Neuroendocrine tumors of the midgut
Author:
Mikael Häggström [note 1]
The processing of neuroendocrine tumors (NET) of the midgut includes:
- Gross processing
- Microscopic evaluation
- Immunohistochemistry
- For diagnosis if not clear from initial microscopy
- Grading
Gross processing
Microscopic evaluation
Characteristics:[1]
- Round regular nuclei
- Stippled (salt and pepper) chromatin
- Moderate to abundant cytoplasm
Diagnostic immunohistochemistry
If the diagnosis is not clear from light microscopy:
-
![Synaptophysin: positive in almost all cases,[1] and is generally enough for confirmation.](https://upload.wikimedia.org/wikipedia/commons/thumb/7/7e/Synaptophysin_immunohistochemistry_of_neuroendocrine_tumor.jpg/330px-Synaptophysin_immunohistochemistry_of_neuroendocrine_tumor.jpg?utm_source=commons.wikimedia.org&utm_campaign=imageinfo&utm_content=thumbnail)
Synaptophysin: positive in almost all cases,[1] and is generally enough for confirmation. -
![Chromogranin: mostly positive[1]](https://upload.wikimedia.org/wikipedia/commons/thumb/4/44/Immunohistochemistry_of_positive_chromogranin_in_a_grade_2_neuroendocrine_tumor_of_the_terminal_ileum.jpg/500px-Immunohistochemistry_of_positive_chromogranin_in_a_grade_2_neuroendocrine_tumor_of_the_terminal_ileum.jpg?utm_source=commons.wikimedia.org&utm_campaign=imageinfo&utm_content=thumbnail)
Chromogranin: mostly positive[1]
![Synaptophysin: positive in almost all cases,[1] and is generally enough for confirmation.](/File:Synaptophysin_immunohistochemistry_of_neuroendocrine_tumor.jpg)
![Chromogranin: mostly positive[1]](/File:Immunohistochemistry_of_positive_chromogranin_in_a_grade_2_neuroendocrine_tumor_of_the_terminal_ileum.jpg)
- Argyrophil: positive in almost all cases[1]
- Argentaffin mostly positive[1]
- Neuron specific enolase, PGP9.5 and CD56 are sensitive but unspecific.[1]
Grading
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:[2]
| G | Mitotic count (per 2.0mm2) | Ki-67 index (%) |
|---|---|---|
| GX | Grade cannot be assessed | |
| G1 | < 2 | < 3% |
| G2 | 2 to 20 | 3% - 20% |
| G3 | > 20 | > 20% |
Mitotic count
The mitotic count should be estimated by counting mitoses over 8 mm2 (or more), and then dividing that count by 4 (or proportionally more for a larger area).[3] Further information: Evaluation#Counts per mm2
Ki-67 index
- Homogenously darkly stained (not just stippled).
- Not be located in stroma.
- Be at least half within the field of view.
- Be large enough.
The counting is made in areas with the highest concentration of Ki-67 positive cells, called "hot spots".[4]
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.[4]
- 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.[4] Officially, at least 500 cells should be counted.[5]
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 1] G3 neoplasms are called neuroendocrine carcinomas (NECs).
Stage
Use the AJCC standard, and take both gross and microscopic evaluation into account:[6]
| 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 (including no lymph nodes submitted or found) |
| 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 |
Mesenteric lymph node metastasis from neuroendocrine tumors of the midgut:
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Report
It should include:
- Diagnosis of neuroendocrine tumor
- Grade
- T and N stage by AJCC standard
- Whether the resection is radical
Notes
- ↑ Neuroendocrine tumors of the intestines were formerly called carcinoid tumours
- ↑ For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
Main page
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Cite error: Invalid
<ref>tag; no text was provided for refs namedstanford - ↑ >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.
- ↑ First reference states 40 high power fields (HPFs) and second reference states that one HPF can be assumed to be 0.2 mm2:
-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:. 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:. ISSN 0885-3177. - ↑ 4.0 4.1 4.2 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:. 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:. 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.
Image sources