Well-differentiated Neuroendocrine Neoplasm, Pancreas



Well-differentiated Neuroendocrine Neoplasm, Pancreas


Vikram Deshpande, MD





Key Facts


Etiology/Pathogenesis



  • MEN1


  • von Hippel-Lindau syndrome


  • Tuberous sclerosis


  • Sporadic


Clinical Issues



  • Surgical resection remains mainstay of therapy for tumors confined to pancreas


  • Features associated with adverse outcome include



    • Mitosis > 2/10 HPF


    • Tumor necrosis


    • Vascular invasion


    • High Ki-67 labeling index


Microscopic Pathology



  • Monotonous population of round cells arranged in wide range of patterns including nested, trabecular, glandular, and solid


Ancillary Tests



  • Chromogranin and synaptophysin



    • Diffusely and strongly positive


  • Ki-67


Top Differential Diagnoses



  • Acinar cell carcinoma


  • Solid pseudopapillary neoplasm


  • Poorly differentiated endocrine carcinoma






This well-circumscribed solid mass in the pancreas is typical of a well-differentiated neuroendocrine tumor.






This pancreatic endocrine neoplasm has a microcystic appearance that mimics a serous cystadenoma.


TERMINOLOGY


Abbreviations



  • Pancreatic endocrine neoplasm (PEN)


Synonyms



  • Pancreatic endocrine tumor


  • Islet cell tumor


  • Pancreatic neuroendocrine tumor


Definitions



  • Low- to intermediate-grade neuroendocrine neoplasm of pancreas


ETIOLOGY/PATHOGENESIS


Syndromic



  • Multiple endocrine neoplasia syndrome (MEN1)


  • von Hippel-Lindau syndrome


  • Tuberous sclerosis


Sporadic



  • Majority of cases are nonsyndromic and sporadic


CLINICAL ISSUES


Presentation



  • Epidemiology



    • Peak incidence between 30-60 years


    • No significant gender predilection


  • Presenting symptoms



    • Abdominal pain


    • Jaundice


    • Asymptomatic, detected by imaging



      • Such incidentally detected pancreatic endocrine neoplasms are increasingly common


  • Endocrine function



    • Functioning tumors



      • Insulinoma


      • Glucagonoma


      • Somatostatinoma


      • Gastrinoma


      • Vipomas


    • Nonfunctional tumors



      • More common than functional tumors


Treatment



  • Surgical approaches



    • Surgical resection remains mainstay of therapy for tumors confined to pancreas



      • Enucleation is restricted to small tumors (typically < 2 cm)


    • Options for tumors metastatic to liver



      • Resection of primary and surgical debulking of metastatic tumor


      • Long-acting somatostatin analogs (octreotide and lanreotide)


      • Liver-directed therapy including embolization, chemoembolization, radiofrequency ablation


      • Novel agents such as inhibitor of VEGF, inhibitor of tyrosine kinase, and mTOR pathway


Prognosis



  • Outcome is variable



    • Histological and immunohistochemical features help estimate risk of aggressive behavior


  • Features associated with adverse outcome include



    • Mitosis > 2/10 HPF


    • Tumor necrosis


    • Vascular invasion


    • Perineural invasion


    • High Ki-67 labeling index


    • Cytokeratin 19 positive tumor


    • Size > 2 cm



IMAGE FINDINGS


CT Findings



  • Solid, or less commonly, solid and cystic, wellcircumscribed, enhancing lesion


MACROSCOPIC FEATURES


General Features



  • Solid, round to oval, well-circumscribed mass


  • Approximately 5% of tumors are cystic



    • Either multilocular or unicystic


Size



  • Tumors < 0.5 cm are termed microadenomas


MICROSCOPIC PATHOLOGY


Histologic Features



  • Monotonous population of round cells



    • Wide range of patterns including nested, trabecular, glandular, and solid


  • Nuclear chromatin is typically coarse with “salt and pepper” appearance


  • Less common cytoplasmic variations include oncocytic, vacuolated lipid-rich variant, and rhabdoid


  • Morphological appearance generally does not predict functional status



    • Exceptions to this rule



      • Amyloid deposits are indicative of insulinoma


  • Large nucleoli may be present


ANCILLARY TESTS


Immunohistochemistry



  • Chromogranin and synaptophysin



    • Diffusely and strongly positive


    • Recommended for confirmation of diagnosis


  • Other neuroendocrine markers, such as CD56, CD57, and NCAM are not specific for neuroendocrine differentiation


  • Cytokeratins



    • Positive for keratin 8 and 18


  • Ki-67



    • Along with mitotic counts, it is the only widely accepted predictive marker


  • Immunohistochemistry for peptide hormones



    • Rarely required for diagnosis


    • Nonfunctional tumors may stain for multiple peptides


  • Marker for PENs in metastatic setting



    • ISL1 positivity would support primary endocrine tumor in pancreas


DIFFERENTIAL DIAGNOSIS


Acinar Cell Carcinoma

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Well-differentiated Neuroendocrine Neoplasm, Pancreas

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