Neuroendocrine tumors of the midgut
The processing of neuroendocrine tumors (NET) of the midgut includes:
- Gross processing
- Microscopic evaluation
- For diagnosis if not clear from initial microscopy
- Round regular nuclei
- Stippled (salt and pepper) chromatin
- Moderate to abundant cytoplasm
If the diagnosis is not clear from light microscopy:
- Synaptophysin: positive in almost all cases, and is generally enough for confirmation.
- Chromogranin: mostly positive
- Argyrophil: positive in almost all cases
- Argentaffin mostly positive
- Neuron specific enolase, PGP9.5 and CD56 are sensitive but unspecific.
Neuroendocrine lesions are graded histologically according to markers of cellular proliferation, rather than cellular polymorphism. For this purpose, it is recommended that mitotic count and Ki-67 index is determined for all gastroenteropancreatic neuroendocrine neoplasms:
|G||Mitotic count (per 10 HPF)||Ki-67 index (%)|
|GX||Grade cannot be assessed|
|G1||< 2||< 3%|
|G2||2 to 20||3% - 20%|
|G3||> 20||> 20%|
At least 40 HPFs should be counted.
The mitotic count applies to a HPF area 0.2 mm2. Thus, calculation of the mitotic count varies for different microscope types:
|Microscope type||Area per HPF||Mitotic count calculation|
|Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece||0.096 mm2||Mitoses in 40 HPFs x 0.52|
|AO with 10x eyepiece||0.12 mm2||Mitoses in 40 HPFs x 0.41|
|Olympus with 10x eyepiece||0.16 mm2||Mitoses in 40 HPFs x 0.31|
|Nikon Eclipse E400 with 10x eyepiece and 40x objective||0.25 mm2||Mitoses in 40 HPFs x 0.20|
|Leitz Ortholux||0.27 mm2||Mitoses in 40 HPFs x 0.19|
|Leitz Diaplan||0.31 mm2||Mitoses in 40 HPFs x 0.16|
The counting is made in areas with the highest concentration of Ki-67 positive cells, called "hot spots".
The main methods are:
- 'Eye-balling' , which is apparently the most common method for determining the Ki-67 index. In 'eye-balling', an impression is made without actually counting individual cells. It can be done on one single view intermediate power (× 10 objective), or by scrolling at higher magnification.
- Manual counting, which is indicated if eye-balling is within a factor of 2 from any grading limit (such as between 1.5% and 6%). It should be done by photographing (and perhaps printing) the slide so that cells can be marked as they are counted. Officially, at least 500 cells should be counted.
If the mitotic count and Ki-67 index are discordant, the figure which gives the highest grade is used.
G1 and G2 neuroendocrine neoplasms are called neuroendocrine tumors (NETs).[notes 2] G3 neoplasms are called neuroendocrine carcinomas (NECs).
Use the AJCC standard, and take both gross and microscopic evaluation into account:
|Primary Tumor (T)|
|T Category||Tumor Criteria|
|TX||Primary tumour cannot be assessed|
|T0||No evidence of primary tumour|
|T1||Invades the lamina propria or submucosa, and less than or equal to 1 cm in size|
|T2||Invades the muscularis propria, or greater than 1 cm in size|
|T3||Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa|
|T4||Invades visceral peritoneum (serosal) or other organs or adjacent structures|
|Regional Lymph Node (N)|
|N Category||N Criteria|
|NX||Regional lymph nodes cannot be assessed|
|N0||No regional lymph node metastasis|
|N1||Regional lymph node metastasis less than 12 nodes|
|N2||Large mesenteric masses (> 2 cm) and / or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels|
It should include:
- Diagnosis of neuroendocrine tumor
- T and N stage by AJCC standard
- Whether the resection is radical
- Unless otherwise specified in boxes, reference is: . Infiltrating Ductal Carcinoma of the Breast (Carcinoma of No Special Type). Stanford University School of Medicine. Retrieved on 2019-10-02.
- >WHO Classification of Tumours of the Digestive System (4 ed.). Lyon: International Agency for Research on Cancer. 2010. pp. 13–14. ISBN 978-92-832-2432-7.
- Rindi, G.; Klöppel, G.; Alhman, H.; Caplin, M.; Couvelard, A.; de Herder, W. W.; Erikssson, B.; Falchetti, A.; et al. (2006). "TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system ". Virchows Archiv 449 (4): 395–401. doi:10.1007/s00428-006-0250-1. ISSN 0945-6317.
- Klimstra, David S.; Modlin, Irvin R.; Coppola, Domenico; Lloyd, Ricardo V.; Suster, Saul (2010). "The Pathologic Classification of Neuroendocrine Tumors ". Pancreas 39 (6): 707–712. doi:10.1097/MPA.0b013e3181ec124e. ISSN 0885-3177.
- Reid, Michelle D; Bagci, Pelin; Ohike, Nobuyuki; Saka, Burcu; Erbarut Seven, Ipek; Dursun, Nevra; Balci, Serdar; Gucer, Hasan; et al. (2014). "Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies ". Modern Pathology 28 (5): 686–694. doi:10.1038/modpathol.2014.156. ISSN 0893-3952.
- Basile, Maíra Leite; Kuga, Fábio Seiji; Del Carlo Bernardi, Fabíola (2019). "Comparation of the quantification of the proliferative index KI67 between eyeball and semi-automated digital analysis in gastro-intestinal neuroendrocrine tumors ". Surgical and Experimental Pathology 2 (1). doi:10.1186/s42047-019-0045-8. ISSN 2520-8454.
- AJCC, 8th edition: "29 - Neuroendocrine Tumors of the Stomach". AJCC Cancer Staging Manual (8 ed.). Springer. 2017. pp. 355. ISBN 978-3-319-40617-6.