Difference between revisions of "Neuroendocrine tumour of the pancreas"

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{{ Infobox diagnosis
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Name      = {{PAGENAME}}
| Image      = Pancreatic insulinoma (2).JPG
| Image      = Pancreatic neuroendocrine tumour - 2 -- high mag.jpg
| Width      =
| Width      =
| Caption    = Pancreatic neuroendocrine tumour (insulinoma). [[H&E stain]].
| Caption    = Pancreatic neuroendocrine tumour. [[H&E stain]].
| Synonyms  = pancreatic islet cell tumour (obsolete term)
| Synonyms  = pancreatic islet cell tumour (obsolete term)
| Micro      = nests of cells or cords, stippled chromatin, moderate quantity of cytoplasm, +/-hyaline globules
| Micro      = nests of cells or cords, stippled chromatin, moderate quantity of cytoplasm, +/-hyaline globules
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| LMDDx      = [[solid pseudopapillary neoplasm]], [[acinar cell carcinoma]], [[invasive ductal carcinoma of the pancreas]]
| LMDDx      = [[solid pseudopapillary neoplasm]], [[acinar cell carcinoma]], [[invasive ductal carcinoma of the pancreas]]
| Stains    =
| Stains    =
| IHC        =
| IHC        = chromogranin +ve, synaptophysin +ve, insulin +/-ve, glucagon +/-ve, gastrin +/-ve, somatostatin +/-ve
| EM        =
| EM        =
| Molecular  =
| Molecular  =
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| Site      = [[pancreas]]
| Site      = [[pancreas]]
| Assdx      =
| Assdx      =
| Syndromes  = [[Multiple endocrine neoplasia I]], [[von Hippel-Lindau disease]]
| Syndromes  = [[Multiple endocrine neoplasia I]], [[von Hippel-Lindau disease]], [[neurofibromatosis type 1]]
| Clinicalhx =
| Clinicalhx =
| Signs      =
| Signs      =
| Symptoms  =
| Symptoms  = dependent on subtype
| Prevalence = uncommon
| Prevalence = uncommon
| Bloodwork  =
| Bloodwork  =
| Rads      =
| Rads      = pancreatic mass
| Endoscopy  =
| Endoscopy  =
| Prognosis  =
| Prognosis  =
| Other      =
| Other      =
| ClinDDx    =
| ClinDDx    = [[invasive ductal carcinoma of the pancreas]], other pancreatic tumours
| Tx        =
| Tx        =
}}
}}
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It may be abbreviated '''PanNET'''.<ref name=pmid22198808/>
It may be abbreviated '''PanNET'''.<ref name=pmid22198808/>


Previously, it was referred to as '''pancreatic islet cell tumour''' or '''islet cell tumour'''; thes terms are now considered to be outdated.<ref name=pmid22198808>{{Cite journal  | last1 = Burns | first1 = WR. | last2 = Edil | first2 = BH. | title = Neuroendocrine Pancreatic Tumors: Guidelines for Management and Update. | journal = Curr Treat Options Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1007/s11864-011-0172-2 | PMID = 22198808 }}</ref>
Previously, it was referred to as '''pancreatic islet cell tumour''' or '''islet cell tumour'''; these terms are now considered to be outdated.<ref name=pmid22198808>{{Cite journal  | last1 = Burns | first1 = WR. | last2 = Edil | first2 = BH. | title = Neuroendocrine Pancreatic Tumors: Guidelines for Management and Update. | journal = Curr Treat Options Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1007/s11864-011-0172-2 | PMID = 22198808 }}</ref>


Neuroendocrine tumours in general are dealt with in the ''[[neuroendocrine tumours]]'' article.
Neuroendocrine tumours in general are dealt with in the ''[[neuroendocrine tumours]]'' article.
Line 46: Line 46:
**[[Neurofibromatosis type 1]].<ref name=pmid15249710>{{Cite journal  | last1 = Alexakis | first1 = N. | last2 = Connor | first2 = S. | last3 = Ghaneh | first3 = P. | last4 = Lombard | first4 = M. | last5 = Smart | first5 = HL. | last6 = Evans | first6 = J. | last7 = Hughes | first7 = M. | last8 = Garvey | first8 = CJ. | last9 = Vora | first9 = J. | title = Hereditary pancreatic endocrine tumours. | journal = Pancreatology | volume = 4 | issue = 5 | pages = 417-33; discussion 434-5 | month =  | year = 2004 | doi = 10.1159/000079616 | PMID = 15249710 }}</ref>
**[[Neurofibromatosis type 1]].<ref name=pmid15249710>{{Cite journal  | last1 = Alexakis | first1 = N. | last2 = Connor | first2 = S. | last3 = Ghaneh | first3 = P. | last4 = Lombard | first4 = M. | last5 = Smart | first5 = HL. | last6 = Evans | first6 = J. | last7 = Hughes | first7 = M. | last8 = Garvey | first8 = CJ. | last9 = Vora | first9 = J. | title = Hereditary pancreatic endocrine tumours. | journal = Pancreatology | volume = 4 | issue = 5 | pages = 417-33; discussion 434-5 | month =  | year = 2004 | doi = 10.1159/000079616 | PMID = 15249710 }}</ref>


===Classification===  
===WHO classification of 2017===
Five categories:<!-- https://www.esp-congress.org/fileadmin/user_upload/Congress_2016/IAP_ESP_Presentations/Mon/0830-1200/SY-02/SY-02-004-Kl%C3%B6ppel-Update%20of%20WHO%20classification%20of%20endocrine%20pancreatic%20tumours.pdf -->
*NET G1.  Ki67 Index < 3%, Mitotic Index < 2/10HPF
*NET G2.  Ki67 Index 3-20%,  Mitotic Index 2-20/10HPF
*NET G3.  Ki67 Index > 20%,  Mitotic Index > 20/10 HPF  AND well-differentiated, expressing neuroendocrine differentiation and hormones
*Neuroendocrine carcinoma (NEC G3).  Ki 67 Index > 20%,  Mitotic Index > 20/10 HPF  Poorly differentiated, expressing neuroendocrine differentiation but lacking exocrine markers.
*[[MiNEN]].  mixed endocrine-nonendocrine neoplasm:  components of a non-endocrine carcinoma (mostly ductal adenocarcinoma or acinar cell carcinoma) combined with a neuroendocrine neoplasm
 
===Classification by product===  
Based on peptide produced in the pancreatic islets:
Based on peptide produced in the pancreatic islets:
#Glucagon from alpha cells ([[glucagonoma]]).  
#Glucagon from alpha cells ([[glucagonoma]]).  
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==Gross==
==Gross==
*Usually in the head of the pancreas - 68% in one series,<ref name=pmid22869477>{{Cite journal  | last1 = Oh | first1 = TG. | last2 = Chung | first2 = MJ. | last3 = Park | first3 = JY. | last4 = Bang | first4 = SM. | last5 = Park | first5 = SW. | last6 = Chung | first6 = JB. | last7 = Song | first7 = SY. | title = Prognostic factors and characteristics of pancreatic neuroendocrine tumors: single center experience. | journal = Yonsei Med J | volume = 53 | issue = 5 | pages = 944-51 | month = Sep | year = 2012 | doi = 10.3349/ymj.2012.53.5.944 | PMID = 22869477 | PMC = 3423842}}</ref> and 50% in another series.<ref name=pmid22869477>{{Cite journal  | last1 = Oh | first1 = TG. | last2 = Chung | first2 = MJ. | last3 = Park | first3 = JY. | last4 = Bang | first4 = SM. | last5 = Park | first5 = SW. | last6 = Chung | first6 = JB. | last7 = Song | first7 = SY. | title = Prognostic factors and characteristics of pancreatic neuroendocrine tumors: single center experience. | journal = Yonsei Med J | volume = 53 | issue = 5 | pages = 944-51 | month = Sep | year = 2012 | doi = 10.3349/ymj.2012.53.5.944 | PMID = 22869477 }}</ref>
*Usually in the head of the pancreas - 68% in one series,<ref name=pmid22869477>{{Cite journal  | last1 = Oh | first1 = TG. | last2 = Chung | first2 = MJ. | last3 = Park | first3 = JY. | last4 = Bang | first4 = SM. | last5 = Park | first5 = SW. | last6 = Chung | first6 = JB. | last7 = Song | first7 = SY. | title = Prognostic factors and characteristics of pancreatic neuroendocrine tumors: single center experience. | journal = Yonsei Med J | volume = 53 | issue = 5 | pages = 944-51 | month = Sep | year = 2012 | doi = 10.3349/ymj.2012.53.5.944 | PMID = 22869477 | PMC = 3423842}}</ref> and 50% in another series.<ref name=pmid22869477/>
 
==Microscopic==
==Microscopic==
Features:
Features:
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Image: Pancreatic insulinoma (4) Insulin immuostain.JPG | Insulinoma - insulin IHC. (WC)
Image: Pancreatic insulinoma (4) Insulin immuostain.JPG | Insulinoma - insulin IHC. (WC)
</gallery>
</gallery>
<gallery>
Image: Pancreatic neuroendocrine tumour -- very low mag.jpg | Pancreatic NET - very low mag. (WC/Nephron)
Image: Pancreatic neuroendocrine tumour -- low mag.jpg | Pancreatic NET - low mag. (WC/Nephron)
Image: Pancreatic neuroendocrine tumour -- intermed mag.jpg | Pancreatic NET - intermed. mag. (WC/Nephron)
Image: Pancreatic neuroendocrine tumour - alt -- intermed mag.jpg | Pancreatic NET - intermed. (WC/Nephron) mag.
Image: Pancreatic neuroendocrine tumour -- high mag.jpg | Pancreatic NET - high mag. (WC/Nephron)
Image: Pancreatic neuroendocrine tumour -- very high mag.jpg | Pancreatic NET - very high mag. (WC/Nephron)
Image: Pancreatic neuroendocrine tumour - 2 -- intermed mag.jpg | Pancreatic NET - intermed. mag. (WC/Nephron)
Image: Pancreatic neuroendocrine tumour - 2 -- high mag.jpg | Pancreatic NET - high mag. (WC/Nephron)
</gallery>
[[File: PANC NET LG 1 sl 1.png| Low grade pancreatic neuroendocrine tumor]]
[[File: PANC NET LG 1 sl 2.png| Low grade pancreatic neuroendocrine tumor]]
[[File: PANC NET LG 1 sl 3.png| Low grade pancreatic neuroendocrine tumor]]
[[File: PANC NET LG 1 sl 4.png| Low grade pancreatic neuroendocrine tumor]]
[[File: PANC NET LG 1 sl 5.png| Low grade pancreatic neuroendocrine tumor]]
Low grade pancreatic neuroendocrine tumor.  A. Stromal trabeculums (black arrows) support the uniform, non-necrotic tumor that has sharp edges (green arrows). B. Modestly variable, rounded nuclei show open chromatin and nucleoli. Individual pyknotic nuclei (black arrows) are insufficient as evidence of necrosis sufficient to increase grade. C. Immunostain. Cytoplasm is diffusely synaptophysin positive. D.  Immunostain. Cytoplasm shows stippled chromogranin positivity. E. Immunostain. Only scattered nuclei are Ki67 positive.
www:
www:
*[http://path.upmc.edu/cases/case172/micro.html Islet cell tumour (upmc.edu)].
*[http://path.upmc.edu/cases/case172/micro.html Islet cell tumour (upmc.edu)].
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==IHC==
==IHC==
*CK19 +ve -- should be done as a routine in pancreatic NETs; poor prognostic factor.<ref name=pmid19956064>{{Cite journal  | last1 = Jain | first1 = R. | last2 = Fischer | first2 = S. | last3 = Serra | first3 = S. | last4 = Chetty | first4 = R. | title = The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. | journal = Appl Immunohistochem Mol Morphol | volume = 18 | issue = 1 | pages = 9-15 | month = Jan | year = 2010 | doi = 10.1097/PAI.0b013e3181ad36ea | PMID = 19956064 }}</ref>
*CK19 +ve.
**Considered a poor prognostic factor<ref name=pmid19956064>{{Cite journal  | last1 = Jain | first1 = R. | last2 = Fischer | first2 = S. | last3 = Serra | first3 = S. | last4 = Chetty | first4 = R. | title = The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. | journal = Appl Immunohistochem Mol Morphol | volume = 18 | issue = 1 | pages = 9-15 | month = Jan | year = 2010 | doi = 10.1097/PAI.0b013e3181ad36ea | PMID = 19956064 }}</ref> - disputed by an older paper.<ref>{{Cite journal  | last1 = La Rosa | first1 = S. | last2 = Rigoli | first2 = E. | last3 = Uccella | first3 = S. | last4 = Novario | first4 = R. | last5 = Capella | first5 = C. | title = Prognostic and biological significance of cytokeratin 19 in pancreatic endocrine tumours. | journal = Histopathology | volume = 50 | issue = 5 | pages = 597-606 | month = Apr | year = 2007 | doi = 10.1111/j.1365-2559.2007.02662.x | PMID = 17394496 }}</ref>
*Chromogranin +ve.
*Synaptophysin +ve.
*CD56 +ve.
*[[PAX8]] +ve (74% of cases<ref name=pmid20890270>{{Cite journal  | last1 = Sangoi | first1 = AR. | last2 = Ohgami | first2 = RS. | last3 = Pai | first3 = RK. | last4 = Beck | first4 = AH. | last5 = McKenney | first5 = JK. | last6 = Pai | first6 = RK. | title = PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. | journal = Mod Pathol | volume = 24 | issue = 3 | pages = 412-24 | month = Mar | year = 2011 | doi = 10.1038/modpathol.2010.176 | PMID = 20890270 }}</ref>).


Note:
Functional tumours:
*''CK19'' should '''not''' be confused with ''CA19-9''.
*Insulin.
*Glucagon.
*Somatostatin.
*Gastrin.


A panel:
A panel:
*Chromogranin, synaptophysin, CD10, PR, beta-catenin, CK7, pankeratin, Ki-67.
*Chromogranin, synaptophysin, CD10, PR, beta-catenin, CK7, pankeratin, Ki-67, CK19.
 
Notes:
*''CK19'' should '''not''' be confused with ''CA19-9''.
*If the tumour is '''not''' functional (clinically) one can forgo the stains for functional tumours.


==Sign out==
==Sign out==
<pre>
<pre>
TAIL OF PANCREAS AND SPLEEN, DISTAL PANCREATECTOMY AND SPLENECTOMY:
TAIL OF PANCREAS AND SPLEEN, PARTIAL PANCREATECTOMY AND SPLENECTOMY:
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR.
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR, pT1, pN0.
-- INTERMEDIATE GRADE (G2).
-- NARROWLY EXCISED.
-- PLEASE SEE TUMOUR SUMMARY.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- SPLEEN WITHIN NORMAL LIMITS.
- FOUR BENIGN LYMPH NODES.
</pre>
 
<pre>
TAIL OF PANCREAS AND SPLEEN, PARTIAL PANCREATECTOMY AND SPLENECTOMY:
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR, pT1, pN0.
-- LOW GRADE (G1).
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- SPLEEN WITHIN NORMAL LIMITS.
- SPLEEN WITHIN NORMAL LIMITS.
- FOUR BENIGN LYMPH NODES.
- FOUR BENIGN LYMPH NODES.
- NEGATIVE FOR MALIGNANCY.
</pre>
</pre>



Latest revision as of 20:21, 3 March 2019

Neuroendocrine tumour of the pancreas
Diagnosis in short

Pancreatic neuroendocrine tumour. H&E stain.

Synonyms pancreatic islet cell tumour (obsolete term)

LM nests of cells or cords, stippled chromatin, moderate quantity of cytoplasm, +/-hyaline globules
LM DDx solid pseudopapillary neoplasm, acinar cell carcinoma, invasive ductal carcinoma of the pancreas
IHC chromogranin +ve, synaptophysin +ve, insulin +/-ve, glucagon +/-ve, gastrin +/-ve, somatostatin +/-ve
Site pancreas

Syndromes Multiple endocrine neoplasia I, von Hippel-Lindau disease, neurofibromatosis type 1

Symptoms dependent on subtype
Prevalence uncommon
Radiology pancreatic mass
Clin. DDx invasive ductal carcinoma of the pancreas, other pancreatic tumours

Neuroendocrine tumour of the pancreas, also pancreatic neuroendocrine tumour, is a relatively uncommon tumour.

It may be abbreviated PanNET.[1]

Previously, it was referred to as pancreatic islet cell tumour or islet cell tumour; these terms are now considered to be outdated.[1]

Neuroendocrine tumours in general are dealt with in the neuroendocrine tumours article.

General

WHO classification of 2017

Five categories:

  • NET G1. Ki67 Index < 3%, Mitotic Index < 2/10HPF
  • NET G2. Ki67 Index 3-20%, Mitotic Index 2-20/10HPF
  • NET G3. Ki67 Index > 20%, Mitotic Index > 20/10 HPF AND well-differentiated, expressing neuroendocrine differentiation and hormones
  • Neuroendocrine carcinoma (NEC G3). Ki 67 Index > 20%, Mitotic Index > 20/10 HPF Poorly differentiated, expressing neuroendocrine differentiation but lacking exocrine markers.
  • MiNEN. mixed endocrine-nonendocrine neoplasm: components of a non-endocrine carcinoma (mostly ductal adenocarcinoma or acinar cell carcinoma) combined with a neuroendocrine neoplasm

Classification by product

Based on peptide produced in the pancreatic islets:

  1. Glucagon from alpha cells (glucagonoma).
  2. Insulin from beta cells (insulinoma) - most common ~ 50% of islet cell tumours.
  3. Somatostatin from D cells (somatostatinoma).
  4. Pancreatic polypeptide from PP cells.

Others:

  1. Vasoactive intestinal peptide (VIPoma).
  2. Gastrin (gastrinoma).
    • May be seen in Zollinger-Ellison syndrome.
      • Triad: pancreatic gastrinoma, gastric acid hypersecretion, marked peptic ulcers in the small bowel.[5]

Gross

  • Usually in the head of the pancreas - 68% in one series,[6] and 50% in another series.[6]

Microscopic

Features:

  • Nests of cells or cords.
  • Stippled chromatin - key feature.
  • Moderate cytoplasm.
  • +/-Hyaline globules.

DDx:

Images

Low grade pancreatic neuroendocrine tumor Low grade pancreatic neuroendocrine tumor Low grade pancreatic neuroendocrine tumor Low grade pancreatic neuroendocrine tumor Low grade pancreatic neuroendocrine tumor

Low grade pancreatic neuroendocrine tumor. A. Stromal trabeculums (black arrows) support the uniform, non-necrotic tumor that has sharp edges (green arrows). B. Modestly variable, rounded nuclei show open chromatin and nucleoli. Individual pyknotic nuclei (black arrows) are insufficient as evidence of necrosis sufficient to increase grade. C. Immunostain. Cytoplasm is diffusely synaptophysin positive. D. Immunostain. Cytoplasm shows stippled chromogranin positivity. E. Immunostain. Only scattered nuclei are Ki67 positive.


www:

IHC

  • CK19 +ve.
    • Considered a poor prognostic factor[7] - disputed by an older paper.[8]
  • Chromogranin +ve.
  • Synaptophysin +ve.
  • CD56 +ve.
  • PAX8 +ve (74% of cases[9]).

Functional tumours:

  • Insulin.
  • Glucagon.
  • Somatostatin.
  • Gastrin.

A panel:

  • Chromogranin, synaptophysin, CD10, PR, beta-catenin, CK7, pankeratin, Ki-67, CK19.

Notes:

  • CK19 should not be confused with CA19-9.
  • If the tumour is not functional (clinically) one can forgo the stains for functional tumours.

Sign out

TAIL OF PANCREAS AND SPLEEN, PARTIAL PANCREATECTOMY AND SPLENECTOMY:
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR, pT1, pN0.
-- INTERMEDIATE GRADE (G2).
-- NARROWLY EXCISED.
-- PLEASE SEE TUMOUR SUMMARY.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- SPLEEN WITHIN NORMAL LIMITS.
- FOUR BENIGN LYMPH NODES.
TAIL OF PANCREAS AND SPLEEN, PARTIAL PANCREATECTOMY AND SPLENECTOMY:
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR, pT1, pN0.
-- LOW GRADE (G1).
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- SPLEEN WITHIN NORMAL LIMITS.
- FOUR BENIGN LYMPH NODES.

Micro

The sections show pancreas with a large well-circumscribed tumour that centrally has a large cyst-like cavity. The tumour cells have moderate pale grey cytoplasm and round nuclei with salt and pepper chromatin. The tumour cells are arranged in cords and nests. No cholesterol clefts are readily apparent. No hyaline globules are identified. No papillary structures are apparent.

No necrosis is identified. No degenerative changes are apparent. Mitotic activity is seen focally. There are 2 mitoses per 10 high power fields, were one high power field has an area of 0.2376 mm*mm.

See also

References

  1. 1.0 1.1 Burns, WR.; Edil, BH. (Dec 2011). "Neuroendocrine Pancreatic Tumors: Guidelines for Management and Update.". Curr Treat Options Oncol. doi:10.1007/s11864-011-0172-2. PMID 22198808.
  2. Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 496. ISBN 978-0443066573.
  3. Charlesworth, M.; Verbeke, CS.; Falk, GA.; Walsh, M.; Smith, AM.; Morris-Stiff, G. (Feb 2012). "Pancreatic Lesions in von Hippel-Lindau Disease? A Systematic Review and Meta-synthesis of the Literature.". J Gastrointest Surg. doi:10.1007/s11605-012-1847-0. PMID 22370733.
  4. Alexakis, N.; Connor, S.; Ghaneh, P.; Lombard, M.; Smart, HL.; Evans, J.; Hughes, M.; Garvey, CJ. et al. (2004). "Hereditary pancreatic endocrine tumours.". Pancreatology 4 (5): 417-33; discussion 434-5. doi:10.1159/000079616. PMID 15249710.
  5. Zollinger RM, Ellison EH (1955). "Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas". Ann. Surg. 142 (4): 709–23; discussion, 724–8. doi:10.1097/00000658-195510000-00015. PMC 1465210. PMID 13259432. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1465210/.
  6. 6.0 6.1 Oh, TG.; Chung, MJ.; Park, JY.; Bang, SM.; Park, SW.; Chung, JB.; Song, SY. (Sep 2012). "Prognostic factors and characteristics of pancreatic neuroendocrine tumors: single center experience.". Yonsei Med J 53 (5): 944-51. doi:10.3349/ymj.2012.53.5.944. PMC 3423842. PMID 22869477. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423842/.
  7. Jain, R.; Fischer, S.; Serra, S.; Chetty, R. (Jan 2010). "The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver.". Appl Immunohistochem Mol Morphol 18 (1): 9-15. doi:10.1097/PAI.0b013e3181ad36ea. PMID 19956064.
  8. La Rosa, S.; Rigoli, E.; Uccella, S.; Novario, R.; Capella, C. (Apr 2007). "Prognostic and biological significance of cytokeratin 19 in pancreatic endocrine tumours.". Histopathology 50 (5): 597-606. doi:10.1111/j.1365-2559.2007.02662.x. PMID 17394496.
  9. Sangoi, AR.; Ohgami, RS.; Pai, RK.; Beck, AH.; McKenney, JK.; Pai, RK. (Mar 2011). "PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma.". Mod Pathol 24 (3): 412-24. doi:10.1038/modpathol.2010.176. PMID 20890270.