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LECTURE FOR MBBS STUDENTS Disease of Cervix By: Dr. Mohamed Afiq Hidayat Zailani MBBCh, MMedSc-Patho, PhD (Patho) Lecturer, MAHSA University EARLY SCREENING SAVES LIVES! 1. Introduction 2. CIN and Bethesda System. -Definition -Classification...

LECTURE FOR MBBS STUDENTS Disease of Cervix By: Dr. Mohamed Afiq Hidayat Zailani MBBCh, MMedSc-Patho, PhD (Patho) Lecturer, MAHSA University EARLY SCREENING SAVES LIVES! 1. Introduction 2. CIN and Bethesda System. -Definition -Classification -Morphology. CONTENTS: -Overview of test: Speculum, colposcopy, Pap-smear test 3. Carcinoma of Cervix. -Aetiology -Pathogenesis -Precancerous lesions -Morphology -Clinical features INTRODUCTION Cervical carcinoma (For this slide: CC) is a malignant tumour found in the tissues of the cervix. 3th Malaysia. CC is the 4th most common cancer in women globally with estimated 660 000 new cases and 350 000 deaths in 2022. The highest rates of incidence and mortality are in low- and middle-income countries. Reflects major inequities d/t lack of access to national HPV vaccination, cervical screening and treatment services. Women living with HIV are 6 times more likely to develop CC compared to women without HIV. -cer CERVICAL DYSPLASIA / CIN cancerous lesion Cervical dysplasia (a.k.a.pre cervical intraepithelial Cneoplasia,( or CIN.) is a precancerous condition in which abnormal cells grow on the surface of the cervix. CIN is not cancer but may become cancer. common Q in exam. CIN most commonly occurs at the - site : squamocolumnar junction of the cervix, a transitional area between the squamous epithelium of the vagina and the columnar epithelium of the endocervix CIN can also occur in vaginal walls and vulvar epithelium. u CIN 1: - Refers to abnormal cells affecting about one-third of the thickness of the epithelium. CIN 2: m Refers to abnormal cells affecting about one-third to two- thirds of the epithelium. CIN 3: Refers to abnormal cells affecting more than two-thirds of the epithelium. Visualization of ectocervix & external os following  CIN 1 rarely becomes cancer and often goes away on its own. speculum examination  CIN 2 and 3 are more likely to require treatment to prevent cancer. grade grade low A High ↓ / cell of cervix hot yet cancer still precancerous. lesion CIS = severe neoplastic changes & high likely to be cancer, but still a dysplasia (Refer TNM classification) The Bethesda reporting system (BRS) Other than the CIN classification, some doctors describe abnormal changes to squamous cells in the cervix using the Bethesda reporting system. The system describe squamous intraepithelial lesion (SIL) into low grade (LSIL) and high grade (HSIL). CIN 1 CIN 2 & 100 variants of HPV. However, almost 30 variant can cause CC, including HPV 16, 18, 31, 45 HPV infection present in over 99% of cc cases HPV causes lesion called Condyloma Acuminatum (knob-like lesions ↓ condyloma on the ectocervix, usually multiple, measure 1-2 cm A cuminatum adheron HPV INFECTION KEY FACTS: Mode of transmission: sexual intercourse (contact transmission) Site: May affect the genitals, including vulva, vagina, cervix, penis, sexual behavior depend on scrotum, rectum and anus. Clinical presentation: intercouse after sexual ~  Painless, itching, burning sensation, postcoital bleeding, vaginal I disturbance of whitish ~ mucus discomfort, discharge, etc.  HPV can cause lesions called warts (Flat/Common/Genital/Plantar). However, HPV variants that cause cancer does not cause warts (only condyloma acuminatum) Risk Factors: Multiple sexual partner, unprotected sex, smoking, compromised immune system. of Xt mana nmpk ? thickeninggrounding ↑ (A) Condyloma acuminatum shows papillomatosis, (B) Flat LSIL (CIN 1) has koilocytotic atypia (bi/multinucleation, I acanthosis, parakeratosis, and hyperkeratosis.& Each irregular nuclear contours, nuclear enlargement and papillary frond has a tiny blood vessel at its core. hyperchromasia, and cytoplasmic clearing [halos]). bu surrounding a can CERVICAL CARCINOMA same w Risk factor for HPV RISK FACTORS FOR CC: 1. Female with multiple sexual partners 2. A male partner with multiple sexual partners 3. Young age at first intercourse (before17 yo) 4. High parity (> 7) 5. Persistent infection with a high oncogenic risk HPV , eg HPV 16/18 6. Immunosuppression 7. Certain HLA subtypes 8. Use of oral contraceptives (>10 y) 9. Use of nicotine / smoking 10. Others: genital infection, family history, lack of circumcision in male partner. CLINICAL PRESENTATION FOR CC: Common: most common - Vaginal Bleeding - Vaginal Discharge - Pelvic pain - Dysuria symptoms M - Constitutional sx fever fatigue - , - Spread sx (Sx of obstruction/ infection/ pain/ etc)  extend by direct spread to involved adjacent tissues eg paracervical tissues, urinary bladder, ureters, rectum and vagina, lymph nodes, and distant metastases may also be involved. MORPHOLOGY OF CC Gross: ~ memcauliflower Fungating (exophytic), ulcerate, infiltrative, or flat lesions L toward inside of tissue I breast cancer more ulcerative Microscopic: 1. MOST COMMON: Squamous cell carcinoma: Nests and tongues of malignant squamous epithelium (keratinizing or nonkeratinizing) invading the underlying stroma. May form keratin pearls and intercellular bridges. 2. 2nd MOST COMMON: Adenocarcinoma: proliferation of glandular epithelium composed of malignant endocervical cells with large hyperchromatic nuclei and relatively mucin- depleted cytoplasm, resulting in dark appearance of glands. ↓ uz cytoplasm lack of mucin Microscopic: 3. Adenosquamous carcinomas: intermixed glandular and malignant squamous epithelium 4. Neuroendocrine carcinomas: relatively small cells with scant cytoplasm, ill- defined cell borders, finely granular nuclear chromatin (salt and pepper pattern), and absent or inconspicuous nucleoli. Exophytic cervical carcinoma Squamous cell carcinoma of the cervix (keratinizing type) Malignant squamous cells -- form irregular nests invading the stroma. In the center of the nest, ① laminated keratin pearls are - present. Ikeratinizing type Individual cells have abundant eosinophilic keratinized cytoplasm. (Hematoxylin-eosin stain) XMPK pearl Squamous cell carcinoma of the cervix, non- keratinizing type. Malignant squamous cells have abundant eosinophilic cytoplasm, distinct cell borders, and individual cell keratinization individual L occur but only The irregular, large nuclei contain multiple nucleoli. (Hematoxylin-eosin stain) Adenocarcinoma of cervix Marked glandular confluence with cribriform or microacinar architecture Normal Gland appear uniform Irregularly shaped, angulated nucleus or fragmented glands with an adjacent desmoplastic stromal reaction Cells have columnar shape; nuclei are elongated, enlarged and hyperchromatic with coarse chromatin Malignant Gland some here a some a irregular shape Loss of polarity and nuclear of glands overlapping COMPLICATION OF CC Local spread (direct extension) laterally to parametrium and surrounding structures, into vagina, bladder and rectum. – Ureteral compression leads to hydroureter, hydronephrosis, – Bilateral ureteric obstruction leads to obstructive nephropathy, renal L involve kidney failure (most common cause of death, 50%) – Bladder and rectal involvement leads to fistula formation. Spread to lower uterine segment and uterine cavity Lymphatic spread – to regional LNs (parametrial, pelvic, para-aortic, hypogastric, external iliac) – lymphatic (venous outflow) obstruction leads to lower limb oedema, DVT Haematogenous spread (rare) – to liver, spleen, kidney, lung, brain, bone INVESTIGATION & DIAGNOSIS OF CC Prevention: - Routine cervical screening (Pap Smear) for females >20yo - Nationwide HPV vaccination program - HPV DNA test for suspected cases Patients with abnormal cytology or symptoms (e.g. bleeding) are referred to examination by colposcopy Adjunct imaging can be useful (pelvic ultrasound, MRI) Definitive diagnosis requires tissue biopsy FIGO stages for cervical cancer This is a staging system developed by the International Federation of Obstetrics and Gynecology (Federation Internationale de Gynecologie et d'Obstetrique, or FIGO) Staging is based on the results of a physical exam, imaging scans, and biopsies. In general, 4 stages: Stage I, II, III & IV Treatment plan differs according to each stage of CC impo STAGE I. Confined to the cervix only STAGE II CC invades beyond the uterus, but has not extended onto the lower third of the vagina or to the pelvic wall STAGE III spread downward CC involves the lower third of the vagina upward and/or extends to the pelvic wall and/or & go causes hydronephrosis or non- functioning kidney and/or involves pelvic and/or paraaortic lymph nodes STAGE IV part of goes other ~ body. CC extended beyond the true pelvis (pelvic cavity) or has involved (biopsy proven) the mucosa of the bladder or rectum. Treatment: Just remove part of cervix ~ – Microinvasive carcinoma: cone biopsy of cervix – Invasive carcinoma: Hysterectomy partial/total remove cervix & uterus - can't be pregnant anymore. – Irradiation for extensive lesions: Neoadjuvant radiation Treatment & therapy such as cisplatin prognosis Prognosis: – Depends on staging: Stage IV (extension beyond pelvis) has poorer prognosis – Depends on cell type: neuroendocrine carcinoma has poorer prognosis DIFFERENTIAL DIAGNOSIS: 1. Nabothian cyst - A benign, non-cancerous lesion, where the cells trap mucins/mucus inside the glands of the cervix. - Results from obstruction of bartholinduct, usually by a preceding infection. - Sx: dyspareunia, vaginal bleeding, discharge L painful intercourse DIFFERENTIAL DIAGNOSIS: 2. Cervical polyp- ↓ thickening of epithelium L mcm tree growing - Small fingerlike growths originating from the mucosal surface of the cervix. - The small fragile growths hang from a stalk and protrude through the cervical opening. - Subtype: Endocervical polyp is more common than ectocervical polyp - Almost always benign. Malignant transformation may occur in postmenopausal woman cervical polyps Lold female 50/60 · yo - > Remove - Sx: postcoital bleeding, menorrhagia, vaginal discharge. occur after sexual intercourse L I heavy bleeding DIFFERENTIAL DIAGNOSIS: 3. Cervicitis -Define: Inflammation of the cervical lining - Aetiology:  Commonly STI (Chlamydia, Gonorrhea, Herpes virus, HPV, Trichomoniasis)  Others: A device inserted into the pelvic area such as a cervical cap, diaphragm, IUD, or pessary Allergy to spermicides used for birth control Allergy to latex in condoms Exposure to a chemical Reaction to douches or vaginal deodorants - Sx: Bleeding, discharge, painful intercourse

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