Endometrial hyperplasia

Transcription

Mojgan Devouassoux-Shisheboran
Hôpital de la Croix Rousse
HCLyon
• Non invasive proliferation of the endometrium
resulting from sustained unopposed estrogen
stimulation
• Frequent anovulatory cycles (perimenopause,
adolescents, Stein-Leventhal)
• Postmenopausal with excess endogenous estrogen
or receiving exogenous estrogen
• Abnormal uterine bleeding
• May be incidentally found in a biopsy for
infertility or during HRT
• 8 to 12% of lesions in endometrial specimens
classification WHO/ISGYP
• Hyperplasia (without atypia)
– Simple
– Complex
• Atypical hyperplasia
– Simple
– Complex
• All types of hyperplasias are characterized by:
–
–
–
–
An increase in the gland-to-stroma ratio
Irregularities in gland shape
Variation in gland size
Curettage : ≥ 3 K7
classification WHO/ISGYP
Simple
Complex
without atypia
atypical
Architectural
criteria
Cytological
criteria
Hyperplasia without atypia
Simple
Complex
Simple hyperplasia
• Abundant material (at least 2 or 3 blocks)
• Numerous proliferating glands, dilated,
cystic with irregular size and shape
• Stroma is abundant G/S ratio > 1 but < 3
Dilated, cystic glands with varying degree of irregular
branching with infolding and outpouching of the glands,
separated by abundant stroma
Cytologically, the glandular epithelium resembles
proliferative endometrium (pseudostratified, oval nuclei
with evenly dispersed chromatin, mitoses)
Simple non atypical hyperplasia : diffuse
Simple non atypical hyperplasia
differential diagnosis
• Disordered proliferative endometrium :
secondary to anovulatory cycles, focal
branching and glandular dilatation
Simple hyperplasia
differential diagnosis
Endometrial polyps : numerous
irregular, dilated, proliferative type
glands, but focal lesion, surrounded
by normal endometrium , polypoid
shape, thick-walled vessels and
fibrous stroma
Complex hyperplasia
• More densely crowded glands showing increased
structural complexity with more outpouchings and
infoldings. Glands are closely packed with little
intervening stroma (G/S ratio > 3)
Complex hyperplasia
• Usually a mixture of simple (diffuse) and
complex (focal) hyperplasia
Complex hyperplasia without atypia
Pseudostratified epithelium
with small nuclei, oval
contours, resembling cells in
normal proliferative phase,
may show ciliated metaplasia
Artifacts
Fragmentation, stromal
collapse, telescoping resulting
in a “gland within gland”
appearance.
Hyperplasia with atypia
Cytological atypia : look at
higher power (atypia may be
focal in a background of diffuse
non atypical hyperplasia
Atypical hyperplasia
Nuclear features
• Stratification
• Loss of polarity
• Enlarged, rounded
• Irregular shapes
• Coarsening of chromatin
(vesicular appearance)
• Prominent nucleoli
Cytoplasmic features
• Eosinophilic cytoplasm
Architectural features
• Simple (very rare)
• Often complex
Complex atypical
hyperplasia
• Complex glands are
closely spaced
• Thin rim of stroma
between glands
• Papillary infolding or
tufts without
fibrovascular core
projecting into the
lumen
• Round and vesicular
nuclei
• Eosinophilic cytoplasm
Atypical complex hyperplasia
Squamous metaplasia
Differential diagnosis
well differentiated endometrioid carcinoma
Well differentiated carcinoma may have
bland nuclei
Based on architectural criteria :
1. Cribriform pattern, glands back-to-back
without stroma between the glands,
2. Exophytic papillae (extensive papillary
pattern)
3. Fibroblastic stroma (Desmoplastic
Norris et al, 1983
response)
Well differentiated
endometrioid carcinoma
• Cribriform pattern with confluent
glandular proliferation, without
stroma between glands
ACH with morules
squamous metaplasia fills and expands glands
leaving a partial rim of columnar gland cells and
giving a false aspect of cribriform pattern
Well differentiated endometrioid
carcinoma
• Exophytic papillae
• Extensive papillary
pattern with
fibrovascular core
Outcome of patients with
hyperplasia (n = 170)
Type
Nbre
d’hyperplasie de
ptes
Simple
93
Régression Persistance
Progression
vers ADK
74 (80%)
18 (19%)
1 (1%)
Complexe
29
23 (80%)
5 (17%)
1 (3%)
Simple
atypique
13
9 (69%)
3 (23%)
1 (8%)
Complexe
atypique
35
20 (57%)
5 (14%)
10 (29%)
Kurman et Norris 1985
2%
23%
Adenocarcinoma on FU hysterectomy
after diagnostic of AH
Gusberg et Kaplan
(1963)
21%
Tavassoli et Kraus
(1978)
25%
Kurman et Norris
(1982)
17%
Janicek et Rosenshein
(1994)
43%
Trimble et al (GOG)
(2006)
42,6%
• Associated with adenocarcinoma in 17 to
43% of cases
• Progress to adenocarcinoma in 23% of
cases in 4 years
= precursor of type I adenocarcinoma
Atypical hyperplasia (AH)
Classification used : Poor reproductibility amongst
pathologists in the diagnosis of AH
Study from GOG, 2006
• 302 cases of AH
• reviewed by 3 experts (Silverberg, Zaino, Trimble)
• both underestimation and overestimation
• 39% AH
• 29% carcinoma
• 25% < AH
EIN
Endometrial intraepithelial neoplasia
• In an attempt to improve on diagnostic
accuracy of endometrial hyperplasia and
to simplify the classification, Mutter
introduced the EIN terminology
Mutter, 2000
Baker et al, 2001
Non atypical endometrial lesions :
physiological response to a estrogenic stimuli,
polyclonal
Continuum lésionnel
proliferative
endometrium
Disordered
proliferative
Estrogen stimuli
Simple
hyperplasia
EIN
• Precancerous lesions and neoplasia
• Monoclonal
• Gene mutations (loss of PTEN and PAX2)
• 13% AH/2,3% NAH vs 19% EIN/0.6% no EIN
progress to ADK in 4 years (Baak et al, 2005)
Model of endometrial tumorogenesis
Mutter, 2000
Mutation PTEN
Perte expression PAX 2
prolifération sous effet
des oestrogènes
Anomalies
Précancer
œstrogène
indépendant
géniques
Transformation maligne
par accumulation
d’anomalies géniques
permettant l’invasion
(PIK3CA)
Pour PTEN, l’imprégnation oestrogénique joue un rôle de
promoteur au début, puis ensuite la prolifération tumorale
devient oestrogéno-indépendante au fur et à mesure de la
sélection des clones tumoraux
Réponse aux oestrogènes
EIN - morphology
• There is not a
perfect correlation
between AH and
EIN
• 37% of EIN are
classified as non
atypical hyperplasia
by WHO
EIN - ACH
EIN - NACH
Hyperplasia :WHO
• Low power : architectural criteria
– Simple
– Complex
• High power : cyto-nuclear criteria
– Non atypical
– Atypical
Endomètre prolifératif en préménopause
Prolifération persistante postménopausique
++
Disordered proliferative endometrium
Simple hyperplasia
Complex hyperplasia
Gene
mutations :
PTEN, PAX2
+/-
++
+/-
Gene
mutations :
PIK3CA
Estrogen stimuli
Adenocarcinoma
Progesteron
therapy
AH: therapeutic modalities
• In contrast to simple hyperplasia, atypical
hyperplasia is less hormone sensitive with
relaps and the end of the treatment
• Often simple hysterectomy but in < 40 YO
a medical treatment may be considered
Atypical hyperplasia and well differentiated
carcinoma in young patients may be treated
by progesterone TTT (DIU ou PO)
• Endometrioïd carcinoma grade 1
• Stage IA:
– No myoinvasion on T2 IRM
– No pelvic or aortic lymph node on CT
• Negative complete extension work up
• Acceptance of regular follow up with
curettage
Atypical hyperplasia and well differentiated
carcinoma in young patients may be treated
by progesterone TTT (DIU ou PO)
• AH (n=18) (FU = 11 months)
–
–
–
–
Complete regression
Regression to NAH
Persistence
Recurrence as ADK
67%
11%
22%
2 patients
• ADK (n=26) (FU = 12 months)
– Complete regression
– Persistence
42%
58%
Wheeler D, Kurman R. AJSP 2007; 31(7):988
Endometrioïd carcinoma
TTT progesterone 600mg/day
•
•
•
7 patients 20 to 34 YO
Evaluation every month
At 16 weeks : 5 cases with complete
response
–
–
1 pregnancy
No relapse after 5 years and 3 months
Kamoi et al, Int J Gynecol Cancer 2008
Endometrioïd carcinoma
TTT progesterone 600mg/day
1. Dystrophic glandular epithelium :
eosinophilic and vacuolated cytoplasm
(secretory changes)
2. Glandular fragmentation and
lymphocytic infiltrate
3. More morules
4. Atrophic glands with deciduolised
stroma
Kamoi et al, Int J Gynecol Cancer 2008
Reponse to progesterone TTT
• Architectural changes : dilated glands,
cribriforming and papillary changes
Stroma plus fibreux
• More mucinous and squamous metaplasia
• Rounded nuclei but less atypical and less
mitoses
Reponse to progesterone TTT
• Cyto-nuclear characteristics more than
architecture is indicative of therapeutic
response (no atypical nuclei, no mitosis)
• If after 6 months, atypical nuclei persist
: therapeutic feature
Mentrikoski et al, AJCP 2012; 138: 524
Therapeutic effects of progesterone
CAH in infertility work up of a 34 YO12NH11035
After 6 months of progesterone
Pathological management in
endometrial curetage for uterine
bleeding « hyperplasia »
• Hyperplasia : pathological terminology
• Hypertrophy : gross terminology
• In post menopausal : endometrial
thickness by sonography > 5 mm
– Secretory endometrium or progesterone TTT
Endometrium on progesterone
TTT
Secretory
endometrium
ACH
– Secretory endometrium or progesterone TTT
– Disordered proliferative endometrium
Disordered
proliferative
endometrium
– Secretory endometrium or progesterone
TTT
– Disordered proliferative endometrium
– Look for a polyp
–
–
–
–
Secretory endometrium or progesterone TTT
Look for a polyp
Look for chronic endometritis
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–
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Secretory endometrium or progesterone TTT
Look for a polyp
Look for chronic endometritis
Number of blocks (hyperplasia > 2 blocks)
Low power: numerous, irregular glands
Obj X 2
Obj X 20 ou 40
• Rule out « dyshormonal » (fonctionnal
bleeding)
• Proliferative or secretory type
endometrium without hyperplasia,
endometritis or malignancy
Terminology
Intra epithelial carcinoma (EIC)
• Precursor of type II cancers
Intra mucosal carcinoma
• Type I or type II carcinoma without
myometrial invasion
ZONE DE SECURITE
Carcinoma in situ
• Avoid this term leading in confusion
between intra epithelial carcinoma and
intramucosal carcinoma in clinician’s
mind
ANAPATH!!!!!
Alexandre Vasiljevic

Endometrial hyperplasia

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