Insulinoma classification
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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 into malignant potential into 2 sub-types: Benign(90%)and Malignant(10%) Insulinoma 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:
- Solitary
- Multiple
- 90% of insulinoma are solitary while 10% can be multiple in 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
- 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 |
- 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 combined differentiation and grading characteristics to classify the belligerence of pancraetic 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 classifed as neuroendocrine neoplasma(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.