Pancreatic Cyst Dilemmas:
From Guidelines to Molecular Markers
Webinar Excerpt
Case Reviews
Webinar Faculty
Do features point to benign disease?
Dina H. – 50 year old female patient
- Married, working mother of 2 teenagers
- Evaluation of a body/tail junction cyst
- 1.8 cm x 1.6 cm
- Consists of a single compartment without communication with the pancreatic ductal system
- Outer wall thin
- Mural nodule
- No evidence of chronic pancreatitis
- Fluid aspirated from cyst showed abundant extracellular mucin
- Presence of macrophages
- Debris and rare groups of benign-appearing ductal cells
- No evidence of high-grade dysplasia or malignancy
- Many features point to benign disease
- Mural nodule creates significant concern that cancer may be present
- CEA and cytology provide insufficient support to discriminate between benign vs aggressive disease
| Fluid Chemistry | |
| AccuCEA | 43 ng/mL |
| Amylase | 169,313 U/L |
| Molecular Results | |
| DNA Quantity | Low |
| DNA Quality | Poor |
| Oncogene Point Mutations | |
| KRAS Point Mutation | No mutation detected |
| GNAS Point Mutation | Not ordered |
| Tumor Suppressor Genes (LOH) | No amplification |
| Benign | Statistically Indolent | Statistically Higher Risk | Aggressive |
| This Patient |
- Molecular analysis indicates BENIGN biologic behavior
- Surgery not performed
- Patient has been followed for over 48 months without clinical evidence of progression
Surgery or surveillance?
Kelly G. – 86 year old female patient
- Widow, lives alone, 6 grandchildren
- Cystic lesion in head of the pancreas
- Endoscopic ultrasound revealed a complex head cyst
- 3.1 cm x 2.1 cm
- Composed of tubular structures in continuity with the main pancreatic duct as well as a side branch
- No solid component, no nodules, no masses
- Aspirate fluid had thick, mucinous character
- Cytology exam revealed markedly degenerated specimen with atypical ductal cells and focal extracellular mucin
- Degeneration precludes definitive evaluation
- Large size raises possibility of aggressive disease
- Qualifies for surgical resection
- Cytologic atypia adds to concern
- Advanced age encourages a conservative approach
| Fluid Chemistry | |
| AccuCEA | 694 ng/mL |
| Amylase | 134 U/L |
| Molecular Results | |
| DNA Quantity | Low |
| DNA Quality | Good |
| Oncogene Point Mutations | |
| KRAS Point Mutation | No mutation |
| GNAS Point Mutation | Not ordered |
| Tumor Suppressor Genes (LOH) | No LOH detected |
| Benign | Statistically Indolent | Statistically Higher Risk | Aggressive |
| This Patient |
- Molecular analysis provides support for BENIGN biologic behavior
- Surgery not performed
- Patient has been followed for over 30 months without clinical evidence of progression
When do molecular alterations begin?
Jack Z. – 65 year old male patient
- Married business owner, 3 children, 1 grandchild
- Pancreatic cystic disease revealed during a workup for cirrhosis
- Endoscopic ultrasound showed mildly prominent pancreatic duct in the neck region, 3.2 mm in diameter
- Cyst found in pancreatic head region, 1.3 cm x 0.9 cm
- No masses or lymphadenopathy
- Clear fluid aspirated and submitted for testing
- First-line testing shows changes of a mild-to-moderate nature
- Cytology was inadequate for interpretation
| Fluid Chemistry | |
| AccuCEA | 13,800 ng/mL |
| Amylase | 24 U/L |
| Molecular Results | |
| DNA Quantity | Moderate |
| DNA Quality | Good |
| Oncogene Point Mutations | |
| KRAS Point Mutation | High clonality mutation, codon 12 GGT to GAT |
| GNAS Point Mutation | No mutation detect |
| Tumor Suppressor Genes (LOH) | No LOH detected |
| Benign | Statistically Indolent | Statistically Higher Risk | Aggressive |
| This Patient |
- Molecular analysis supports STATISTICALLY INDOLENT disease
- This patient exemplifies a common finding in pancreatic cyst lesions: molecular alterations occur early in the molecular pathogenesis of this disease, and thus are the most helpful when first-line testing shows changes of a mild-to-moderate nature
- While mutational change is detected, the extent is still within the range seen with benign or non-progressive disease
- Patient continues to do well under surveillance for 56 months
Is testing the solid component enough?
Larry T. – 76 year old male patient
- Retired, divorced, recently moved to the area
- 3.0 cm hypoechoic mass in mid-body of the pancreas adjacent to a 2.5 cm anechoic cystic mass
- No adenopathy
- Changes suggestive of chronic pancreatitis detected
- Upstream dilation of the pancreatic duct
- Multiple additional cysts present in the pancreas w/ thin walls and no mural nodules
- Both the hypoechoic lesion and the anechoic cyst lesion were biopsied
- After sampling the solid component, cytology failed to find evidence of malignancy
- The hypoechoic mass showed a few ribbons of mucinous cells in a background of inflammation
- The anechoic cyst fluid showed debris and a few inflammatory cells
| Fluid Chemistry | |
| AccuCEA | 259,850 ng/mL |
| Amylase | |
| Molecular Results | |
| DNA Quantity | Greatly elevated |
| DNA Quality | Good |
| Oncogene Point Mutations | |
| KRAS Point Mutation | High clonality mutation, codon 12 GGT to GTT |
| GNAS Point Mutation | Not ordered |
| Tumor Suppressor Genes (LOH) | Two high-clonality (9p, 17q) |
| Benign | Statistically Indolent | Statistically Higher Risk | Aggressive |
| This Patient |
- Molecular analysis provides full support for AGGRESSIVE disease
- Cytology of the sampled solid component failed to identify atypia or malignancy
- Surgery was performed, disclosing pancreatic adenocarcinoma occupying part of the cyst wall lining
Limitations and Disclaimers1
Although PancraGEN is highly specific for malignancy, some malignant cysts may not be detected. There may also be individuals who are falsely identified as having a malignant cyst. Diagnosis and appropriate patient management are the responsibility of the referring physician or health care provider.
References
- Al-Haddad MA, Kowalski T, Siddiqui A, et al. Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts. Endoscopy. 2015;47(2):136-146.
- V. Chernyak et al, Incidental pancreatic cystic lesions Radiology 2015 274 161-9
- BU Wu, et al, Prediction of malignancy in cystic neoplasms of the pancreas: a population based cohort study, Am J Gastro 2014 109 121-9
- Loren D, Kowalski T, Siddiqui A, et al. Influence of integrated molecular pathology test results on real-world management decisions for patients with pancreatic cysts: analysis of data from a national registry cohort. Diagnostic Pathology. 2016;11:5. doi:10.1186/s13000-016-0462-x.
- Gaujoux S., , Brennan, M., et al. Cystic Lesions of the Pancreas: Changes in the Presentation and Management of 1,424 Patients at a Single Institution over a 15-year Time Period. J Am Coll Surg. 2011 April; 212(4): doi:10.1016/j.jamcollsurg.2011.01.016.
- Kaimalkliotis, P., Riff, B., et al. Sendai and Fukuoka Consensus Guidelines Identify Advanced Neoplasia in Patients With Suspected Mucinous Cystic Neoplasms of the Pancreas. Clinical Gastroenterology and Hepatology 2015;13:1808–1815: doi:10.1016/j.cgh.2015.03.017
- Kushnir VM, Mullady DK, Das K, et al. J Clin Gastroenterol. 2019;53(9):686-692. DOI: 10.1097/MCG.0000000000001118.
- Gonda TA, Viterbo D, Gausman V, et al. Clin Gastroenterol Hepatol. 2017;15:913-919.