D R L I N A A L H A F F A R

P R O F P A T H O L O G Y

Female Genital Systemand Breast

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Female Genital Systemand Breast

Vulva Nonneoplastic Epithelial Disorders Tumors Condylomas Carcinoma of the Vulva Vagina Vaginitis Malignant Neoplasms Cervix Cervicitis Neoplasia of the Cervix Squamous Intraepithelial Lesion (SIL,

Cervical Intraepithelial Lesion) Invasive Carcinoma of the Cervix Endocervical Polyp Uterus Endometritis Adenomyosis Endometriosis Endometrial Hyperplasia Endometrial Carcinoma Endometrial Polyps Leiomyoma Leiomyosarcoma

Fallopian Tubes Ovaries Follicle and Luteal Cysts Polycystic Ovarian Syndrome Tumors of the Ovary Surface Epithelial Tumors Diseases of Pregnancy Ectopic Pregnancy Gestational Trophoblastic Disease Hydatidiform Mole: Complete and Partial Invasive Mole Gestational Choriocarcinoma Placental Site Trophoblastic Tumor Breast Clinical Presentations of Breast Disease Inflammatory Processes Stromal Neoplasms Benign Epithelial Lesions Carcinoma Epidemiology and Risk Factors

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CERVIXCERVICAL SQUAMOUS NEOPLASIA :

Incidence associated with sexual intercourse (especially number of male partners)

Human papillomavirus HPV postulated as main causative factor, with cigarette smoking as independent risk factor

Pre-invasive phase of intraepithelial neoplasia can be detected by cervical cytology( PAP Smear )

Cervical Intraepithelial Neoplasia (CIN) graded from 1 to 3 according to severity of abnormality

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CERVICAL SQUAMOUS NEOPLASIA :

Human papillomaviruses and neoplasia of the lower female

genital tract : Genital warts or condylomata

have been recognised for centuries. The features associated with human

papillomavirus infection are: koilocytosis hyperkeratosis parakeratosis papillomatosis individual cell keratinisation

(dyskeratosis) multinucleation.

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CERVICAL SQUAMOUS NEOPLASIA :

The categorization of cervicalintraepithelial neoplasia into :

Low grade SIL (CIN 1)

high grade SIL (CIN 2 and 3) reflects the clinical management of the disease.

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UTERINE CORPUS

Iatrogenic changes in the endometrium:

exogenous hormones, including oral contraceptive preparations and hormone replacement therapy

the use of a mechanical intra-uterine contraceptive device

tamoxifen administration for patients with breast cancer.

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Endometrial hyperplasiaNew WHO Classification

I- Hyperplasia without atypia

II- Hyperplasia With Atypia also called endometrial

intraepithelial neoplasia (EIN), is associated with a much

higher risk (20%–50%).

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Endometrial adenocarcinoma

May result from unopposed estrogenic action or in atrophic post-menopausal endometrium

Two histologic types :

1- endometrioidadenocarcinoma

2- serous adenocarcinoma

The extent of myometrial invasion at the time of diagnosis is the single most important prognostic factor.

Involvement of the endocervix also has an adverse effect on prognosis.

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ABNORMALITIES OF THE MYOMETRIUM Adenomyosis (myometrial endometriosis )

Adenomyosis ( myometrialendometriosis) is a common finding in hysterectomy specimens and refers to the presence of endometrial glands and stroma deep within the myometrium.

Endometriosis :It occurs in peri-menopausal multiparous women and is of uncertain etiology, although it may be regarded as a form of 'diverticulosis',

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Smooth muscle tumors

Benign : Uterine leiomyomas (fibroids) are the commonest benign tumors

Associated with infertility Malignant : Leiomyosarcomas

have varying malignant potential correlated with their mitoticactivity

The precise etiology of leiomyomas is unknown.

They may present clinically with: abdominal mass urinary problems due to pressure on the

bladder abnormal uterine bleeding.

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OVARY

OVARIAN CYSTS :

The various types of non-neoplastic cysts are :

follicular luteinized follicular corpus luteum corpus albicans corpus luteum cyst of pregnancy Endometriotic

Polycystic ovary PCO syndrome The polycystic ovary syndrome is the

association of amenorrhoea, hyperoestrogenism and multiple follicular cysts of the ovary

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OVARIAN NEOPLASMS

May be solid or cystic, benign or malignant

Borderline lesions have low risk of malignant behavior

Commonest fatal gynecological malignancy in many countries Ovarian tumors may be

divided into 4 broad categories:

epithelial (serous,mucinous,….) germ cell (seminoma ,

teratoma,..) sex-cord stromal metastatic

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OVARIAN NEOPLASMS

Mucinous cystadenoma

Borderline:

Proliferation

Mucinous cytadenocarcinoma :

Proliferation +Invasion

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OVARIAN NEOPLASMS

Serous cystadenocarcinoma:

Proliferation + invasion

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Mature cystic teratoma

The commonest ovarian tumour,

Syn : Benign or mature cystic teratoma (dermoid cyst).

The majority arise from an oocyte that has completed the first meiotic division.

at any age, usually in younger patients.

characteristically contain hair, sebaceous material and teeth .

Histologically, Squamous epithelium, bronchial epithelium, cartilage and intestinal epithelium

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Diseases of Pregnancy ECTOPIC PREGNANCY

Def : Pregnancy outside uterine cavity

Fallopian tube is commonest site

Leads to pain and hemorrhage when it ruptures

The incidence of ectopic pregnancy in the United Kingdom is 10-12 per 1000 pregnancies;

65% of cases occur in the 25-34 year age range.

After one ectopic pregnancy the risk of recurrence is 10-20%.

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Diseases of PregnancyGestational Trophoblastic Disease

HYDATIDIFORM MOLE الرحى العدارية

Characterized by swollen chorionic villi and trophoblastic hyperplasia

Associated with high hCGlevels

I- Partial mole: triploid karyotype; fetus may be present

II- Complete mole: 46XX karyotype; no fetus

May be complicated by choriocarcinoma

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Hydatidiform mole :A Genetic analysis :

Partial moles are triploidand result from fertilization of one ovum by two spermatozoa.

(XXY, XXX and XYY).

Complete moles are diploid, but comprise only paternal chromosomes ('empty' ovum )

characteristically 46XX

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Hydatidiform moleHistology :

Partial mole A fetus may be present Few abnormal villi The rest may be fibrotic or hydropic

with trophoblastic hyperplasia . Stromal vessels are present

Complete mole Grossly, the placenta is obviously

abnormal with swollen villi. Histologically, the edema is confirmed there is an absence of stromal vessels trophoblastic hyperplasia affecting all

villi.

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Breast pathology

NORMAL STRUCTURE AND FUNCTION:

The main function of the breast is

the production and expression of

milk

The lobules are the secretory

units of the breast.

Each lobule consists of a variable

number of acini, or glands,

embedded within loose

connective tissue and connecting

to the intralobular duct

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Pregnancy and lactation

Estrogens, progesterone and prolactin, together with other hormones, are important in the development of the breast during pregnancy

Lactation.Breast histology from a woman 30 weeks pregnant, showing the acinilined by cells containing secretory

vacuoles, and with secretions in their lumens

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CLINICAL FEATURES OF BREAST LESIONS

Physiological changes must be distinguished from pathological

lesions :

Many breast conditions present as a lump or lumps

Always note the characteristics of the lump and the age of the

patient

Discharge from the nipple occurs with some conditions

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DIAGNOSTIC METHODS

Imaging-mammography andultrasound

Fine needle aspiration cytology FNAc

Core biopsy

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Screening for breast cancer

Trials in Sweden and the USA suggest that women whose cancers detected by regular mammographic screening have an increased survival rate.

Because the tumors are detected when they are either pre-invasive or invasive but small.

Unscreened women present when the tumour has grown to a size sufficient to be felt,

at which stage there is a higher probability of metastases

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The probable pathological causes of presenting clinical lesions at different ages - in women- I

Probable pathological cause

>55 years35-55 years25-35 years<25 yearsClinical presentation

Phyllodestumour

FibroadenomaPhyllodestumour

FibroadenomaFibroadenomaMobile lump

Fibrocystic change

Fibrocystic change

UncommonIll-defined lump or lumpy areas

Sclerosingadenosis

CarcinomaCarcinomaCarcinoma*UncommonFirm lump ±tethering

Fat necrosis

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The probable pathological causes of presenting clinical lesions at different ages in women – II -

Probable pathological cause

>55 years35-55 years25-35 years<25 yearsClinical presentation

Nipple discharge

Duct ectasiaDuct ectasiaUncommonUncommonClear

Duct papilloma

Duct papillomaUncommonUncommonBloody

Paget's disease

Paget's diseaseNipple adenoma

Nipple adenoma

Nipple ulceration, eczema

Nipple adenoma

Nipple adenoma

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Inflammatory lesion

Infections of the breast are uncommon,

usually complications of lactation

(Staphylococcus aureus is the commonest organism )

Mammary duct ectasia can cause nipple discharge, uncommon in younger women

Fat necrosis is due to trauma, more frequent in the obese

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PROLIFERATIVE CONDITIONS OF THE BREAST

Increase in frequency towards menopause, then rapid decrease

Present as diffuse granularity or ill-defined lump

Variety of histological changes :

Adenosis commoner in younger age group,

cysts commoner nearer the menopause

Women with atypical hyperplasia are at increased risk of developing breast cancer

Gynaecomastia is enlargement of breasts in men

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The commonest proliferative condition of the breast is fibrocystic change FCC

Fibrocystic change FCC

Incidence

Estimates indicate that at least 10% of women develop clinically apparent benign proliferative breast disease, although breast tissue from women at postmortemshows such changes to be present in 50% or more, suggesting that lesser degrees of change are much more common

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Fibrocystic change FCC

Clinical and gross features

Proliferative lesions occur between the ages of 30 and 55, with a marked decrease in incidence after the menopause.

Histological features

adenosis

sclerosing adenosis

epithelial hyperplasia

papillomatosis

cysts

apocrine metaplasia

fibrosis

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Significance of proliferative lesions

Up to 70% are not at an increased risk of developing cancer

However, if the biopsy contains areas of atypical hyperplasia, the woman has a risk of developing cancer 5 times higher

The risk increases if there is a family history of breast cancer.

Cysts alone do not appear to increase the risk.

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Lesions in men :Gynecomastia

The breast tissue in men contains only ductular structures with no evidence of acini

Gynaecomastia is benign enlargement of the male breast tissue

Gynecomastia occurs most commonly in adolescence and in older age groups

it is probably due to hormonal effects relating to oestrogens,

possibly a result of endocrine disturbances such as hyperthyroidism, pituitary disorders and tumors of the adrenals and testis.

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BENIGN TUMORS

The commonest type of benign tumor of the breast is a combined product of both connective tissue and epithelial cells; purely epithelial tumors are less frequent.

The benign breast tumors comprise:

Fibroadenomas : Commonest type of benign tumor, mainly in young women Arises from connective tissue and epithelium .

Clinically, mobile on palpation duct papillomas connective tissue tumors.

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BREAST CARCINOMA

20% of all cancers in women

Commonest cause of death in women in 35-55 age group

In the UK, any woman has a 1 in 9 chance of developing breast cancer

In USA the chance is about 1 in 8

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BREAST CARCINOMA : Risk factors

female sex; risk increases with age

long interval between menarche and menopause

older age at first full-term pregnancy

obesity and high-fat diet family history of breast

cancer geographic factors The highest rates are in North

America, North-West Europe, Australia and New Zealand, with the lowest in South-East Asia and Africa

atypical hyperplasia in previous breast biopsy

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BREAST CARCINOMAFamily history and genetic factors

incidence of breast cancer in the UK related to age. There is a marked increase

between the ages of 40 and 50, but the highest incidence is in those aged 60-70 years

a history of a relative having breast cancer can be found in at least 10% of new cases.

However, a proportion of these will be sporadic cancers and not due to familial (inherited genetic) factors.

The risk of developing breast cancer is increased in first-degree relatives particularly if that person is pre-menopausal.

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BREAST CARCINOMA

Etiological mechanisms : Overexposure to estrogens

and underexposure to progesterone

No definite relationship to oral contraceptives

Some tumors contain receptors for estrogen and progesterone and respond to hormone manipulation

No good evidence for viral involvement

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The histological types of invasive carcinoma

The histological types of invasive carcinoma are:

invasive ductal carcinoma (75%)

Invasive lobular carcinoma (10%)

mucinous (3%)

tubular (2%)

medullary (3%)

papillary (2%)

others (5%).

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Paget's disease of the nipple

2% of all breast carcinomas

Erosion of the nipple clinically resembling eczema

Associated with underlying ductal carcinoma in situ or invasive carcinoma

Within the epidermis of the nipple, large, pale-staining malignant cells can be seen histologically

The malignant cells are derived from the adjacent breast carcinomas

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Spread of breast carcinomas

Directly into skin and muscle

Via lymphatics to axillary and other local lymph nodes

Via blood stream to lungs, bone, liver and brain

May be considerable delay before metastasis occurs

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