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| ==[[Extranodal NK-T-cell lymphoma overview|Overview]]== | | ==[[Extranodal NK-T-cell lymphoma overview|Overview]]== |
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| ==[[Extranodal NK-T-cell lymphoma historical perspective|Historical Perspective]]== | | ==[[Extranodal NK-T-cell lymphoma historical perspective|Historical Perspective]]== |
| Extranodal NK cell lymphoma probably was first reported by McBride as a disease which rapidly destructs nose and face with progressing necrotic [[granuloma]]. The natural history of extranodal [[NK cell]] lymphoma was generally aggressive and lethal, this disease was initially termed as "[[rhinitis]] gangrenosa progressiva". Since the lesions usually was in midline and was aggressive and lethal, the term "lethal midline [[granuloma]] (LMG)" was used. First known case of natural-killer-cell lymphoma was diagnosed in a 19-years old boy. The diagnosis of natural-killer-cell lymphoma was confirmed by pathology as [[Wegener's granulomatosis|Wegener's Granulomatosis]] was ruled out.
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| ==[[Extranodal NK-T-cell lymphoma classification|Classification]]== | | ==[[Extranodal NK-T-cell lymphoma classification|Classification]]== |
| In contrast with [[B-cell lymphoma]], the classification of such a rare [[neoplasm]] has been controversial, since the [[Cytological|cytologic]] features have not been very useful. Further, by many entities, T-cell and natural killer cell (NK) neoplasms do not share any similar immuno-[[phenotype]]. Because of such matters, clinical features became handier for classification and somehow even more important than the precise cell of origin. since the majority of [[Cytotoxic T-cells|cytotoxic T-cell]] and NK cell lymphomas are located out of [[lymph nodes]], the gene expressing cytotoxic molecules may predispose to [[apoptosis]] by [[tumor]] cells and by standard cells.Three major categories of [[Extranodal NK-T-cell lymphoma|extranodal T/NK cell]] tumors include: [[Extranodal NK/T-cell lymphoma]], nasal type lymphoma, [[Extranodal NK/T-cell lymphoma]], [[enteropathy]] type lymphoma, [[Extranodal NK/T-cell lymphoma]], [[subcutaneous]] panniculitis-like, [[Extranodal NK-T-cell lymphoma]] may be classified according to [[WHO]] into 2 subtypes:, [[NK cell]]-derived [[neoplasms]], namely, aggressive NK cell [[leukemia]], [[Extranodal NK-T-cell lymphoma|Extranodal NK/T-cell lymphoma]], nasal type, Based on the organ involvement, [[extranodal NK-T-cell lymphoma]] may be classified into: [[Extranodal NK-T-cell lymphoma]], nasal type, [[Extranodal NK-T-cell lymphoma]], extra nasal type
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| ==[[Extranodal NK-T-cell lymphoma pathophysiology|Pathophysiology]]== | | ==[[Extranodal NK-T-cell lymphoma pathophysiology|Pathophysiology]]== |
| [[Natural killer cell|NK cells]] are [[CD3]] and myloperoxidase negative on their surface. [[Natural killer cell|NK cell]]<nowiki/>s have [[germline]] configuration of T-cell receptor and immunoglobulin genes. [[NK cells]] originate from a bipotent NK/T-progenitor cell so they have a lot in common with T cells. [[NK cells]] express T-associate markers such as [[CD2]], [[CD3]]<nowiki/>e, [[CD7]], [[CD8]], [[CD16]], [[CD56]], [[CD57]]. Most tumors involve NK cells but also involve T cells as neoplastic cells, that is the main reason of classification as NK/T-cell lymphoma rather than NK-cell [[lymphoma]]. the immunophenotype of NK lymphoma cells is classically positive for [[CD2]], [[CD56]], and cytoplasmic [[CD3]] epsilon. they are negative for surface [[CD3]]. Unlike normal NK cells, the tumor cells are usually negative for [[CD7]] and [[CD16]]. they express cytotoxic granule associated proteins [[granzyme B]], T-cell restricted intracellular antigen (TIA-1), and [[perforin]]. [[Extranodal NK-T-cell lymphoma|NK/T cell lymphoma]] expressing [[CD56]] is rare but most commonly occurs int he head and neck region, skin, and soft tissue. genes involved in the pathogenesis of [[extranodal NK-T-cell lymphoma]] include.:[[HLA-DQ|HLA DQA1*0501]], [[HLA-DQ|HLA DQB1*0201]]. these genes also are relevant with [[celiac disease]].On gross pathology, angiocentric and angiodestructive pattern of growth with associated geographical [[necrosis]] and [[ulceration]] are characteristic findings of [[extranodal NK-T-cell lymphoma]].[[Coagulative necrosis]] and [[apoptotic]] bodies are frequently encountered., [[Extranodal NK/T-cell lymphoma]], nasal type occurs in nasal cavity and upper aerodigestive tract., [[Extranodal NK-T-cell lymphoma|Extranodal NK/T cell lymphoma]], nasal type affects the nose and facial mid line exhibiting aggressive destruction., on microscopic histopathological analysis, medium sized tumor cells and polymorphic infiltrate of non-neoplastic inflammatory cells are characteristic findings of [[extranodal NK-T-cell lymphoma]]. the tumor cells are small to medium in size with occasional large and anaplastic forms. the lymphoma cells may be admixed with a polymorphic infiltrate of nonneoplastic [[Inflammation|inflammatory]] cells including small [[lymphocytes]], [[plasma cells]], [[histiocytes]], and [[eosinophils]].
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| ==[[Extranodal NK-T-cell lymphoma causes|Causes]]== | | ==[[Extranodal NK-T-cell lymphoma causes|Causes]]== |
| Extranodal NK/T-cell lymphoma is caused by transition mutation of [[p53]]. [[P53]] overexpresion has assosiation with poor prognosis.
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| ==[[Extranodal NK-T-cell lymphoma differential diagnosis|Differentiating Extranodal NK-T-cell lymphoma from other Diseases]]== | | ==[[Extranodal NK-T-cell lymphoma differential diagnosis|Differentiating Extranodal NK-T-cell lymphoma from other Diseases]]== |
| Extranodal NK-T-cell lymphoma must be differentiated from other diseases such as NK cell lukemia, [[lymphomatoid granulomatosis]], [[Diffuse large B cell lymphoma|EBV-positive diffuse large B cell lymphoma, NOS]], [[anaplastic large cell lymphoma]], non specific inflammatory process, [[enteropathy associated T cell lymphoma]], [[peripheral T cell lymphoma]], [[hepatosplenic T cell lymphoma]]. Extranodal NK/T-cell lymphoma, nasal type must be diffrentiated from [[Wegener's granulomatosis|Wegner's granulomatosis]], [[Polymorphic]] reticulosis, and Midline malignant [[Lymphomas|lymphoma]]
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| ==[[Extranodal NK-T-cell lymphoma epidemiology and demographics|Epidemiology and Demographics]]== | | ==[[Extranodal NK-T-cell lymphoma epidemiology and demographics|Epidemiology and Demographics]]== |
| NK cell lymphoma shows a poor [[prognosis]] because of rapid local progression and distant [[metastasis]].The [[median]] age of onset is approximately 50 years and it is common in elderly. [[extranodal NK/T-cell lymphoma]] is a rare disease in children and often it is associated with mosquito-bite [[hypersensitivity]] or other [[EBV]]-associated disease[[Natural Killer cell|.Natural Killer (NK) cell]] lymphoma is a rare disease. [[Extranodal NK-T-cell lymphoma|extranodal NK/T cell lymphoma]], nasal type (NKTCL) and aggressive NK-cell leukemia (ANKCL) have a higher incidence in Asia, Central, and South America.NK T cell lymphoma, nasal type (NNKTL) consist 3000-10000 out of 100000 cases of [[non-Hodgkin lymphoma]] in Asia and South America and less than 1000 in 10000 patient in western countries.
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| ==[[Extranodal NK-T-cell lymphoma risk factors|Risk Factors]]== | | ==[[Extranodal NK-T-cell lymphoma risk factors|Risk Factors]]== |
| There is a strong association between with extranodal NK/T-cell lymphoma and [[EBV]] virus.There is a strong assosiation between Extranodal NK/T-cell lymphoma andFas(Po-1/CD95) mutations.
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| ==[[Extranodal NK-T-cell lymphoma screening|Screening]]== | | ==[[Extranodal NK-T-cell lymphoma screening|Screening]]== |
| According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for extranodal NK-T-cell lymphoma.
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| ==[[Extranodal NK-T-cell lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | | ==[[Extranodal NK-T-cell lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| If left untreated, patients with extranodal NK-T-cell lymphoma, nasal type may progress to develop [[proptosis]] and [[hard palate]] perforation. Common complications of extranodal NK-T-cell lymphoma include [[hepatosplenomegaly]] and [[pancytopenia]]. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. Prognosis is generally regarded as poor.
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| ==Diagnosis== | | ==Diagnosis== |
| [[Extranodal NK-T-cell lymphoma staging|Staging]] | [[Extranodal NK-T-cell lymphoma history and symptoms|History and Symptoms]] | [[Extranodal NK-T-cell lymphoma physical examination|Physical Examination]] | [[Extranodal NK-T-cell lymphoma laboratory findings|Laboratory Findings]] | [[Extranodal NK-T-cell lymphoma CT|CT]] | [[Extranodal NK-T-cell lymphoma MRI|MRI]] | [[Extranodal NK-T-cell lymphoma other imaging findings|Other Imaging Findings]] | [[Extranodal NK-T-cell lymphoma other diagnostic studies|Other Diagnostic Studies]] | | [[Extranodal NK-T-cell lymphoma diagnostic study of choice|Diagnostic study of choice]] | [[Extranodal NK-T-cell lymphoma history and symptoms|History and Symptoms]] | [[Extranodal NK-T-cell lymphoma physical examination|Physical Examination]] | [[Extranodal NK-T-cell lymphoma laboratory findings|Laboratory Findings]] | [[Extranodal NK-T-cell lymphoma electrocardiogram|Electrocardiogram]] | [[Extranodal NK-T-cell lymphoma x ray|X-Ray Findings]] | [[Extranodal NK-T-cell lymphoma echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Extranodal NK-T-cell lymphoma CT scan|CT-Scan Findings]] | [[Extranodal NK-T-cell lymphoma MRI|MRI Findings]] | [[Extranodal NK-T-cell lymphoma other imaging findings|Other Imaging Findings]] | [[Extranodal NK-T-cell lymphoma other diagnostic studies|Other Diagnostic Studies]] |
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| Extranodal NK/T cell lymphoma survival rate is not well predicted by [[Ann Arbor staging system]]. A new system was introduced based on [[B symptoms]], [[Ann Arbor Staging|Ann Arbor system]], [[LDH]] level, and regional [[lymphadenopathy]] combined. Another parallel mechanism for extranodal NK/T cell lymphoma is based on [[tumor]] [[biologic]] and micro-environmental factors. High [[Ki-67 (Biology)|Ki-67]] [[nuclear]] antigen is a [[marker]] for actively proliferation [[tumor]] [[Cell (biology)|cell]] which could be a related factor with mass bulk.
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| combination of these two findings on [[immunophenotyping]] of [[Frozen section procedure|frozen section]] specimen cells and [[Reverse transcription polymerase chain reaction|RT-PCR]] are confirmatory for [[Extranodal NK-T-cell lymphoma|Extranodal NK/T cell lymphoma]]:Detection of [[CD56]] and EBER1 on tumor cells and [[EBV]] [[DNA]] ([[RT-PCR]]).Pathological examination of [[frozen section]] specimen may misled the NK/T cell diagnosis.Circulating cell free EBV DNA levels by [[RT-PCR]] is a diagnostic factor for [[EBV]] associated [[malignancies]], Like [[Extranodal NK-T-cell lymphoma|extranodal NK/T cell lymphoma]]. Measuring both [[BamHI]] W DNA and LMP1 DNA is more useful as a prognosis predictor, these [[DNA|DNAs]] will decrease with treatment and increase with relapse. Recently, determination of negative immune checkpoints are considered as a drug target,in the case of [[Extranodal NK-T-cell lymphoma|extranodal NK/T cell lymphoma]], [[PD-L1]] will be expressed in the tumor, and patients with higher concentration of soluble [[PD-L1]] showed worse prognosis.
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| The most common symptoms of extranodal NK-T-cell lymphoma include [[fever]], [[weight loss]], skin rash, [[night sweats]], protrusion of eye, swelling of the face, discharge from the nose, nose bleeds, blockage of the nasal passages, chest pain, [[abdominal pain]], [[bone pain]], and painless swelling in the neck, axilla, groin, thorax, and abdomen. [[Extranodal NK-T-cell lymphoma|Extranodal NK/T cell lymphoma]], nasal type, which is the most common sub type, is usually found as an ulcerative and [[Necrosis|necrotic]] [[granuloma]] in the [[nasal cavity]], [[palate]], and [[nasopharynx]]. [[Tumor]] can spread to surrounding tissue such as facial skin, [[paranasal sinus]], and [[orbits]], and cause exensive destruction of midline lesions. The most common symptoms at the time of diagnosis are nasal obstruction and bloody rhinorea.
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| Common physical examination findings of extranodal NK-T-cell lymphoma include [[fever]], [[rash]], [[ulcer]], [[proptosis]], midfacial destructive lesions, [[epistaxis]], nasal obstruction due to mass, chest tenderness, abdomen tenderness, bone tenderness, [[Lymphadenopathy|peripheral lymphadenopathy]], and [[Lymphadenopathy|central lymphadenopathy]].
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| Laboratory tests for extranodal NK-T-cell lymphoma include [[complete blood count]] (CBC), blood chemistry studies, cytogenetic analysis, [[flow cytometry]], [[immunohistochemistry]], and [[immunophenotyping]].
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| X-rays graphy of patients with extranodal NK/T cell lymphoma is not very usefull in order of diagnosis. Radiography show non-specific tumor changes.
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| [[CT]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma. Computerized tomography (CT) may be performed to detect metastasis and assess the local extent of extranodal NK-T-cell lymphoma.
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| [[MRI]] may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.Magnetic resonance imaging (MRI) may be performed to better define local soft tissue and bony involvement of extranodal NK-T-cell lymphoma.
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| ==Treatment== | | ==Treatment== |
| [[Extranodal NK-T-cell lymphoma medical therapy|Medical Therapy]] | [[Extranodal NK-T-cell lymphoma surgery|Surgery]] | [[Extranodal NK-T-cell lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Extranodal NK-T-cell lymphoma future or investigational therapies|Future or Investigational Therapies]] | | [[Extranodal NK-T-cell lymphoma medical therapy|Medical Therapy]] | [[Extranodal NK-T-cell lymphoma interventions|Interventions]] | [[Extranodal NK-T-cell lymphoma surgery|Surgery]] | [[Extranodal NK-T-cell lymphoma primary prevention|Primary Prevention]] | [[Extranodal NK-T-cell lymphoma secondary prevention|Secondary Prevention]] | [[Extranodal NK-T-cell lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Extranodal NK-T-cell lymphoma future or investigational therapies|Future or Investigational Therapies]] |
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| The predominant therapy for extranodal NK-T-cell lymphoma is [[radiation therapy]]. Adjudicative [[chemotherapy]] and [[stem cell transplant]] may be required.
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| Surgical intervention is not recommended for the management of extranodal NK/T cell lymphoma.
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| There are no established measures for the primary prevention of extranodal NK/T cell lymphoma.
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| Effective measures for the secondary prevention of extranodal NK-T-cell lymphoma include: [[Lactate dehydrogenase|LDH]] , [[MLH1|MLH]]1, PDGFRA, [[Vascular endothelial growth factor|VEGF]], [[PD-L1]], PD-1, [[Cyclin D1]], [[p53]], [[Ki-67]].
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| High dose chemotherapy and [[autologous]] [[haematopoietic]] [[stem cell transplantation]] is used for varying types of [[lymphoma]], however there is a lac of such experience in treating extranodal NK-T cell lymphoma. Further clinical trials are needed to prove that this therapy is handy and can be used as a method of therapy. [[Autologous]] [[transplantation]] appears to provide a great survival benefit only for those who attended a complete remission at the time of transplantation.
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| ==Case Studies== | | ==Case Studies== |
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