Neuroendocrine tumors of the midgut: Difference between revisions

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==Microscopic evaluation==
==Microscopic evaluation==
Characteristics:<ref name=stanford/>
[[File:Well-differentiated neuroendocrine tumor with salt-and-pepper chromatin.png|thumb|Salt-and-pepper chromatin, seen on H&E, Pap stain and comparison to actual salt and pepper.]]
Characteristics:<ref name=stanford-carcinoids>{{cite web|url=https://surgpathcriteria.stanford.edu/gitumors/ileum-carcinoid-well-differentiated-neuroendocrine-neoplasm-tumor/printable.html|title=Carcinoid / Well Differentiated Neuroendocrine Neoplasm / Tumor of the Ileum, Distal Jejunum and Cecum|website=Stanford University School of Medicine|accessdate=2022-06-18}}</ref>
*Round regular nuclei
*Round regular nuclei
*Stippled (salt and pepper) chromatin
*Stippled to granular (salt and pepper) chromatin
*Moderate to abundant cytoplasm
*Moderate to abundant cytoplasm


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If the diagnosis is not clear from light microscopy:
If the diagnosis is not clear from light microscopy:
<gallery mode=packed heights=180>
<gallery mode=packed heights=180>
File:Synaptophysin immunohistochemistry of neuroendocrine tumor.jpg|'''Synaptophysin''': positive in almost all cases,<ref name=stanford/> and is generally enough for confirmation.
File:Synaptophysin immunohistochemistry of neuroendocrine tumor.jpg|'''Synaptophysin''': positive in almost all cases,<ref name=stanford-carcinoids/> and is generally enough for confirmation.
File:Immunohistochemistry of positive chromogranin in a grade 2 neuroendocrine tumor of the terminal ileum.jpg|'''Chromogranin''': mostly positive<ref name=stanford/>
File:Immunohistochemistry of positive chromogranin in a grade 2 neuroendocrine tumor of the terminal ileum.jpg|'''Chromogranin''': mostly positive<ref name=stanford-carcinoids/>
</gallery>
</gallery>
*'''Argyrophil''': positive in almost all cases<ref name=stanford/>
*'''Argentaffin''' mostly positive<ref name=stanford/>
*'''Neuron specific enolase''', '''PGP9.5''' and '''CD56''' are sensitive but unspecific.<ref name=stanford/>


==Grading==
==Grading==
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{| class="wikitable"
{| class="wikitable"
|-
|-
! G !! Mitotic count (per 2.0mm<sup>2</sup>) !! Ki-67 index (%)
! G !! Mitotic count (per mm<sup>2</sup>) !! Ki-67 index (%)
|-
|-
| GX || colspan=2 | Grade cannot be assessed
| GX || colspan=2 | Grade cannot be assessed
|-
|-
| G1 || < 2 || < 3%
| G1 || < 1 || < 3%
|-
|-
| G2 || 2 to 20 || 3% - 20%
| G2 || 1 to 10 || 3% - 20%
|-
|-
| G3 || > 20 || > 20%
| G3 || > 10 || > 20%
|}
|}


===Mitotic count===
===Mitotic count===
[[File:Mitoses in neuroendocrine tumor.jpg|thumb|Mitoses in a neuroendocrine tumor.]]
[[File:Mitoses in neuroendocrine tumor.jpg|thumb|Mitoses in a neuroendocrine tumor.]]
The mitotic count should be estimated by counting mitoses over 8 mm<sup>2</sup> (or more), and then dividing that count by 4 (or proportionally more for a larger area).<ref name="mitotic">'''First reference states 40 high power fields (HPFs) and second reference states that one HPF can be assumed to be 0.2 mm<sup>2</sup>''':<br>-{{cite journal|last1=Rindi|first1=G.|last2=Klöppel|first2=G.|last3=Alhman|first3=H.|last4=Caplin|first4=M.|last5=Couvelard|first5=A.|last6=de Herder|first6=W. W.|last7=Erikssson|first7=B.|last8=Falchetti|first8=A.|last9=Falconi|first9=M.|last10=Komminoth|first10=P.|last11=Körner|first11=M.|last12=Lopes|first12=J. M.|last13=McNicol|first13=A-M.|last14=Nilsson|first14=O.|last15=Perren|first15=A.|last16=Scarpa|first16=A.|last17=Scoazec|first17=J-Y.|last18=Wiedenmann|first18=B.|title=TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system|journal=Virchows Archiv|volume=449|issue=4|year=2006|pages=395–401|issn=0945-6317|doi=10.1007/s00428-006-0250-1}}<br>- {{cite journal|last1=Klimstra|first1=David S.|last2=Modlin|first2=Irvin R.|last3=Coppola|first3=Domenico|last4=Lloyd|first4=Ricardo V.|last5=Suster|first5=Saul|title=The Pathologic Classification of Neuroendocrine Tumors|journal=Pancreas|volume=39|issue=6|year=2010|pages=707–712|issn=0885-3177|doi=10.1097/MPA.0b013e3181ec124e}}</ref> {{Further|Evaluation#Counts per mm2}}
The mitotic count should be estimated by counting mitoses over 8 mm<sup>2</sup> (or more), and then dividing that count by 8 (or proportionally more for a larger area).<ref name="mitotic">'''First reference states 40 high power fields (HPFs) and second reference states that one HPF can be assumed to be 0.2 mm<sup>2</sup>''':<br>-{{cite journal|last1=Rindi|first1=G.|last2=Klöppel|first2=G.|last3=Alhman|first3=H.|last4=Caplin|first4=M.|last5=Couvelard|first5=A.|last6=de Herder|first6=W. W.|last7=Erikssson|first7=B.|last8=Falchetti|first8=A.|last9=Falconi|first9=M.|last10=Komminoth|first10=P.|last11=Körner|first11=M.|last12=Lopes|first12=J. M.|last13=McNicol|first13=A-M.|last14=Nilsson|first14=O.|last15=Perren|first15=A.|last16=Scarpa|first16=A.|last17=Scoazec|first17=J-Y.|last18=Wiedenmann|first18=B.|title=TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system|journal=Virchows Archiv|volume=449|issue=4|year=2006|pages=395–401|issn=0945-6317|doi=10.1007/s00428-006-0250-1}}<br>- {{cite journal|last1=Klimstra|first1=David S.|last2=Modlin|first2=Irvin R.|last3=Coppola|first3=Domenico|last4=Lloyd|first4=Ricardo V.|last5=Suster|first5=Saul|title=The Pathologic Classification of Neuroendocrine Tumors|journal=Pancreas|volume=39|issue=6|year=2010|pages=707–712|issn=0885-3177|doi=10.1097/MPA.0b013e3181ec124e}}</ref> {{Further|Evaluation#Counts per mm2}}


===Ki-67 index===
===Ki-67 index===
[[File:Counting Ki-67 index in immunohistochemistry.jpg|thumb|Counting Ki-67 index. To count as positive, a nucleus should be:
[[File:Counting Ki-67 index in immunohistochemistry.jpg|thumb|Counting Ki-67 index. To count as positive, a nucleus should:
<br>- Homogenously darkly stained (not just stippled).
<br>- Not be located in stroma.
<br>- Not be located in stroma.
<br>- Be at least half within the field of view.
<br>- Be at least half within the field of view.
<br>- Be large enough.]]
<br>- Be large enough.<br>Otherwise, even weakly positive nuclei count as positive.]]
The counting is made in areas with the highest concentration of Ki-67 positive cells, called "hot spots".<ref name="ReidBagci2014">{{cite journal|last1=Reid|first1=Michelle D|last2=Bagci|first2=Pelin|last3=Ohike|first3=Nobuyuki|last4=Saka|first4=Burcu|last5=Erbarut Seven|first5=Ipek|last6=Dursun|first6=Nevra|last7=Balci|first7=Serdar|last8=Gucer|first8=Hasan|last9=Jang|first9=Kee-Taek|last10=Tajiri|first10=Takuma|last11=Basturk|first11=Olca|last12=Kong|first12=So Yeon|last13=Goodman|first13=Michael|last14=Akkas|first14=Gizem|last15=Adsay|first15=Volkan|title=Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies|journal=Modern Pathology|volume=28|issue=5|year=2014|pages=686–694|issn=0893-3952|doi=10.1038/modpathol.2014.156}}</ref>
The counting is made in areas with the highest concentration of Ki-67 positive cells, called "hot spots".<ref name="ReidBagci2014">{{cite journal|last1=Reid|first1=Michelle D|last2=Bagci|first2=Pelin|last3=Ohike|first3=Nobuyuki|last4=Saka|first4=Burcu|last5=Erbarut Seven|first5=Ipek|last6=Dursun|first6=Nevra|last7=Balci|first7=Serdar|last8=Gucer|first8=Hasan|last9=Jang|first9=Kee-Taek|last10=Tajiri|first10=Takuma|last11=Basturk|first11=Olca|last12=Kong|first12=So Yeon|last13=Goodman|first13=Michael|last14=Akkas|first14=Gizem|last15=Adsay|first15=Volkan|title=Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies|journal=Modern Pathology|volume=28|issue=5|year=2014|pages=686–694|issn=0893-3952|doi=10.1038/modpathol.2014.156}}</ref>