Chapter 093. Gynecologic Malignancies (Part 8) Clinical Presentation and Staging Patients with cervix cancer generally are asymptomatic, and the disease is detected on routine pelvic examination. Others present with abnormal bleeding or postcoital spotting that may increase to intermenstrual or prominent menstrual bleeding. Yellowish vaginal discharge, lumbosacral back pain, lower-extremity edema, and urinary symptoms may be present. The staging of cervical carcinoma is clinical and generally completed with a pelvic examination under anesthesia with cystoscopy and proctoscopy. Chest x- rays, intravenous pyelograms, and CT are generally required, and MRI may be used to assess extracervical extension. Stage 0 is carcinoma in situ, stage I is disease confined to the cervix, stage II disease invades beyond the cervix but not to the pelvic wall or lower third of the vagina, stage III disease extends to the pelvic wall or lower third of the vagina or causes hydronephrosis, and stage IV is present when the tumor invades the mucosa of bladder or rectum or extends beyond the true pelvis (Fig. 93-1). Five-year survivals by stage are: stage I, 85%; stage II, 65%; stage III, 35%; and stage IV, 7% (Table 93-1). Figure 93-1 Anatomic display of the stages of cervix cancer defined by location, extent of tumor, frequency of presentation, and 5-year survival. Cervix Cancer: Treatment Carcinoma in situ (stage 0) can be managed successfully by cone biopsy or by abdominal hysterectomy. For stage I disease, results appear equivalent for either radical hysterectomy or radiation therapy. Patients with disease stages II–IV are primarily managed with external beam irradiation and intracavitary treatment or combined modality therapy. Retroperitoneal lymphadenectomy has no proven therapeutic role. Pelvic exenterations have become increasingly rare due to improved radiation control. However, they are sometimes performed for centrally recurrent or persistent disease. In women with locally advanced disease (stages IIB–IVA), platinum-based chemotherapy given concomitantly with radiation therapy improves survival compared to radiation therapy alone. Cisplatin, 75 mg/m 2 over 4 h, followed by 5- fluorouracil (5-FU), 4 g given by 96-h infusion on days 1–5 of radiation therapy, is a common regimen. Two additional cycles of chemotherapy are given at 3-week intervals. Three randomized trials of platinum-based chemotherapy reduced the risk of recurrence by 30–50% across a wide spectrum of stages and presentations and were found to improve the survival rate in bulky stage I as well as locally advanced (stages IIB–IV) cervical cancer. Chemotherapy has some palliative benefit in patients with unresectable advanced disease or recurrent disease. Active agents with ≥20% response rates include cisplatin, paclitaxel, vinorelbine, ifosfamide, and topotecan. The combination of topotecan and cisplatin has a modest survival advantage over cisplatin alone. Gestational Trophoblastic Neoplasia Gestational trophoblastic diseases are a group of related diseases that form a spectrum from benign hydatidiform mole to trophoblastic malignancy (placental- site trophoblastic tumor and choriocarcinoma). Malignant forms account for <1% of female gynecologic malignancies and can be cured with appropriate chemotherapy. Deaths from this disease have become rare in the United States. Epidemiology The incidence is about 1 per 1500 pregnancies in the United States and is nearly tenfold higher in Asia. Maternal age >45 years is a risk factor for hydatidiform mole as is a prior history of molar pregnancy. Choriocarcinoma occurs in ~1 in 25,000 pregnancies or 1 in 20,000 live births. Prior history of hydatidiform mole is a risk factor for choriocarcinoma. A woman with a previous molar pregnancy is 1000 times more likely to develop choriocarcinoma than a woman with a prior normal-term pregnancy. Pathology and Etiology The trophoblastic neoplasms have been divided by morphology into complete or partial hydatidiform mole, invasive mole, placental-site trophoblastomas, and choriocarcinomas. Hydatidiform moles contain clusters of villi with hydropic changes, hyperplasia of the trophoblast, and the absence of fetal vessels. Invasive moles differ only by invasion into the uterine myometrium. Placental-site trophoblastic tumors are predominately made up of cytotrophoblast cells arising from the placental implantation site. Choriocarcinomas consist of anaplastic trophoblastic tissue with both cytotrophoblastic and syncytiotrophoblastic elements and no identifiable villi. Complete moles result from uniparental disomy in which loss of the maternal genes (23 autosomes plus X) occurs by unknown mechanisms and is followed by duplication of the paternal haploid genome (23 autosomes plus X). Uncommonly (5%), moles result from dispermic fertilization of an empty egg, resulting in either 46XY or 46XX genotype. Partial moles result from dispermic fertilization of an egg with retention of the maternal haploid set of chromosomes, resulting in diandric triploidy (Chap. 62). . Chapter 093. Gynecologic Malignancies (Part 8) Clinical Presentation and Staging Patients with cervix cancer generally. (placental- site trophoblastic tumor and choriocarcinoma). Malignant forms account for <1% of female gynecologic malignancies and can be cured with appropriate chemotherapy. Deaths from this disease have