uterine pathology-2014-dr. khurshid anwar

8/10/2019 Uterine Pathology-2014-Dr. Khurshid Anwar

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And hold fast, all together, by the rope which God (stretches out for you), an

be not divided among yourselves; and remember with gratitude God's favou

on you; for ye were enemies and He joined your hearts in love, so that by H

Grace, ye became brethren; and ye were on the brink of the pit of F ire, and

saved you from it. Thus doth God make His Signs clear to you: That ye may

guided.[003:103]

Todays Quranic verse


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REPRODUCTIVE SYSTEM-4

UTERINE

PATHOLOGY

Dr. Khurshid Anwar

https://www.facebook.com/pages/Human-Pathology/169869373198364


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ENDOMETRITIS

Commonly consequence of pelvic inflammatory disease frequently due to N. gonorrh

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 abnormalitiesLate complications; infertility & ectopic pregnancy

TUBERCULOUS ENDOMETRITIS IN ENDEMIC COUNTRIES


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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 (


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Adenomyosis

Definition

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

Epidemiology Highest incidence in women in mid- to late 40s Common finding in hysterectomy specimens

Clinical findings Menorrhagia, dysmenorrhea, pelvic pain

Definitive diagnosis with myometrial biopsy

Treatment is hysterectomy.


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Endometriosis Epidemiology

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

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 femalerelatives

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 estrogendue 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, hearbone etc.


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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


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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 factorsMultiple sexual partners, Vaginal douching, Previous episodes of PID, Unprotected s

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. fragi l is, streptococci, Clostr idium p erfr ingens, Mycob acter ia 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.


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Dysfunctional uterine bleeding

Bleeding in the absence of any organic (structural) cause

Anovulatory cycles

Inadequate luteal phase

Contraceptive induced bleedingPostmenopausal bleeding


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E d t i l h l i


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Endometrial hyperplasia

Epidemiology and pathogenesisProlonged estrogen stimulation

Early menarche or late menopause, Nulliparity , Obesity, Increased aromatization of

androgens to estrogen, PCOS, Taking estrogen without progesterone, Anovulatorymenstrual cycles, estrogen secreting ovarian tumors and hereditary NPCC

ClassificationSimple 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

Complex hyperplasia with Atypia (Atypical hyperplasia)

Glandular crowding and dysplastic epithelium & greatest risk for endometrial can

(20-50%)

Endometrial hyperplasia is associated with inactivating mutation of PTEN

DiagnosisEndometrial biopsy

Clinically

Menorrhagia,metrorrhagia,menometrorrhagia

postmenopausalbleeding

Simple Hyperplasia Complex Hyperplasia


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Simple Hyperplasia Complex Hyperplasia

Atypical Hyperplasia Atypical Hyperplasia


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COMMON TUMORS OF

BODY OF UTERUS

&ENDOMETRIUM

Hi l i Cl ifi i f M li N l f U i C


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Histologic Classification of Malignant Neoplasms of Uterine Corp

Endometrial Carcinoma

EndometrioidAdenocarcinoma

Adenocarcinoma with squamous differentiation

(Adenoacanthoma & Adenosquamous carcinoma)

Other types

(Serous, Clear cell , Mucinous & Squamous cell carcinoma)

Undifferentiated carcinoma

Non-epithelial NeoplasmsEndometrial stromal tumors

Stromal nodule, Low grade stromal sarcoma, High grade stromal sarcoma


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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


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

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

Diagnosis Endometrial biopsy

Treatment 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.

P th i f d i (T I)


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Pathogenesis of adenocarcinoma (Type-I)

Pathogenesis of Serous Papillary adenocarcinoma (Type-II)

FBXW7

PPP2R1ACCNE1


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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

PrecursorHyperplasia EIN

Molecular Genetics PTEN, PIK3CA, KRAS,MSI, Catenin, p53

P53, Aneuploidy, PIK3CA

Histology Mucinous, tubal and squamousdifferentiation

Small tufts and papillae wigreater cytological atypia

Behavior Indolent Aggressive

Myometrial and vascularinfiltration

Intraperitoneal & lymphatspread

Diagnosis of endometrial cancer


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Diagnosis of endometrial cancer Endometrial biopsy (outpatient);

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


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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 thepelvis.

Stage IV- carcinoma extends outside pelvis (distant metastases) orinvolves the mucosa of the bladder or rectum.

Leiomyoma (Fibroid)


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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:

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

They rarely transform into leiomyosarcomas (


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Leiomyoma- microscopic features

Gross; Multiple sharplycircumscribed, whorled cut surface

Microscopic; whorls and bundles ofsmooth muscle cells

L i


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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


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Leiomyosarcoma-microscopic features

Malignant mixed mllerian tumors MMMT


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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%


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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 butpenetrates lymphatic channels, 50% recur after 10-15 years, distant metastasis and death occ

in 15%

Endometrial stromal sarcoma

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


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GESTATIONAL TROPHOBLASTIC DISEASE


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GESTATIONAL TROPHOBLASTIC DISEASE

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

potential

Invasive MoleHydatidiform mole, generally of the complete typein which villi penetrate deeply in the myometrium

and/or its blood vessels lung, brain nodules

15% of complete molesHCG

Hystrectomy

Hydatidiform moleBenign

1;80-2000Complete XX (85%)- XY no embryoPartial (69, XXX or 69, XXY) +embryo

Bunch of grapesCystically dilated avascular chorionic villi

HCGCurettage

ChoriocarcinomaMalignant 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 syncytiotrophoblastHCG

Cytotoxic drugs


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THANKS FOR YOUR ATTENTION

uterine pathology-2014-dr. khurshid anwar

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