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| {{Enteropathy-associated T-cell lymphoma}} | | {{Enteropathy-associated T-cell lymphoma}} |
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| {{CMG}}; {{AE}} {{AS}} | | {{CMG}}; {{AE}} {{Nnasiri}} |
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| {{SK}} Enteropathy-type T-cell lymphoma; Intestinal T-cell lymphoma; EATL; ETTL | | {{SK}} Enteropathy-type T-cell lymphoma; Intestinal T-cell lymphoma; EATL; ETTL |
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| ==Overview== | | ==[[Enteropathy-associated T-cell lymphoma overview|Overview]]== |
| '''Enteropathy-associated T-cell Lymphoma''' (EATL), also '''enteropathy-type T-cell lymphoma''' (ETTL), is a type of [[T-cell non-hodgkin lymphoma]] that affects the small intestine, it is composed of large lymphoid cells. Enteropathy-associated T-cell lymphoma has two subtypes, type I enteropathy-associated T-cell lymphoma which has a strong association with celiac disease and it is more common in western countries and type II enteropathy-associated T-cell lymphoma which is mostly found among the Asian population. Genes involved in the pathogenesis of this disease include 8q24, T-cell receptor (TCR) beta and gamma, and 16q genes. On gross pathology, multiple intestinal ulcers are characteristic findings of EATL. On microscopic histopathological analysis, monotonous cells, round or angulated vesicular nuclei, and prominent nucleoli are characteristic findings of enteropathy-associated T-cell lymphoma. There are no established causes for enteropathy-associated T-cell lymphoma. EATL must be differentiated from other diseases such as peptic ulcer, poorly-differentiated adenocarcinoma, MALT lymphoma, diffuse large B cell lymphoma, and mantle cell lymphoma. The incidence of enteropathy-associated T-cell lymphoma is very low worldwide. There are no established risk factors for enteropathy-associated T-cell lymphoma. Common complications of enteropathy-associated T-cell lymphoma include ulcer, obstruction, and perforation of small intestine. Prognosis is generally poor. According to the Lugano classification, there are four stages of enteropathy-associated T-cell lymphoma based on the number of nodes and extranodal involvement. The most common symptoms of enteropathy-associated T-cell lymphoma include fever, weight loss, skin rash, night sweats, chest pain, abdominal pain, bone pain, and painless swelling in the neck, axilla, groin, thorax, and abdomen. Common physical examination findings of enteropathy-associated T-cell lymphoma include fever, rash, ulcer, chest tenderness, abdomen tenderness, bone tenderness, peripheral lymphadenopathy. Lymph node or endoscopic tissue biopsy is diagnostic of enteropathy-associated T-cell lymphoma. CT scan may be helpful in the diagnosis of enteropathy-associated T-cell lymphoma. Findings on CT scan suggestive of enteropathy-associated T-cell lymphoma include bowel wall thickening, mesenteric fat infiltration, mesentric lymph node cavitation, intussusception, and small-sized spleen. Other diagnostic studies for enteropathy-associated T-cell lymphoma include bone marrow aspiration and bone marrow biopsy. There is no treatment, the mainstay of therapy is supportive care. The optimal therapy depends on the extent and the location of the lymphoma in the small intestine. Surgery is not the first line treatment option for patients with enteropathy-associated T-cell lymphoma. Local debulking is usually reserved for patients with tumor masses with a high risk of obstruction, hemorrhage, and perforation.
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| ==Historical Perspective== | | == [[Enteropathy-associated T-cell lymphoma historical perspective|Historical perspective]] == |
| [Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event]. | |
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| The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
| | == [[Enteropathy-associated T-cell lymphoma classification|Classification]] == |
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| In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
| | ==[[Enteropathy-associated T-cell lymphoma pathophysiology|Pathophysiology]]== |
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| In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
| | ==[[Enteropathy-associated T-cell lymphoma causes|Causes]]== |
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| There have been several outbreaks of [disease name], including -----.
| | ==[[Enteropathy-associated T-cell lymphoma differential diagnosis|Differentiating Enteropathy-associated T-cell lymphoma from Other Diseases]]== |
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| In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
| | ==[[Enteropathy-associated T-cell lymphoma epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Classification== | | ==[[Enteropathy-associated T-cell lymphoma risk factors|Risk Factors]]== |
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| | ==[[Enteropathy-associated T-cell lymphoma screening|Screening]]== |
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| * Enteropathy-associated [[T-cell lymphoma]] may be classified according to [[World Health Organization]] (WHO) into 2 subtypes:<ref name="biomedcentral">Enteropathy-associated T-cell lymphoma. BioMed Central. http://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-7-172. Accessed on January 28, 2016</ref><ref name="pmid25478355">{{cite journal |vauthors=V G, Kudva R, Amprayil AJ |title=Enteropathy associated T cell lymphoma - a case report of an uncommon extranodal T cell lymphoma |journal=J Clin Diagn Res |volume=8 |issue=10 |pages=FD10–2 |date=October 2014 |pmid=25478355 |pmc=4253173 |doi=10.7860/JCDR/2014/9740.4999 |url=}}</ref>
| | ==[[Enteropathy-associated T-cell lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| :* Type I enteropathy-associated T-cell lymphoma
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| :* Type II enteropathy-associated T-cell lymphoma
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| {| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
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| |+ '''Enteropathy-associated T-cell lymphoma classification'''<ref name="biomedcentral">Enteropathy-associated T-cell lymphoma. BioMed Central. http://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-7-172. Accessed on January 28, 2016</ref><ref name="cancer.gov">Enteropathy-associated T-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 26, 2016</ref><ref name="pmid30181834">{{cite journal |vauthors=Hussain N, Hussain F, Chatterjee T, Upalakalin JN, Lynch T |title=An unexpected deterrent in diagnosing refractory celiac disease and enteropathy-associated T-cell lymphoma: a gluten-free diet |journal=J Community Hosp Intern Med Perspect |volume=8 |issue=4 |pages=233–236 |date=2018 |pmid=30181834 |pmc=6116147 |doi=10.1080/20009666.2018.1483693 |url=}}</ref>
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| ! style="background: #4479BA;; color:#FFF;" | Name
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| ! style="background: #4479BA;; color:#FFF;" | Description
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| | style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Classical enteropathy-associated T-cell lymphoma (Type I Enteropathy-associated T-cell lymphoma)
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| * Covers 80-90% of all enteropathy-associated T-cell lymphoma cases.
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| * Is usually associated with refractory celiac disease that is sometimes accompanied by intestinal [[ulceration]] ([[ulcerative jejunitis]])
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| * Most show adult onset disease or are diagnosed as having [[celiac disease]] in the same clinical episode in which the [[lymphoma]] is diagnosed.
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| * Frequently has large-cell or pleomorphic [[cytology]].
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| * Seldom expresses [[CD8]] and [[CD56]].
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| | style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Monomorphic enteropathy-associated T-cell lymphoma (Type II enteropathy-associated T-cell lymphoma)
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| * Encountered in Asia and other regions where celiac disease is rare.
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| * Is sporadic, seldom associated with [[celiac disease]].
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| * Covers 10-20% of all enteropathy-associated T-cell lymphoma cases.
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| * Is characterized by monomorphic cytology.
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| * Frequent expression of [[CD8]] and [[CD56]].
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| * The tumor forms an ulcerating mucosal mass that invades the wall of the intestine.
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| * Poor prognosis, death occurs from abdominal complications such as [[small bowel obstruction]], [[perforation]].
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| |}
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| ==Pathophysiology== | | ==Diagnostic criteria== |
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| | | [[Diagnostic criteria|Diagnostic Criteria]] | [[Enteropathy-associated T-cell lymphoma history and symptoms|History and Symptoms]] | [[Enteropathy-associated T-cell lymphoma physical examination|Physical Examination]] | [[Enteropathy-associated T-cell lymphoma laboratory findings|Laboratory Findings]] | [[Enteropathy-associated T-cell lymphoma electrocardiogram|Electrocardiogram]] | [[Enteropathy-associated T-cell lymphoma x ray|X Ray]] | [[Enteropathy-associated T-cell lymphoma CT|CT]] | [[Enteropathy-associated T-cell lymphoma MRI|MRI]] | [[Enteropathy-associated T-cell lymphoma echocardiography and ultrasound|Echocardiography or Ultrasound]] | [[Enteropathy-associated T-cell lymphoma other imaging findings|Other Imaging Findings]] | [[Enteropathy-associated T-cell lymphoma other diagnostic studies|Other Diagnostic Studies]] |
| * '''Enteropathy-associated T-cell Lymphoma''' (EATL), also '''enteropathy-type T-cell lymphoma''' (ETTL), is a type of [[T-cell lymphoma]] that affects the [[small intestine]]. <ref name="pmid22943012">{{cite journal |vauthors=Bautista-Quach MA, Ake CD, Chen M, Wang J |title=Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features |journal=J Gastrointest Oncol |volume=3 |issue=3 |pages=209–25 |date=September 2012 |pmid=22943012 |pmc=3418529 |doi=10.3978/j.issn.2078-6891.2012.024 |url=}}</ref>
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| *Frequent activating mutations in the [[JAK-STAT pathway]] in EATL suggests that deregulation of [[cytokine]] signaling is the early event in lymphomagenesis.
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| *Intraepithelial T cells are presumed to be the cell of origin of EATL (and RCD II).
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| * Variable degrees of transformations can be seen on [[histopathology]] of this tumor, but usually presents as large lymphoid cells.<ref name="cancer.gov">Enteropathy-associated T-cell lymphoma.
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| Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 27, 2016</ref>
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| * These cancerous [[T-cells]] are a possible consequence of either refractory cases of [[celiac disease]] or chronic untreated celiac disease patients.
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| * Most commonly occurs in the [[jejunum]] or [[ileum]].
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| *SETD2 was found to be the most often silenced gene in EATL according to studies.<ref name="pmid28424246">{{cite journal |vauthors=Moffitt AB, Ondrejka SL, McKinney M, Rempel RE, Goodlad JR, Teh CH, Leppa S, Mannisto S, Kovanen PE, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Iqbal J, Yu J, Naresh K, Villa D, Gascoyne RD, Said J, Czader MB, Chadburn A, Richards KL, Rajagopalan D, Davis NS, Smith EC, Palus BC, Tzeng TJ, Healy JA, Lugar PL, Datta J, Love C, Levy S, Dunson DB, Zhuang Y, Hsi ED, Dave SS |title=Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2 |journal=J. Exp. Med. |volume=214 |issue=5 |pages=1371–1386 |date=May 2017 |pmid=28424246 |pmc=5413324 |doi=10.1084/jem.20160894 |url=}}</ref>
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| *The [[JAK-STAT pathway]] is the most frequently mutated pathway. <ref name="pmid28424246">{{cite journal |vauthors=Moffitt AB, Ondrejka SL, McKinney M, Rempel RE, Goodlad JR, Teh CH, Leppa S, Mannisto S, Kovanen PE, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Iqbal J, Yu J, Naresh K, Villa D, Gascoyne RD, Said J, Czader MB, Chadburn A, Richards KL, Rajagopalan D, Davis NS, Smith EC, Palus BC, Tzeng TJ, Healy JA, Lugar PL, Datta J, Love C, Levy S, Dunson DB, Zhuang Y, Hsi ED, Dave SS |title=Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2 |journal=J. Exp. Med. |volume=214 |issue=5 |pages=1371–1386 |date=May 2017 |pmid=28424246 |pmc=5413324 |doi=10.1084/jem.20160894 |url=}}</ref>
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| *[[Mutations]] in [[KRAS]], [[TP53]], and [[TERT]] Type I EATL and type II EATL (monomorphic intestinal T cell lymphoma) identified as well which have overlapping genetic alterations.
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| ==Causes==
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| *There are no established causes for enteropathy-associated T-cell lymphoma.
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| ==Differentiating ((Enteropathy-associated T cell lymphoma)) from Other Diseases==
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| Enteropathy-associated T-cell lymphoma must be differentiated from other diseases such as:<ref name="biomedcentral">Enteropathy-associated T-cell lymphoma. BioMed Central. http://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-7-172. Accessed on January 28, 2016</ref><ref name="pmid74567">{{cite journal |vauthors=Isaacson P, Wright DH |title=Intestinal lymphoma associated with malabsorption |journal=Lancet |volume=1 |issue=8055 |pages=67–70 |date=January 1978 |pmid=74567 |doi= |url=}}</ref>
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| * [[Peptic ulcer]]
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| * Poorly-differentiated [[adenocarcinoma]]
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| * [[MALT lymphoma]]
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| * [[Diffuse large B cell lymphoma]] (DLBCL)
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| * [[Mantle cell lymphoma]]
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| ==Epidemiology and Demographics==
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| *Enteropathy-associated T cell lymphoma is a very rare form of [[extranodal]] [[non-Hodgkin lymphoma]], with an average incidence of 0.10 to 1.5 per 100,000 inhabitants per year, mostly occurs in the older adult, peak [[incidence]] average of 59 years old and involves [[proximal small intestine]] ([[duodenum]] and [[jejunum]]). Type II EATL is more common in the Asian population and not related to [[celiac disease]], whereas type I EATL is more frequently happens in western Europe.<ref name="pmid18618372">{{cite journal |vauthors=Verbeek WH, Van De Water JM, Al-Toma A, Oudejans JJ, Mulder CJ, Coupé VM |title=Incidence of enteropathy-associated T-cell lymphoma: a nation-wide study of a population-based registry in The Netherlands |journal=Scand. J. Gastroenterol. |volume=43 |issue=11 |pages=1322–8 |date=2008 |pmid=18618372 |doi=10.1080/00365520802240222 |url=}}</ref>
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| ==Risk Factors==
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| *There are no established risk factors for enteropathy-associated T cell lymphoma.
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| ==Screening==
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| *There is insufficient evidence to recommend routine screening for enteropathy-associated T-cell lymphoma.
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| ==Natural History, Complications, and Prognosis==
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| * Enteropathy-associated T-cell lymphoma is usually a fast-growing (aggressive) lymphoma.<ref name="canadiancancer">Enteropathy-associated T-cell lymphoma . Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/enteropathy-associated-t-cell-lymphoma/?region=on Accessed on January 27, 2016 </ref>
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| * It is associated with [[celiac disease]] (sprue).
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| * Most adults are diagnosed with [[celiac disease]] at the same time as their lymphoma or shortly before their lymphoma is diagnosed.
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| * Enteropathy-associated T-cell lymphoma may spread to the [[Liver|liver,]] [[spleen]], [[lymph nodes]], [[gallbladder]], [[stomach]], colon or skin.
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| ==Diagnosis==
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| ===Diagnostic Study of Choice===
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| *Endoscopic biopsy is the diagnostic study of choice for enteropathy-associated T cell lymphoma, though CT scan and other imaging studies can be helpful.<ref name="Di SabatinoBiagi2012">{{cite journal|last1=Di Sabatino|first1=A.|last2=Biagi|first2=F.|last3=Gobbi|first3=P. G.|last4=Corazza|first4=G. R.|title=How I treat enteropathy-associated T-cell lymphoma|journal=Blood|volume=119|issue=11|year=2012|pages=2458–2468|issn=0006-4971|doi=10.1182/blood-2011-10-385559}}</ref>
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| ===History and Symptoms===
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| *Symptoms of the enteropathy-associated T-cell lymphoma include:<ref name=cancer.gov> Enteropathy-associated T-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 26, 2016</ref>
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| **[[Fever]]
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| **[[Weight loss]]
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| **[[Night sweats]]
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| **[[Diarrhea]]
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| **Skin rash
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| **Chest pain
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| **[[Abdominal pain]]
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| **[[Bone pain]]
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| **Painless swelling in the neck, axilla, groin, thorax, and abdomen
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| ===Physical Examination===
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| ===Vitals===
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| * [[Fever]] is often present<ref name=cancer.gov> Enteropathy-associated T-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 26, 2016</ref>
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| ===Skin===
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| * [[Rash]]
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| * [[Ulcer]]
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| ===HEENT===
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| * [[Lymphadenopathy|Cervical lymphadenopathy]]
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| ===Thorax===
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| * Thoracic masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
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| * Chest tenderness
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| ===Abdomen===
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| * [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
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| * Abdomen tenderness
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| ===Extremities===
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| * [[Lymphadenopathy|Peripheral lymphadenopathy]]
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| * Bone tenderness
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| ===Laboratory Findings===
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| *Laboratory tests for enteropathy-associated T-cell lymphoma include:<ref name=cancer.gov> Enteropathy-associated T-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 26, 2016</ref>
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| **[[Complete blood count]] (CBC)
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| **Blood chemistry studies
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| **Cytogenetic analysis
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| **[[Flow cytometry]]
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| **[[Immunohistochemistry]]
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| **[[Immunophenotyping]]: [[CD3]]+, [[CD4]]-, [[CD5]]-, [[CD7]]+, [[CD30]]+, [[CD56]]+, [[CD103]]+, [[CD8]]+/-, and TCR beta+/-
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| ===Electrocardiogram===
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| There are no ECG findings associated with enteropathy-associated T cell lymphoma.
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| ===X-ray===
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| There are no x-ray findings associated with [disease name].
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| OR
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| An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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| OR
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| There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
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| ===Echocardiography or Ultrasound===
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| There are no echocardiography/ultrasound findings associated with [disease name].
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| OR
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| Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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| OR
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| There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
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| ===CT scan===
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| There are no CT scan findings associated with [disease name].
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| OR
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| [Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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| OR
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| There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
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| ===MRI===
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| There are no MRI findings associated with [disease name].
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| OR
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| [Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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| OR
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| There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
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| ===Other Imaging Findings===
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| There are no other imaging findings associated with [disease name].
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| OR
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| [Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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| ===Other Diagnostic Studies===
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| There are no other diagnostic studies associated with [disease name].
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| OR
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| [Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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| OR
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| Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
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| ==Treatment== | | ==Treatment== |
| ===Medical Therapy===
| | [[Enteropathy-associated T-cell lymphoma medical therapy|Medical Therapy]] | [[Enteropathy-associated T-cell lymphoma surgery |Surgery]] | [[Enteropathy-associated T-cell lymphoma primary prevention|Primary Prevention]] | [[Enteropathy-associated T-cell lymphoma secondary prevention|Secondary Prevention]] | [[Enteropathy-associated T-cell lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Enteropathy-associated T-cell lymphoma future or investigational therapies|Future or Investigational Therapies]] |
| There is no treatment for [disease name]; the mainstay of therapy is supportive care.
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| OR
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| Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
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| OR
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| The majority of cases of [disease name] are self-limited and require only supportive care.
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| OR
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| [Disease name] is a medical emergency and requires prompt treatment.
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| OR
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| The mainstay of treatment for [disease name] is [therapy].
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| OR
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| The optimal therapy for [malignancy name] depends on the stage at diagnosis.
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| OR
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| [Therapy] is recommended among all patients who develop [disease name].
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| OR
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| Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
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| OR
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| Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
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| OR
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| Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
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| OR
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| Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
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| ===Surgery===
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| Surgical intervention is not recommended for the management of [disease name].
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| OR
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| Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
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| OR
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| The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
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| OR
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| The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
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| OR
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| Surgery is the mainstay of treatment for [disease or malignancy].
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| ===Primary Prevention===
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| There are no established measures for the primary prevention of [disease name].
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| OR
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| There are no available vaccines against [disease name].
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| OR
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| Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
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| OR
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| [Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3]. | |
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| ===Secondary Prevention===
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| There are no established measures for the secondary prevention of [disease name].
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| OR
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| Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
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| ==References== | | ==Case Studies== |
| {{reflist|2}}
| | [[Enteropathy-associated T-cell lymphoma case study one|Case #1]] |
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