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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, 2012
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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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