histological classification 2013 Tumours of the Ovary

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    Epithelial-stromal tumoursSerous tumours

    BenignSerous cystadenomaSerous surface papilloma

    Serous adenofibroma

    Borderline TumoursAtypical proliferative serous tumor, Serous borderline tumor, usualtype (Surface or Cystic)Non-invasive micropapillary (low grade) serous carcinoma, Serous

    borderline tumor, micropapillary typeMalignant

    Low grade serous adenocarcinomaHigh grade serous adenocarcinomaTransitional-like adenocarcinoma

    WHO histological classification 2013

    Tumours of the Ovary

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    Transitional cell tumours

    Benign Brenner tumour

    Atypical proliferative Brenner tumour, Borderline Brennertumour

    Malignant Brenner tumour

    WHO histological classification 2013Tumours of the Ovary

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    a) High-grade ovarian carcinomas withstromal invasion

    b) Urologic TCC component >10%

    c) Large cystic spaces (70%), broad

    undulating papillae with smooth

    borders (60%), microspaces (90%)

    d) Lack of benign or borderline

    Brenner component

    e) Frequent high-grade serouscarcinoma component

    Eichhorn JH & Young RH Am J Surg Pathol 2004

    Transitional Cell Carcinoma (TCC)

    Eichhorn AJSP 2004

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    Transitional Cell Tumors (TCT)(Material)

    19 TCT

    5 Benign

    1 Malignant

    13 Brenner Tumors

    6 Transitional cell carcinomas (TCC)

    7 Borderline

    Cuatrecasas M et al. AJSP 2009

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    Transitional Cell Tumors (TCT)(Methods)

    EGFRRASCyclin D1p16

    Rbp53

    Immunohistochemistry(TMA)

    MutationalAnalysis

    FISH

    K-RAS

    BRAF

    CTNNB1PIK3CA

    p53

    -- EGFR

    Hypermethylation p16Rb

    LOH --p16

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    TCT

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    Transitional Cell Tumors of the Ovary

    (Mutations)p53mutations (4/4)Transitional cell carcinomas (4)

    9

    Malignant Brenner Tumor Transitional Cell Carcinoma

    Exon 9PIK3CA mutations (2):

    Borderline Brenner (1)

    Malignant Brenner (1)

    Cuatrecasas M et al. AJSP 2009

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    - +++

    -

    MalignantBrenner

    TCC

    p16 LOH

    P53 (chromosome instability)

    Molecular Genetics

    +++

    +

    +

    EGFR-RAS-MAPK

    PIK3CA mutations

    Cuatrecasas M. et al. AJSP 2009

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    67%

    WT1

    TCC

    Mg Brenner

    p53 ER p16 Cyclin D1 PiK3ca

    86% 71% 29%

    - -- - + +

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    80-90%

    10-20%

    43%90%

    70-100%

    30%

    Malignant

    Brenner

    TCC

    Stage I

    Stages II-IV

    Stage I survival

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    Histologic Subtypes of OvarianCarcinomas

    Serous high grade

    Serous low grade Clear cell

    Endometrioid Mucinous

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    New classification: Frequency

    HG serous

    LG serous

    Clear cell

    Endometrioid

    Mucinous

    Unclassifiable

    TP44

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    HGC

    CCC

    ECMC

    LGSC

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    Stage ClearCell

    Endometrioid Mucinous Low-GradeSerous

    CarcinomaNOS

    I-II 26.2% 29.4% 8.5% 1.9% 30% 4.0%

    III-IV 4.9% 3.5% 1.1% 4.9% 84.2% 1.4%

    All 10.4% 10.3% 3.6% 3.5% 70% 2.1%

    High-GradeSerous

    Ovarian Carcinomas:Stage at presentation (early vs advanced) according to

    Histologic Subtype

    Gilks CB et al.

    Mod Pathol 2009; 22:215A

    E d t i id d Cl C ll T d l

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    Endometrioid and Clear Cell Tumors develop

    from Ovarian Endometriosis

    Endometriosis

    Retrogrademenstruation

    Borderline

    tumor

    Carcinoma

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    Ovarian Atypical Endometriosis

    Endometrioid or Clear Cell Carcinomas

    15-32% of cases

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    Clear cell carcinoma

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    I Tumor confined to ovaries or fallopian tube(s) T1

    IA Tumor limited to one ovary (capsule intact) or fallopian tube, T1a

    No tumor on ovarian or fallopian tube surface

    No malignant cells in the ascites or peritoneal washings

    IB Tumor limited to both ovaries (capsules intact) or fallopian tubes T1b

    No tumor on ovarian or fallopian tube surface

    No malignant cells in the ascites or peritoneal washings

    IC Tumor limited to one or both ovaries or fallopian tubes, T1c

    with any of the following:

    IC1 Surgical spillIC2 Capsule ruptured before surgery or tumor on ovarian or fallopian tube surface

    IC3 Malignant cells in the ascites or peritoneal washings

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    1

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    II Tumor involves one or both ovaries or fallopian tubes with

    pelvic extension (below pelvic brim) or primary peritoneal

    cancer T2

    IIA Extension and/or implants on the uterus and/or fallopian

    tubes/and/or ovaries T2a

    IIB Extension to other pelvic intraperitoneal tissues T2b

    IIC Any of above, but with ascites or positive peritoneal washings

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    Uterine serosa

    O i C i i l i

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    Ovarian Carcinomas involving

    Retroperitoneal LNs Less than 10% of ovarian carcinomas have

    extended beyond the pelvis with exclusivelyRetroperitoneal Lymph Node involvement

    Literature evidence indicates that these caseshave better prognosis than tumors withabdominal peritoneal involvement

    No pathological distinction between high-gradeserous and low-grade serous carcinomas

    New Stage III - FIGO 2012

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    New Stage III FIGO 2012

    III One or both ovaries, fallopian tubes, or primary peritoneal cancer with

    pathologically proved spread to the peritoneum outside the pelvis and/ormetastasis to the retroperitoneal lymph nodes

    IIIB Macroscopic peritoneal metastasis beyond the pelvis 2 cm or less with or withoutmetastasis to the retroperitoneal lymph nodes

    IIIC Macroscopic peritoneal metastasis beyond the pelvis more than 2 cm with orwithout metastasis to the retroperitoneal lymph nodes

    (Note 1: includes extension of tumor to capsule of liver and spleen without parenchymal

    involvement of either organ)

    IIIA Metastasis to the retroperitoneal lymph nodes with or without microscopicperitoneal involvement beyond the pelvis

    IIIA1 Positive retroperitoneal lymph nodes only

    IIIA1(i) Metastasis ( 1 cm in size)IIIA1(ii) Metastasis (> 1 cm in size)

    IIIA2 Microscopic extrapelvic peritoneal involvement with or without positiveretroperitoneal lymph nodes

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    Ovarian Carcinomas

    Low-grade serous carcinomas may arisein lymph nodes from endosalpingiosis

    Djordjevic B, Malpica A.Am J Surg Pathol 2010, 2012

    SBT in Lymph Nodes (30%)

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    SBT in Lymph Nodes (30%)

    LN: Mullerian cysts (endosalpingiosis)

    SBT in lymph node

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    SBT in lymph node

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    Metastatic colonic carcinoma

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    Metastatic colonic carcinoma

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    Metastatic colonic carcinoma

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    Nodal Endosalpingiosis in Ovarian

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    Nodal Endosalpingiosis in Ovarian

    Serous Borderline Tumors with Lymph Node Involvement

    Ovarian

    SBT

    CervicalADCa

    EndometrialEndometrioid

    ADCa

    SBT withoutLNInv

    N. Cases 30 30 30 36 36

    NodalEndosalp 33 % 0% 3% 66% 14%

    SBT withLNInv

    Djordjevic et al

    Am J Surg Pathol 2010

    NodalEndosalp

    +

    LNI

    Intraglandularpattern

    50%

    Intraglandularpattern

    50%

    NodalEndos

    LNI

    8%8%

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    Diagnosis

    Serous borderline tumor and low-grade

    serous carcinoma (in situ andmicroinvasive) arising from extensivenodal endosalpingiosis

    (PCS-5514)

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    Metastatic HGSC in LNLN Endosalpingiosis SBT LGSC

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    Ovarian Carcinomas involving Lymph Nodes

    Less than 10% of ovarian carcinomas have extended beyond the pelvis withexclusively Retroperitoneal Lymph Node involvement

    Literature evidence indicates that these cases have better prognosis thantumors with abdominal peritoneal involvement

    Low-grade serous carcinomas may arise in lymph nodes fromendosalpingiosis

    Most of these cases probably represent separate primary low-grade

    serous carcinomas arising in lymph nodes from endosalpingiosiswhich explains their favorable prognosis

    New Stage III - FIGO 2012

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    Stage III

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    Hig-grade Serous

    MucinousEndometrioidClear Cell

    Low-grade

    PIK3CA20q amp

    PTENb-catenin

    KRASBRAF

    ERB2

    KRAS TP53/Rb pathwayChromosomal

    instability

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