Pancreatic Cyst FNA: Limited Material, Mucin, and a Preliminary Report
A 58-year-old woman has an incidental 2.8 cm unilocular cyst in the pancreatic head. Serum CEA is 6.1 ng/mL; she has no jaundice, weight loss, or pancreatitis history. EUS-FNA yields 4 mL of turbid fluid. Rapid on-site evaluation shows abundant extracellular mucin and rare clusters of bland columnar cells without high-grade atypia. Two passes remain. The laboratory can prepare a cell block, perform flow cytometry, send microbiology, and run a small molecular panel for KRAS and GNAS, but molecular turnaround is 10 working days. The surgeon asks whether the cyst is malignant and wants a recommendation within a week; the patient is anxious and wants surgery. The cytopathologist must decide how to allocate the remaining material and how to phrase the preliminary report. The cyst has no solid component or main duct dilation.
1. How should the remaining two passes and the 4 mL aspirate be allocated? State which tests you would prioritize and why.
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The first priority is a representative cell block, because morphology remains the only way to detect high-grade atypia or carcinoma. I would submit the sediment from one pass for a cell block and use the supernatant for cyst fluid CEA and amylase. Cyst fluid CEA above roughly 192 ng/mL supports a mucinous cyst, while a low amylase argues against a pseudocyst. If cellularity is low, I would reserve residual fluid for KRAS/GNAS testing rather than sending all material to microbiology or flow cytometry. Flow cytometry is not indicated for an epithelial cyst unless the aspirate is lymphoid; microbiology is low-yield without fever or a cystic infection picture.
A second pass should be held for a repeat cell block or molecular testing if the first is acellular. The key judgement is that negative cytology from cyst fluid cannot exclude malignancy, so the report should state the adequacy and limitations explicitly. I would not let the surgeon's one-week deadline force a premature 'benign' interpretation; the preliminary report can say 'mucin-rich fluid, rare bland epithelium, pending cell block and molecular studies.'
2. Final results: cell block shows mucin and rare bland epithelium, negative for malignancy; fluid CEA 480 ng/mL, amylase 45 U/L; KRAS G12D detected at 18% variant allele frequency; GNAS wild type. How do you interpret these results and what do you recommend?
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The combination indicates a mucinous neoplasm, not a pseudocyst. The high fluid CEA and low amylase establish a mucinous cyst, and KRAS G12D supports a neoplastic mucinous lesion. GNAS wild type does not exclude an intraductal papillary mucinous neoplasm, because GNAS mutations are present in only a subset; KRAS is common in both IPMN and mucinous cystic neoplasm. Negative cytology reduces but does not eliminate the probability of high-grade dysplasia or invasive carcinoma, especially with a 2.8 cm cyst and limited sampling.
The recommendation should be multidisciplinary rather than a binary 'benign versus malignant' answer. In a fit patient, resection may be considered for a mucinous neoplasm of this size; in a comorbid patient, MRI/EUS surveillance is reasonable. I would state that the findings are compatible with a mucinous neoplasm with malignant potential, that malignancy cannot be excluded cytologically, and that final surgical pathology is required if resection is performed. The patient should not be told the cyst is benign.
3. The rapid on-site preliminary report said 'positive for mucinous neoplasm', while the final report says 'negative for malignancy'. Is this a discrepancy, and how should it be communicated?
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This is not a true discrepancy; it reflects two different axes of reporting. 'Positive for mucinous neoplasm' addresses whether a neoplastic process is present, whereas 'negative for malignancy' addresses whether invasive carcinoma or high-grade carcinoma was identified. The ambiguity lies in the word 'positive', which clinicians often hear as 'positive for cancer'. The final report should include an explanatory comment connecting the two statements: mucinous neoplasm present; no cytologic evidence of malignancy; malignancy not excluded due to sampling.
I would review the communication pathway as a quality issue, not change the final diagnosis to match the preliminary wording. The report should use standardized terminology and avoid unqualified 'positive'. If the preliminary phrase influenced the surgical decision, the cytopathologist and surgeon should discuss the findings directly. Documenting the distinction protects the patient and the laboratory.