Pancreas
Neuroendocrine neoplasms
Clear cell pancreatic endocrine tumor
Authors: Adam L. Booth, M.D., Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 15 October 2019
Minor changes: 4 January 2021
Copyright: 2019-2021, PathologyOutlines.com, Inc.
PubMed Search: Clear cell [title] pancreatic endocrine tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Booth A, Gonzalez R. Clear cell pancreatic endocrine tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasclearcellendocrine.html. Accessed January 23rd, 2021.
Definition / general
- An uncommon morphologic variant of pancreatic well differentiated neuroendocrine tumor, associated with von Hippel-Lindau syndrome (VHL) and multiple endocrine neoplasia type I (MEN I) syndrome
Essential features
- Clear, vacuolated cytoplasm due to accumulation of lipid, glycogen or mucin
- Characteristic “salt and pepper” nuclear chromatin features
- Can be easily misdiagnosed due to morphologic similarities with primary and metastatic tumors of the pancreas
Terminology
- Also known as lipid rich variant
ICD coding
- ICD10: C25.4 - malignant neoplasm of endocrine pancreas
Epidemiology
- Adults ages 40 - 60
- No sex predilection
- Syndromic patients may present at an earlier age (Pathol Res Pract 2016;212:747)
Sites
- Most commonly in the head of the pancreas
Pathophysiology
- In VHL, the disease results from deletions or mutations in the VHL tumor suppressor gene on chromosome 3p25.5 (Mod Pathol 2011;24:S66)
- Mutations in MEN1 on chromosome 11q result in loss of function of tumor suppressor protein menin (Mod Pathol 2011;24:S66)
- Sporadic tumors consistently result from allelic loss of chromosome 11q
Clinical features
- Patients with VHL or MEN I may be screened following clinical suspicion
- Patients may present for evaluation of abdominal symptoms or abnormal laboratory results
- Some cases may be found incidentally on imaging (Mod Pathol 2011;24:S66)
- Pancreatic neuroendocrine tumors in VHL or MEN I are typically non functional (Arch Pathol Lab Med 2006;130:963)
Diagnosis
- Imaging may identify a suspicious mass
- Definitive diagnosis is made following endoscopic biopsy or surgical resection
Radiology description
- Hyperintense, enhancing mass, well circumscribed with sharp boarders on computed tomography (Radiographics 2010;30:1445)
Prognostic factors
- Worse prognosis with high Ki67 proliferative index, tumor size > 2 cm, non functioning tumors, tumor necrosis and poor response to chemotherapy (J Hepatobiliary Pancreat Sci 2015;22:586, Mod Pathol 2011;24:S66)
Case reports
- 29 year old man with liver and pancreatic lesions (Diagn Cytopathol 2009;37:365)
- 32 year old woman with abdominal pain and a pancreatic mass (Cytojournal 2016;13:7)
- 47 year old woman presenting with a mass in the pancreatic tail (Neuro Endocrinol Lett 2017;38:83)
- 60 year old woman with pancreatic cysts and octreotide avid lesions (Virchows Arch 2013;463:593)
- 64 year old man with a nodule in the head of the pancreas (Cytopathology 2013;24:197)
Treatment
- Surgical resection and chemotherapy (Mod Pathol 2011;24:S66)
Gross description
- Most often solid, solitary, homogenous, tan to yellow (Am J Surg Pathol 2001;25:602)
- If extensive fibrosis present, may be gray and firm (J Hepatobiliary Pancreat Sci 2015;22:586)
- Hereditary syndromes may present with multiple tumors
- Rarely a cystic component can be seen (Neuro Endocrinol Lett 2017;38:83)
Microscopic (histologic) description
- Solitary, well circumscribed
- Widely variable architectural patterns: nested, trabecular, glandular, ribbon-like, tubuloacinar, mixed patterns are common; however, there is usually a dominant pattern (Arch Pathol Lab Med 2006;130:963)
- Small / medium round, polygonal cells with clear, vacuolated cytoplasm due to lipid accumulation
- Central nucleus with characteristic "salt and pepper" chromatin pattern and inconspicuous nucleoli (Arch Pathol Lab Med 2009;133:350)
Microscopic (histologic) images
Contributed by Aatur Singhi, M.D., Ph.D.
Nests of tumor cells
Clear, vacuolated cytoplasm
Salt and pepper chromatin
Synaptophysin positivity
Cytology description
- Isolated or small clusters of round monomorphic tumor cells (Cytopathology 2013;24:197)
- Numerous small cytoplasmic vacuoles imparting a “foamy” appearance
- Eccentric nuclei with fine nuclear chromatin, without prominent nucleoli (J Hepatobiliary Pancreat Sci 2015;22:586)
Cytology images
Image hosted on other servers:
Papanicolaou stain of FNA
Positive stains
Negative stains
Electron microscopy description
- Variably sized cytoplasmic lipid globules and dense neurosecretory granules (Arch Pathol Lab Med 2009;133:350)
Molecular / cytogenetics description
- von Hippel Lindau disease
- Autosomal dominant mutation in VHL tumor suppressor gene on chromosome 3p25.5 (Arch Pathol Lab Med 2010;134:1080)
- Multiple endocrine neoplasia type I
- Autosomal dominant germline mutation in MEN1 tumor suppressor gene on chromosome 11q13
- Sporadic tumors may arise from chromosomal alterations, epigenetic changes or functional genomic alterations
Videos
Pancreatic neuroendocrine neoplasms: overview
Sample pathology report
- Pancreas, partial pancreatectomy:
- Well differentiated pancreatic neuroendocrine tumor, clear cell variant (grade 1) (see synoptic report)
- Surgical margins free of malignancy
Differential diagnosis
- Metastatic
- Renal cell carcinoma, clear cell type: positive for AE1/AE3, CD10, PAX8, CAIX; negative for neuroendocrine markers (Arch Pathol Lab Med 2010;134:1080)
- Primary
- Ductal adenocarcinoma with clear cell features: positive for AE1/AE3; negative for neuroendocrine markers
- Serous cystadenoma, solid variant: positive for PAS, AE1/AE3, vimentin; negative for synaptophysin
- Solid pseudopapillary neoplasm, clear cell variant: positive for beta catenin (nuclear and cytoplasmic), CD10, CD56, vimentin; variable neuroendocrine markers; loss of E-cadherin (J Hepatobiliary Pancreat Sci 2015;22:586)
- Clear cell sugar tumor / PEComa: positive for PAS, HMB45
- Peripancreatic region
- Adrenocortical tumors: positive for inhibin, MelanA; weak with AE1/AE3; negative for chromogranin A (J Hepatobiliary Pancreat Sci 2015;22:586)
- Clear cell hepatocellular carcinoma: positive for Arginase1, HepPar1; negative for neuroendocrine markers
Additional references
Board review style question #1
- Which of the following statements regarding clear cell pancreatic endocrine tumor is true?
- A diagnosis should not stimulate genetic evaluation for the VHL syndrome
- Frequently immunoreactive for cytokeratins
- Only seen in the setting of VHL disease
- Immunohistochemistry can distinguish from histologically similar metastatic clear cell renal cell carcinoma in VHL disease
- Tumors associated with VHL syndrome and MEN1 syndrome are often functional tumors
Board review style answer #1
D. Immunohistochemistry can distinguish clear cell pancreatic endocrine tumors from histologically similar metastatic clear cell renal cell carcinoma in VHL disease
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Board review style question #2
- A patient is diagnosed with a clear cell pancreatic endocrine tumor. What genetic mutation is likely to be present?
- Mutation in APC tumor suppressor gene on chromosome 5q21-22
- Mutation in c-KIT proto-oncogene gene on chromosome 4q11-4q13
- Mutation in CDH1 gene on chromosome 16q22.1
- Mutation in MET proto-oncogene located on chromosome 17q31.1-34
- Mutation in VHL tumor suppressor gene on chromosome 3p25.5
Board review style answer #2
E. Mutation in VHL tumor suppressor gene on chromosome 3p25.5
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