Female Genital Tumor

Chapter 17

Female Genital Tumor Dr. Yang

Section one

Premalignant and Malignant Disorders of the Uterine Cervix

Dysplasia and Carcinoma in Situ of the Cervix 

CIN – Cervical intraepithelial neoplasia. Formerly called dysplasia – disordered growth and development of the epithelial lining of the cervix.

正常子宫颈鳞状上皮 • • This is normal cervical nonkeratinizing squamous epithelium. The squamous cells show maturation from basal layer to surface.

CIN 

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CIN I (mild dysplasia)– disordered growth of the lower third of the epithelial lining. CIN II (moderate dysplasia) – abnormal maturation of two-thirds of the lining. CIN III (severe dysplasia) – encompasses more than two-thirds of the epithelial thickness with carcinoma in situ (CIS) representing

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CIN I CIN II CIN III Ca in situ

Bethesda System Specimen type – conventional smear (Pap smear); liquid-based; other  Result : *Negative for intraepithelial lesion or no malignancy *ASC-US atypical squamous cell of undetermined significance *ASC-H cannot exclude HSIL *LSIL low-grade squamous intraepithelial lesion(CIN I) *HSIL high-grade (CIN II CIN III) *Squamous cell carcinoma 

Recommendation 

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It is recommended that all patients with CIN II and CIN III be treated when diagnosed. Because a certain percentage of all dysplasias, especially high-grade lesions, will progress to an invasive cancer if left untreated.

Epidemiology and Etiology  

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CIN -- commonly in their 20s. The peak incidence of carcinoma in situ is in women aged 25-35. The incidence of cervical cancer rises after the age of 40.

Risk factors   

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Multiple sexual partners Early onset of sexual activity High risk sexual partner (history of multiple sexual partners, HPV infection, lower genital tract neoplasia, prior sexual exposure to someone with cervical neoplasia) A history of STDs Cigarette smoking; immunodeficiency; multiparity; long term oral contraceptive pill use

HPV—high risk factor 

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Condoms cannot be against HPV, it can be transmitted by labial-scrotal contact. >80% CIN --HPV(+) >90% Cx Ca --HPV(+) Over 70 subtypes low-risk – 6, 11, 42, 43, 44( Condylomata ; CIN I) intermediate-risk – 33, 35, 51, 52 (CINII CINIII) high-risk – 16,18,31,39,45,56,58,59,68 (invasive cancer)

Other HPV types 23%

HPV18 14%

HPV45 8% HPV31 5%

HPV16 50%

Pathology 

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Adenocarcinoma in situ(ACIS) – the presence of endocervical glands lined by atypical columnar epithelium that cytologically resembles the cells of endocervical adenocarcinoma, but that occur in the absence of stromal invasion. Method– cone biopsy.

This is the gross appearance of a cervical squamous cell carcinoma that is still limited to the cervix (stage I). The tumor is a fungating red to

Here is another cervical squamous cell carcinoma. Note the IUD string protruding from the cervix. This implies that someone could have done a Pap smear when it was inserted. There is a natural history of progression of dysplasia to carcinoma, so

Clinical Findings 

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Symptoms and Signs – most people no. People with sexually active should be given cytologic exmination once a year. Special examination -- abnormal pap smear should be done. eg. Repeat cytology; HPV testing; the Schiller test; colposcopy; directed biopsy; endocervical curettage; cone biopsy.

Special examination 

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1 Repeat cytology. AUS-US – repeat every 4-6 months; AUS-H – colposcopy 2 HPV testing. 3 Schiller test. Glycogen + iodine --deep mahogany-brown color. Nonstaining: columnar\scar\cyst\cancer. 4 Colposcopic examination. 5 Cone biopsy.

Colposcopic examination 

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Normal findings: original squamous epithelium; transformation zone; columnar epithelium. Abnormal findings: leukoplakia or hyperkeratosis; acetowhite epithelium; mosaicism or punctation reflecting abnormal vascular patterns of the surface capillaries

Treatment     

Cryotherapy Laser ablation Cold knife conization Laser cone excision Leep– loop electro-surgical excision procedure.

* It depends on: size of leision; endocervical gland involvement; margin status of any excisional specimen; ECC result.

Follow up  

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Pap smears every 3-4 months Endocervical curettage every 6 months Completed childbearing – hysterectomy Figure 17-2

Cancer of the Cervix

Cancer of the Cervix 

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The second common cause of cancer-related morbidity and mortality The average age is 51 Over 95% of patients with early cancer of the cervix can be cured

Etiology and Epidemiology   

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Risk factors – the same with CIN HPV – the central HPV16 – the most prevalent in squamous cell carcinoma HPV18 – most prevalent in adenocarcinoma Others – immunosuppression \HIV \STD \tobacco \high parity \oral contraceptive use.

Pathogenesis and natural history 

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HPV infection: asymptomatic latent infection; active infection; neoplastic transformation Spread : direct extension; lymphatic spread – main (parametrial, hypogastric, obturator, external iliac, sacral); stage IIB –pelvic lymph nodes 30-40% (+) para-aortic nodes 15-30%(+). Stage IVA– para-aortic 45% (+) blood-borne metastasis. (liver, lungs, others)

Pathology    

Squamous cell carcinoma – 70-75% Adenocarcinoma –20-25% Adenosquamous – 3-5% Undifferentiated carcinoma

Pathology 

Squamous cell carcinomas and verrucous carcinomas. *3types: large cell nonkeratinizing; large cell keratinizing; small cell carcinoma.– worse prognosis.

Pathology Adenocarcinoma : types: mucinous; endometrioid; clear cell; Serous. 

Clinical findings 

Symptoms: 1.Abnormal vaginal bleeding: blood-stained leukorrhea; scant spotting or frank bleeding . 2. leukorrhea: sanguineous or purulent, odorous, and nonpruritic. Postcoital bleeding. 3.Others: pelvic pain; fistula formation; weakness; weight loss; anemia.

Clinical findings 

Physical signs: barrel-shaped enlarge; friable; cauliflower-like; ulceration; necrotic; adjacent vaginal fornices be involved; extensive parametrial; uterosacral and cardinal ligaments loss mobility and fixation.

Clinical findings 

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Biopsy: adequate– schiller-positive areas; ulcerative; granular; nodular; papillary leision.colposcopy; endocervical curettage; conization. Conization: mark the area

Clinical staging 

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Is staged by clinical examination, and evaluation of the bladder, ureters, and rectum. Chest x-ray; IVP; CT; cystoscopy; proctoscopy; PET; MRI; lymphangiography CT and surgicopathologic can not change the stage by examination before.

FIGO staging of cervical cancer  

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Stage o: carcinoma in situ Stage I A: invasive Cx Ca by microscopy only Stage I A1: deeper ≤3mm, wider≤7mm Stage I A2: 3mm<deeper<5mm Stage I B: visible lesion or microscopic than IA. Stage I B1:<4cm

FIGO staging of cervical cancer  Stage II: extend not to pelvic sidewall or lower        

third of vagina Stage IIA: vaginal involvement without parametrial. Stage IIB: parametrial involvement Stage III: extend to pelvic sidewall or/and lower third of vagina and/or hydronephrosis Stage IIIA: lower third of vagina Stage IIIB: pelvic sidewall Stage IV: extension beyond the true pilvis or mucosa of rectum or bladder Stage IVA: adjacent organ Stage IVB: distant metastases

Differential diagnosis     

Cervical ectropion Cervicitis Condyloma acuminata Tuberculosis Ulceration (syphilis, lymphogranuloma, chancroid)

Prevention   

Risk factors Screening treatment intervention education

Treatment one -- Early stage( stage IA2 to IIA): Radical hysterectomy and pelvic lymphadenecomy Primary radiation with concomitant chemotherapy Ovaries may be left intact and be transposed 

Early stage A 

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Stage IA1 – extrafascial hysterectomy ; conization for wishing preserve fertility Stage IA2 – modified radical hysterectomy (ligated uterine artery where it crosses over the ureter; divided uterosacral and cardinal ligaments midway towards their attachment to sacrum and pelvic sidewall and resected upper third of

Early stage A 

Stage IB-IIA– type III hysterectomy (ligated uterine artery at its origin from the superior vesical or internal iliac artery; resected uterosacral and cardinal ligaments at their attachments to the sacrum and pelvic sidewall and resected upper half of the vagina. Lymphadenectomy.)

Early stage B 

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Postoperative adjuvant radiation with concomitant chemotherapy --Positive lymph nodes; positive or close resection margins or microscopic parametrial involvement. Large tumor size; deep cervical stromal invasion; lymphovascular space invasion. -- benefit

Early stage C 

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Primary radiaton with concomitant chemotherapy External beam radiation is generally used in combination with intracavitary irradiation. The superiority of radiation with concomitant platinum-based chemotherapy over radiation alone

Treatment two 

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Locally advanced disease( stage IIB to IVA): Primary radiaton with concomitant chemotherapy Extended field radiation – para-aortic lymph node metastases.

Treatment three 

Disseminated primary ( stage IVB ) and persistent or recurrent disease. -- radiaton with concomitant chemotherapy

Treatment four 

Total pelvic exenteration for isolated central pelvic recurrence of disease

Postreatment 

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Invasive cervical cancer – 35% recurrent or persistent 50% death in the first year; 25% second year; 15% third year.

Prognosis 

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Factors : stage; lymph node status; tumor volume; depth of cervical stromal invasion; lymphovascular space invasion; lesser extent; histologic type; grade. Survival rate 5 years: stage O 99100%; IA >95%; IB-IIA 80-90%; IIB 65%; III 40%; IV <20%

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