Todays Quranic verse

And hold fast, all together, by the rope which God (stretches out for you), and
be not divided among yourselves; and remember with gratitude God's favour
on you; for ye were enemies and He joined your hearts in love, so that by His
Grace, ye became brethren; and ye were on the brink of the pit of Fire, and He
saved you from it. Thus doth God make His Signs clear to you: That ye may be
guided. [003:103]

REPRODUCTIVE SYSTEM-4
UTERINE

PATHOLOGY
Dr. Khurshid Anwar
https://www.facebook.com/pages/Human-Pathology/169869373198364

ENDOMETRITIS
Commonly consequence of pelvic inflammatory disease frequently due to N. gonorrhea
or C. trachomatis
May be due to retained products of conception, retained foreign body or IUD
Acute (neutrophilic) /Chronic (lymphoplamacytic)
Clinically characterized by fever, abdominal pain & menstural abnormalities
Late complications; infertility & ectopic pregnancy

TUBERCULOUS ENDOMETRITIS IN ENDEMIC COUNTRIES

Epidemiology
Benign
Can protrude through the cervix into the vagina (0.5-3 cm)
Clinical findings
Common cause of menorrhagia in 20- to 40-year-old age bracket
Spotting between menstrual periods or after menopause
Progress to endometrial carcinoma is very rare (<5%)
Association with tomoxifen
Diagnosis
Vaginal ultrasound
Dilation and curettage (D&C)
Histologically
Hyperplastic (dilated glands), Atrophic, Functional
Treatment
Dilation and curettage
Hysteroscopy

Stromal cells are monoclonal and have cytogenetic rearrangement at 6p21

Endometrial Polyp

Adenomyosis

Definition
Growth of basal layer of endometrium down into the myometrium. Presence or
invagination of nests of endometrial stroma or glands or both well down (2-3 mm)
beneath the endomyometrial interface in the myometrium, accompanied uterine
enlargement (reactive hypertrophy). These glands do not undergo cyclic bleeding

Epidemiology

Clinical findings

Definitive diagnosis with myometrial biopsy

Treatment is hysterectomy.

Highest incidence in women in mid- to late 40s

Common finding in hysterectomy specimens

Menorrhagia, dysmenorrhea, pelvic pain

Endometriosis

Epidemiology

Presence of functional endometrial glands and stroma in a location outside of endomyometrium.

Cyclic bleeding of gland and stromal implants
Prevalence is highest in women with dysmenorrhea (40-60%)
Average age at time of diagnosis is 25 to 29 years old.
Multifactorial inheritance: approximately 7% occurrence rate in first-degree female
relatives

Pathogenesis

Regurgitation theory (reverse menses through fallopian tubes-most common)

Metaplastic theory (coelomic metaplasia
Vascular or lymphatic dissemination theory

Endometriotic tissue exhibits increased levels of PGE2 & increased production of estrogen
due to high aromatase activity of stromal cells

Common sites

Ovaries (most common), pouch of Douglas, uterine ligaments, recto-vaginal septum,

fallopian tubes,
Other sites; peritoneal cavity, periumblical region, intestine, lymph nodes, lung, heart,
bone etc.

Endometriosis

Clinical findings

Dysmenorrhea (most common) , dyspareunia and infertility

Abnormal bleeding: (premenstrual spotting, menorrhagia)
Widespread fibrosis leading to adhesions among pelvic structures
Painful defecation during menses ( implants located in rectal pouch)
Intestinal obstruction and increased risk for ectopic pregnancy
Enlargement of ovaries (Blood-filled cysts- chocolate cyst)

Diagnosis

Laparoscopy useful for diagnosis and treatment

Red brown nodules or implants have a "powder burn" appearance (1-2 cm-diameter)
Histologically presence of 2 of 3 findings- endometrial gland, endometrial stroma,
hemosiderin pigment

Treatment

Combination oral contraceptives

Progestins (e.g., medroxyprogesterone acetate)

COX-2 inhibitors & aromatase inhibitors

Gonadotropin-releasing hormone agonists

Laparoscopic removal of implants

PID (Pelvic Inflammatory Disease)

Epidemiology

Diagnosed in 2% to 5% of women in STD clinics

Most common cause of female infertility and ectopic pregnancy
Risk factors
Multiple sexual partners, Vaginal douching, Previous episodes of PID, Unprotected sex

Most but not all cases of PID are STD/STI.

Causes of PID

Most often due to N. gonorrhoeae or C. trachomatis

Coexisting infection in 45% of cases

Other pathogens

B. fragilis, streptococci, Clostridium perfringens, Mycobacteria tuberculosis,

cytomegalovirus (CMV)

Gross findings

Fallopian tubes are filled with pus .

Most common cause of hydrosalpinx

Pus resorbs, leaving a clear fluid distending the tube.

Dysfunctional uterine bleeding

Bleeding in the absence of any organic (structural) cause
Anovulatory cycles
Inadequate luteal phase
Contraceptive induced bleeding
Postmenopausal bleeding

Endometrial hyperplasia
Epidemiology and pathogenesis
Prolonged estrogen stimulation
Early menarche or late menopause, Nulliparity , Obesity, Increased aromatization of
androgens to estrogen, PCOS, Taking estrogen without progesterone, Anovulatory
menstrual cycles, estrogen secreting ovarian tumors and hereditary NPCC

Diagnosis
Endometrial biopsy

Classification

Simple hyperplasia without atypia

Increased number of cystically dilated glands
Simple hyperplasia with atypia
Complex hyperplasia without atypia
Increased number of dilated glands with branching & glandular crowding
Clinically
Complex hyperplasia with Atypia (Atypical hyperplasia)
Glandular crowding and dysplastic epithelium & greatest risk for endometrial cancer
Menorrhagia,
(20-50%)
metrorrhagia,

menometrorrhagia
postmenopausal
bleeding

Endometrial hyperplasia is associated with inactivating mutation of PTEN

Simple Hyperplasia

Atypical Hyperplasia

Complex Hyperplasia

Atypical Hyperplasia

COMMON TUMORS OF
BODY OF UTERUS

&
ENDOMETRIUM

Histologic Classification of Malignant Neoplasms of Uterine Corpus

Endometrial Carcinoma
Endometrioid
Adenocarcinoma
Adenocarcinoma with squamous differentiation
(Adenoacanthoma

& Adenosquamous carcinoma)

Other types
(Serous, Clear cell , Mucinous & Squamous cell carcinoma)
Undifferentiated carcinoma

Non-epithelial Neoplasms
Endometrial stromal tumors
Stromal nodule, Low grade stromal sarcoma, High grade stromal sarcoma

Myometrial tumors
Leiomyoma
Smooth muscle tumor of uncertain malignant potential

Leiomyosarcoma
Mixed endometrial stromal and smooth muscle tumor

Mixed epithelial - nonepithelial tumors

Malignant mixed mesodermal tumor (MMMT)
(Homologous & Heterologous)

Miscellaneous

Metastatic tumors

Endometrial carcinoma

Epidemiology and pathogenesis

Most common gynecologic tumor, Median age at onset, 60 years old (55-65)
Prolonged estrogen stimulation (Type-I)
Same risk factors as endometrial hyperplasia

OCPs decrease risk (Type-I).

Due to antiestrogen effect of progestins OCPs: risk for endometrial cancer

Increased risk for breast cancer (Type-I)

Endometrial atrophy association (Type-II)
Types of endometrial cancer

(1) Endometroid carcinoma -well-differentiated adenocarcinoma (Type-I) 80%

Most common type & better prognosis

(2) Serous carcinoma- papillary adenocarcinoma (Type-II) 20%

Less common & highly aggressive cancer

Cancer characteristics

Clinical findings

Diagnosis

Treatment

Spreads down into the endocervix

Spreads out into the uterine wall
Lungs are the most common site of metastasis

Postmenopausal bleeding (90%), leucorrhea, enlargement of uterus

Endometrial biopsy

Surgery, radiation, hormones (tamoxifen), or chemotherapy depending on stage

5 year survival in stage I is 90% dropping to 30-50% in stage II and < 20% in stage III &IV.

Pathogenesis of adenocarcinoma (Type-I)

Pathogenesis of Serous Papillary adenocarcinoma (Type-II)

FBXW7
PPP2R1A
CCNE1

Characteristics

Type I

Type II

Age

55-65 (perimenopausal)

65-75 (postmenopausal)

Clinical setting

Unopposed estrogen

Atrophy, Thin physique

Risk factors

Hyperestrinism, Obesity,
Infertility Hypertension,
Diabetes

Endometrial atrophy

Morphology

Endometroid

Serous, Clear cell, MMT

Precursor

Hyperplasia

EIN

Molecular Genetics

PTEN, PIK3CA, KRAS,

MSI, Catenin, p53

P53, Aneuploidy, PIK3CA,

Histology

Mucinous, tubal and squamous

differentiation

Small tufts and papillae with

greater cytological atypia

Behavior

Indolent

Aggressive

Myometrial and vascular

infiltration

Intraperitoneal & lymphatic

spread

Diagnosis of endometrial cancer

Endometrial biopsy (outpatient);

If biopsy not diagnostic => Dilation and curettage=D&C (inpatient)

Staging endometrial carcinoma

Stage I- carcinoma confined to uterine corpus.
Stage II- carcinoma involves the corpus and the cervix.
Stage III- carcinoma extends outside the uterus, but not outside the
pelvis.
Stage IV- carcinoma extends outside pelvis (distant metastases) or
involves the mucosa of the bladder or rectum.

Leiomyoma (Fibroid)

Epidemiology

Most common benign connective tissue (smooth muscle) tumor in women

Most frequently diagnosed gynecologic tumor
Occurs in 30% to 50% of women > 30 years old
More common in blacks than whites
Monoclonal with rearrangement in chromosome 6 & 12
Estrogen-sensitive tumors

May become larger during pregnancy and atrophic after menopause

Tumor characteristics

Commonly undergo the following:

They rarely transform into leiomyosarcomas (<1%).

Menorrhagia (when located in submucosa)

Infertility, abortions
Obstructive delivery
Cramping during menses
Pressure on colon (constipation)
Pressure on bladder

(1) Degeneration
(2) Dystrophic calcification
(3) Hyalinization - Reason for the term "fibroids"

Clinical findings

Increased frequency, urgency, incontinence

Diagnosis

Treatment

Transabdominal or transvaginal ultrasound

MRI

Myotomy if women want to preserve fertility

Hysterectomy

Morphology
Gross; Multiple sharply

circumscribed, whorled cut surface

Microscopic; whorls and bundles of
smooth muscle cells

Leiomyoma- microscopic features

Leiomyosarcoma
Most common sarcoma of the uterus
Almost always solitary
Arise de novo, very rarely from leiomyoma
Tumor characteristics

Polypoidal or diffusely infiltrating

Soft hemorrhagic , necrotic mass
Numerous atypical mitoses, cellular atypia and foci of necrosis
Histological criteria for malignancy is nuclear atypia and mitotic index, generally >10
mitotic figures/10 HPF indicates malignancy

Peak incidence is at 40 to 60 (mostly postmenopausal)

Recurrence is frequent after removal and 50% metastasize
5 year survival is 10-40 %
Often recur and more than half eventually metastasize through the blood stream.
Treatment is surgery

Leiomyosarcoma-microscopic features

Malignant mixed mllerian tumors-MMMT

(carcinosarcomas)
Endometrial adenocarcinoma + malignant mesenchymal tumor
Primarily occur in postmenopausal women
Bulky, necrotic tumors that often protrude through the cervical os
Mesenchymal component may include muscle, cartilage, and bone.
Strong association with previous irradiation
Poor prognosis
Treatment is surgery
5 year survival 15-25%

ENDOMETRIAL STROMAL TUMORS

Benign stromal nodules,
Circumscribed aggregate of endometrial stromal cells in the myometrium

Low grade stromal sarcoma

(endolymphatic stromal myosis),
Well differentiated endometrial stroma lying between muscle bundles of myometrium but
penetrates lymphatic channels, 50% recur after 10-15 years, distant metastasis and death occur
in 15%

Endometrial stromal sarcoma

Histologically malignant tumor, infiltrating myometrium, widespread metastasis and 5 year
survival is 50%

GESTATIONAL TROPHOBLASTIC DISEASE

Spectrum of tumors and tumor like conditions characterized by proliferation
of pregnancy associated trophoblastic tissue of progressive malignant
potential

Hydatidiform mole

Benign
1;80-2000
Complete XX (85%)- XY no embryo
Partial (69, XXX or 69, XXY) +embryo
Bunch of grapes
Cystically dilated avascular chorionic villi
HCG
Curettage

Invasive Mole

Hydatidiform mole, generally of the complete type,

in which villi penetrate deeply in the myometrium
and/or its blood vessels lung, brain nodules
15% of complete moles
HCG
Hystrectomy

Choriocarcinoma

Malignant tumor derived from normal or abnormal placental tissue, composed of a proliferation of
cytotrophoblast and syncytiotrophoblast, without villi formation.
1-2% of complete moles
Clusters of cytotrophoblast separated by streaming masses of syncytiotrophoblast
HCG
Cytotoxic drugs

THANKS FOR YOUR ATTENTION