Uterine Pathology Guide

Sufia Husain.
Pathology Department
KSU, Riyadh
March 2018
Reference: Robbins & Cotran Pathology and Rubin’s Pathology
The Uterine Corpus Pathology

Uterus with bilateral tube and ovaries, posterior view
http://pixgood.com

http://www.humpath.com/IMG/jpg/uterus_03_1.jpg
http://www.wikilectures.eu/images/thumb/8/82/Vagina_uterus.png/720px-
Vagina_uterus.png

http://pixgood.com/uterus-histology.html
http://pixgood.com/uterus

Lecture Outline
Lecture: Endometrial hyperplasia, uterine cancer and
fibroids (leiomyomas).
At the end of this lecture, the student should know:
Lesions of endometrium of uterus: know the risk factors,
clinical presentation, macroscopic and histological
features of
Endometrial hyperplasia
Endometrial carcinoma
Lesions of myometrium of uterus:
Leiomyoma : understand the pathology and clinical
features of uterine leiomyomas andis aware that
leiomyoma (fibroid) is the commonest neoplasm arising
in the female genital tract.
Leiomyosarcoma

 Endometrial hyperplasia is a
process in which there is a
proliferation of endometrial glands
resulting in an increase in the
gland/stroma ratio of the
endometium when compared to
normal.
 It is induced by persistent,
prolonged stimulation of the
endometrium by high levels of
estrogen.
 The endometrial hyperplasia may
progress to endometrial
carcinoma.
 The risk of developing carcinoma
depends on the level and duration
of the estrogen excess, the severity
of the endometrial hyperplasia and
associated cellular atypia.
Endometrial Hyperplasia

Causes of Endometrial Hyperplasia: any condition in which
there
is high estrogen level can lead to endometrial hyperplasia e.g.
a.Anovulatory menstrual cycles (failure of ovulation).
b.Excessive endogenous production of estrogen (by the body)
e.g. in
 polycystic ovary syndrome (Stein-Leventhal syndrome),
 granulosa cell tumors of the ovary
 cortical stromal hyperplasia (excessive ovarian cortical
function)
a.Exogenous administration or intake of estrogenic steroids
without counter balancing progestins, over a long period of
time.
Endometrial Hyperplasia: causes

• Mild type of hyperplasia tends to occur in younger
patients. Most of the mild hyperplasia cases regress, either
spontaneously or after treatment.
• The more severe type of hyperplasia occur mainly in
perimenopausal or postmenopausal women. This form has
a significant premalignant potential.
• Patients with endometrial hyperplasia usually present with
abnormal uterine bleeding.
Endometrial Hyperplasia: clinical

Endometrial hyperplasia
http://pixgood.com/endometrial-hyperplasia.html

Endometrial Hyperplasia: classification
In endometrial hyperplasia there is proliferation of both glands and stroma but the proliferation
of the glands is much more leading to over crowding of glands. Endometrial hyperplasia is
classified based on (A) and (B):
CLASSIFICATION OF ENDOMETRIAL HYPERPLASIA:
I. Simple hyperplasia
• Without atypia
• With atypia
II. Complex hyperplasia
• Without atypia
• With atypia Note: atypia/ pleomorphism = loss of polarity, vesicular
nuclei, prominent nucleoli, rounded cells.

http://quizlet.com/22858165/srwk3

 Simple hyperplasia (cystic
hyperplasia): glands are
varibly shaped and sized
and cystically dilated with
abundant cellular stroma
and give a "Swiss Cheese"
appearance.
 There is a mild increase in
the gland-to-stroma ratio
 These lesions rarely progress
to adenocarcinoma
 Simple hyperplasia may
progress to cystic atrophy
Simple hyperplasia without atypia

 Uncommon
 It has the Architecture of simple hyperplasia, but
there is cytologic atypia within the glandular
epithelial cells
 10% of such lesions progress to carcinoma
Simple hyperplasia with atypia

 Proliferation of endometrial
glands resulting in complex
crowded glands with
papillary infoldings and
irregular shapes. The
crowded glands are back-
to-back with very little
intervening stroma.
 The epithelial cells remain
cytologically normal.
 3% progression to
carcinoma
Complex hyperplasia without atypia

 Complex proliferation of
endometrial glands (back-to-
back irregular glands) with
atypia.
 The nuclei show loss of polarity
and are enlarged and
rounded and may have
irregular nuclear membranes
 Commonly about 30% of
women with this diagnosis have
carcinoma somewhere in the
uterus when a hysterectomy is
performed
 About 30% progress to
carcinoma
Complex hyperplasia with atypia

 Some endometrial hyperplasia revert to normal
spontaneously or with medical treatment, others persist as
hyperplasia, and a few progresses to endometrial
adenocarcinoma.
 The risks for developing adenocarcinoma in each are as
follows:
 Simple hyperplasia without atypia — 1%
 Complex hyperplasia without atypia — 3%
 Simple hyperplasia with atypia (simple atypical hyperplasia) — 10%
 Complex hyperplasia with atypia (complex atypical hyperplasia) —
30%
 Atypical hyperplasia in postmenopausal women appears
to have a higher rate of progression to adenocarcinoma.
Endometrial Hyperplasia: Clinical behavior and premalignant potential

 Obesity
 Western diet
 Nulliparity
 Diabetes Mellitus
 Hypertension
 Hyperestrinism
Endometrial Hyperplasia,
Risk Factors

Endometrial
adenocarcinoma
This is a common neoplasm in women.
Overall it is the fifth commonest cancer in
women.
•Endometrial cancers arise mainly in
postmenopausal women
•They cause postmenopausal bleeding
•Early detection and cures are possible
•These tumors are classified into two
broad categories:
 Type I carcinomas (also known as
endometrioid carcinoma): accounts
for 80% of endometrial cancers. It is
the most common type. e.g.
endometrioid adenocarcinoma and
its variants.
 Type II carcinomas: they are
papillary serous carcinoma and
clear cell carcinoma. Papillary
serous is the more common form of
type II carcinoma.
www.healthtap.com

• Endometrioid carcinoma is associated with estrogen excess and
endometrial hyperplasia. The majority of the carcinomas are well
differentiated.
• Endometrial hyperplasia is a precursor to endometrioid carcinoma
• Risk factors for type I are they same as that of endometrial hyperplasia
and include:
 Obesity
 Western diet
 Nulliparity
 Diabetes Mellitus
 Hypertension
 Hyperestrinism
 Estrogen therapy
 chronic anovulation
 Late menopause
 Tamoxifen therapy
 High socioeconomic status.
The disease may follow atypical hyperplasia but may occur independently
of it especially in older patients.
Type I endometrial carcinoma/ endometrioid carcinoma

Usual sequence of events in Type I endometrioid
carcinoma

1. Majority of endometrioid
carcinomas have PTEN
gene mutations.
2. Also there maybe
inactivation of DNA
mismatch repair genes
3. p53 mutations is seen in
half of the poorly
differentiated
endometrioid carcinomas.
Type I endometrioid carcinoma: genetics
http://www.proteinatlas.org/images_dictionary/endometrial_cancer__1__figo_1__overview.jpg

Endometrial carcinoma
Picture Taken from Robbins and Cotran Pathologic basis of disease. 8th edition, Chapter 21, 2010 Sanders

Type II endometrial carcinomas:
Serous carcinoma
 Serous carcinoma arises in older women, with endometrial atrophy (small atrophic
uterus).
 They occur in late in life, about one decade later than type I carcinoma
 There is no association with hyperestrinism or preexisting hyperplasia
 They represent 15% of cases of all endometrial carcinoma
 Mutations in p53 are present in at least 90% of serous endometrial carcinoma
 The precursor of serous carcinoma is endometrial intraepithelial carcinoma (its like
carcinoma in situ)
 These tumors are large bulky poorly differentiated tumors which invade early into
the myometrium and have a poor prognosis. Extrauterine extension is common.

CHARACTERISTICS OF TYPE I AND TYPE II ENDOMETRIAL CARCINOMAS
FEATURES TYPE I TYPE II
HISTOLOGIC TYPE Endometriod
adenocarcinoma
Serous or clear cell
carcinoma
AGE Premenopausal and
perimenopausal (50-60 yrs)
Post menopausal (~ 70 yrs)
UNOPPOSED ESTROGEN Present Absent
PRECURSOR LESION Hyperplasia with atypia Endometrial intraepithelial
carcinoma
GROWTH Slow growing Rapidly progressing
GRADE Low High
MYOMETRIAL INVASION Usually superficial Usually deep
PROGNOSIS Favorable Poor
GENETIC ALTERATIONS
NOTED
PTEN, microsatellite instability P53 mutations

• Most patients are between
50 and 60 years.
• Many of the patients tend
to be nulliparous and
obese.
• Patients have abnormal
vaginal bleeding and
excessive leucorrhea.
• Elderly women present with
postmenopausal bleeding.
• The diagnosis of
endometrial cancer must
be confirmed by biopsy or
curettage and histologic
examination of the tissue.
Endometrial adenocarcinoma: clinical
features
http://upload.wikimedia.org/wikipedia/commons/0/00/Endometrial_hyperplasia.jpg

 Grossly:
 May look close to normal or exophytic or infiltrative
 Microscopy:
 Both type I and II are adenocarcinomas.
 In both cases tumors originate in the endometrium and can
eventually infiltrate the underlying myometrium, enter
vascular spaces and metastasize to lymph nodes.
 Serous carcinoma has much greater cytologic atypia and
are more poorly differentiated and is therefore more
aggressive
 Tumor spreads by:
 Direct myometrial invasion with extension to the periuterine
structures
 Through lymphatics to lymph nodes
 In the late stages, metastasize to the lungs, liver, bones,
others
Endometrial carcinoma: basic
morphology

• Clinical behavior of endometrial
adenocarcinoma depends on the histologic
type, the grade (degree of differentiation) and
the stage (extent of spread).
• Endometrioid carcinoma (type I) has a better
prognosis than the other histologic types.
• Serous carcinomas (type II) have poorer
prognosis
• Stage is the major determinant of survival.
Endometrial adenocarcinoma:
prognosis

How endometrial
carcinoma can spread
(stages 1, 2 and 3 of endometrial carcinoma)
"Diagram showing stage 1A and 1B, 2 and 3A to 3C cancer of the womb CRUK 196, 206 and 224" by Cancer
Research UK - Original email from CRUK. Licensed under CC BY-SA 4.0 via Wikimedia Commons -
http://commons.wikimedia.org/wiki/File:Diagram_showing_stage_1A and 1B ,
2_and3A_to_3C_cancer_of_the_womb_CRUK_206.svg#/media/File:Diagram_showing_stage_1A_and_1B,_2 and
3A_to_3C__cancer_of_the_womb_CRUK 196 and 206 and 224.svg

• Leiomyoma is a benign tumor of smooth muscle origin.
• It is the most common neoplasm of the female genital tract
and probably the most common neoplasm in women.
• The tumor is estrogen responsive. Estrogen stimulates their
growth. Leiomyomas often increases in size during pregnancy
and decrease in size after menopause.
• About 40% of leiomyomas have an associated chromosomal
abnormality
• They are benign tumors with no appreciable malignant
potential (incidence of malignant transformation to sarcoma is
0.1-0.5%).
Leiomyoma (fibroid) of uterus

Clinical features
 It can be single or multiple (mostly multiple).
 Irregular abnormal bleeding and sometimes pelvic pain.
 It may cause anemia from heavy bleeding.
 Can have urinary frequency if the fibroid is compressing the
urinary bladder.
 It may interfere with implantation and therefore cause
infertility.
 In pregnant women it may cause abortion, obstructed labor,
post partum hemorrhage etc.
 Alternatively it maybe entirely asymptomatic
Leiomyoma (fibroid) of uterus

Leiomyoma may be located
anywhere in the
myometrium.
• Submucosal tumors are
present immediately below
the endometrium.
• Intramural tumors, the most
common, lie within the
myometrium.
• Subserosal fibroids lie
beneath the serosal surface
of the uterus or are
pedunculated and attached
to the serosa.
• Pedunculated ones may
loose their connection to the
uterus forming a "parasitic
leiomyoma".
Uterine Leiomyoma
http://www.fibroidoptions.com/images/fibroid1.jpg
http://www.humpath.com/IMG/jpg/uterine_leiomyoma_0412_3.jpg

Leiomyoma gross:
Well circumscribed, spherical, dense and firm-to-
hard masses.
Cut section shows whorled, tan-white cut surfaces.
"Leiomyoma" by Ed Uthman from Houston, TX, USA - Leiomyoma. Licensed under CC BY 2.0
via Wikimedia Commons -
http://commons.wikimedia.org/wiki/File:Leiomyoma.jpg#/media/File:Leiomyoma.jpg

Leiomyoma: Microscopically, there are interlacing bundles
of smooth muscle cells with collagenous stroma between
bundles. The individual muscle cells are uniform in size and
shape. They have the characteristic oval to elongated
nucleus. Mitotic figures are scarce.
http://pixgood.com/myometrium.html
http://pixgood.com/leiomyoma-histology.html

 It is the malignant tumor of the smooth
muscle.
 It is rare.
 Sites include the uterus and soft tissue
 Poor prognosis.
Leiomyosarcoma

Uterine Pathology Guide

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