Mucoepidermoid carcinoma of the palate mimicking a pyogenic granuloma in a 30-year-old woman.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland adenocarcinoma, more frequently affecting female patients in the fifth decade of life. When MEC arises in the minor salivary glands, the palate is the primary site. This case report describes an MEC on the palate of a 30-year-old woman. The lesion was initially treated as a pyogenic granuloma, but the final diagnosis based on histopathology was low-grade MEC. The patient was referred for cancer treatment, and no recurrence was observed during 3 years of follow-up. Some malignant tumors can mimic nonneoplastic reactive lesions clinically, which highlights the importance of biopsy and proper microscopic analysis of the resulting specimens.

Acquired oral syphilis: A multicenter study of 339 patients from South America.

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.

A cellular target engagement assay for the characterization of SHP2 (PTPN11) phosphatase inhibitors.

The nonreceptor protein-tyrosine phosphatase (PTP) SHP2 is encoded by the proto-oncogene PTPN11 and is a ubiquitously expressed key regulator of cell signaling, acting on a number of cellular processes and components, including the Ras/Raf/Erk, PI3K/Akt, and JAK/STAT pathways and immune checkpoint receptors. Aberrant SHP2 activity has been implicated in all phases of tumor initiation, progression, and metastasis. Gain-of-function PTPN11 mutations drive oncogenesis in several leukemias and cause developmental disorders with increased risk of malignancy such as Noonan syndrome. Until recently, small molecule-based targeting of SHP2 was hampered by the failure of orthosteric active-site inhibitors to achieve selectivity and potency within a useful therapeutic window. However, new SHP2 allosteric inhibitors with excellent potency and selectivity have sparked renewed interest in the selective targeting of SHP2 and other PTP family members. Crucially, drug discovery campaigns focusing on SHP2 would greatly benefit from the ability to validate the cellular target engagement of candidate inhibitors. Here, we report a cellular thermal shift assay that reliably detects target engagement of SHP2 inhibitors. Using this assay, based on the DiscoverX InCell Pulse enzyme complementation technology, we characterized the binding of several SHP2 allosteric inhibitors in intact cells. Moreover, we demonstrate the robustness and reliability of a 384-well miniaturized version of the assay for the screening of SHP2 inhibitors targeting either WT SHP2 or its oncogenic E76K variant. Finally, we provide an example of the assay's ability to identify and characterize novel compounds with specific cellular potency for either WT or mutant SHP2.

Perilipin 1 and adipophilin immunoexpression suggests the presence of lipid droplets in tooth germ, ameloblastoma, and ameloblastic carcinoma.

BACKGROUND: Increased lipogenesis and lipid droplet accumulation are observed in diverse tumors, and these processes are associated with poor prognosis in several tumors, representing potential therapeutic targets. The presence of lipid droplets in odontogenic tissues and/or tumors is unknown. METHODS: Immunohistochemistry for perilipin 1 and adipophilin was performed in 12 human tooth germs (TG), 27 conventional ameloblastoma (AM), and 8 ameloblastic carcinoma (AC) samples. Cytoplasmic staining was analyzed using an immunoreactive score (IRS), and the results were compared for the TG, AM, and AC samples by Kruskal-Wallis test followed by Dunn's post-test and confirmed by Mann-Whitney U test. RESULTS: Perilipin 1 was negative in 91.7% of the TG samples, positive in 48.2% of the AM samples, and positive in 87.5% of the AC samples. Adipophilin was positive in 100% of the TG samples, 92.6% of the AM samples, and 100% of the AC samples. The perilipin 1 and adipophilin IRS revealed statistically significant differences between the TG, AM, and AC samples (p = .007 and p = .018, respectively). The perilipin 1 levels among the TG and AC samples were statically significant (**p = .0085), as well as the adipophilin levels when TG and AM samples were compared (**p < .0029). CONCLUSIONS: Adipophilin exhibits significant activity in human tooth development. The immunoexpression of perilipin 1 and adipophilin in the AM and AC samples suggests the presence of lipid droplets, providing further evidence of metabolic alterations in these tumors. Additional studies with larger samples and alternative techniques are necessary to confirm these findings.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 55.7 years. 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. CONCLUSION: 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.

Toward a New Era for the Management of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are malignant cells separate from primary tumors, which can migrate through the peripheral blood, colonize other tissues, and lead to the formation of metastases. The first description of CTCs dates back to 1869 when Thomas Ashworth recognized malignant cells similar to the ones of the primary tumor in the blood vessels of an autopsied patient with metastatic cancer. Currently, CTCs have been identified in various types of cancer and have been recognized for their clinical value in the prediction of prognosis, diagnosis of minimal residual diseases, assessment of tumor sensitivity to anticancer drugs, and personalization of therapies. However, research about these topics has several limitations, principally the rarity of CTCs in bloodstream and their heterogeneous characteristics, which makes detection and isolation difficult. As a result of these limitations, current studies are focused on improvement of isolation and characterization techniques to achieve better sensitivity in clinical applications. This review covers the methods of CTC isolation and detection and current research progression on CTC in different cancer types. The clinical applications, limitations, and perspectives of CTCs are also discussed.

Respiratory scleroma: A clinicopathologic study of 51 cases from Guatemala.

OBJECTIVES: To evaluate clinical and pathologically cases of respiratory scleroma diagnosed in a 30-year period in Guatemala. MATERIAL AND METHODS: Fifty-one cases of respiratory scleroma diagnosed from 1988 to 2018 in a single pathology service in Guatemala were confirmed using Warthin-Starry staining. Immunohistochemical reactions against CD68, LCA, CD20, CD3, and CD138 were performed to illustrate the inflammatory infiltrate. Scanning electron microscopy (SEM) was performed to illustrate bacteria morphology. RESULTS: All 51 cases affected patients from poor areas of Guatemala, particularly women (66.7%), with a mean age of 31 years (range 7-66 years). Nose was affected in most cases (96.1%). Other sites involved included pharynx, larynx, palate, maxillary sinuses, and upper lip. Depending on the stage, the disease manifested as ulcerations, nasal deformities, or laryngeal stenosis. Nasal obstruction, epistaxis, dysphonia, fetid discharge, and pain were the main symptoms. Mikulicz cells (CD68+) in a plasma cell-rich inflammatory background (CD138+, CD20+, CD3+/-) were the typical microscopic presentation. In SEM, each macrophagic vacuole contained few to dozens of Klebsiella rhinoscleromatis diplobacilli. Treatment consisted of long-term trimethoprim and sulfamethoxazole, with adequate control of disease. CONCLUSION: Respiratory scleroma is a rare infectious disease affecting the upper respiratory tract, in poor regions of the world, including Guatemala.

Gingival squamous cell carcinoma mimicking a non-neoplastic proliferative lesion in an older patient.

OBJECTIVE: To report a case of gingival squamous cell carcinoma (SCC) in an elderly patient mimicking a non-neoplastic proliferative lesion. BACKGROUND: Oral SCC is a well-recognised malignancy of the oral cavity that may mimic benign reactive proliferative processes. METHODS: An excisional biopsy was performed, and the diagnosis was gingival SCC. CONCLUSION: It is essential that both the clinician and pathologist to be aware of such a presentation to allow for proper diagnosis and treatment.

Detection of MAPK/ERK pathway proteins and KRAS mutations in adenomatoid odontogenic tumors.

OBJECTIVE: This study aimed to assess the frequency of KRAS mutation and its association with the presence of the MAPK/ERK signaling pathway proteins in adenomatoid odontogenic tumors. STUDY DESIGN: Paraffin-embedded tissue samples from nine cases of adenomatoid odontogenic tumor were used. Genomic DNA was extracted from each sample; in one case, genetic mutations in 50 cancer-associated genes were examined by next-generation sequencing. Hotspot mutations in the RAS family were analyzed by Luminex assay using the remaining eight cases. Subsequently, immunohistochemistry for KRAS, CRAF, BRAF, EGFR, ERK, MEK, and BRAFV600E was performed. RESULTS: A KRAS G12D missense mutation was detected in the DNA sequence of the tumor cells, but it was not detected in the stromal tissue. KRAS G12V and KRAS G12R mutations were detected in two and four cases, respectively. For immunohistochemistry, all the cases were EGFR, KRAS, BRAF, CRAF positive, one case was ERK negative,and one case was MEK and ERK negative, all the other remaining cases were MEK and ERK positive. CONCLUSION: KRAS mutation at codon 12 and the presence of MAPK/ERK pathway proteins were detected suggesting their association with tumorigenesis of adenomatoid odontogenic tumors.

Agrin has a pathological role in the progression of oral cancer.

BACKGROUND: The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin-a member of this matrix-in progression of oral squamous cell carcinoma (OSCC). METHODS: We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics. Finally, we evaluated the clinical relevance of agrin interactome. RESULTS: Agrin was elevated in malignant and premalignant lesions. Further, we show that agrin silencing interferes with cancer cell motility, proliferation, invasion, colony and tumour spheroid formation, and it also reduces the phosphorylation of FAK, ERK and cyclin D1 proteins in OSCC cells. In orthotopic model, agrin silencing reduces tumour aggressiveness, like vascular and neural invasion. From a clinical perspective, agrin contextual hubs predict a poor clinical prognosis related with overall survival. CONCLUSIONS: Altogether, our results demonstrate that agrin is a histological marker for the progression of oral cancer and is a strong therapeutic target candidate for both premalignant and OSCC lesions.

Oral juvenile xanthogranuloma in a child: Clinical, histological and immunohistochemical profile of a rare entity.

Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis (non-LCH) affecting normolipemic infants and children most frequently in the first year of life, often showing spontaneous regression within 3 to 6 years. Classic JXG is characterized by a yellowish asymptomatic papule or nodule, often located in the skin of the head, neck and upper trunk. Oral JXG has been reported, but is rare. Histologically, JXG is composed mainly of an infiltrate of macrophages with a variable degree of lipidization (foamy macrophages), and (most of the time) scattered Touton-type giant cells. Because of the rarity of oral lesions and possible variations in the clinical and histological presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathological evaluation with adjuvant immunohistochemical studies. Our review of the English-language literature disclosed 33 cases of oral JXG, including this case report. The purpose of this study is to present a new case of this uncommon entity as well as to review and discuss its main clinicopathologic features and immunohistochemical findings.

Immunohistochemical expression of podoplanin (D2-40), lymphangiogenesis, and neoangiogenesis in tooth germ, ameloblastomas, and ameloblastic carcinomas.

BACKGROUND: Ameloblastoma is a benign but locally aggressive odontogenic tumor, while ameloblastic carcinoma is its malignant counterpart. Angiogenesis and lymphangiogenesis in malignancies have been correlated with higher aggressiveness and poor prognosis, as well as greater expression of podoplanin by tumoral cells. METHODS: Immunohistochemical expression of podoplanin, CD34, and CD105 (endoglin) was evaluated in 53 ameloblastomas and three ameloblastic carcinomas; additionally, immunohistochemistry for podoplanin was also performed in 10 tooth germs. Microvessel density of blood and lymphatic vessels was calculated and compared between ameloblastomas and ameloblastic carcinomas. Immunoexpression of podoplanin by ameloblastic cells was evaluated in tooth germs, ameloblastomas, and ameloblastic carcinomas. RESULTS: Podoplanin was similarly expressed by odontogenic epithelial cells of tooth germs and ameloblastomas, while its expression was lower in ameloblastic carcinomas. There was no difference in microvessel density assessed by CD34 between ameloblastomas and ameloblastic carcinomas; nevertheless, the latter presented higher amounts of lymphatic and new formed blood vessels. CONCLUSIONS: Results suggest that podoplanin does not seem to be involved in invasion mechanisms of ameloblastic carcinomas, as its expression was decreased in the malignant tumoral cells. On the other hand, the increased lymphatic microvessel density and neoangiogenesis found in ameloblastic carcinomas could be related to its aggressiveness and potential for metastasis.

Methyltransferase Inhibition Enables Tgfß Driven Induction of CDKN2A and B in Cancer Cells.

CDKN2A/B deletion or silencing is common across human cancer, reinforcing the general importance of bypassing its tumor suppression in cancer formation or progression. In rhabdomyosarcoma (RMS) and neuroblastoma, two common childhood cancers, the three CDKN2A/B transcripts are independently expressed to varying degrees, but one, ARF, is uniformly silenced. Although TGFß induces certain CDKN2A/B transcripts in HeLa cells, it was unable to do so in five tested RMS lines unless the cells were pretreated with a broadly acting methyltransferase inhibitor, DZNep, or one targeting EZH2. CDKN2A/B induction by TGFß correlated with de novo appearance of three H3K27Ac peaks within a 20 kb cis element ∼150 kb proximal to CDKN2A/B. Deleting that segment prevented their induction by TGFß but not a basal increase driven by methyltransferase inhibition alone. Expression of two CDKN2A/B transcripts was enhanced by dCas9/CRISPR activation targeting either the relevant promoter or the 20 kb cis elements, and this "precise" manipulation diminished RMS cell propagation in vitro. Our findings show crosstalk between methyltransferase inhibition and TGFß-dependent activation of a remote enhancer to reverse CDKN2A/B silencing. Though focused on CDKN2A/B here, such crosstalk may apply to other TGFß-responsive genes and perhaps govern this signaling protein's complex effects promoting or blocking cancer.

[The occupational therapist's role in an interdisciplinary team within the Rehabilitation and External Aids Program]. / El rol del Terapeuta Ocupacional en el equipo interdisciplinario del Programa de Rehabilitación y Externación Asistida.

The role of an occupational therapist in the Mental Health team, particularly in the Rehabilitation and Assisted Discharge Program (PREA), is to provide a focus on the person and on a meaningful occupation for him. The interdisciplinary team of each device, involving an occupational therapist, performs planning goals and implementing the means to achieve through strategies of psychosocial rehabilitation. Meanwhile, intervention strategies are developed and individual support for each person is given to carry out a project of life in the community, building a social, occupational and significant work in order to enhance users' recovery.

Oral epithelioid rhabdomyosarcoma: Report of a rare case and literature review of a distinct variant of rhabdomyosarcoma.

Epithelioid rhabdomyosarcoma is a new and rare morphological variant of rhabdomyosarcoma, with only a few reports in the literature. We aimed to describe an atypical case of this variant involving the oral cavity. A 33-year-old male patient presented with an asymptomatic, gingival mass adjacent to the left maxillary canine with progressive growth over approximately 3 months. Microscopic and immunohistochemical assessment of the biopsy specimen were consistent with epithelioid rhabdomyosarcoma. After initial chemotherapy and radiotherapy, the patient had a partial response. Surgical resection was performed, followed by adjuvant chemotherapy. After local and distant recurrences, the patient died 22 months after the initial diagnosis. According to the literature, epithelioid rhabdomyosarcoma still lacks data regarding its aetiologic factors and therapeutic options. Whether this tumour is a true subtype or simply a variant of other subtypes of rhabdomyosarcoma also remains unconfirmed. Final diagnosis leads to a broad array of microscopic and immunohistochemical analyses.

Baseline Power of Theta Oscillations Predicts Mystical-Type Experiences Induced by DMT in a Natural Setting.

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. The present study investigated changes in neural oscillations elicited by inhaled DMT, and whether baseline electroencephalography (EEG) recordings could predict the subjective effects reported by the participants. Healthy volunteers (N = 35) were measured with EEG before and during the acute effects of DMT consumed in a natural setting. Source-localized neural oscillations were correlated with the results of multiple questionnaires employed to assess the subjective effects of the drug. DMT resulted in a marked reduction of alpha and beta oscillations, and increased posterior spectral power in the delta, theta and gamma bands. The power of fronto-temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. The robustness of these results was supported using a machine learning model for regression trained and tested following a cross-validation procedure. These results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. They also suggest that baseline EEG screenings before administration of a serotonergic psychedelic could be useful to estimate the likelihood of inducing mystical-type experiences, previously linked to sustained positive effects in well-being and improved outcome of therapeutic interventions.

Mixed odontogenic tumors: A review of the clinicopathological and molecular features and changes in the WHO classification.

BACKGROUND: Ameloblastic fibromas and ameloblastic fibrosarcomas are rare odontogenic tumors, and controversy exists in the classification of cases presenting hard-tissue production: Ameloblastic fibrodentinoma (AFD) and ameloblastic fibro-odontoma (AFO). These cases are currently considered "developing odontomas" (hamartomatous lesions). AIM: To analyze the clinicopathologic features of these lesions and discuss the changes in the 2017 World Health Organization classification. METHODS: An electronic literature search was performed in the PubMed/MEDLINE database. An electronic search of the English language literature was performed and last updated in September 2020 in the PubMed/MEDLINE database using the following terms: "ameloblastic fibroma", "ameloblastic fibrodentinoma", "ameloblastic fibro-odontoma", "ameloblastic sarcoma", "ameloblastic fibrosarcoma", "ameloblastic fibrodentinosarcoma", "ameloblastic fibroodontosarcoma" and "odontogenic carcinosarcoma". The inclusion criteria were odontogenic tumor series, case reports and systematic reviews that provided sufficient clinical, radiological and microscopic documentation to confirm the diagnosis. RESULTS: The database search strategy resulted in 947 papers. Articles focusing on other topics, articles that were not in English, duplicate articles, and articles without fulfilling the inclusion criteria were excluded. Finally, 96 publications were included in this review to describe and discuss the main features of the searched entities. Several aspects of AFO and AFD, such as biological behavior, age of occurrence, amount of hard tissue, and potential for malignant transformation into odontogenic sarcomas, support the neoplastic nature in most of the reported cases. Considering the clinical, radiographic, histopathological and molecular characteristics of odontogenic lesions with hard tissue production, we suggest that these types of lesions should continue to be recognized as odontogenic tumors by maintaining the classically used terms. CONCLUSION: This recommendation will be relevant for future clinical, microscopic, and molecular studies to better understand the biology of these interesting odontogenic tumors.

Comparison of orosomucoid-1 immunoexpression and angiogenesis between oral squamous cell carcinoma cases with different histological grades.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignancy in this region, and thus, further elucidation of its tumoral mechanisms is important. One of the main roles of the acute-phase protein orosomucoid-1 (ORM1) is the promotion of angiogenesis, which is key for tumor nutrition and growth. AIM: Our aim was to evaluate the immunohistochemical expression of ORM1 and the angiogenic activity indicated by microvascular density (MVD) in OSCC samples according to histological grade. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections from 45 OSCC cases were submitted to immunohistochemistry: 25 were well-differentiated OSCC, 18 were moderately differentiated OSCC and 2 were poorly differentiated OSCC. ORM1 staining was evaluated by a semiquantitative method, and CD34-positive blood vessels were quantified to calculate the MVD. The results were statically analyzed. RESULTS: All cases exhibited immunoexpression of ORM1 and CD34. However, no significant differences were found between the expression of both markers among the histological grades. In addition, the presence of ORM1 in inflammatory cells and in the extracellular matrix was detected in most cases. CONCLUSION: These results suggest that the induction of angiogenesis is not the main role of ORM1 in OSCC and may be associated with the regulation of the immune/inflammatory response or the transport of protumoral molecules, such as sialyl-Lewis X or phorbol esters, which requires confirmation in future studies.

Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings.

BACKGROUND: N,N-dimethyltryptamine is a short-acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date have addressed the neural and psychological effects of N,N-dimethyltryptamine alone, either administered intravenously or inhaled in freebase form, and none have been conducted in natural settings. AIMS: Our primary aim was to study the acute effects of inhaled N,N-dimethyltryptamine in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. "set" and "setting"), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming N,N-dimethyltryptamine in familiar and comfortable settings. METHODS: We combined state-of-the-art wireless electroencephalography with psychometric questionnaires to study the neural and subjective effects of naturalistic N,N-dimethyltryptamine use in 35 healthy and experienced participants. RESULTS: We observed that N,N-dimethyltryptamine significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of some features of mystical-type experiences. N,N-dimethyltryptamine also increased global synchrony and metastability in the gamma band while decreasing those measures in the alpha band. CONCLUSIONS: Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time the results suggest potential electroencephalography markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.

Extranodal NK/T cell lymphoma, nasal type: An updated overview.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is an aggressive malignancy associated with Epstein-Barr virus infection, with a geographic and racial predilection for some Asian and Latin American countries. ENKTCL-NT manifests as a necrotic process affecting nasal or upper aerodigestive structures and, rarely, extranasal sites such as skin, and the gastrointestinal tract. ENKTCL-NT was characterized by its poor prognosis irrespective of clinical stage and therapy. However, during the last two decades, advances in its clinicopathologic, genetic and molecular characterization have been achieved, as have changes in the chemotherapy regimens that, in combination with radiotherapy, are significantly improving the survival of these patients, especially in initial stages. For these reasons, we present an overview of the historical background of ENKTCL-NT along with an updated review of its potential etiological factors, clinicopathologic and molecular features, as well as its prognostic models, current treatment protocols, and future directions on potential promising therapeutic approaches.