PATH 9: Pathology of the Cervix/Uterus

Question 1

Pathogenesis/Risk factors of Cervical Intraepithelial Neoplasia (CIN)?

Answer 1

• CIN is aPrecursor lesion
• Nearly all invasive SqCC arise from this precursor lesion

Precancerous changes Graded on basis of histology

• CIN I –Mild dysplasia
• CIN II –Moderate dysplasia
• CIN III –Severe dysplasia
• Progression from low grade to high grade is not inevitable!: Higher the grade of CIN the greater the likelihood of progression.

Top Risk Factor: Infection with high risk HPV (Multiple sexual partners) (MOST IMPORTANT)

Question 2

Risk Factors and Clinical Presentation of Cervical Carcinoma?

Answer 2

Risk Factors:

• Infection with high risk HPV (Multiple sexual partners) (MOST IMPORTANT)
• Infection with HIV
• Infection with Chlamydia
• Tobacco smoking (2x increase in risk)
• Oral Contraceptives
• High parity (3 pregnancies or more increases risk, hormones increased in pregnancy make it easier for HPV to infect cells)

Clinical Presentation:

Most cases diagnosed at pre-invasive stage and may be asymptomatic

More advanced:

• Vaginal bleeding (post coital bleeding)
• Leukorrhea
• Painful coitus (dyspareunia)
• Dysuria

Question 3

Types of Cervical Carcinoma?

Answer 3

Squamous cell Carcinoma (75%) - Most common

Adenocarcinoma / Adenosquamouscarcinoma (20%)

Small cell neuroendocrine carcinoma (<5%) - Nastiest presentation, poorest prognosis

Question 4

Cervical Carcinoma Prevention?

Answer 4

A negative HPV test is more reliable than a normal cervical smear

HPV Vaccine Can prevent 9/10 cervical cancers

Question 5

Causes of Dysfunctional Uterine Bleeding

Answer 5

Abnormal bleeding in the absence of a well defined organic lesion in the uterus.

Due to Hormonal Imbalance (HIGH estrogen relative to Progesterone): Improper development of corpus luteum => lack of progesterone=> excess bleeding

Cause Depends upon the age of the women:

• Prepuberty: Precocious puberty (hypothalamic, pituitary, ovary)
• Adolescence: Anovulatory cycles
• Reproductive age: Anovulatory cycles, pregnancy comps, organic lesion, Inadequate luteal phase
• Perimenopausal: Anovulatory cycles, organic lesions
• Postmenopausal: Organic lesions, endometrial atrophy

Question 6

Inflammation of the endometrium?

Answer 6

Endometritis

Question 7

Growth of the basal layer of the endometrium down into the myometrium. Nests of endometrial glands and stroma are found in between muscle bundles

Answer 7

Adenomyosis

Question 8

Endometrial glands and stroma in outside the endomyometrium

Theory of origin?

Morphology?

Answer 8

Endometriosis

Regurgitation theory (most accepted) Menstrual backflow through tubes with subsequent implantation

‘Chocolate cysts’ in ovaries

Question 9

Types of endometrial hyperplasia?

Answer 9

Histologically defined: Increased gland to stromal ratio

Classified based on the architectural crowding and cytological atypia:

• An increased gland to stromal ratio without atypia –Hyperplasia without atypia
• An increased gland to stromal ratio with nuclear atypia –Hyperplasia with atypia

Hyperplasia with atypia may lead to carcinomia

Question 10

Risk factors for Endometrial carcinoma?

Answer 10

• Hormone Replacement Therapy
• Tamoxifen
• Nulliparity
• Obesity
• Diabetes
• Lynch Syndrome (HNPCC): inherited defect of mismatch repair genes
• Cowden’s Syndrome: Mutations in the tumor suppressor gene PTEN. Sporadic cases of endometrioid carcinoma harbour mutations of PTEN
• Family History

Question 11

Clinical Presentation of Endometrial carcinoma?

Answer 11

• Marked vaginal discharge and irregular bleeding
• 60% of patients present with Stage I disease (Confined to the uterine corpus (90% 5 year survival))
• With progression the uterus become palpably enlarged and may become fixed to surrounding pelvic organs
• Late metastasizing: eventually spreads to regional Lymph Nodes and distant sites

Question 12

Staging of Endometrial carcinoma?

Answer 12

• Stage I –Confined to the uterine corpus (90% 5 year survival)
• Stage II –Extension into the cervix but not beyond uterus (30-50% 5 year survival)
• Stage III –Beyond the uterus into the true pelvis (20% 5 year survival)
• Stage IV-Distant metastasis or involvement of other viscera (20% 5 year survival)

Question 13

Smooth Muscle Tumors of the Uterus?

Answer 13

Leiomyoma aka”Fibroids”:

• Most common benign tumor in women
• Arises from smooth muscle cells in myometrium
• Estrogens/Oral Contraceptive can stimulate growth
• Characteristic whorled appearance
• Fibrosis, calcification, ischemic necrosis, cystic degeneration and hemorrhage
• “Red degeneration” in pregnancy
• RARELY transforms into leiomyosarcoma

Leiomyosarcoma:

• Typically arise de novo from the mesenchymal cells of the myometrium and NOT from pre-existing leiomyoma
• Nearly always SOLITARY LESIONS - Soft, hemorrhagic
• Some lie at interface between benign and malignant and are termed ‘Smooth muscle tumors of Uncertain Malignant Potential’ (STUMP)
• Diagnostic features for malignancy: Coagulative necrosis, Cytologic atypia, Increased mitosis
• Many metastasize –typically to the lungs

Question 14

Most common benign tumor in woman?

Answer 14

Leiomyoma aka “Fibroids”: Benign tumors arising from smooth muscle cells in myometrium. RARELY transforms into leiomyosarcoma