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Molecular Diagnostics in Cytopathology pp 355–376Cite as

Molecular Diagnostics in Pancreatic and Biliary Cytology

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Abstract

Increasing discoveries of the molecular alterations underlying pancreatic and biliary lesions have led to the utilization of cytology samples for molecular testing. Currently in pancreaticobiliary cytology, routine molecular testing has limited diagnostic utility except in the preoperative evaluation of pancreatic cysts and the detection of malignancy in biliary duct brushings. Because of the significant morbidity and mortality associated with pancreatic surgeries, it is of paramount importance to distinguish benign from premalignant/malignant cystic lesions preoperatively. In some institutions, molecular testing is being routinely performed on pancreatic cyst fluid to improve the detection of mucinous cysts, where the detection of a KRAS and/or GNAS mutation is highly specific for a mucinous etiology, and GNAS mutations are diagnostic of intraductal papillary mucinous neoplasm. The addition of molecular testing can be particularly helpful in cases where cytology and/or CEA are noncontributory and thus significantly improves the sensitivity of pancreatic cyst fluid analysis. With bile duct brushings, the addition of fluorescence in situ hybridization (FISH) to cytology is an established ancillary test for the diagnosis of bile duct carcinoma, and next-generation sequencing has also shown promise as a valuable ancillary tool. Late mutations in the progression to malignancy such as p16 (CDKN2A/INK4A) and SMAD4 deletions support a high-risk lesion in both pancreatic cyst fluids and bile duct brushing specimens.

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Abbreviations

ACC:

Acinar cell carcinoma

CEA:

Carcinoembryonic antigen

DNA:

Deoxyribonucleic acid

EUS:

Endoscopic ultrasound

FISH:

Fluorescence in situ hybridization

FNA:

Fine-needle aspiration

GNAS :

Guanine nucleotide-binding protein, alpha stimulating

IPMN:

Intraductal papillary mucinous neoplasm

KRAS :

Kirsten rat sarcoma viral oncogene homolog

MCN:

Mucinous cystic neoplasm

NGS:

Next-generation sequencing

PanNEC:

Pancreatic neuroendocrine carcinoma

PanNET:

Pancreatic neuroendocrine tumor

PCF:

Pancreatic cyst fluid

PDAC:

Pancreatic ductal adenocarcinoma

pRb:

Retinoblastoma protein

SCA:

Serous cystadenoma

SPN:

Solid pseudopapillary neoplasm

VHL :

von Hippel-Lindau

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Author information

Authors and Affiliations

  1. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Mingjuan Lisa Zhang

  2. Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    Martha Bishop Pitman

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  1. Mingjuan Lisa Zhang
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Corresponding author

Correspondence to Martha Bishop Pitman .

Editor information

Editors and Affiliations

  1. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    Sinchita Roy-Chowdhuri

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Paul A. VanderLaan

  3. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    John M. Stewart

  4. Department of Laboratory Medicine, University of Toronto, Toronto, ON, Canada

    Gilda da Cunha Santos

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Zhang, M.L., Pitman, M.B. (2019). Molecular Diagnostics in Pancreatic and Biliary Cytology. In: Roy-Chowdhuri, S., VanderLaan, P., Stewart, J., Santos, G. (eds) Molecular Diagnostics in Cytopathology. Springer, Cham. https://doi.org/10.1007/978-3-319-97397-5_15

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  • DOI: https://doi.org/10.1007/978-3-319-97397-5_15

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