Update on Biliary Tumors - Gastrointestinal Pathology · 2019. 9. 14. · Cholangiocarcinoma...

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www.ascp.org Update on Biliary Tumors Jiaqi Shi, MD, PhD University of Michigan

Transcript of Update on Biliary Tumors - Gastrointestinal Pathology · 2019. 9. 14. · Cholangiocarcinoma...

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    Update on Biliary Tumors

    Jiaqi Shi, MD, PhD

    University of Michigan

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    Disclosure

    I have not had a significant financial interest or other

    relationship with the manufacturer(s) of the product(s) or

    provider(s) of the service(s) that will be discussed in my

    presentation.

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    Biliary Neoplasms

    Intrahepatic

    Extrahepatic• Perihilar bile duct

    • Distal bile duct

    • Gallbladder

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    Anatomy of extrahepatic biliary system

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    Distal bile duct

    Perihilar bile duct

    Gallbladder

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    WHO 4th Edition WHO 5th Edition

    BilIN

    -1: Low grade

    -2: Intermediate grade

    -3: High grade

    BilIN

    -low grade (low, intermediate)

    -high grade

    Intraductal/Intracystic papillary neoplasm (IPNB/ICPN)

    -Low, intermediate, high-grade intraepithelial

    neoplasia

    Intraductal/Intracholecystic papillary neoplasm (IPNB/ICPN)

    -low, high-grade intraepithelial neoplasia

    -Intraductal tubular/tubulopapillary neoplasm (ITPN)-B

    Adenoma

    Tubular

    Papillary

    Tubulopapillary

    Pyloric gland adenoma of the gallbladder

    Signet ring cell carcinoma Poorly cohesive carcinoma with or w/o signet ring cells

    NET G1, G2, NEC NET G1-G3, NEC

    Mixed adenoneuroendocrine carcinoma Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN)

    Changes of Biliary Tumor Classifications in WHO 5th Edition

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    Preinvasive lesions of the biliary tract

    • Biliary intraepithelial neoplasia(BilIN)

    • Pyloric gland adenoma

    • Intraductal papillary neoplasm of bile duct (IPNB)/Intracholecystic papillary neoplasm (ICPN)

    o Intraglandular neoplasms of the peribiliary glands?

    o Intraductal tubulopapillary neoplasm of the bile duct (ITPN-B)

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    BilIN

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    Normal LG BilIN

    HG BilIN LG+HG BilIN

    Microscopic

    KRAS-40%, early event

    TP53—late event

    Risk of recurrence:

    extensive BilIN, RAS

    involvement, pos margin

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    Pyloric Gland

    Adenoma

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    Grossly visible

    50-60% associated with stone

    PJ, FAP syndrome

    Paneth cells, NE cells

    CTNNB1 mutation-60%

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    Pyloric Gland

    Adenoma with

    “squamous

    morules”

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    ~ 1/3 of PGA

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    Pyloric Gland Metaplasia

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    Pyloric Gland Adenoma

    VS

    VS

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    IPNB with LGD

    Gastric

    Most unclear etiology,

    associated with PSC, stone,

    fluke

    40-80% IPNB a/w invasive

    carcinoma

    Half IPNBs contain ≥2

    epithelial types (PB most

    common in US, Int/Gast in

    Asia)

    KRAS, p16, TP53,

    GNAS/RNF43-intestinal

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    ICPN with LGD

    Gastric

    More common in female

    No known association

    with stone

    Invasive Ca in ~50% ICPN

    More mixed than IPMN

    KRAS

    TP53, GNAS rare

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    IPNB with

    HGD

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    Invasive

    adenoCA

    arising in

    IPNB with

    HGD

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    Epithelial

    phenotypes

    Inv CA derived

    from PB type

    IPNB is a/w worse

    outcome than CA

    derived from

    Int/Gast type

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    PB Intestinal

    Gastric Oncocytic

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    Histol Histopathol (2017) 32: 1001-1015

    No difference in

    survival

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    Cystic

    micropapillary

    neoplasm of

    peribiliary glands

    – flat branch duct

    type IPNB?

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    Virchows Arch. 2014 Feb;464(2):157-63

    World J Gastroenterol. 2016 Feb 21;22(7):2391-7

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    ICPN: noninvasive, overall uniform papillary architecture,

    thin or edematous fibrovascular stalks

    Papillary GBC: invasive cancers, grossly predominant

    polypoid growth, histologically papillary or papillotubular

    adenocarcinomas with an overall architecture that was more

    complex than that expected in IPNBs

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    Whole-exome and Sanger

    sequencing

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    Intraductal

    tubulopapillary

    neoplasm

    (ITPN) of the

    bile duct

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    Histol Histopathol (2017) 32:

    1001-1015

    • Solid

    • Tubular

    • No/little mucin

    • Necrosis

    • Uniform HGD

    Currently grouped under IPNB

    Courtesy of Dr. Olca Basturk, MSK

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    Precursor biliary lesions

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    BilIN IPNB ITPN-B

    Microscopic Macroscopic Macroscopic

    Flat or micropapillary

    (

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    Now on to the EVIL…

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    Cholangiocarcinoma classifications

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    • Anatomic location: Intrahepatic (ICC), extrahepatic (ECC)

    • Macroscopic growth pattern: mass forming, periductal

    infiltrating, intraductal, mixed

    • Microscopic:

    o Intrahepatic: small duct, large duct

    o Extrahepatic: adenocarcinoma and variants

    • Cell of origin: stem cells in canals of Hering, stem cells in

    peribiliary glands

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    Staging primary cancers of distal bile duct

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    pTNM AJCC 7th Edition AJCC 8th Edition

    Tis Carcinoma in situ Carcinoma in situ /HGD (BilIN3)

    T1 Tumor confines to bile duct Tumor invades 12 mm

    T4 Tumor involves celiac axis or SMA Tumor involves celiac axis, SMA,

    and/or CHA

    N N1-regional LN met N1: 1-3 LNs; N2: ≥4 LNs

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    Depth of tumor invasion better predicts prognosis

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    Surgery. 2009 Aug;146(2):250-7

    N=147

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    N=370

    Br J Surg. 2015 Mar;102(4):399-406.

    The number of involved nodes

    was a strong predictor of

    survival

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    Measuring tumor depth in cholangiocarcinoma

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    Depth of invasion

    - - - Invasive tumor thickness

    Tumor depth measured from the basement membrane of adjacent normal or dysplastic epithelium

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    The four‐tier ITT classification with cut‐off points of 1, 5 and 10 mm seems to be a better T system than those in the seventh

    and eighth editions of the AJCC classification.

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    Br J Surg. 2018 Jun;105(7):867-875

    DOI could be

    measured in only 182

    (45%)

    ITT can measure all

    ITT:

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    Staging primary cancers of perihilar bile duct

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    pTNM AJCC 7th Edition AJCC 8th Edition

    Tis Carcinoma in situ Carcinoma in situ /HGD (BilIN3)

    T1 Tumor confines to bile duct up to muscle layer or

    fibrous tissue

    same

    T2 Tumor invades beyond bile duct to adipose

    tissue or liver

    same

    T3 Tumor invades unilateral PV or HA branches same

    T4 Tumor invades main PV or its bilat branches,

    or CHA, or 2nd order biliary radicals bilat, or

    unilat 2nd order biliary radicals with contralat

    PV/HA

    Tumor invades main PV or its bilat

    branches, or CHA, or unilat 2nd order

    biliary radicals with contralat PV/HA

    N N1:regional LN; N2: periaortic, pericaval,

    SMA, CA LN

    N1:1-3 LNs; N2:≥4 LNs

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    Removal of Bismuth type IV tumors from the T4 determinants

    enhance the prognostic prediction

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    Br J Surg. 2014 Jan;101(2):79-88

    N=1352Modified Bismuth-Corlette

    classification of hilar

    cholangiocarcinoma

    Ann Surg. 1992 Jan;215(1):31-8

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    The newly released classification American Joint Committee on Cancer 8th edition

    staging system demonstrated a poor to moderate ability to predict prognosis of

    patients undergoing liver resection for perihilar cholangiocarcinoma, which was

    only slightly better than the previous edition

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    Surgery. 2018 Aug;164(2):244-250N=214

    7th Ed. 8th Ed.

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    A four‐tier ITT classification with cut‐off points of 1, 5 and 8 mm is an adequate alternative to the current layer‐based AJCC T classification in perihilar cholangiocarcinoma

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    Br J Surg. 2019 Mar;106(4):427-435

    N=440AJCC ITT

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    Staging primary cancers of gallbladder

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    pTNM AJCC 7th Edition AJCC 8th Edition

    Tis Carcinoma in situ Carcinoma in situ

    T1 Tumor invades lamina propria or muscular layer same

    T2 Tumor invades perimuscular connective

    tissue, but not into liver or serosa

    T2a: peritoneal side

    T2b: hepatic side

    T3 Tumor perforates serosa or invades

    liver/other organ

    same

    T4 Tumor invades main PV or HA or ≥2

    extrahepatic organs

    same

    N N1:regional LN; N2: periaortic, pericaval,

    SMA, CA LN

    N1:1-3 regional LNs; N2:≥4 LNs

    (Recommend ≥6 LN be harvested)

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    Ann Surg. 2015 Apr;261(4):733-9

    Peritoneal side: only free serosal side

    Hepatic side: any infiltration of liver part

    Higher LVI, PNI, LN

    metastasis in

    hepatic side tumor

    No difference in T1

    & T3

    https://www.ncbi.nlm.nih.gov/pubmed/24854451

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    Genomics of gallbladder and extrahepatic bile duct carcinoma

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    WHO 5th Edition

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    Take Home Message

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    • Yes, it went blue, but not too bad

    • Dysplasia grading: 3-tiered to 2-tiered

    • Adenomas: split into PGA or IPNB/ICPN

    • NENs: unified with other GI NENs

    • AJCC: find your

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    Thank you for

    your attention!

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