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==Overview==
==Overview==
'''Enteropathy-associated T-cell Lymphoma''' (EATL), also '''enteropathy-type T-cell lymphoma''' (ETTL), is a type of T-cell [[Non-Hodgkin lymphoma|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|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|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, [[Mesenteric|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]].
'''Enteropathy-associated T-cell Lymphoma''' (EATL), also '''enteropathy-type T-cell lymphoma''' (ETTL), is a type of T-cell [[Non-Hodgkin lymphoma|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|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|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, [[Mesenteric|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]].
==Historical Perspective==
The association between celiac disease and enteropathy-associated T cell lymphoma was made during 2008 by World Health Organization.<ref name="pmid21300984">{{cite journal |vauthors=Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES |title=The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications |journal=Blood |volume=117 |issue=19 |pages=5019–32 |date=May 2011 |pmid=21300984 |pmc=3109529 |doi=10.1182/blood-2011-01-293050 |url=}}</ref><ref name="pmid213009842">{{cite journal |vauthors=Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES |title=The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications |journal=Blood |volume=117 |issue=19 |pages=5019–32 |date=May 2011 |pmid=21300984 |pmc=3109529 |doi=10.1182/blood-2011-01-293050 |url=}}</ref>
==Classification==
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>
:* Type I enteropathy-associated T-cell lymphoma
:* Type II enteropathy-associated T-cell lymphoma
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+ '''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>
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Description
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Classical enteropathy-associated T-cell lymphoma  (Type I Enteropathy-associated T-cell lymphoma)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Covers 80-90% of all enteropathy-associated T-cell lymphoma cases.
* Is usually associated with refractory celiac disease that is sometimes accompanied by intestinal [[ulceration]] ([[ulcerative jejunitis]])
* Most show adult onset disease or are diagnosed as having [[celiac disease]] in the same clinical episode in which the [[lymphoma]] is diagnosed.
* Frequently has large-cell or pleomorphic [[cytology]].
* Seldom expresses [[CD8]] and [[CD56]].
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Monomorphic enteropathy-associated T-cell lymphoma  (Type II enteropathy-associated T-cell lymphoma)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Encountered in Asia and other regions where celiac disease is rare.
* Is sporadic, seldom associated with [[celiac disease]].
* Covers 10-20% of all enteropathy-associated T-cell lymphoma cases.
* Is characterized by monomorphic cytology.
* Frequent expression of [[CD8]] and [[CD56]].
* The tumor forms an ulcerating mucosal mass that invades the wall of the intestine.
*  Poor prognosis, death occurs from abdominal complications such as [[small bowel obstruction]], [[perforation]].
|}
==Pathophysiology==
* '''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>
*Frequent activating [[mutations]] in the [[JAK-STAT pathway]] in EATL suggests that deregulation of [[cytokine]] signaling is the early event in lymphomagenesis.
*Intraepithelial T cells are presumed to be the cell of origin of EATL (and RCD II).
* 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.
Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 27, 2016</ref>
* These cancerous [[T-cells]] are a possible consequence of either refractory cases of [[celiac disease]] or chronic untreated [[celiac disease]] patients.
* Most commonly occurs in the [[jejunum]] or [[ileum]].
*[[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>
*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>
*[[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.
==Causes==
*There are no established causes for enteropathy-associated T-cell lymphoma.
==Differentiating Enteropathy-associated T cell lymphoma from Other Diseases==
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>
* [[Peptic ulcer]]
* Poorly-differentiated [[adenocarcinoma]]
* [[MALT lymphoma]]
* [[Diffuse large B cell lymphoma]] (DLBCL)
* [[Mantle cell lymphoma]]
==Epidemiology and Demographics==
*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>
==Risk Factors==
*There are no established risk factors for enteropathy-associated T cell lymphoma.
==Screening==
*There is insufficient evidence to recommend routine screening for enteropathy-associated T-cell lymphoma.
==Natural History, Complications, and Prognosis==
* 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>
* It is associated with [[celiac disease]] (sprue).
* Most adults are diagnosed with [[celiac disease]] at the same time as their lymphoma or shortly before their lymphoma is diagnosed.
* Enteropathy-associated T-cell lymphoma may spread to the [[Liver|liver,]] [[spleen]], [[lymph nodes]], [[gallbladder]], [[stomach]], colon or skin.
==Diagnosis==
===Diagnostic Study of Choice===
*[[Endoscopic]] biopsy is the diagnostic study of choice for enteropathy-associated T cell lymphoma, though [[CT-scans|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>
===History and Symptoms===
*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>
**[[Fever]]
**[[Weight loss]]
**[[Night sweats]]
**[[Diarrhea]]
**[[Skin rash]]
**[[Chest pain]]
**[[Abdominal pain]]
**[[Bone pain]]
**Painless swelling in the neck, [[axilla]], [[groin]], [[thorax]], and [[abdomen]]
===Physical Examination===
===Vitals===
* [[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>
===Skin===
* [[Rash]]
* [[Ulcer]]
===HEENT===
* [[Lymphadenopathy|Cervical lymphadenopathy]]
===Thorax===
* [[Thoracic]] masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
* [[Chest]] tenderness
===Abdomen===
* [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
* Abdomen [[tenderness]]
===Extremities===
* [[Lymphadenopathy|Peripheral lymphadenopathy]]
* [[Bone]] tenderness
===Laboratory Findings===
*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>
**[[Complete blood count]] (CBC)
**[[Blood chemistry tests|Blood chemistry]] studies
**[[Cytogenetic]] analysis
**[[Flow cytometry]]
**[[Immunohistochemistry]]
**[[Immunophenotyping]]: [[CD3]]+, [[CD4]]-, [[CD5]]-, [[CD7]]+, [[CD30]]+, [[CD56]]+, [[CD103]]+, [[CD8]]+/-, and TCR beta+/-
===Electrocardiogram===
*There are no [[ECG]] findings associated with enteropathy-associated T cell lymphoma.
===X-ray===
*There are no [[x-ray]] findings associated with enteropathy-associated T cell lymphoma.
===Echocardiography or Ultrasound===
*There are no [[echocardiography]]/[[ultrasound]] findings associated with enteropathy-associated T cell lymphoma.
===CT scan===
* [[CT scan]] may be helpful in the diagnosis of enteropathy-associated T-cell lymphoma.<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>
* Findings on [[CT]] scan suggestive of enteropathy-associated T-cell lymphoma include:<ref name="LeeIm2003">{{cite journal|last1=Lee|first1=Hyun Ju|last2=Im|first2=Jung-Gi|last3=Goo|first3=Jin Mo|last4=Kim|first4=Kyoung Won|last5=Choi|first5=Byung Ihn|last6=Chang|first6=Kee Hyun|last7=Han|first7=Joon Koo|last8=Han|first8=Moon Hee|title=Peripheral T-Cell Lymphoma: Spectrum of Imaging Findings with Clinical and Pathologic Features1|journal=RadioGraphics|volume=23|issue=1|year=2003|pages=7–26|issn=0271-5333|doi=10.1148/rg.231025018}}. Accessed on January 28, 2016</ref><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}}. Accessed on January 28, 2016</ref>
:* [[Bowel]] wall thickening
:* [[Mesenteric]] fat infiltration
:* Mesenteric lymph node cavitation
:* [[Intussusception]]
:* Small-sized [[spleen]]
===MRI===
*[[MRI]] may be helpful in the diagnosis of enteropathy-associated T-cell lymphoma, especially in those EATL involved epithelial layers of the [[small intestine]] and also for response to treatment<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>
===Other Imaging Findings===
* Other diagnostic studies 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><ref name="LeeIm2003">{{cite journal|last1=Lee|first1=Hyun Ju|last2=Im|first2=Jung-Gi|last3=Goo|first3=Jin Mo|last4=Kim|first4=Kyoung Won|last5=Choi|first5=Byung Ihn|last6=Chang|first6=Kee Hyun|last7=Han|first7=Joon Koo|last8=Han|first8=Moon Hee|title=Peripheral T-Cell Lymphoma: Spectrum of Imaging Findings with Clinical and Pathologic Features1|journal=RadioGraphics|volume=23|issue=1|year=2003|pages=7–26|issn=0271-5333|doi=10.1148/rg.231025018}}. Accessed on January 28, 2016</ref>
:* [[PET]] scan
:* Barium study
:* [[Colonoscopy]]
* Findings on barium study suggestive of enteropathy-associated T-cell lymphoma include:
:* Multiple [[aphthous ulcers]]
:* Segmental [[luminal]] narrowing
* Finding on [[colonoscopy]] suggestive of enteropathy-associated T-cell lymphoma includes:
:* [[Aphthous ulcers]]
===Other Diagnostic Studies===
*Other diagnostic studies 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>
** [[Bone marrow aspiration]]
** [[Bone marrow biopsy]]
==Treatment==
===Medical Therapy===
*There is no treatment for enteropathy-associated T-cell lymphoma; the mainstay of therapy is supportive care. The optimal therapy for enteropathy-associated T-cell lymphoma depends  on the extent and the location of the lymphoma in the small intestine.<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 26, 2016 </ref> [[Stem cell transplant]] can be helpful in those patients that are in [[remission]] phase of disease.<ref name="pmid16865575">{{cite journal |vauthors=Rongey C, Micallef I, Smyrk T, Murray J |title=Successful treatment of enteropathy-associated T cell lymphoma with autologous stem cell transplant |journal=Dig. Dis. Sci. |volume=51 |issue=6 |pages=1082–6 |date=June 2006 |pmid=16865575 |doi=10.1007/s10620-006-8013-z |url=}}</ref>
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+ '''Treatment of enteropathy-associated T-cell 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 26, 2016 </ref>'''
! style="background: #4479BA; color:#FFF;" | Therapy
! style="background: #4479BA; color:#FFF;" | Description
|-
| style="padding: 5px 5px; background: #DCDCDC;" | Supportive therapy
| style="padding: 5px 5px; background: #F5F5F5;" | 
* People often need nutritional support
* A [[gluten-free diet]] is also recommended
|-
| style="padding: 5px 5px; background: #DCDCDC;" | Surgery
| style="padding: 5px 5px; background: #F5F5F5;" |
* May be an option
* Done to remove the damaged [[small intestine]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | Chemotherapy
| style="padding: 5px 5px; background: #F5F5F5;" |
* May be offered to people who can tolerate it:
:* Following surgery
:* When the cancer cannot be removed by surgery or is extensive
* Combination [[chemotherapy]] is often used for this aggressive lymphoma
* Drug regimen: (CHOP) [[Cyclophosphamide]] {{and}} [[Doxorubicin]]  {{and}} [[Vincristine]] {{and}} [[Prednisone]]
|}
===Surgery===
* Surgery is not the first ­line treatment option for patients with enteropathy-associated T-cell lymphoma.<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}}. Accessed on January 28,2016</ref>
* Local [[debulking]] is usually reserved for patients with tumor masses with a high risk of [[obstruction]], [[hemorrhage]], and perforation.
===Primary Prevention===
*There are no established measures for the primary prevention of enteropathy-associated T cell lymphoma.
===Secondary Prevention===
There are no established measures for the secondary prevention of enteropathy-associated T cell lymphoma.
==References==
{{reflist|2}}

Revision as of 16:28, 6 March 2019


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2] Sowminya Arikapudi, M.B,B.S. [3]

Synonyms and keywords: Enteropathy-type T-cell lymphoma; Intestinal T-cell lymphoma; EATL; ETTL

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.


Historical Perspective

The association between celiac disease and enteropathy-associated T cell lymphoma was made during 2008 by World Health Organization.[1][2]

Classification

Enteropathy-associated T-cell lymphoma may be classified according to World Health Organization (WHO) into 2 subtypes:[3][4]

  • Type I enteropathy-associated T-cell lymphoma
  • Type II enteropathy-associated T-cell lymphoma
Enteropathy-associated T-cell lymphoma classification[3][5][6]
Name Description
Classical enteropathy-associated T-cell lymphoma (Type I Enteropathy-associated T-cell lymphoma)
  • Covers 80-90% of all enteropathy-associated T-cell lymphoma cases.
  • Is usually associated with refractory celiac disease that is sometimes accompanied by intestinal ulceration (ulcerative jejunitis)
  • Most show adult onset disease or are diagnosed as having celiac disease in the same clinical episode in which the lymphoma is diagnosed.
  • Frequently has large-cell or pleomorphic cytology.
  • Seldom expresses CD8 and CD56.
Monomorphic enteropathy-associated T-cell lymphoma (Type II enteropathy-associated T-cell lymphoma)
  • Encountered in Asia and other regions where celiac disease is rare.
  • Is sporadic, seldom associated with celiac disease.
  • Covers 10-20% of all enteropathy-associated T-cell lymphoma cases.
  • Is characterized by monomorphic cytology.
  • Frequent expression of CD8 and CD56.
  • The tumor forms an ulcerating mucosal mass that invades the wall of the intestine.
  • Poor prognosis, death occurs from abdominal complications such as small bowel obstruction, perforation.

Pathophysiology

  • 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. [7]
  • Frequent activating mutations in the JAK-STAT pathway in EATL suggests that deregulation of cytokine signaling is the early event in lymphomagenesis.
  • Intraepithelial T cells are presumed to be the cell of origin of EATL (and RCD II).
  • Variable degrees of transformations can be seen on histopathology of this tumor, but usually presents as large lymphoid cells.[5]
  • These cancerous T-cells are a possible consequence of either refractory cases of celiac disease or chronic untreated celiac disease patients.
  • Most commonly occurs in the jejunum or ileum.
  • SETD2 was found to be the most often silenced gene in EATL according to studies.[8]
  • The JAK-STAT pathway is the most frequently mutated pathway. [8]
  • 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.

Causes

  • There are no established causes for enteropathy-associated T-cell lymphoma.

Differentiating Enteropathy-associated T cell lymphoma from Other Diseases

Enteropathy-associated T-cell lymphoma must be differentiated from other diseases such as:[3][9]

Epidemiology and Demographics

  • 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.[10]

Risk Factors

  • There are no established risk factors for enteropathy-associated T cell lymphoma.

Screening

  • There is insufficient evidence to recommend routine screening for enteropathy-associated T-cell lymphoma.

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

  • Endoscopic biopsy is the diagnostic study of choice for enteropathy-associated T cell lymphoma, though CT scan and other imaging studies can be helpful.[12]

History and Symptoms

Physical Examination

Vitals

Skin

HEENT

Thorax

Abdomen

Extremities

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with enteropathy-associated T cell lymphoma.

X-ray

  • There are no x-ray findings associated with enteropathy-associated T cell lymphoma.

Echocardiography or Ultrasound

CT scan

  • CT scan may be helpful in the diagnosis of enteropathy-associated T-cell lymphoma.[5]
  • Findings on CT scan suggestive of enteropathy-associated T-cell lymphoma include:[13][12]

MRI

  • MRI may be helpful in the diagnosis of enteropathy-associated T-cell lymphoma, especially in those EATL involved epithelial layers of the small intestine and also for response to treatment[5]

Other Imaging Findings

  • Other diagnostic studies for enteropathy-associated T-cell lymphoma include:[5][13]
  • Findings on barium study suggestive of enteropathy-associated T-cell lymphoma include:
  • Finding on colonoscopy suggestive of enteropathy-associated T-cell lymphoma includes:

Other Diagnostic Studies

Treatment

Medical Therapy

  • There is no treatment for enteropathy-associated T-cell lymphoma; the mainstay of therapy is supportive care. The optimal therapy for enteropathy-associated T-cell lymphoma depends on the extent and the location of the lymphoma in the small intestine.[11] Stem cell transplant can be helpful in those patients that are in remission phase of disease.[14]
Treatment of enteropathy-associated T-cell lymphoma[11]
Therapy Description
Supportive therapy
Surgery
Chemotherapy
  • May be offered to people who can tolerate it:
  • Following surgery
  • When the cancer cannot be removed by surgery or is extensive

Surgery

  • Surgery is not the first ­line treatment option for patients with enteropathy-associated T-cell lymphoma.[12]
  • Local debulking is usually reserved for patients with tumor masses with a high risk of obstruction, hemorrhage, and perforation.

Primary Prevention

  • There are no established measures for the primary prevention of enteropathy-associated T cell lymphoma.

Secondary Prevention

There are no established measures for the secondary prevention of enteropathy-associated T cell lymphoma.

References

  1. ↑ Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES (May 2011). "The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications". Blood. 117 (19): 5019–32. doi:10.1182/blood-2011-01-293050. PMC 3109529. PMID 21300984.
  2. ↑ Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES (May 2011). "The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications". Blood. 117 (19): 5019–32. doi:10.1182/blood-2011-01-293050. PMC 3109529. PMID 21300984.
  3. ↑ 3.0 3.1 3.2 Enteropathy-associated T-cell lymphoma. BioMed Central. http://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-7-172. Accessed on January 28, 2016
  4. ↑ V G, Kudva R, Amprayil AJ (October 2014). "Enteropathy associated T cell lymphoma - a case report of an uncommon extranodal T cell lymphoma". J Clin Diagn Res. 8 (10): FD10–2. doi:10.7860/JCDR/2014/9740.4999. PMC 4253173. PMID 25478355.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Enteropathy-associated T-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed on January 26, 2016
  6. ↑ Hussain N, Hussain F, Chatterjee T, Upalakalin JN, Lynch T (2018). "An unexpected deterrent in diagnosing refractory celiac disease and enteropathy-associated T-cell lymphoma: a gluten-free diet". J Community Hosp Intern Med Perspect. 8 (4): 233–236. doi:10.1080/20009666.2018.1483693. PMC 6116147. PMID 30181834.
  7. ↑ Bautista-Quach MA, Ake CD, Chen M, Wang J (September 2012). "Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features". J Gastrointest Oncol. 3 (3): 209–25. doi:10.3978/j.issn.2078-6891.2012.024. PMC 3418529. PMID 22943012.
  8. ↑ 8.0 8.1 Moffitt AB, Ondrejka SL, McKinney M, Rempel RE, Goodlad JR, Teh CH, Leppa S, Mannisto S, Kovanen PE, Tse E, Au-Yeung R, 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 (May 2017). "Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2". J. Exp. Med. 214 (5): 1371–1386. doi:10.1084/jem.20160894. PMC 5413324. PMID 28424246. Vancouver style error: initials (help)
  9. ↑ Isaacson P, Wright DH (January 1978). "Intestinal lymphoma associated with malabsorption". Lancet. 1 (8055): 67–70. PMID 74567.
  10. ↑ Verbeek WH, Van De Water JM, Al-Toma A, Oudejans JJ, Mulder CJ, Coupé VM (2008). "Incidence of enteropathy-associated T-cell lymphoma: a nation-wide study of a population-based registry in The Netherlands". Scand. J. Gastroenterol. 43 (11): 1322–8. doi:10.1080/00365520802240222. PMID 18618372.
  11. ↑ 11.0 11.1 11.2 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
  12. ↑ 12.0 12.1 12.2 Di Sabatino, A.; Biagi, F.; Gobbi, P. G.; Corazza, G. R. (2012). "How I treat enteropathy-associated T-cell lymphoma". Blood. 119 (11): 2458–2468. doi:10.1182/blood-2011-10-385559. ISSN 0006-4971.
  13. ↑ 13.0 13.1 Lee, Hyun Ju; Im, Jung-Gi; Goo, Jin Mo; Kim, Kyoung Won; Choi, Byung Ihn; Chang, Kee Hyun; Han, Joon Koo; Han, Moon Hee (2003). "Peripheral T-Cell Lymphoma: Spectrum of Imaging Findings with Clinical and Pathologic Features1". RadioGraphics. 23 (1): 7–26. doi:10.1148/rg.231025018. ISSN 0271-5333.. Accessed on January 28, 2016
  14. ↑ Rongey C, Micallef I, Smyrk T, Murray J (June 2006). "Successful treatment of enteropathy-associated T cell lymphoma with autologous stem cell transplant". Dig. Dis. Sci. 51 (6): 1082–6. doi:10.1007/s10620-006-8013-z. PMID 16865575.
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