Insulinoma classification: Difference between revisions
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#Poorly differentiated endocrine carcinomas with high-grade [[malignant]] behavior. | #Poorly differentiated endocrine carcinomas with high-grade [[malignant]] behavior. | ||
#*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> | #*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> | ||
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> | 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> | ||
*Group A of abundant [[B cells]] with trabecular arrangement and uniform [[insulin]] [[immunofluorescence]]. | *Group A of abundant [[B cells]] with trabecular arrangement and uniform [[insulin]] [[immunofluorescence]]. | ||
*Group B of scarce B cells with [[medullary]] arrangement and irregular [[immunofluorescence]]. | *Group B of scarce B cells with [[medullary]] arrangement and irregular [[immunofluorescence]]. | ||
=== [[American Joint Committee on Cancer|American Joint Cancer Committee]] ([[AJCC]]) 7th edition 2010 calssification === | === [[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> | 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''' | | '''Stage''' | ||
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=== European Neuroendocrine Tumor Society (ENETS) classification: === | === 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''' | | '''Stage''' | ||
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=== [[WHO]] 2010 classification system === | === [[WHO]] 2010 classification system === | ||
*WHO classification system combined differentiation and grading characteristics to classify the belligerence of a [[pancreatic neuroendocrine tumor]]. | *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> | *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" | {| class="wikitable" style="text-align:center" | ||
|'''Grade of tumor''' | |'''Grade of tumor''' | ||
Revision as of 14:35, 22 September 2017
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Insulinoma Microchapters |
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Insulinoma classification On the Web |
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American Roentgen Ray Society Images of Insulinoma classification |
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Risk calculators and risk factors for Insulinoma classification |
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
Insulinoma may be classified according to malignant potential into 2 sub-types:
- Benign
- Malignant
- 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).[1] In one of the recent research papers, the recurrence was described as 4 times more common in individuals with MEN 1.[2]
Insulinoma is also classified into 2 subtypes based on the number:
It may be classified into 2 subtypes based on the functionality (clinical manifestations):
- Functional
- Non-functional[3]
- According to WHO, functioning 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 carcinomas with high-grade malignant behavior.
Previously insulinoma was classified into 2 subtypes based on hormonal level as determined by radioimmunoassay: [8]
- Group A of abundant B cells with trabecular arrangement and uniform insulin immunofluorescence.
- Group B of scarce B cells with medullary arrangement and irregular immunofluorescence.
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 |
| 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 |
| 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][7]
| 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 |
| 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
- ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Bosman, F. T. (2010). WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer. ISBN 978-9283224327.
- ↑ 7.0 7.1 Sun J (2017). "Pancreatic neuroendocrine tumors". Intractable Rare Dis Res. 6 (1): 21–28. doi:10.5582/irdr.2017.01007. PMC 5359348. PMID 28357177.
- ↑ 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.
- ↑ 9.0 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.
- ↑ 10.0 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.
- ↑ Bosman, F. T. (2010). WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer. ISBN 978-9283224327.