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{{Insulinoma}}
{{Insulinoma}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{ADS}}
==Overview==
==Overview==
*There is no established system for the classification of [disease name].
Insulinoma may be classified according to their [[malignant]] potential into 2 sub-types: [[Benign]] (90%) and [[malignant]] (10%). It is also classified into 2 subtypes based on the number: solitary (90%) and multiple (10%). Previously insulinoma was classified into 2 subtypes based on [[hormonal]] level as determined by [[radioimmunoassay]] into group A and group B. The staging of [[malignant]] insulinoma is based on the [[AJCC|AJCC 2010]], ENETS and modified ENETS staging classification.
OR
*[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].
OR
*[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3].
*[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].
OR
*Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.
OR
*If the staging system involves specific and characteristic findings and features:
*According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].
OR
*The staging of [malignancy name] is based on the [staging system].
OR
*There is no established system for the staging of [malignancy name].


==Classification==
==Classification==
 
{|
* Insulinoma may be classified according to malignant potential into 2 sub-types:  
! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Classification of insulinoma
**Benign
|-
**Malignant
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Criteria
***90% of insulinoma are benign in nature while 10% has a malignant potential to invade adjacent soft tissues or structures. The malignant type is mostly associated with MEN 1 syndrome.They also have a recurrence rate which is higher in those with MEN1 (21% at 10 and 20 years) than without it(5% at 10 and 7% at 20 years)<ref>{{Cite journal
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Classification
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Features
|-
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''[[Malignant|Malignancy]] potential'''
| style="background:#DCDCDC;" align="center" + |[[Benign|'''Benign''']]
| style="background:#F5F5F5;" + |
*90% of insulinomas are benign in nature.
|-
| style="background:#DCDCDC;" align="center" + |[[Malignant|'''Malignant''']]
| style="background:#F5F5F5;" + |
* 10% of Insulinomas have a [[malignant]] potential to invade adjacent [[Soft tissue|soft tissues]] or structures.
*The [[malignant]] type is mostly associated with [[Multiple endocrine neoplasia type 1|MEN 1 syndrome]].
*They also have a recurrence rate which is higher in those with [[MEN1]] (21% at 10 and 20 years) than without it (5% at 10 and 7% at 20 years).<ref>{{Cite journal
  | author = [[F. J. Service]], [[M. M. McMahon]], [[P. C. O'Brien]] & [[D. J. Ballard]]
  | author = [[F. J. Service]], [[M. M. McMahon]], [[P. C. O'Brien]] & [[D. J. Ballard]]
  | title = Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study
  | title = Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study
Line 33: Line 31:
  | pages = 711–719
  | pages = 711–719
  | year = 1991
  | year = 1991
| month = July
  | pmid = 01677058
  | pmid = 01677058
}}</ref>
}}</ref> In one of the recent research papers, the recurrence was described as 4 times more common in individuals with [[MEN 1 syndrome|MEN 1]].<ref name="pmid28567298">{{cite journal| author=Ahmad N, Almutawa AM, Abubacker MZ, Elzeftawy HA, Bawazir OA| title=Recurrent insulinoma in a 10-year-old boy with Down's syndrome. | journal=Endocrinol Diabetes Metab Case Rep | year= 2017 | volume= 2017 | issue= | pages= | pmid=28567298 | doi=10.1530/EDM-16-0155 | pmc=5445445 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28567298 }} </ref>
 
|-
* Insulinoma is also classified into 2 subtypes based on the number of tumor(s):
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''Based on number'''
**Solitary
| style="background:#DCDCDC;" align="center" + |[[Solitary|'''Solitary''']]
**Multiple
| style="background:#F5F5F5;" + |
***90% of insulinoma are solitary while 10% can be multiple in number
*90% of insulinomas are [[solitary]].
 
|-
* Previously insulinoma was classified into 2 subtypes based on hormonal level as determined by radioimmunoassay<ref name="pmid6311653">{{cite journal| author=Berger M, Bordi C, Cüppers HJ, Berchtold P, Gries FA, Münterfering H et al.| title=Functional and morphologic characterization of human insulinomas. | journal=Diabetes | year= 1983 | volume= 32 | issue= 10 | pages= 921-31 | pmid=6311653 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6311653 }} </ref>:  
| style="background:#DCDCDC;" align="center" + |'''Multiple'''
**Group A of abundant B cells with trabecular arrangement and uniform insulin immunofluorescence
| style="background:#F5F5F5;" + |
**Group B of scarce B cells with medullary arrangement and irregular immunofluorescence
*10% of insulinomas can be multiple in number.
* Insulinoma being a pancreatic neuroendocrine tumor may be classified/staged into several subtypes based on American Joint Cancer Committee(AJCC) 7th edition 2010 <ref name="pmid27646952">{{cite journal| author=Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C et al.| title=Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. | journal=J Clin Oncol | year= 2017 | volume= 35 | issue= 3 | pages= 274-280 | pmid=27646952 | doi=10.1200/JCO.2016.67.8193 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27646952 }} </ref><ref name="pmid25816036">{{cite journal| author=Yang M, Zeng L, Zhang Y, Wang WG, Wang L, Ke NW et al.| title=TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution. | journal=Medicine (Baltimore) | year= 2015 | volume= 94 | issue= 12 | pages= e660 | pmid=25816036 | doi=10.1097/MD.0000000000000660 | pmc=4554009 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25816036 }} </ref> :
|-
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''Based on the functionality'''
'''(clinical manifestations)'''
| style="background:#DCDCDC;" align="center" + |'''Functional'''
| rowspan="2" style="background:#F5F5F5;" + |
* According to [[WHO]], functioning [[Pancreatic endocrine tumor|pancreatic endocrine tumors]] are classified as:
#Well-differentiated [[endocrine tumors]], with [[benign]] or uncertain behavior.
#Well-differentiated [[endocrine]] [[carcinomas]] with low-grade [[malignant]] behavior.
#Poorly differentiated [[endocrine]] [[Carcinoma|carcinomas]] with high-grade [[malignant]] behavior.
:'''Note:''' Most insulinomas are classified as well-differentiated [[endocrine tumors]] ([[WHO]] 1) but occasionally they belong to [[WHO]] 2 or 3. <ref name="de HerderNiederle2007">{{cite journal|last1=de Herder|first1=Wouter W.|last2=Niederle|first2=Bruno|last3=Scoazec|first3=Jean-Yves|last4=Pauwels|first4=Stanislas|last5=Klöppel|first5=Günter|last6=Falconi|first6=Massimo|last7=Kwekkeboom|first7=Dik J.|last8=Öberg|first8=Kjel|last9=Eriksson|first9=Barbro|last10=Wiedenmann|first10=Bertram|last11=Rindi|first11=Guido|last12=O’Toole|first12=Dermot|last13=Ferone|first13=Diego|title=Well-Differentiated Pancreatic Tumor/Carcinoma: Insulinoma|journal=Neuroendocrinology|volume=84|issue=3|year=2007|pages=183–188|issn=0028-3835|doi=10.1159/000098010}}</ref><ref name="pmid21629514">{{cite journal |vauthors=Schott M, Klöppel G, Raffel A, Saleh A, Knoefel WT, Scherbaum WA |title=Neuroendocrine neoplasms of the gastrointestinal tract |journal=Dtsch Arztebl Int |volume=108 |issue=18 |pages=305–12 |year=2011 |pmid=21629514 |pmc=3103981 |doi=10.3238/arztebl.2011.0305 |url=}}</ref><ref>{{cite book | last = Bosman | first = F. T. | title = WHO classification of tumours of the digestive system | publisher = International Agency for Research on Cancer | location = Lyon | year = 2010 | isbn = 978-9283224327 }}</ref><ref name="pmid28357177">{{cite journal |vauthors=Sun J |title=Pancreatic neuroendocrine tumors |journal=Intractable Rare Dis Res |volume=6 |issue=1 |pages=21–28 |year=2017 |pmid=28357177 |pmc=5359348 |doi=10.5582/irdr.2017.01007 |url=}}</ref>
|-
| style="background:#DCDCDC;" align="center" + |'''Non-functional<ref name="pmid15522939">{{cite journal| author=Mittendorf EA, Liu YC, McHenry CR| title=Giant insulinoma: case report and review of the literature. | journal=J Clin Endocrinol Metab | year= 2005 | volume= 90 | issue= 1 | pages= 575-80 | pmid=15522939 | doi=10.1210/jc.2004-0825 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15522939 }} </ref>'''
|-
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''Based on [[hormonal]] level determined by [[radioimmunoassay]]<ref name="pmid6311653">{{cite journal| author=Berger M, Bordi C, Cüppers HJ, Berchtold P, Gries FA, Münterfering H et al.| title=Functional and morphologic characterization of human insulinomas. | journal=Diabetes | year= 1983 | volume= 32 | issue= 10 | pages= 921-31 | pmid=6311653 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6311653 }} </ref>'''
'''(previously used)'''
| style="background:#DCDCDC;" align="center" + |'''Group A'''
| style="background:#F5F5F5;" + |
*Abundant [[B cells]] with a [[Trabecula|trabecular]] arrangement and uniform [[insulin]] [[immunofluorescence]].
|-
| style="background:#DCDCDC;" align="center" + |'''Group B'''
| style="background:#F5F5F5;" + |
*Scarce [[B cells]] with a [[medullary]] arrangement and irregular [[immunofluorescence]].
|}


=== [[American Joint Committee on Cancer|American Joint Cancer Committee]] ([[AJCC]]) 7th edition 2010 calssification ===
The staging of [[malignant]] insulinoma being a [[pancreatic neuroendocrine tumor]] may be classified into several subtypes based on [[American Joint Committee on Cancer|American Joint Cancer Committee]] ([[AJCC]]) 7th edition 2010: <ref name="pmid27646952">{{cite journal| author=Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C et al.| title=Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. | journal=J Clin Oncol | year= 2017 | volume= 35 | issue= 3 | pages= 274-280 | pmid=27646952 | doi=10.1200/JCO.2016.67.8193 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27646952  }} </ref><ref name="pmid25816036">{{cite journal| author=Yang M, Zeng L, Zhang Y, Wang WG, Wang L, Ke NW et al.| title=TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution. | journal=Medicine (Baltimore) | year= 2015 | volume= 94 | issue= 12 | pages= e660 | pmid=25816036 | doi=10.1097/MD.0000000000000660 | pmc=4554009 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25816036  }} </ref>
{| class="wikitable" align="right"
{| class="wikitable" align="right"
| '''Stage'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Stage'''
|'''T'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''T'''
|'''N'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''N'''
|'''M'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''M'''
|-
|-
|IA
| style="background:#DCDCDC;" align="center" + |IA
|T1
| style="background:#F5F5F5;" + |T1
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IB
| style="background:#DCDCDC;" align="center" + |IB
|T2
| style="background:#F5F5F5;" + |T2
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIA
| style="background:#DCDCDC;" align="center" + |IIA
|T3
| style="background:#F5F5F5;" + |T3
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIB
| style="background:#DCDCDC;" align="center" + |IIB
|T1-3
| style="background:#F5F5F5;" + |T1-3
|N1
| style="background:#F5F5F5;" + |N1
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|III
| style="background:#DCDCDC;" align="center" + |III
|T4
| style="background:#F5F5F5;" + |T4
|Any N
| style="background:#F5F5F5;" + |Any N
| M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IV
| style="background:#DCDCDC;" align="center" + |IV
|Any T
| style="background:#F5F5F5;" + |Any T
|Any N
| style="background:#F5F5F5;" + |Any N
|M1
| style="background:#F5F5F5;" + |M1
|}
|}
{| class="wikitable" style="text-align:center"
{| class="wikitable" align="center"
|+'''AJCC 2010'''
| colspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |'''AJCC 2010'''
! rowspan="4"| T
|-
| T1
! rowspan="4" style="background:#DCDCDC;" align="center" + | T
|<2 cm in greatest dimension
| style="background:#DCDCDC;" align="center" + | T1
| style="background:#F5F5F5;" + |<2 cm in greatest dimension
|-
|-
|T2
| style="background:#DCDCDC;" align="center" + |T2
|>2 cm in greatest dimension
| style="background:#F5F5F5;" + |>2 cm in greatest dimension
|-
|-
|T3
| style="background:#DCDCDC;" align="center" + |T3
|Beyond the pancreas but without involvement of the superior mesentric artery
| style="background:#F5F5F5;" + |Beyond the [[pancreas]] but without involvement of the [[superior mesenteric artery]]
|-
|-
|T4
| style="background:#DCDCDC;" align="center" + |T4
|Involvement of the celiac axis or superior mesenteric artery(unresectable tumor)
| style="background:#F5F5F5;" + |Involvement of the ''[[celiac axis]]'' or [[superior mesenteric artery]] (unresectable [[tumor]])
|-
|-
! rowspan="2"| N
! rowspan="2" style="background:#DCDCDC;" align="center" + | N
|N0
| style="background:#DCDCDC;" align="center" + |N0
|No regional lymph node metastasis
| style="background:#F5F5F5;" + |No regional [[lymph node]] [[metastasis]]
|-
|-
|N1
| style="background:#DCDCDC;" align="center" + |N1
|Regional lymph node metastasis
| style="background:#F5F5F5;" + |Regional [[lymph node]] [[metastasis]]
|-
|-
! rowspan="2"| M
! rowspan="2" style="background:#DCDCDC;" align="center" + | M
|M0
| style="background:#DCDCDC;" align="center" + |M0
|No distant metastasis
| style="background:#F5F5F5;" + |No distant [[metastasis]]
|-
|-
|M1
| style="background:#DCDCDC;" align="center" + |M1
|Distant metastasis
| style="background:#F5F5F5;" + |Distant [[metastasis]]
|-
|-
|}
|}


 
=== European Neuroendocrine Tumor Society (ENETS) classification: ===
* Being a pancreatic neuroendocrine tumor, it is also staged by European Neuroendocrine Tumor Society (ENETS)as <ref name="pmid27646952">{{cite journal| author=Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C et al.| title=Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. | journal=J Clin Oncol | year= 2017 | volume= 35 | issue= 3 | pages= 274-280 | pmid=27646952 | doi=10.1200/JCO.2016.67.8193 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27646952  }} </ref><ref name="pmid25816036">{{cite journal| author=Yang M, Zeng L, Zhang Y, Wang WG, Wang L, Ke NW et al.| title=TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution. | journal=Medicine (Baltimore) | year= 2015 | volume= 94 | issue= 12 | pages= e660 | pmid=25816036 | doi=10.1097/MD.0000000000000660 | pmc=4554009 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25816036  }} </ref>:
Being a [[pancreatic neuroendocrine tumor]], it is also staged by European Neuroendocrine Tumor Society (ENETS) as: <ref name="pmid27646952">{{cite journal| author=Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C et al.| title=Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. | journal=J Clin Oncol | year= 2017 | volume= 35 | issue= 3 | pages= 274-280 | pmid=27646952 | doi=10.1200/JCO.2016.67.8193 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27646952  }} </ref><ref name="pmid25816036">{{cite journal| author=Yang M, Zeng L, Zhang Y, Wang WG, Wang L, Ke NW et al.| title=TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution. | journal=Medicine (Baltimore) | year= 2015 | volume= 94 | issue= 12 | pages= e660 | pmid=25816036 | doi=10.1097/MD.0000000000000660 | pmc=4554009 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25816036  }} </ref>  
{| class="wikitable" align="right"
{| class="wikitable" align="right"
| '''Stage'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Stage'''
|'''T'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''T'''
|'''N'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''N'''
|'''M'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''M'''
|-
|-
|I
| style="background:#DCDCDC;" align="center" + |I
|T1
| style="background:#F5F5F5;" + |T1
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIA
| style="background:#DCDCDC;" align="center" + |IIA
|T2
| style="background:#F5F5F5;" + |T2
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIB
| style="background:#DCDCDC;" align="center" + |IIB
|T3
| style="background:#F5F5F5;" + |T3
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIIA
| style="background:#DCDCDC;" align="center" + |IIIA
|T4
| style="background:#F5F5F5;" + |T4
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|III B
| style="background:#DCDCDC;" align="center" + |III B
|Any T
| style="background:#F5F5F5;" + |Any T
|N1
| style="background:#F5F5F5;" + |N1
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IV
| style="background:#DCDCDC;" align="center" + |IV
|Any T
| style="background:#F5F5F5;" + |Any T
|Any N
| style="background:#F5F5F5;" + |Any N
|M1
| style="background:#F5F5F5;" + |M1
|}
|}
{| class="wikitable" style="text-align:center"
{| class="wikitable" style="text-align:center"
|+'''ENETS'''
| colspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |'''ENETS'''
! rowspan="4"| T
| T1
|Tumor limited to pancreas,<2 cm
|-
|-
|T2
! rowspan="4" style="background:#DCDCDC;" align="center" + | T
|Tumor limited to pancreas,2-4 cm  
| style="background:#DCDCDC;" align="center" + |T1
| style="background:#F5F5F5;" + |[[Tumor]] limited to [[pancreas]], <2 cm
|-
|-
|T3
| style="background:#DCDCDC;" align="center" + |T2
|>4cm, or invading the duodenum or common bile duct
| style="background:#F5F5F5;" + |[[Tumor]] limited to [[pancreas]], 2-4 cm
|-
|-
|T4
| style="background:#DCDCDC;" align="center" + |T3
|Tumor invades adjacent structures
| style="background:#F5F5F5;" + |>4cm, or invading the [[duodenum]] or [[common bile duct]]
|-
|-
! rowspan="2"| N
| style="background:#DCDCDC;" align="center" + |T4
|N0
| style="background:#F5F5F5;" + |[[Tumor]] invades adjacent structures
|No regional lymph node metastasis
|-
|-
|N1
! rowspan="2" style="background:#DCDCDC;" align="center" + | N
|Regional lymph node metastasis
| style="background:#DCDCDC;" align="center" + |N0
| style="background:#F5F5F5;" + |No regional [[lymph node]] [[metastasis]]
|-
|-
! rowspan="2"| M
| style="background:#DCDCDC;" align="center" + | N1
|M0
| style="background:#F5F5F5;" + |Regional [[lymph node]] [[metastasis]]
|No distant metastasis
|-
|-
|M1
! rowspan="2" style="background:#DCDCDC;" align="center" + | M
|Distant metastasis
| style="background:#DCDCDC;" align="center" + |M0
| style="background:#F5F5F5;" + |No distant [[metastasis]]
|-
| style="background:#DCDCDC;" align="center" + |M1
| style="background:#F5F5F5;" + |Distant [[metastasis]]
|-
|-
|}
|}


* In its new 8th edition of AJCC which is planned to be published on January 1, 2018; recent research<ref name="pmid27646952">{{cite journal| author=Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C et al.| title=Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. | journal=J Clin Oncol | year= 2017 | volume= 35 | issue= 3 | pages= 274-280 | pmid=27646952 | doi=10.1200/JCO.2016.67.8193 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27646952  }} </ref> had developed a modified ENETS(mENETS) staging classification:
=== [[WHO]] 2010 classification system ===
*WHO classification system combined differentiation and grading characteristics to classify the belligerence of a [[pancreatic neuroendocrine tumor]].
*The aggressiveness of tumor was expressed in form of [[mitotic]] count and staining of a nuclear antigen called [[Ki-67]]: <ref>{{cite book | last = Bosman | first = F. T. | title = WHO classification of tumours of the digestive system | publisher = International Agency for Research on Cancer | location = Lyon | year = 2010 | isbn = 978-9283224327 }}</ref><ref name="pmid28357177">{{cite journal |vauthors=Sun J |title=Pancreatic neuroendocrine tumors |journal=Intractable Rare Dis Res |volume=6 |issue=1 |pages=21–28 |year=2017 |pmid=28357177 |pmc=5359348 |doi=10.5582/irdr.2017.01007 |url=}}</ref>
{| class="wikitable" style="text-align:center"
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Grade of tumor'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Mitotic Count'''(Mitoses per 10 high powerfields)
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Expression of Ki 67'''
|-
| style="background:#DCDCDC;" align="center" + |Grade 1
| style="background:#F5F5F5;" + |<2
| style="background:#F5F5F5;" + |≤3%
|-
| style="background:#DCDCDC;" align="center" + |Grade 2
| style="background:#F5F5F5;" + |2-10
| style="background:#F5F5F5;" + |3-20%
|-
| style="background:#DCDCDC;" align="center" + |Grade 3
| style="background:#F5F5F5;" + |>20
| style="background:#F5F5F5;" + |>20%
|-
|}
*Grade 1 and 2 tumors were classified as [[Neuroendocrine|neuroendocrine neoplasm]] (NET) and grade 3 were classified as neuroendocrine carcinoma (NEC).
 
* In its new 8th edition of [[AJCC]] which is planned to be published on January 1, 2018; [[AJCC]] had developed a modified ENETS (mENETS) staging classification:<ref name="pmid27646952">{{cite journal| author=Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C et al.| title=Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. | journal=J Clin Oncol | year= 2017 | volume= 35 | issue= 3 | pages= 274-280 | pmid=27646952 | doi=10.1200/JCO.2016.67.8193 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27646952  }} </ref>


{| class="wikitable" align="right"
{| class="wikitable" align="right"
| '''Stage'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Stage'''
|'''T'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''T'''
|'''N'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''N'''
|'''M'''
| style="background:#4479BA; color: #FFFFFF;" align="center" + |'''M'''
|-
|-
|IA
| style="background:#DCDCDC;" align="center" + |IA
|T1
| style="background:#F5F5F5;" + |T1
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IB
| style="background:#DCDCDC;" align="center" + |IB
|T2
| style="background:#F5F5F5;" + |T2
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIA
| style="background:#DCDCDC;" align="center" + |IIA
|T3
| style="background:#F5F5F5;" + |T3
|N0
| style="background:#F5F5F5;" + |N0
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IIB
| style="background:#DCDCDC;" align="center" + |IIB
|T1-3
| style="background:#F5F5F5;" + |T1-3
|N1
| style="background:#F5F5F5;" + |N1
|M0
| style="background:#F5F5F5;" + |M0
|-
|-
|III
| style="background:#DCDCDC;" align="center" + |III
|T4
| style="background:#F5F5F5;" + |T4
|Any N
| style="background:#F5F5F5;" + |Any N
| M0
| style="background:#F5F5F5;" + |M0
|-
|-
|IV
| style="background:#DCDCDC;" align="center" + |IV
|Any T
| style="background:#F5F5F5;" + |Any T
|Any N
| style="background:#F5F5F5;" + |Any N
|M1
| style="background:#F5F5F5;" + |M1
|}
|}
{| class="wikitable" style="text-align:center"
{| class="wikitable" style="text-align:center"
|+'''mENETS'''
| colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" coolspan="4" + |'''mENETS'''
! rowspan="4"| T
| T1
|Tumor limited to pancreas,<2 cm
|-
|-
|T2
! rowspan="4" style="background:#DCDCDC;" align="center" + |T
|Tumor limited to pancreas,2-4 cm  
| style="background:#DCDCDC;" align="center" + |T1
| style="background:#F5F5F5;" + |[[Tumor-associated calcium signal transducer 1|Tumor]] limited to [[pancreas]], <2 cm
|-
|-
|T3
| style="background:#DCDCDC;" align="center" + |T2
|>4cm, or invading the duodenum or common bile duct
| style="background:#F5F5F5;" + |[[Tumor]] limited to [[pancreas]], 2-4 cm
|-
|-
|T4
| style="background:#DCDCDC;" align="center" + |T3
|Tumor invades adjacent structures
| style="background:#F5F5F5;" + |>4cm, or invading the [[duodenum]] or [[common bile duct]]
|-
|-
! rowspan="2"| N
| style="background:#DCDCDC;" align="center" + |T4
|N0
| style="background:#F5F5F5;" + |[[Tumor]] invades adjacent structures
|No regional lymph node metastasis
|-
|-
|N1
! rowspan="2" style="background:#DCDCDC;" align="center" + | N
|Regional lymph node metastasis
| style="background:#DCDCDC;" align="center" + |N0
| style="background:#F5F5F5;" + |No regional [[lymph node]] metastasis
|-
|-
! rowspan="2"| M
| style="background:#DCDCDC;" align="center" + |N1
|M0
| style="background:#F5F5F5;" + |Regional [[lymph node]] metastasis
|No distant metastasis
|-
|-
|M1
! rowspan="2" style="background:#DCDCDC;" align="center" + | M
|Distant metastasis
| style="background:#DCDCDC;" align="center" + |M0
| style="background:#F5F5F5;" + |No distant [[metastasis]]
|-
| style="background:#DCDCDC;" align="center" + |M1
| style="background:#F5F5F5;" + |Distant [[metastasis]]
|-
|-
|}
|}
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[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
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Latest revision as of 14:39, 5 December 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]

Overview

Insulinoma may be classified according to their malignant potential into 2 sub-types: Benign (90%) and malignant (10%). It is also classified into 2 subtypes based on the number: solitary (90%) and multiple (10%). Previously insulinoma was classified into 2 subtypes based on hormonal level as determined by radioimmunoassay into group A and group B. The staging of malignant insulinoma is based on the AJCC 2010, ENETS and modified ENETS staging classification.

Classification

Classification of insulinoma
Criteria Classification Features
Malignancy potential Benign
  • 90% of insulinomas are benign in nature.
Malignant
  • 10% of Insulinomas have a malignant potential to invade adjacent soft tissues or structures.
  • The malignant type is mostly associated with MEN 1 syndrome.
  • They also have a recurrence rate which is higher in those with MEN1 (21% at 10 and 20 years) than without it (5% at 10 and 7% at 20 years).[1] In one of the recent research papers, the recurrence was described as 4 times more common in individuals with MEN 1.[2]
Based on number Solitary
Multiple
  • 10% of insulinomas can be multiple in number.
Based on the functionality

(clinical manifestations)

Functional
  1. Well-differentiated endocrine tumors, with benign or uncertain behavior.
  2. Well-differentiated endocrine carcinomas with low-grade malignant behavior.
  3. Poorly differentiated endocrine carcinomas with high-grade malignant behavior.
Note: Most insulinomas are classified as well-differentiated endocrine tumors (WHO 1) but occasionally they belong to WHO 2 or 3. [3][4][5][6]
Non-functional[7]
Based on hormonal level determined by radioimmunoassay[8]

(previously used)

Group A
Group B

American Joint Cancer Committee (AJCC) 7th edition 2010 calssification

The staging of malignant insulinoma being a pancreatic neuroendocrine tumor may be classified into several subtypes based on American Joint Cancer Committee (AJCC) 7th edition 2010: [9][10]

Stage T N M
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1-3 N1 M0
III T4 Any N M0
IV Any T Any N M1
AJCC 2010
T T1 <2 cm in greatest dimension
T2 >2 cm in greatest dimension
T3 Beyond the pancreas but without involvement of the superior mesenteric artery
T4 Involvement of the celiac axis or superior mesenteric artery (unresectable tumor)
N N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M M0 No distant metastasis
M1 Distant metastasis

European Neuroendocrine Tumor Society (ENETS) classification:

Being a pancreatic neuroendocrine tumor, it is also staged by European Neuroendocrine Tumor Society (ENETS) as: [9][10]

Stage T N M
I T1 N0 M0
IIA T2 N0 M0
IIB T3 N0 M0
IIIA T4 N0 M0
III B Any T N1 M0
IV Any T Any N M1
ENETS
T T1 Tumor limited to pancreas, <2 cm
T2 Tumor limited to pancreas, 2-4 cm
T3 >4cm, or invading the duodenum or common bile duct
T4 Tumor invades adjacent structures
N N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M M0 No distant metastasis
M1 Distant metastasis

WHO 2010 classification system

  • WHO classification system combined differentiation and grading characteristics to classify the belligerence of a pancreatic neuroendocrine tumor.
  • The aggressiveness of tumor was expressed in form of mitotic count and staining of a nuclear antigen called Ki-67: [11][6]
Grade of tumor Mitotic Count(Mitoses per 10 high powerfields) Expression of Ki 67
Grade 1 <2 ≤3%
Grade 2 2-10 3-20%
Grade 3 >20 >20%
  • Grade 1 and 2 tumors were classified as neuroendocrine neoplasm (NET) and grade 3 were classified as neuroendocrine carcinoma (NEC).
  • In its new 8th edition of AJCC which is planned to be published on January 1, 2018; AJCC had developed a modified ENETS (mENETS) staging classification:[9]
Stage T N M
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1-3 N1 M0
III T4 Any N M0
IV Any T Any N M1
mENETS
T T1 Tumor limited to pancreas, <2 cm
T2 Tumor limited to pancreas, 2-4 cm
T3 >4cm, or invading the duodenum or common bile duct
T4 Tumor invades adjacent structures
N N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M M0 No distant metastasis
M1 Distant metastasis

References

  1. ↑ F. J. Service, M. M. McMahon, P. C. O'Brien & D. J. Ballard (1991). "Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study". Mayo Clinic proceedings. 66 (7): 711–719. PMID 01677058.
  2. ↑ Ahmad N, Almutawa AM, Abubacker MZ, Elzeftawy HA, Bawazir OA (2017). "Recurrent insulinoma in a 10-year-old boy with Down's syndrome". Endocrinol Diabetes Metab Case Rep. 2017. doi:10.1530/EDM-16-0155. PMC 5445445. PMID 28567298.
  3. ↑ de Herder, Wouter W.; Niederle, Bruno; Scoazec, Jean-Yves; Pauwels, Stanislas; Klöppel, Günter; Falconi, Massimo; Kwekkeboom, Dik J.; Öberg, Kjel; Eriksson, Barbro; Wiedenmann, Bertram; Rindi, Guido; O’Toole, Dermot; Ferone, Diego (2007). "Well-Differentiated Pancreatic Tumor/Carcinoma: Insulinoma". Neuroendocrinology. 84 (3): 183–188. doi:10.1159/000098010. ISSN 0028-3835.
  4. ↑ Schott M, Klöppel G, Raffel A, Saleh A, Knoefel WT, Scherbaum WA (2011). "Neuroendocrine neoplasms of the gastrointestinal tract". Dtsch Arztebl Int. 108 (18): 305–12. doi:10.3238/arztebl.2011.0305. PMC 3103981. PMID 21629514.
  5. ↑ Bosman, F. T. (2010). WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer. ISBN 978-9283224327.
  6. ↑ 6.0 6.1 Sun J (2017). "Pancreatic neuroendocrine tumors". Intractable Rare Dis Res. 6 (1): 21–28. doi:10.5582/irdr.2017.01007. PMC 5359348. PMID 28357177.
  7. ↑ Mittendorf EA, Liu YC, McHenry CR (2005). "Giant insulinoma: case report and review of the literature". J Clin Endocrinol Metab. 90 (1): 575–80. doi:10.1210/jc.2004-0825. PMID 15522939.
  8. ↑ Berger M, Bordi C, Cüppers HJ, Berchtold P, Gries FA, Münterfering H; et al. (1983). "Functional and morphologic characterization of human insulinomas". Diabetes. 32 (10): 921–31. PMID 6311653.
  9. ↑ 9.0 9.1 9.2 Luo G, Javed A, Strosberg JR, Jin K, Zhang Y, Liu C; et al. (2017). "Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems". J Clin Oncol. 35 (3): 274–280. doi:10.1200/JCO.2016.67.8193. PMID 27646952.
  10. ↑ 10.0 10.1 Yang M, Zeng L, Zhang Y, Wang WG, Wang L, Ke NW; et al. (2015). "TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution". Medicine (Baltimore). 94 (12): e660. doi:10.1097/MD.0000000000000660. PMC 4554009. PMID 25816036.
  11. ↑ Bosman, F. T. (2010). WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer. ISBN 978-9283224327.

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