior to that in the late RT group (HR = 1.61, 95% CI 1.09-2.37, P = 0.02). Patients experienced similar local recurrence-free survival (LRFS), objective response rates (ORR), and toxicity between these two arms (P > 0.05 for all) in the analysis of each subgroup. The survival benefit of upfront RT was not correlated with the RT dose, concurrent chemoradiotherapy (CCRT) (or not), or the CT regimen (P > 0.05 for all). Without compromises in terms of toxicity, RT dose, and treatment modality, upfront RT can significantly benefit OS, PFS, and CR compared to late RT in combination treatment. These findings verified that the upfront RT regimen is more suitable for patients with LS-ENKTL.

Chemorefractory extranodal nasal-type natural-killer/T-cell lymphoma with great response to pembrolizumab in a young patient: a case report

IntroductionExtranodal, natural-killer/T-cell lymphoma of nasal type is a rare but aggressive disease usually presenting as progressive necrotic lesions in the nasal cavity that responds poorly to chemotherapy. In this paper, we report a relapsing, chemorefractory case of extranodal natural-killer/T-cell lymphoma responding to checkpoint inhibitor immunotherapy with pembrolizumab.Case presentationA 32-year-old Hispanic woman with a history of recurrent sinusitis and preseptal abscess presented with a hoarse voice, swelling around the right eye, and diplopia. Laryngoscopy showed infiltrating tissue extending to bilateral laryngeal ventricles and false vocal cords. On immunohistochemical examination of laryngeal biopsy, the neoplastic cells showed positivity for CD3 (cytoplasmic), CD7, CD56, granzyme B, CD30, and Epstein–Barr virus-encoded ribonucleic acid (RNA). Extranodal natural-killer/T-cell lymphoma, nasal type, was confirmed. In the absence of distant organ involvement, the decision was to perform chemotherapy with etoposide, ifosfamide, mesna, cisplatin, and dexamethasone (VIPD protocol) followed by concurrent chemoradiation with weekly doses of cisplatin and two cycles of VIPD as adjuvant treatment. However, 1 month after completion of the treatment; disease recurrence was demonstrated. The patient was scheduled to receive salvage chemotherapy with steroid, methotrexate, ifosfamide, L- asparaginase, and etoposide (SMILE) protocol and CD30-targeting monoclonal antibodies. However, the mass was chemorefractory without response to either l-asparaginase-based salvage chemotherapy in combination with high-dose methotrexate or brentuximab vedotin. However, this case of chemorefractory extranodal natural-killer/T-cell lymphoma, nasal type, responded well to the novel drug pembrolizumab, which was able to control the disease.ConclusionCheckpoint inhibitors are potential treatment option in selected chemorefractory extranodal natural-killer/T-cell lymphoma, nasal type, cases.

"Successful Treatment of Extranodal Natural Killer T Cell Lymphoma Nasal Type Complicated by Severe Hemophagocytic Syndrome A Case Report"

"Successful Treatment of Extranodal Natural Killer T Cell Lymphoma Nasal Type Complicated by Severe Hemophagocytic Syndrome A Case Report"

Comparison of tumor mutation burden of 300 various non-Hodgkin lymphomas using panel based massively parallel sequencing

BackgroundTumor mutation burden is an emerging biomarker for immunotherapy. Although several clinical trials for immunotherapy in lymphoma have been carried out, the mutation burden of various lymphomas is not well known yet. Thus, the objective of this study was to compare tumor mutation burden of various non-Hodgkin lymphomas using panel based massively parallel sequencing.MethodsWe conducted 405 gene panel based massively parallel sequencing of 300 non-Hodgkin lymphomas and investigate the number of SNV/Indel in each lymphoma.ResultsThe number of SNV/Indel was higher in mature B-cell lymphoma than in mature T- and NK-cell lymphoma. (P < 0.001) The number of SNV/Indel in primary mediastinal large B-cell lymphoma and primary diffuse large B-cell lymphoma of the central nervous system was the highest, which was significantly higher than that in diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS).(P = 0.030 and P = 0.008, respectively) The SNV/Indel number in EBV-positive DLBCL NOS was significantly lower than that in DLBCL NOS. (P = 0.048) Peripheral T-cell lymphoma, NOS showed no significant difference in the number of SNV/Indel from extranodal NK/T-cell lymphoma, nasal type (P = 0.942) or angioimmunoblastic T-cell lymphoma (P = 0.739). The number of SNV/Indel in anaplastic large cell lymphoma, ALK-positive was significantly lower than that in anaplastic large cell lymphoma, ALK-negative (P = 0.049). It was the lowest among all the lymphomas considered.ConclusionVarious lymphomas have different mutation burdens. Thus, tumor mutation burden can be used as a promising biomarker for immunotherapy in lymphomas.

Epstein-Barr Virus-Associated T- and NK-Cell Lymphoproliferative Diseases: A Review of Clinical and Pathological Features.

Simple SummaryIn most Epstein–Barr virus (EBV)-infected individuals, the virus establishes a lifelong latent infection with no specific clinical manifestation. However, EBV primary infection and secondary reactivation may cause various EBV-associated lymphoproliferative disorders (LPD), including hematologic malignancies. Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV, more commonly encountered in Asians and Latin Americans. They encompass a spectrum of disorders ranging from indolent reactive lesions to malignant and aggressive diseases. Despite novel insights from high-throughput molecular studies, the pathogenesis of these disorders is not well understood, and EBV-positive T/NK LPD diagnoses remain challenging due to their rarity and considerable overlap. Indeed, this article discusses new insights into EBV-positive T/NK LPD and focuses on diagnosis challenges, describing the difficulties to clarify the borders between overlapping LPD subtypes.Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV. The 2017 World Health Organization (WHO) classification recognizes the following entities characterized by different outcomes: chronic active EBV infection of T- or NK-cell types (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, EBV-positive aggressive NK-cell leukemia, extra nodal NK/T-cell lymphoma nasal type, and the new provisional entity known as primary EBV-positive nodal T/NK-cell lymphoma. In addition, EBV associated-hemophagocytic lymphohistiocytosis is part of EBV-positive T/NK LPD, but has not been included in the WHO classification due to its reactive nature. Despite novel insights from high-throughput molecular studies, EBV-positive NK/T-cell LPD diagnoses remain challenging, especially because of their rarity and overlap. Until now, an accurate EBV-positive NK/T LPD diagnosis has been based on its clinical presentation and course correlated with its histological features. This review aims to summarize clinical, pathological and molecular features of EBV-positive T/NK LPD subtypes and to provide an overview of new understandings regarding these rare disorders.

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes. Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour.