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