Diseases of the female genital system and breast

Anatomy of female genital system

Diseases of female genital system Diseases of the cervix Diseases of body of uterus Diseases of pregnancy Tumors of the ovary Diseases of the breast

Normal cervix

Normal cervix Squamocoluminar junction is the seat of most of the epithelial diseases that occur in the cervix

Diseases of the cervix Chronic cervicitis Neoplasia of the cervix

Chronic cervicitis Erosion of cervix

Chronic cervicitis Nabothian cyst

Cervical polyps

Chronic cervicitis

Diseases of the cervix Chronic cervicitis Neoplasia of the cervix

Neoplasia of the cervix Cervical intraepithelial neoplasia(CIN) Invasive carcinoma of the cervix

CIN CIN I CIN II CIN III

Normal cervical squamous epithelium CIN I

CIN II

CIN III

Risk factors for CIN and invasive carcinoma Sexual intercourse Early age at first intercourse(≤ 17 years old) Smoking Human papillomavirus (HPV 16, 18, 33) HIV infection Male factors

Neoplasia of the cervix Cervical intraepithelial neoplasia(CIN) Invasive carcinoma of the cervix

Invasive carcinoma of the cervix Arise from transformation zone Vast majority are squamous cell carcinomas Preceded by CIN Average is 50 years

Cervical carcinoma (early microinvasion)

Cervical carcinoma (early stage) Abnormal hardness of the cervix

Fungating ulcerated areas destroy the cervix Cervical carcinoma ( late stage) Fungating ulcerated areas destroy the cervix

Pap smear ( diagnostic cervical cytology)

Invasive carcinoma of the cervix

Clinical feature Unscheduled vaginal bleeding Leukorrhea Painful coitus (dyspareunia) Dysuria (advanced stage)

Prognosis The size and depth of invasion of the primary tumor The prescence and the extent of lymph node metastasis

Outline of female genital system Diseases of the cervix Diseases of body of uterus Diseases of pregnancy Tumors of the ovary Diseases of the breast

Diseases of body of uterus Adenomyosis Endometriosis Endometrial hyperplasia Tumors of the endometrium and myometrium

Adenomyosis and endometriosis Adenomyosis: growth of endometrium down into the myometrium Endometriosis: growth of endometrium outside the uterus ovaries fallopian tubes round ligaments pelvic peritoneum

Adenomyosis and endometriosis

Adenomyosis

Endometriosis (uterine serosa)

“Chocolate” cyst of the ovary

Clinical feature Adenomyosis Endometriosis Cyclic pelvic pain Dysmenorrhea Dyspareunia (painful intercourse) Infertility(30% of cases) Menstrual abnormalities dysmenorrhea

Diseases of body of uterus Adenomyosis Endometriosis Endometrial hyperplasia Tumors of the endometrium and myometrium

Endometrial hyperplasia Occurs in the third and fourth decades In response to estrogen stimulation Functional uterine bleeding

Endometrial hyperplasia

Diseases of body of uterus Adenomyosis Endometriosis Endometrial hyperplasia Tumors of the endometrium and myometrium

Tumors of the endometrium Tumors of the myometrium Leiomyoma and leiomyosarcoma Endometrial carcinoma

Endometrial carcinoma The most common cancer of the female genital tract Mean age : 56 years (80% of women are postmenopausal)

Risk factors Obesity Hyperestrogenic state Diabetes Late menopause Prolonged use of estrogen Estrogen-secreting tumors Hyperestrogenic state Previous pelvic irradiation Lower parity

Endometrial carcinoma (early stage)

Endometrial carcinoma

Endometrial adenocarcinoma

Clinical feature Irregular bleeding Postmenopausal bleeding Blood-stained discharge

Diagnosis of endometrial disease Transvaginal ultrasonography Hysteroscopy Endometrial biopsy

Tumors of myometrium Leiomyoma and leiomyosarcoma

Leiomyoma Commonest tumor of all pelvic tumors (affect over half of all women over the age of 30) Benign tumor Arise from the smooth muscle cells in the myometrium

Risk factors Age: rare under 30 years. Parity: more common in nulliparous and women with low fertility. Genetic: often with a family history

Features of leiomyoma Estrogen sensitive Fast growing in pregnancy Shrink at menopause

Submucosal leiomyoma

Submucosal, intramural, subserosal leiomyomas Smooth muscle tumors of the uterus are often multiple. Seen here are submucosal, intramural, and subserosal leiomyomata of the uterus.                            

Leiomyoma

Clinical features Abnormal menstrual bleeding Dysmenorrhea Infertility Compression

Leiomyosarcoma

Leiomyosarcoma

Outline of female genital system Diseases of the cervix Diseases of body of uterus Diseases of pregnancy Tumors of the ovary Diseases of the breast

Diseases of pregnancy Gestational trophoblastic tumors Hydatidiform mole Invasive mole Choriocarcinoma

Hydatidiform mole Chracterised by swollen chorionic villi and trophoblastic hyperplasia Associated with high HCG levels Complete mole: no fetus Partial mole: fetus or placenta may be present May be complicated by chriocarcinoma

Complete mole

Hydatidiform mole

Doppler scan

Partial mole

Clinical feature Amenorrhea followed by continuous or intermittent vaginal bleeding Other symptoms of pregnancy: vomoting Human chorionic gonadotropian (HCG) Enlarged soft uterus (often larger than dates would suggest)

Invasive mole Hemorrhage

Choriocarcinoma Malignant tumor of trophoblastic tissue With a propensity for invading vessel walls Blood-borne metastasis occur early to many sites (lung, brain…)

Etiology 50% develop from a hydatidiform mole 20% arise after a normal pregnancy

Choriocarcinoma Hemorrhagic necrotic masses

Choriocarcinoma Villi are not present Proliferation of bizarre trophoblastic cells Highly aggressive

Choriocarcinoma Dissemination to lung

Prognosis Excellent as the tumors respond well to cytotoxic chemotherapy

Outline of female genital system Diseases of the cervix Diseases of body of uterus Diseases of pregnancy Tumors of the ovary Diseases of the breast

Classification of ovarian tumor

Tumors of the ovary Responsible for more deaths than any other gynaecological malignancy

Serous cystadenoma

Serous papillary cystadenoma

Serous adenocarcinoma

Mucinous cystadenoma

Mucinous adenocarcinoma

Krukenberg tumor (metastatic carcinoma from gastrointestinal tract)

Krukenberg tumor (metastatic carcinoma from gastrointestinal tract)

Outline of female genital system Diseases of the cervix Diseases of body of uterus Diseases of pregnancy Tumors of the ovary Diseases of the breast

Normal breast

Key facts for proliferative conditions of the breast Present as diffuse granularity, ill-defined lump or discrete swelling Increased in frequency towards menopause, then rapid decrease Variety of histological changes

Fibrocystic changes

Fibrocystic changes

Key facts Fibrocystic disease Increased risk of subsequent development of carcinoma is related to the presence of epithelial hyperplasia, particularly atypical hyperplasia Sclerosing adenosis can be clinically and radiologically confused with carcinoma

Predisposing factors for breast carcinoma Atypical epithelial proliferation Mutations of BRCA 1 and 2 genes Long interval between menarche and menopause Older age at first pregnancy Obesity High-fat diet Lonizing radiation

Breast carcinoma

Carcinoma Fibroadenoma

Paget’s disease

Prognosis Tumor grade and type Size of the tumor Lymph node status Estrogen receptor status

Estrogen receptror staining

Progesterone receptor staining

Cerb-B2 staining

Diagnostic methods Fine-needle aspiration cytology Tru-cut biopsy Examination of frozen section Mammography and ultrasound

Fine Needle Aspiration

Fine needle aspiration under control of mammography

Diagnostic methods Fine-needle aspiration cytology Tru-cut biopsy Examination of frozen section Mammography and ultrasound

Case study A 35-year-old sales assistant at a discount frozen-food warehouse, attends her doctor for a routine cervical smear. She is asymptomatic and well, but has not visited her doctor for the previous five years and has not had a smear in that time. The cervical cytological report shows severe dyskarosis.

She is recalled and has colposcopy performed which demonstrates the abnormal area of the cervical squamous epithelium which is biopsied. The changes seen colposcopically extend up the endocervical canal, and the upper margin of the abnormality can not be seen. Histology shows that this is indeed an area of CIN (cervical intraepithelial neoplasia) grade 3, at the transformation zone, with atypical cells extending through the full thickness of the epithelium and showing no maturation towards the surface.

Mitotic figures, including abnormal forms, are present through all layers. There is no evidence of invasion in the biopsy. She then has a cone biopsy performed. This confirms that CIN 3 is present at the transformation zone. There is no evidence of invasive squamous-cell carcinoma, no glandular atypia and the sever atypia is completely excised at both ecto- and endocervical margins.

Questions If she had not had the disease identified by screening what would have been her risk of developing invasive cervical carcinoma?

Questions What are the risk factors for developing cervical carcinoma?

Diseases of reproductive system Diseases of male reproductive system Sexually transmitted disease (STD) Diseases of female reproductive system

Male reproductive system

Normal prostate

Normal prostate

Normal adult prostate

Diseases of prostate gland Prostatitis Nodular hyperplasia of the prostate Carcinoma of the prostate

Chronic prostatis

Nodular hyperplasia of the prostate The most common disorder of the prostate A common non-neoplastic lesion Often involves peri-urethral zone

Nodular hyperplasia of the prostate Nodular hyperplasia affects most males over the age of 70 years Nodular hyperplasia is termed glandular and stromal hyperplasia

Etiology Androgen-estrogen imblance Other factors Dehydrotesterone (DHT) is the main stimulator DHT binds to nuclear receptors on both stromal and epithelial cells Other factors

Affected lobes Arises most commonly in the inner, periurethral glands of the prostate Arises particularly from those that lie above the seminal vesicles

Gross feature Nodular pattern of hyperplastic glandular acini separated by fibrous stroma Some nodules are cystically dilated and contain a milky fluid Other nodules contain numerous calcific concretions(corpora amylacea)

Nodular prostatic hyperplasia Normal prostate gland

Nodular prostatic hyperplasia

Histological feature Reveals two components: hyperplasia of both glands and of stroma The acini are larger than normal

Prostatic hyperplasia

Prostatic hyperplasia

Clinical presentation Compression of the urethra difficulties with micturition Complications- prolonged prostatic obstruction can lead to outflow diseases

Acute cystitis

Trabeculation of the bladder Stone formation Enlarged prostate gland

Treatment Anti-androgens Surgical treatment

Prostate gland Prostatitis Nodular hyperplasia of the prostate Carcinoma of the prostate

PIN (prostatic intraepithelial neoplasia) low grade

PIN (high grade)

Prostatic carcinoma Adenocarcinoma occurring in males usually > 50 years (peak incidence: 60-85 years) Metastasis mainly to bone (osteosclerotic metastasis) Obstructs bladder outflow Many are hormone(androgen)-dependent Genetic and environmental factors may play a role in pathogenesis

Types of prostatic carcinoma Latent- small foci of well-differentiated carcinoma, remain confined to prostate for a long period Invasive- invade locally and metastasize Occult- not clinically apparent in primary site but present as metastatic disease

Prostatic carcinoma

Adenocarcinoma of the prostate Well differentiated Poorly differentiated

Prostatic adenocarcinoma with prominent nucleoli

Carcinoma of the prostate

PSA staining of prostate carcinoma

Clinical feature Often clinically silent Urinary symptoms (delay in starting to pass urine, poor stream, terminal dribbling) Hard, craggy prostate on rectal examination

Spread of prostatic carcinoma Direct Lymphatic Hematogenic: most commonly to bone

Bone metastasis of prostatic carcinoma

Treatment Radical prostatectomy Reduce androgen levels Orchidectomy Treatment with estrogenic drugs

Squamous carcinoma of the penis

Squamous carcinoma of the penis

Germ cell neoplasms Most common types of testicular neoplasm Most common in the 15 to 34 age range Types: Seminoma (malignant) Embryonal carcinoma (malignant) Teratoma (benign and malignant) Yolk sac tumor (malignant)

Seminoma of the testis

Seminoma

Embryonal carcinoma

Teratoma

Yolk sac tumor

Outline Diseases of male reproductive system Sexually transmitted disease(STD)

Classical veneral diseases Syphilis Gonorrhea Chancroid Lymphogranuloma venereum Granuloma inguinale

Sexually transmitted diseases (STD) Spectrum has broadened Transmitted by sexual contact Transmitted by other means

Classification of important STDs

Sexually transmitted disease(STD) Gonorrhea Syphilis Condylomata acuminata

Gonorrhea Causative organism: Neisseria gonorrheae Almost always acqiured during sexual intercourse Morphology: intense suppurative inflammation

Neisseria gonorrheae

Gonorrhea Purulent urethral discharge

Abscess of epididymitis

Purulent infection of eye Gonorrhea

Clinical feature Presence of dysuria Urinary frequency Mucopurulent urethral or vaginal exudate

Complication Disseminated infection Chronic stricture Chronic scarring of fallopian tubes (salpingitis) Chronic urethral stricture Male sterility Female infertility

Transmitted to infants Neonatal gonorrhea Transmitted to infants Ophthalmia neonatorum Blindness

Standard for diagnosis Detection of gonococci Bacterial culture

Syphilis Causative organism: Treponema pallidum, a kind of spirochete Almost always acqiured during sexual intercourse

Pathological change Infiltration of lymphocytes and plasma cells Endoarteritis Gumma ( a kind of granuloma)

Histological feature

Clinicopathological feature Acquired syphilis Congenital syphilis

Acquired syphilis Primary stage Secondary stage Tertiary stage

Primary stage Chancre

Secondary stage Lymphode enlargement Syphilid

Systemic involement in tertiary syphilis Gumma formation

Tertiary stage Gumma

Clinicopathological feature Acquired syphilis Congenital syphilis

Congenital syphilis Osteochondritis Perichondritis Syphilitic hepatitis Syphilitic pneumonia Desquamation of skin Early death Osteochondritis Perichondritis Bone deformities

Malformation of the teeth Saddle nose

Sexually transmitted disease(STD) Gonorrhea Syphilis Condylomata acuminata

Condylomata acuminata (veneral warts) Causative organism: Human papillomavirus(HPV)6,11 Spread of infection Sexal intercourse Indirect contact

Condylomata acuminata

Condylomata acuminata Koliocytosis

Gold criteria for diagnosis In situ hybridization (ISH) Electronmicroscopy

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Case study A 74-year-old retired fruit-farm labourer says that he has been feeling unusually tired and has lost his appetite. Initial blood tests show that he is anemic, with an Hb of 9.8g/dl and has renal failure with a blood urea of 26mmol/l and a creatinine of 280mmol/l.On further enquiry, you find out that he has had a poor urinary system, with some frequency, nocturia and a post-micturitional dribble.

Physical examination Rectal examination reveals a rubbery, firm, smooth enlargement of the prostate gland. Further investigations include an intravenous urogram (IVU) which showed both kidneys to be functioning but also showed bilateral hydronephrosis with hydroureter.

Questions what is the most likely diagnosis?

Questions what further tests may be helpful?

Questions what abnormality is seen in the bladder?