Insulinoma classification: Difference between revisions

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! style="background:#4479BA; color: #FFFFFF;" align="center" + |Features
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Features
|-
|-
| rowspan="2" style="background:#DCDCDC;" align="center" + |[[Malignant]] potential
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''[[Malignant]] potential'''
| style="background:#DCDCDC;" align="center" + |[[Benign]]
| style="background:#DCDCDC;" align="center" + |[[Benign|'''Benign''']]
|style="background:#F5F5F5;" + |
| style="background:#F5F5F5;" + |
*90% Insulinoma are benign in nature
*90% Insulinoma are benign in nature.
|-
|-
| style="background:#DCDCDC;" align="center" + |[[Malignant]]
| style="background:#DCDCDC;" align="center" + |[[Malignant|'''Malignant''']]
| style="background:#F5F5F5;" + |
| style="background:#F5F5F5;" + |
* 10% Insulinona has a [[malignant]] potential to invade adjacent soft tissues or structures.
* 10% Insulinona has a [[malignant]] potential to invade adjacent soft tissues or structures.
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}}</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>
}}</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>
|-
|-
|rowspan="2" style="background:#DCDCDC;" align="center" + |Based on number
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''Based on number'''
| style="background:#DCDCDC;" align="center" + |[[Solitary]]
| style="background:#DCDCDC;" align="center" + |[[Solitary|'''Solitary''']]
| style="background:#F5F5F5;" + |
| style="background:#F5F5F5;" + |
*90% of insulinoma are [[solitary]].
*90% of insulinoma are [[solitary]].
|-
|-
| style="background:#DCDCDC;" align="center" + |Multiple
| style="background:#DCDCDC;" align="center" + |'''Multiple'''
| style="background:#F5F5F5;" + |
| style="background:#F5F5F5;" + |
*10% of insulinoma can be multiple in number.
*10% of insulinoma can be multiple in number.
|-
|-
|rowspan="2" style="background:#DCDCDC;" align="center" + |Based on the functionality
| rowspan="2" style="background:#DCDCDC;" align="center" + |'''Based on the functionality'''
(clinical manifestations)
'''(clinical manifestations)'''
| style="background:#DCDCDC;" align="center" + |Functional
| style="background:#DCDCDC;" align="center" + |'''Functional'''
|rowspan="2" style="background:#F5F5F5;" + |
| rowspan="2" style="background:#F5F5F5;" + |
* According to [[WHO]], functioning [[Pancreatic endocrine tumor|pancreatic endocrine tumors]] are classified as:
* 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 tumors]], with [[benign]] or uncertain behavior.  
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:'''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>
:'''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>
| 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>
| 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)
'''(previously used)'''
| style="background:#DCDCDC;" align="center" + |Group A
| style="background:#DCDCDC;" align="center" + |'''Group A'''
| style="background:#F5F5F5;" + |
| style="background:#F5F5F5;" + |
*Abundant [[B cells]] with a [[Trabecula|trabecular]] arrangement and uniform [[insulin]] [[immunofluorescence]].
*Abundant [[B cells]] with a [[Trabecula|trabecular]] arrangement and uniform [[insulin]] [[immunofluorescence]].
|-
|-
| style="background:#DCDCDC;" align="center" + |Group B
| style="background:#DCDCDC;" align="center" + |'''Group B'''
| style="background:#F5F5F5;" + |
| style="background:#F5F5F5;" + |
*Scarce [[B cells]] with a [[medullary]] arrangement and irregular [[immunofluorescence]].
*Scarce [[B cells]] with a [[medullary]] arrangement and irregular [[immunofluorescence]].
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|}
|}
{| class="wikitable" style="text-align:center"
{| class="wikitable" style="text-align:center"
| colspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |'''ENETS'''
| colspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |'''ENETS'''
|-
|-
! rowspan="4" style="background:#DCDCDC;" align="center" + | T
! rowspan="4" style="background:#DCDCDC;" align="center" + | T
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|}
|}
{| class="wikitable" style="text-align:center"
{| class="wikitable" style="text-align:center"
| coolspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |'''mENETS'''
| style="background:#4479BA; color: #FFFFFF;" align="center" coolspan="4" + |'''mENETS'''
|-
|-
! rowspan="4" style="background:#DCDCDC;" align="center" + |T
! rowspan="4" style="background:#DCDCDC;" align="center" + |T

Revision as of 14:29, 16 October 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
Malignant potential Benign
  • 90% Insulinoma are benign in nature.
Malignant
  • 10% Insulinona 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).[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 insulinoma 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 [9] had developed a modified ENETS (mENETS) staging classification:
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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