Gynecology_Novak

Gynecology_Novak. An enlarged ﬂuid-filled uterine cavity may be a pyometra or a hematometra. The hematometra can be drained by dilation of the cervical canal and will not interfere with treatment. The pyometra also should be drained, and the patient should be given antibiotics to cover bacteroides species, anaerobic staphylococcus and streptococcus species, and aerobic coliform bacterial infection. Placement of a large mushroom catheter through the cervix was advocated, but the catheter itself may become obstructed, leading to further occlusion of the drainage. Repeated dilation of the cervix with aspiration of pus every 2 to 3 days is more effective.


Gynecology_Novak

Gynecology_Novak. If the disease is stage I, a radical hysterectomy and pelvic lymphadenectomy may be performed. However, a pyometra is usually found in patients with advanced disease, and thus radiotherapy is required. External-beam therapy can begin after the pyometra is healed. Patients often have a significant amount of pus in the uterus or a tubo-ovarian abscess without signs of infection; therefore, a normal temperature and a normal white blood cell count do not necessarily exclude infection. Repeat physical examination or pelvic ultrasonography is necessary to ensure adequate drainage.


Gynecology_Novak

Gynecology_Novak. When invasive cervical cancer is found after simple hysterectomy, further treatment is predicated on the extent of disease. Microinvasive disease in patients at low risk for lymph node metastasis does not require further treatment. Invasive disease may be treated with radiotherapy or reoperation involving a pelvic lymphadenectomy and radical excision of parametrial tissue, cardinal ligaments, and the vaginal stump (173). Reoperation Reoperation is indicated for a young patient who has a small lesion and in whom preservation of ovarian function is desirable. It is not indicated for patients who have positive margins or obvious residual disease (173). Survival rates after radical reoperation are similar to those after radical hysterectomy for stage I disease.


Gynecology_Novak

Gynecology_Novak. Concurrent cisplatin-based chemoradiation is recommended for gross residual disease, positive imaging, disease in the lymph nodes or parametrium, or a positive surgical margin; individualized brachytherapy is clearly indicated for a positive vaginal margin (174). Radiation Therapy Survival after radiotherapy depends on the volume of disease, the status of the surgical margins, and the length of delay from surgery to radiotherapy. Patients with microscopic disease have a 95% to 100% 5-year survival rate; the 5-year survival rate is 82% to 84% in those with macroscopic disease and free margins, 38% to 87% in those with microscopically positive margins, and 20% to 47% in those with obvious residual cancer (175–177). A delay in treatment of more than 6 months is associated with a 20% survival rate (177).


Gynecology_Novak

Gynecology_Novak. Acute Hemorrhage Occasionally, a large lesion can produce life-threatening hemorrhage. A biopsy of the lesion should be performed to verify neoplasia, and a vaginal pack soaked in Monsel’s solution (ferric subsulfate) should be packed tightly against the cervix. After proper evaluation, external radiation therapy can be started with the expectation that control of bleeding may require 8 to 10 daily treatments at 180 to 200 cGy per day. Broad-spectrum antibiotics should be used to reduce the incidence of infection. If the patient becomes febrile, the pack should be removed. Rapid replacement of the pack may be necessary, and a fresh pack should be immediately available. This approach to management of hemorrhage in patients previously untreated is preferable to exploration and vascular ligation. Vascular embolization under ﬂuoroscopic control may be required in severe cases, and this procedure may obviate a laparotomy. However, vascular occlusion ultimately may lead to decreased blood


Gynecology_Novak

Gynecology_Novak. Vascular embolization under ﬂuoroscopic control may be required in severe cases, and this procedure may obviate a laparotomy. However, vascular occlusion ultimately may lead to decreased blood ﬂow and oxygenation of the tumor, compromising the effectiveness of subsequent radiotherapy.


Gynecology_Novak

Gynecology_Novak. Ureteral Obstruction Treatment of bilateral ureteral obstruction and uremia in previously untreated patients should be determined on an individual basis. Transvesical or percutaneous ureteral catheters should be placed in patients with no evidence of distant disease, and radiotherapy with curative intent should be instituted. Patients with metastatic disease beyond curative treatment fields should be presented with the options of ureteral stenting, palliative radiotherapy, and chemotherapy. With aggressive management, a median survival rate of 17 months may be achieved for these patients (178).


Gynecology_Novak

Gynecology_Novak. Barrel-Shaped Cervix The expansion of the upper endocervix and lower uterine segment by tumor is referred to as a barrel-shaped cervix. Patients with tumors larger than 6 cm in diameter have a 17.5% central failure rate when treated with radiotherapy alone because the tumor at the periphery of the lower uterine segment is too far from the standard intracavitary source to receive an adequate tumoricidal dose (179). Attempts were made to overcome this problem radiotherapeutically by means of interstitial implants into the tumor with a perineal template, but high central failure rates were reported with this technique (180).


Gynecology_Novak

Gynecology_Novak. One approach is to use a combination of radiotherapy and surgery for treatment of patients with a barrel-shaped cervix. An extrafascial hysterectomy is performed 2 to 3 months after the completion of radiation therapy in an effort to resect a small, centrally persistent tumor. The dose of external radiotherapy is reduced to 4,000 cGy, and a single intracavitary treatment is given, which is followed by an extrafascial hysterectomy (181,182). This method appears to result in a lower rate of central failure (2%), although it is not clear that the overall survival rate is improved. There is disagreement concerning the need for extrafascial hysterectomy, and the GOG is undertaking a randomized study to compare adjuvant hysterectomy with radiotherapy alone in patients who have no evidence of occult metastases in the para-aortic nodes (see stages IB and IIA discussion).


Gynecology_Novak

Gynecology_Novak. The narrow upper vagina of older patients may preclude the use of an intracavitary source of radiation. These patients must receive their entire course of therapy from external sources, leading to a higher central failure rate and more significant bowel and bladder morbidity. If stage I disease is present in such a patient, a radical hysterectomy with pelvic lymphadenectomy is preferable, if the patient’s medical condition allows this approach. There may be a role for IMRT in the management of such tumors. Treatment of recurrent cervical cancer depends on the mode of primary therapy and the site of recurrence. Patients who were treated initially with surgery should be considered for radiation therapy, and those who had radiation therapy should be considered for surgical treatment. Chemotherapy is palliative only and is reserved for patients who are not considered curable by either surgery or radiation therapy.


Gynecology_Novak

Gynecology_Novak. Radiotherapy for recurrence after surgery consists primarily of external treatment. Vaginal ovoids may be placed in patients with isolated vaginal cuff recurrences. Patients with a regional recurrence may require interstitial implantation with a Syed type of template in addition to external therapy. A 25% survival rate can be expected in patients treated with radiation for a postsurgical recurrence (162).


Gynecology_Novak

Gynecology_Novak. Radiation Retreatment Retreatment of recurrent pelvic disease by means of radiotherapy with curative intent is confined to patients who had suboptimal or incomplete primary therapy. This may allow the radiotherapist to deliver curative doses of radiation to the tumor. The proximity of the bladder and rectum to the cancer and the relative sensitivity of these organs to radiation injury are the major deterrents to retreatment with radiation. The insertion of multiple interstitial radiation sources into locally recurrent cancer through a perineal template may help overcome these dosimetric considerations (173,183). The fistula rates are high, and those consequences must be considered before interstitial therapy is initiated. For patients considered curable with interstitial implant therapy, pelvic exenteration is a better treatment choice. Palliative radiotherapy can be given to patients with localized metastatic lesions that are deemed incurable. Painful bony metastases, central nervous


Gynecology_Novak

Gynecology_Novak. exenteration is a better treatment choice. Palliative radiotherapy can be given to patients with localized metastatic lesions that are deemed incurable. Painful bony metastases, central nervous system lesions, and severe urologic or vena caval obstructions are specific indications.


Gynecology_Novak

Gynecology_Novak. Surgical Therapy Surgical therapy for postirradiation recurrence is limited to patients with central pelvic disease. A few carefully selected patients with small-volume disease limited to the cervix may be treated with an extrafascial or radical hysterectomy. However, the difficulty of assessing tumor volume and the 30% to 50% rate of serious urinary complications in these previously irradiated patients have led most gynecologic oncologists to recommend pelvic exenteration as a last chance for cure (184,185).


Gynecology_Novak

Gynecology_Novak. Exenteration There are three types of exenterative procedures: (i) an anterior exenteration (removal of the bladder, vagina, cervix, and uterus), (ii) a posterior exenteration (removal of the rectum, vagina, cervix, and uterus), and (iii) a total exenteration (removal of both bladder and rectum with the vagina, cervix, and uterus (Fig. 36.9). A total exenteration that includes a large perineal phase includes the entire rectum and leaves the patient with a permanent colostomy and a urinary conduit (infralevator). In selected patients, a total exenteration may take place above the levator muscle (supralevator), leaving a rectal stump that may be anastomosed to the sigmoid, thus avoiding a permanent colostomy.


Gynecology_Novak

Gynecology_Novak. Preoperative Evaluation and Patient Selection It is imperative to search for metastatic disease before undergoing an exenteration. The presence of metastatic disease in this setting is considered a contraindication to exenterative procedures. Physical examination includes careful palpation of the peripheral lymph nodes with FNA cytologic sampling of any nodes that appear suspicious. A random biopsy of nonsuspicious supraclavicular lymph nodes is advocated by some clinicians but is not routinely practiced (145,186). A PET/CT scan of the chest and abdomen and pelvis CT helps in the detection of liver metastases and enlarged nodes. Cytologic study of any abnormality should be undertaken with CT-guided FNA. If a positive cytologic diagnosis is obtained, it will obviate the need for exploratory laparotomy.


Gynecology_Novak

Gynecology_Novak. Extension of the tumor to the pelvic sidewall is a contraindication to exenteration; however, this may be difficult for even the most experienced examiner to determine because of radiation fibrosis. If any question of resectability arises, exploratory laparotomy and parametrial biopsies should be offered (187–190). The clinical triad of unilateral leg edema, sciatic pain, and ureteral obstruction is nearly always pathognomonic of unresectable disease on the pelvic sidewall. Preoperatively, the patient should be prepared for a major operation. Total parenteral nutrition may be necessary to place the patient in an anabolic state for optimal healing. A bowel preparation, preoperative antibiotic administration, and prophylaxis for deep venous thrombosis with low-dose heparin or pneumatic calf compression should be undertaken (191). Figure 36.9 Pelvic exenteration specimen.


Gynecology_Novak

Gynecology_Novak. Figure 36.9 Pelvic exenteration specimen. Surgical mortality increases with age, and the operation should rarely be considered in a patient who is older than 70 years. Other medical illnesses should be taken into account. When life expectancy is limited, exenterative surgery is unwise. Anterior Exenteration Candidates for anterior exenteration are those in whom the disease is limited to the cervix and anterior portion of the upper vagina. Proctoscopic examination should be performed because a positive finding would mandate a total exenteration. However, a negative proctoscopic examination finding does not exclude disease in the rectal muscularis, and findings at laparotomy still must be considered. The presence of disease in the posterior vaginal mucosa directly over the rectum mandates removal of the underlying rectum.


Gynecology_Novak

Gynecology_Novak. Posterior Exenteration A posterior exenteration is rarely performed for recurrent cervical cancer. It is indicated, however, for the patient with an isolated posterior vaginal recurrence in which dissection of the ureters through the cardinal ligaments will not be necessary. Total Exenteration Total exenteration with a large perineal phase is indicated when the disease extends to the lower part of the vagina (Fig. 36.9). Because distal vaginal lymphatics may empty into the nodal basins of the inguinal region, these nodes should be carefully evaluated preoperatively. A supralevator total exenteration with low rectal anastomosis is indicated in the patient whose disease is confined to the upper vagina and cervix (192,193). Samples from margins of the rectal edge should be obtained for frozen-section evaluation because occult metastases to the muscularis may occur.


Gynecology_Novak

Gynecology_Novak. The development of techniques to establish continent urinary diversion help improve a woman’s physical appearance after exenteration (194–196). When both a rectal anastomosis and a continent diversion are performed, the patient will not have a permanent external appliance. Associated psychological trauma in such cases may be avoided. Every effort should be made to create a neovagina simultaneously with the exenteration (197). This procedure helps in the reconstruction of the pelvic ﬂoor after extirpation of the pelvic viscera. Regardless of whether a neovagina is constructed, it is desirable to mobilize the omentum on the left gastroepiploic artery to create a new pelvic ﬂoor. Surgical mortality from exenterative procedures has steadily decreased to less than 10%. Common causes of postoperative death are sepsis, pulmonary thromboembolism, and hemorrhage.


Gynecology_Novak

Gynecology_Novak. Fistulas of the gastrointestinal and genitourinary tract are serious surgical complications, with a 30% to 40% mortality rate despite attempts at surgical repair. The risk for fistula formation is decreased if nonirradiated segments of bowel are used for formation of the urinary conduit (191). The 5-year survival rate is 33% to 60% for patients undergoing anterior exenteration and 20% to 46% for those undergoing total exenteration (187–197). Survival rates are worse for patients with recurrent disease (larger than 3 cm), invasion into the bladder, positive pelvic lymph nodes, and recurrence diagnosed within 1 year after radiotherapy (190). The 5-year survival rate of patients with positive pelvic lymph nodes is less than 5%; thus, the performance of an extensive lymphadenectomy in the irradiated field is not warranted. Discontinuation of the procedure is advisable if any nodes are positive for metastatic cancer. Patients who have any disease in the peritoneal cavity have no chance of


Gynecology_Novak

Gynecology_Novak. field is not warranted. Discontinuation of the procedure is advisable if any nodes are positive for metastatic cancer. Patients who have any disease in the peritoneal cavity have no chance of survival.


Gynecology_Novak

Gynecology_Novak. Locally recurrent cervical cancer in a previously irradiated field is associated with a dismal prognosis. Exenterative therapy traditionally was reserved for the highly select patient with centrally recurrent disease, a selection criteria that excludes most patients with recurrence. A technique called the laterally extended endopelvic resection (LEER) procedure was described, which offers a surgical treatment option for patients with recurrent disease involving the pelvic sidewall. The LEER procedure involves extending the lateral resection plane of the traditional pelvic exenteration to include resection of the internal iliac vessels; the endopelvic portion of the obturator internus muscle; and the coccygeus, iliococcygeus, and pubococcygeus muscles. Extension of the surgical plane allows for resection of lateral tumors with a negative margin. Experience with it is limited to one center, which reports as high as a 62% recurrence-free survival, but as high as 70% moderate to severe


Gynecology_Novak

Gynecology_Novak. for resection of lateral tumors with a negative margin. Experience with it is limited to one center, which reports as high as a 62% recurrence-free survival, but as high as 70% moderate to severe morbidity (198).


Gynecology_Novak

Gynecology_Novak. Recurrent cervical cancer is not considered curable with chemotherapy. The delivery of chemotherapy to recurrent tumor in a prior radiated field may be compromised because of altered blood supply caused by radiation. Topotecan and cisplatin had response rates of 15% to 20%, with a median duration of 6 to 9 months (199). Many other agents showed activity against cervical cancer and may be used in attempt to help control symptoms. Several clinical trials with various drugs (e.g., paclitaxel, topotecan, cisplatin, and carboplatin) showed response rates of up to 45%. Most responses are partial; complete responses are unusual and limited to patients with chest metastases in whom the dose of drug delivered to the disease is stronger than that delivered to the fibrotic postirradiated pelvis (200,201). Doublet therapy with cisplatin and paclitaxel is considered standard therapy based on GOG 204, which analyzed four cisplatin-containing doublets for the best efficacy; although no major


Gynecology_Novak

Gynecology_Novak. (200,201). Doublet therapy with cisplatin and paclitaxel is considered standard therapy based on GOG 204, which analyzed four cisplatin-containing doublets for the best efficacy; although no major differences existed in overall survival for the four doublets, the cisplatin and paclitaxel doublet trended toward the best results (153). Other studies showed comparable survival and less toxicity with carboplatin and paclitaxel (154).


Gynecology_Novak

Gynecology_Novak. Palliative Therapy Palliative therapy for patients with incurable disease consists of radiation or chemotherapy or both. Palliative radiation therapy is intended to relieve symptoms of pain or bleeding associated with advanced disease and may be administered as either external beam therapy (teletherapy) or brachytherapy. Special care should be given to previously irradiated sites because additional radiation therapy may be associated with unacceptable morbidity. Single or multiagent palliative chemotherapy may be used with variable response rates. Symptomatic recurrent disease within previously irradiated fields may not respond well to palliative chemotherapy.


Gynecology_Novak

Gynecology_Novak. Primary vaginal cancer is a relatively uncommon tumor, representing only 2% to 3% of malignant neoplasms of the female genital tract. In the United States it is estimated that there were 2,160 new cases in 2009, and 770 deaths from the disease (1). Squamous histology accounts for 80% (202). Primary vaginal cancer should be differentiated from cancers metastatic to the vagina, which constitute the majority of cancers found in the vagina (84%) (203). Staging The FIGO staging of vaginal cancer dictates that a tumor extending to the vagina from the cervix be regarded as a cancer of the cervix, whereas a tumor involving both the vulva and the vagina should be classified as a cancer of the vulva. Table 36.6 FIGO Staging of Vaginal Cancer FIGO, International Federation of Gynecology and Obstetrics. From FIGO Annual Report. Int J Gynecol Obstet 2006;95:S29 and Int J Gynecol Obstet 2009;105:3–4.


Gynecology_Novak

Gynecology_Novak. FIGO, International Federation of Gynecology and Obstetrics. From FIGO Annual Report. Int J Gynecol Obstet 2006;95:S29 and Int J Gynecol Obstet 2009;105:3–4. The FIGO staging for vaginal carcinoma is shown in Table 36.6. Staging is performed by clinical examination and, if indicated, cystoscopy, proctoscopy, and chest and skeletal radiography. Information derived from lymphangiography, CT, MRI, or PET cannot be used to change the FIGO stage; however, it can be used for planning treatment. Less than 30% of vaginal cancers present at stage I (204–206). Surgical staging and resection of enlarged lymph nodes may be indicated in selected patients. FIGO staging does not include a category for microinvasive disease. Because vaginal cancer is rare and treatment is by radiotherapy, there is very little information concerning the spread of disease in relation to depth of invasion, lymph–vascular space invasion, and size of the lesion.


Gynecology_Novak

Gynecology_Novak. Etiology The association of cervical cancer with HPV suggests that vaginal cancer may have a similar association (207). A study of 341 cases revealed that in younger patients the disease seemed to be related to HPV infection, while in older patients there was no association (206). In addition, as many as 30% of women with vaginal cancer have a history of cervical cancer treated within the previous 5 years (208–210). As with cervical cancer, there appears to be a premalignant phase called vaginal intraepithelial neoplasia (VAIN) (see Chapter 19). The exact incidence of progression to invasive vaginal cancer from VAIN is not known; however, there are documented cases of invasive disease occurring despite adequate treatment of VAIN (211,212). By convention, any new vaginal carcinoma developing at least 5 years after cervical cancer is considered a new primary lesion. There are three possible mechanisms for the occurrence of vaginal cancer after cervical neoplasia: 1.


Gynecology_Novak

Gynecology_Novak. Residual disease in the vaginal epithelium after treatment of the cervical neoplasia 2. New primary disease arising in a patient with increased susceptibility to lower genital tract carcinogenesis (the role of HPV in this setting is suspected) 3. Increased susceptibility to carcinogenesis caused by radiation therapy be considered at risk. Therefore, in addition to screening cytology, careful bimanual examination of the entire vagina and vulva is recommended for women at high risk. Symptoms Painless vaginal bleeding and discharge are the most common symptoms of vaginal cancer. With more advanced tumors, urinary retention, bladder spasm, hematuria, and frequency of urination may occur. In a large series, 14% were asymptomatic and diagnosis was made by routine examination or abnormal cytology (206). Tumors developing on the posterior vaginal wall may produce rectal symptoms, such as tenesmus, constipation, or blood in the stool.


Gynecology_Novak

Gynecology_Novak. Diagnosis The diagnostic workup includes a complete history and physical examination, careful speculum examination and palpation of the vagina, and bimanual pelvic and rectal examinations. It is important to rotate the speculum to obtain a careful view of the entire vagina because posterior wall lesions frequently occur and may be overlooked.


Gynecology_Novak

Gynecology_Novak. In early squamous cell lesions, the diagnosis is often suggested by an abnormal Pap test result; however, this is not true for clear cell adenocarcinomas, which are characterized by submucosal growth. In these cases, the diagnosis is suggested by cytologic findings in only 33% of cases. Visually suspicious areas in the vagina should be evaluated with a targeted biopsy using the same instruments as those used for cervical biopsies. Careful palpation of the vagina may be helpful in detecting submucosal irregularities. The most common site of vaginal cancer is in the upper one-third of the vagina on the posterior wall. The developing tumor may be missed during initial inspection because of obscured visualization caused by the blades of the speculum (214). Colposcopy is valuable in evaluating patients with abnormal Pap test results, unexplained vaginal bleeding, or ulcerated erythematous patches in the upper vagina. A colposcopically targeted biopsy may not allow a definitive diagnosis,


Gynecology_Novak

Gynecology_Novak. patients with abnormal Pap test results, unexplained vaginal bleeding, or ulcerated erythematous patches in the upper vagina. A colposcopically targeted biopsy may not allow a definitive diagnosis, and a partial vaginectomy may be necessary to determine invasion. Occult invasive carcinoma may be detected by such an excision, particularly in patients who have a history of prior hysterectomy in whom the vaginal vault closure may bury some of the vaginal epithelium at risk for cancer (215).


Gynecology_Novak

Gynecology_Novak. Pathology Cancer of the vagina spreads most often by direct extension into the pelvic soft tissues and adjacent organs. Metastases to the pelvic and para-aortic lymph nodes may occur in advanced disease. Lesions in the lower one-third of the vagina may spread directly to the inguinal femoral lymph nodes and the pelvic nodes (216). Hematogenous dissemination to the lungs, liver, or bone may occur as a late phenomenon. Squamous cell carcinomas are the most common form of vaginal cancer, occurring in 80% to 90% of cases. These tumors most commonly occur in the upper one-third, posterior wall of the vagina. The mean age of patients with squamous cell cancer is 60 years (217,218). Malignant melanoma is the second most common cancer of the vagina, accounting for 2.8% to 5% of all vaginal neoplasms (219–221). Other histologic subtypes include adenocarcinoma and sarcoma.


Gynecology_Novak

Gynecology_Novak. Primary adenocarcinoma of the vagina is rare, constituting 9% of primary tumors of the vagina. The most common adenocarcinoma of the vagina is metastatic, originating from the colon, endometrium, ovary, or, rarely, pancreas and stomach. In general, adenocarcinomas affect a younger population of women, regardless of whether they were exposed to diethylstilbestrol (DES) in utero (222). Adenocarcinomas may arise in wolffian rest elements, periurethral glands, and foci of endometriosis (223). In women exposed to DES in utero, adenocarcinoma may develop in vaginal adenosis.


Gynecology_Novak

Gynecology_Novak. DES was used in the United States from 1940 until 1971 to maintain high-risk pregnancies in women with a history of spontaneous abortions. In 1970, seven young women were reported with clear cell adenocarcinoma of the vagina (Fig. 36.10); later, an association between this cancer and maternal ingestion of DES during pregnancy was identified (224). Subsequently, more than 500 cases of clear cell cancer of the vagina and cervix were reported to the Registry for Research on Hormonal Transplacental Carcinogenesis.


Gynecology_Novak

Gynecology_Novak. The estimated risk for developing clear cell adenocarcinoma for an exposed offspring is 1 in 1,000 or less. The mean age of diagnosis is 19 years (225). Clear cell adenocarcinoma in women with a history of in utero exposure to DES typically presents in the exocervix or anterior, upper one-third of the vagina. These tumors vary greatly in size and are most frequently exophytic and superficially invasive. Stage is the most important prognostic factor. Other statistically significant Figure 36.10 Vaginal clear cell carcinoma. Note the formation of tubules with hobnail cells lining the lumen. These cells are characterized by nuclear protrusion into the apical cytoplasm.


Gynecology_Novak

Gynecology_Novak. Figure 36.10 Vaginal clear cell carcinoma. Note the formation of tubules with hobnail cells lining the lumen. These cells are characterized by nuclear protrusion into the apical cytoplasm. factors include a tubulocystic growth pattern, size less than 3 cm2, and less than 3 mm of stromal invasion. Because the use of DES in pregnant women was discontinued in 1971, most of these tumors probably have been discovered. It is uncertain, however, what will happen to this cohort of women as they move into their fifth, sixth, and seventh decades of life. Continued surveillance of these women is indicated.


Gynecology_Novak

Gynecology_Novak. Ninety-seven percent of cases of vaginal clear cell adenocarcinoma are associated with adenosis. Adenosis is characterized by the presence of persistent m¨ullerian-type glandular epithelium. Although adenosis is the most common histologic abnormality in women exposed to DES in utero, adenosis can be found in women without a history of exposure. Adenosis typically appears as red, grapelike clusters in the vagina.


Gynecology_Novak

Gynecology_Novak. Malignant melanoma of the vagina is rare and lethal, occurring most often in white women. The average age of these patients is 58 years (226). Most lesions are deeply invasive, corresponding to a Clark level IV when compared with the staging for vulvar melanomas. The most common location of these tumors is in the lower one-third of the vagina (227). Melanomas have a wide variety of size, color, and growth patterns (225,228). Radical excision (vaginectomy, hysterectomy, and pelvic lymphadenectomy) is the mainstay of treatment. The goal of treatment is to avoid local (vaginal) recurrence, which is the most common site of recurrence (226,227). The need to dissect regional lymph nodes is uncertain. Because the disease is deeply invasive, hematogenous spread is the most common lethal recurrence. There is no difference in overall survival of patients with local as opposed to radical excision (226). The survival rate is approximately 10% at 5 years.


Gynecology_Novak

Gynecology_Novak. The most common benign and malignant mesenchymal tumors of the vagina in adult women are smooth muscle tumors (229). Vaginal sarcomas are usually fibrosarcomas or leiomyosarcomas and are extremely rare. Radical local excision, followed by adjuvant chemotherapy or radiation therapy, is the indicated treatment. The most common malignant mesenchymal tumor of the vagina in children and infants is botryoid rhabdomyosarcoma (Fig. 36.11). Botryoid sarcoma is usually found in the vagina during infancy and early childhood, in the cervix during the reproductive years, and in the corpus uteri during postmenopausal years. Preoperative chemotherapy with vincristine, actinomycin D, and cyclophosphamide, followed by conservative surgery or radiation, has improved survival.


Gynecology_Novak

Gynecology_Novak. Figure 36.11 Embryonal rhabdomyosarcoma of the vagina (botryoid sarcoma). This lesion consists of primitive mesenchymal cells and rhabdomyoblasts, which have abundant eosinophilic cytoplasm. With further differentiation, cross striations may become evident. Treatment Treatment selection is based on the clinical examination, CT scan results, chest radiography results, age, and condition of the patient. PET scans may give more accurate information about disease spread than MRI or CT scan alone (230). Most tumors are treated by radiation therapy. Surgery is limited to selected cases. These are as follows: 1. Women with stage I disease involving the upper posterior vagina may be treated by radical vaginectomy and pelvic lymphadenectomy. If the uterus is in situ,itis removed as a radical hysterectomy specimen. When margins are clear and lymph nodes are negative, no additional therapy is necessary. 2.


Gynecology_Novak

Gynecology_Novak. 2. Patients with stage IV disease with either rectovaginal or vesicovaginal fistula may be candidates for primary pelvic exenteration with pelvic and para-aortic lymphadenectomy (225). Low rectal anastomosis, continent urinary diversion, and vaginal reconstruction are indicated and are more successful in these nonirradiated patients than in patients who received prior radiation therapy. 3. Women with central pelvic recurrence after radiation therapy are candidates for pelvic exenteration similar to that used for cervical cancer. 4. Surgical staging with resection of enlarged lymph nodes followed by radiation therapy may improve the control of pelvic disease.


Gynecology_Novak

Gynecology_Novak. 4. Surgical staging with resection of enlarged lymph nodes followed by radiation therapy may improve the control of pelvic disease. Radiation therapy is the treatment of choice for all patients except those described previously. Small superficial lesions may be treated with intracavitary radiation alone (225). Larger, thicker lesions should be treated first with external teletherapy to decrease tumor volume and to treat the regional pelvic nodes, followed by intracavitary and interstitial therapy to deliver a high dose to the primary tumor (218,226). If the uterus is intact and the lesion involves the upper vagina, an intrauterine tandem and ovoids can be used. If the uterus was previously removed, a vaginal cylinder may be used for superficial irradiation. When brachytherapy Table 36.7 Primary Vaginal Carcinoma: 5-Year Survival


Gynecology_Novak

Gynecology_Novak. Table 36.7 Primary Vaginal Carcinoma: 5-Year Survival Data compiled from Pride et al., 1979 (233); Houghton and Iversen, 1982 (229); Benedet et al., 1983 (205); Rubin et al., 1985 (207); Kucera et al., 1985 (228); Eddy et al., 1991 (232); Kirkbride et al., 1995 (234); Perez et al., 1999 (235); Tewari et al., 2001 (236); Otton et al., 2004 (237); Frank et al., 2005 (238); Hellman et al., 2006 (204); Tran et al., 2007 (239).


Gynecology_Novak

Gynecology_Novak. is used, high-and low-dose rate techniques were described. If the lesion is more than 0.5 cm thick, interstitial radiation techniques can improve the dose distribution to the primary tumor. Surgical exploration or laparoscopy at the time of insertion of Syed interstitial implants defines more precisely the placement of the needles and ensures that needles do not pass into adherent loops of bowel. Extended-field radiation may be used for vaginal cancer in a manner similar to its use for cervical carcinoma, although there is no experience reported with the use of this technique in the treatment of vaginal cancer. Likewise, there is little reported experience with combination chemoradiation treatment (231). Although there will never be enough patients for a proper randomized control trial, concurrent use of 5-FU and cisplatin was highly successful in anal and cervical cancer and thus should be considered for treatment of vaginal cancer.


Gynecology_Novak

Gynecology_Novak. Sequelae The proximity of the rectum, bladder, and urethra leads to a major complication rate of 10% to 15% for both surgery and radiation treatment. For large tumors, the risk of bladder or bowel fistula is significant. Radiation cystitis and proctitis are common, as are rectal strictures or ulcerations. Radiation necrosis of the vagina occasionally occurs, requiring debridement, and often leads to fistula formation. Vaginal fibrosis, stenosis, and stricture are common after radiation therapy. Use of vaginal dilators and resumption of regular sexual relations should be encouraged, along with the use of topical estrogen to maintain adequate vaginal function.


Gynecology_Novak

Gynecology_Novak. Survival The overall 5-year survival rate for patients with vaginal cancer is 52% (Table 36.7). This reﬂects the difficulties of treatment and the fact the disease presents at late stage. For patients with stage I disease, the 5-year survival rate is 74%. Most recurrences are in the pelvis, either from enlarged regional nodes or from large central tumors. Radiation techniques, including interstitial implants with Syed applicator and combination chemoradiation, are the mainstay of therapy. Careful evaluation of patients who receive radiation therapy to detect central recurrence may allow some patients to be saved by pelvic exenteration. Because of the rarity of vaginal cancer, these patients should be treated in a center that is familiar with the complexity of treatment and modalities of therapy. 1. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011. CA Cancer J Clin 2011;61:212–236. http://cacancerjournal.org 2.


Gynecology_Novak

Gynecology_Novak. 1. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011. CA Cancer J Clin 2011;61:212–236. http://cacancerjournal.org 2. Womack C, Warren AY. Achievable laboratory standards: a review of cytology of 99 women with cervical cancer. Cytopathology 1998; 9:171. 3. Pettersson F. Annual report on the results of treatment in gynecological cancer. Radiumhemmet, Stockholm, Sweden: International Federation of Gynecology and Obstetrics (FIGO), 1994:132–168.[MB6] 4. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2007;120:885–891. 5. Ursin G, Peters RK, Henderson BE, et al. Oral contraceptive use and adenocarcinoma of the cervix. Lancet 1994;344:1390–1393. 6.


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Gynecology_Novak. 136. Twiggs LB, Potish RA, George RJ, et al. Pretreatment extraperitoneal surgical staging in primary carcinoma of the cervix uteri. Surg Gynecol Obstet 1984;158:243–250. 137. Weiser EB, Bundy BN, Hoskins WJ, et al. Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study). Gynecol Oncol 1989;33:283–289. 138. Stehman FB, Bundy BN, DiSaia PJ, et al. Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 1991;67:2776–2785. 139. Lovecchio JL, Averette HE, Donato D, et al. 5-Year survival of patients with periaortic nodal metastases in clinical stage IB and IIA cervical carcinoma. Gynecol Oncol 1990;38:446. 140.


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Gynecology_Novak. 139. Lovecchio JL, Averette HE, Donato D, et al. 5-Year survival of patients with periaortic nodal metastases in clinical stage IB and IIA cervical carcinoma. Gynecol Oncol 1990;38:446. 140. Rubin SC, Brookland R, Mikuta JJ, et al. Paraaortic nodal metastases in early cervical carcinoma: long-term survival following extended-field radiotherapy. Gynecol Oncol 1984;18:213–217. 141. Boughanim M, Leboulleux S, Rey A, et al. Histologic results of para-aortic lymphadenectomy in patients treated for stage IB2/II cervical cancer with negative [18F]ﬂuorodeoxyglucose positron emission tomography scans in the para-aortic area. J Clin Oncol 2008;26:2558–2561 142. Haie C, Pejovic MH, Gerbaulet A, et al. Is prophylactic paraaortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group. Radiother Oncol 1998;11:101. 143.


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Gynecology_Novak. 143. Rotman M, Pajak TF, Choi K, et al. Prophylactic extended-field irradiation of paraaortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas. Ten-year treatment results of RTOG 79-20. JAMA 1995;274:387. 144. Stehman FB, Bundy BN, Hanjani P, et al. Biopsy of the scalene fat pad in carcinoma of the cervix uteri metastatic to the periaortic lymph nodes. Surg Gynecol Obstet 1987;165:503–506. 145. Kim RY, Levy DS, Brascho DJ, et al. Uterine perforation during intracavitary application: prognostic significance in carcinoma of the cervix. Radiology 1983;147:249–251. 146. White AJ, Buchsbaum HJ, Blythe JG, et al. Use of the bulbocavernosus muscle (Martius procedure) for repair of radiation-induced rectovaginal fistulas. Obstet Gynecol 1982;60:114–118. 147. Bricker EM, Johnston WD. Repair of postirradiation rectovaginal fistula and stricture. Surg Gynecol Obstet 1979;148:499–506. 148.


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Gynecology_Novak. 147. Bricker EM, Johnston WD. Repair of postirradiation rectovaginal fistula and stricture. Surg Gynecol Obstet 1979;148:499–506. 148. Smith ST, Seski JC, Copeland LJ, et al. Surgical management of irradiation-induced small bowel damage. Obstet Gynecol 1985;65:563–567. 149. Bloss JD, Blessing JA, Behrens BC, et al. Randomized trial of cisplatin and ifosfamide with and without bleomycin in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 2002;20:1832–1837. 150. Omura GA, Blessing JA, Vaccarello L, et al. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 1997;15:165. 151.


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Gynecology_Novak. 151. Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 2004;22:3113. 152. Long HJ, Monk BJ, Huang HQ, et al. Clinical results and quality of life analysis of the MVAC combination in carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 2006;100:537– 543. 153. Monk BJ, Sill MW, McMeekin DS, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVb, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2009;27:4649–4655. 154. Pectasides D, Fountzilas G, Papaxoinis G, et al. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer 2009;19:777–781. 155. Simon NL, Gore H, Shingleton HM, et al. Study of superficially invasive carcinoma of the cervix. Obstet Gynecol 1986;68: 19–24.


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Gynecology_Novak. 155. Simon NL, Gore H, Shingleton HM, et al. Study of superficially invasive carcinoma of the cervix. Obstet Gynecol 1986;68: 19–24. 156. Delgado G, Bundy BN, Fowler WC, et al. A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1989;35:314– 320. 157. Landoni F, Maneo A, Columbo A, et al. Randomised study of radical surgery versus radiotherapy for stage IB–IIA cervical cancer. Lancet 1997;350:535–540. 158. Jampolis S, Andras J, Fletcher GH. Analysis of sites and causes of failure of irradiation in invasive squamous cell carcinoma of the intact uterine cervix. Radiology 1975;115:681–685. 159. Million RR, Rutledge F, Fletcher GH. Stage IV carcinoma of the cervix with bladder invasion. Am J Obstet Gynecol 1972;113:239– 246. 160. Gallousis S. Isolated lung metastases from pelvic malignancies. Gynecol Oncol 1979;7:206–214. 161.


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Gynecology_Novak. 160. Gallousis S. Isolated lung metastases from pelvic malignancies. Gynecol Oncol 1979;7:206–214. 161. Nordqvist SR, Sevin BU, Nadji M, et al. Fine-needle aspiration cytology in gynecologic oncology. I. Diagnostic accuracy. Obstet Gynecol 1979;54:719–724. 162. Krebs HB, Helmkamp BF, Sevin B-U, et al. Recurrent cancer of the cervix following radical hysterectomy and pelvic node dissection. Obstet Gynecol 1982;59:422–427. 163. Shingleton HM, Orr JW Jr. Posttreatment surveillance. In: Singer A, Jordan J, eds. Cancer of the cervix. New York: Churchill Livingstone, 1983:135–122. 164. Duggan B, Muderspach LI, Roman LD, et al. Cervical cancer in pregnancy: reporting on planned delay in therapy. Obstet Gynecol 1993;82:598. 165. Hacker NF, Berek JS, Lagasse LD, et al. Carcinoma of the cervix associated with pregnancy. Obstet Gynecol 1982;59:735– 746. 166. Averette HE, Nasser N, Yankow SL, et al. Cervical conization in pregnancy. Am J Obstet Gynecol 1970;106:543–549. 167.


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Gynecology_Novak. 166. Averette HE, Nasser N, Yankow SL, et al. Cervical conization in pregnancy. Am J Obstet Gynecol 1970;106:543–549. 167. Lee RB, Neglia W, Park RC. Cervical carcinoma in pregnancy. Obstet Gynecol 1981;58:584–589. 168. Shingleton HM, Orr JW Jr. Cancer complicating pregnancy. In: Singer A, Jordan J, eds. Cancer of the cervix. New York: Churchill Livingstone, 1983:193–209. 169. Sood AK, Sorosky JI, Mayr N, et al. Cervical cancer diagnosed shortly after pregnancy: prognostic variables and delivery routes. Obstet Gynecol 2000;95:832–838. 170. Committee on Practice Bulletins–Gynecology. Diagnosis and treatment of cervical carcinoma. Obstet Gynecol 2002;99:855. 171. Bader AA, Petru E, Winter R. Long-term follow-up after neoadjuvant chemotherapy for high-risk cervical cancer during pregnancy. Gynecol Oncol 2007;105:269–272. 172. Green TH, Morse WJ Jr. Management of invasive cervical cancer following inadvertent simple hysterectomy. Obstet Gynecol 1969;33:763–769. 173.


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Gynecology_Novak. 172. Green TH, Morse WJ Jr. Management of invasive cervical cancer following inadvertent simple hysterectomy. Obstet Gynecol 1969;33:763–769. 173. Orr JW Jr, Ball GC, Soong SJ, et al. Surgical treatment of women found to have invasive cervix cancer at the time of total hysterectomy. Obstet Gynecol 1986;68:353–356. 174. Journal of the National Comprehensive Cancer Network. JNCCN consensus guidelines for cervical carcinoma. JNCCN December 2010. 175. Durrance FY. Radiotherapy following simple hysterectomy in patients with stage I and II carcinoma of the cervix. AJR Am J Roentgenol 1968;102:165–169. 176. Andras EJ, Fletcher GH, Rutledge F. Radiotherapy of carcinoma of the cervix following simple hysterectomy. Am J Obstet Gynecol 1973;115:647–655. 177. Heller PB, Barnhill DR, Mayer AR, et al. Cervical carcinoma found incidentally in a uterus removed for benign indications. Obstet Gynecol 1986;67:187–190. 178.


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Gynecology_Novak. 177. Heller PB, Barnhill DR, Mayer AR, et al. Cervical carcinoma found incidentally in a uterus removed for benign indications. Obstet Gynecol 1986;67:187–190. 178. Taylor PT, Andersen WA. Untreated cervical cancer complicated by obstructive uropathy and renal failure. Gynecol Oncol 1981;11:162– 174. 179. Fletcher GH, Wharton JT. Principles of irradiation therapy for gynecologic malignancy. Curr Probl Obstet Gynecol 1978;2:2–44. 180. Gaddis O Jr, Morrow CP, Klement V, et al. Treatment of cervical carcinoma employing a template for transperineal interstitial iridium brachytherapy. Int J Radiat Oncol Biol Phys 1983;9:819–827. 181. O’Quinn AG, Fletcher GH, Wharton JT. Guidelines for conservative hysterectomy after irradiation. Gynecol Oncol 1980;9:68–79. 182. Homesley HD, Raben M, Blake DD, et al. Relationship of lesion size to survival in patients with stage IB squamous cell carcinoma of the cervix uteri treated by radiation therapy. Surg Gynecol Obstet 1980;150:529–531.


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Gynecology_Novak. 183. Feder BH, Syed AMN, Neblett D. Treatment of extensive carcinoma of the cervix with the “transperineal parametrial butterﬂy”—a preliminary report on the revival of Waterman’s approach. Int J Radiat Oncol Biol Phys 1978;4:735–742. 184. Mikuta JJ, Giuntoli RL, Rubin EL, et al. The radical hysterectomy. Am J Obstet Gynecol 1977;128:119–127. 185. Symmonds RE, Pratt JH, Welch JS. Extended Wertheim operation for primary, recurrent, or suspected recurrent carcinoma of the cervix. Obstet Gynecol 1964;24:15–27. 186. Ketcham AS, Chretien PB, Hoye RC, et al. Occult metastases to the scalene lymph nodes in patients with clinically operable carcinoma of the cervix. Cancer 1973;31:180–183. 187. Fleisch MC, Pantke P, Beckmann MW, et al. Predictors for longterm survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers. J Surg Oncol 2007;95:476–484. 188.


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Gynecology_Novak. Fleisch MC, Pantke P, Beckmann MW, et al. Predictors for longterm survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers. J Surg Oncol 2007;95:476–484. 188. Rutledge FN, Smith JP, Wharton JT, et al. Pelvic exenteration: an analysis of 296 patients. Am J Obstet Gynecol 1977;129:881–892. 189. Maggioni A, Roviglione G, Landoni F, et al. Pelvic exenteration: ten-year experience at the European Institute of Oncology in Milan. Gynecol Oncol 2009;114:64–68. 190. Hatch KD, Shingleton HM, Soong SJ, et al. Anterior pelvic exenteration. Gynecol Oncol 1988;31:205–216. 191. Orr JW Jr, Shingleton HM, Hatch KD, et al. Gastrointestinal complications associated with pelvic exenteration. Am J Obstet Gynecol 1983;145:325–332. 192. Berek JS, Hacker NF, Lagasse LD. Rectosigmoid colectomy and reanastomosis to facilitate resection of primary and recurrent gynecologic cancer. Obstet Gynecol 1984;64:715–720. 193.


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Gynecology_Novak. 192. Berek JS, Hacker NF, Lagasse LD. Rectosigmoid colectomy and reanastomosis to facilitate resection of primary and recurrent gynecologic cancer. Obstet Gynecol 1984;64:715–720. 193. Hatch KD, Shingleton HM, Potter ME, et al. Low rectal resection and anastomosis at the time of pelvic exenteration. Gynecol Oncol 1988;31:262–267. 194. Kock NG, Nilson AE, Nilsson LO, et al. Urinary diversion via a continent ileal reservoir: clinical results in 12 patients. JUrol 1982;128:469–475. 195. Penalver MA, Bejany DE, Averette HE, et al. Continent urinary diversion in gynecologic oncology. Gynecol Oncol 1989;34:274– 288. 196. Mannel RS, Braly PS, Buller RE. Indiana pouch continent urinary reservoir in patients with previous pelvic irradiation. Obstet Gynecol 1990;75:891–893. 197. Berek JS, Hacker NF, Lagasse LD. Vaginal reconstruction performed simultaneously with pelvic exenteration. Obstet Gynecol 1984;63:318–323. 198.


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Gynecology_Novak. 197. Berek JS, Hacker NF, Lagasse LD. Vaginal reconstruction performed simultaneously with pelvic exenteration. Obstet Gynecol 1984;63:318–323. 198. Hockel M. Laterally extended endopelvic resection: principles and practices. Gynecol Oncology 2008;111:S13–S17. 199. Abu-Rusteem NR, Lee S, Massad LS. Topotecan for recurrent cervical cancer after platinum based therapy. Int J Gynecol Cancer 2000;10:285–288. 200. Thigpen JT. Single agent chemotherapy in carcinoma of the cervix. In: Surwit EA, Alberts DS, eds. Cervix cancer. Boston, MA: Martinus Nijhoff, 1987:119–136. 201. Barter JF, Soong SJ, Hatch KD, et al. Diagnosis and treatment of pulmonary metastases from cervical carcinoma. Gynecol Oncol 1990;38:347–351. 202. Beller U, Benedet JL, Creasman WT, et al. Carcinoma of the vagina: 26th annual report on the results of treatment in gynecological cancer. Int J Gynecol Obstet 2006;95:S29–S42. 203.


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Gynecology_Novak. 202. Beller U, Benedet JL, Creasman WT, et al. Carcinoma of the vagina: 26th annual report on the results of treatment in gynecological cancer. Int J Gynecol Obstet 2006;95:S29–S42. 203. Fu YS. Intraepithelial, invasive and metastatic neoplasms of the vagina. In: Pathology of the uterine cervix vagina and vulva. 2nd ed. Philadelphia: Saunders, 2002:531. 204. Hellman K, Lundell M, Silfversward C, et al. Clinical and histopathological factors related to prognosis in primary squamous cell carcinoma of the vagina. Int J Gynecol Cancer 2006:16;1201–1211. 205. Benedet JL, Murphy KJ, Fairey RN, et al. Primary invasive carcinoma of the vagina. Obstet Gynecol 1983;62:715–719. 206. Hellman K, Silfversward C, Nilsson B, et al. Primary cancer of the vagina factors inﬂuencing the age at diagnosis: the Radiumhemmet Series 1956–1996. Int J Gynecol Oncol Cancer 2004;14:491–501. 207.


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Gynecology_Novak. 207. Rubin SC, Young J, Mikuta JJ. Squamous carcinoma of the vagina: treatment, complications, and long-term follow up. Gynecol Oncol 1985;20:346–353. 208. Benedet JL, Saunders BH. Carcinoma in situ of the vagina. Am J Obstet Gynecol 1984;148:695–700. 209. Lenehan PM, Meffe F, Lickrish GM. Vaginal intraepithelial neoplasia: biologic aspects and management. Obstet Gynecol 1986;68:333–337. 210. Herman JM, Homesley HD, Dignan MB. Is hysterectomy a risk factor for vaginal cancer? JAMA 1986;256:601–603. 211. Frick HC, Jacox HW, Taylor HC. Primary carcinoma of the vagina. Am J Obstet Gynecol 1986;101:695. 212. Hoffman MS, DeCesare SL, Roberts WS, et al. Upper vaginectomy for in situ and occult superficially invasive carcinoma of the vagina. Am J Obstet Gynecol 1992;166:30–33. 213. Al-Kurdi M, Monaghan JM. Thirty-two years experience in management of primary tumors of the vagina. BJOG 1981;88:1145–1150. 214.


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Gynecology_Novak. 213. Al-Kurdi M, Monaghan JM. Thirty-two years experience in management of primary tumors of the vagina. BJOG 1981;88:1145–1150. 214. Rutledge F. Cancer of the vagina. Am J Obstet Gynecol 1967;97:635– 655. 215. Perez CA, Arneson AN, Dehner LP, et al. Radiation therapy in carcinoma of the vagina. Obstet Gynecol 1974;44:862–872. 216. Chung AF, Casey MJ, Flannery JT, et al. Malignant melanoma of the vagina—report of 19 cases. Obstet Gynecol 1980;55:720–727. 217. Iversen K, Robins RE. Mucosal malignant melanomas. Am J Surg 1980;139:660. 218. Norris HJ, Taylor HB. Melanomas of the vagina. Am J Clin Pathol 1966;46:420. 219. Ballon SC, Lagasse LD, Chang NH, et al. Primary adenocarcinoma of the vagina. Surg Gynecol Obstet 1979;149:233–237. 220. Herbst AL, Scully RE. Adenocarcinoma of the vagina in adolescence. Cancer 1970;25:745–757. 221.


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Gynecology_Novak. 220. Herbst AL, Scully RE. Adenocarcinoma of the vagina in adolescence. Cancer 1970;25:745–757. 221. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971;284:878–881. 222. Herbst AL, Cole P, Norusis MJ, et al. Epidemiologic aspects of factors related to survival in 384 registry cases of clear cell adenocarcinoma of the vagina and cervix. Am J Obstet Gynecol 1979;135:876– 886. 223. Reid GC, Schmidt RW, Roberts JA, et al. Primary melanoma of the vagina: a clinicopathologic analysis. Obstet Gynecol 1989;74:190– 199. 224. Morrow CP, DiSaia PJ. Malignant melanoma of the female genitalia: a clinical analysis. Obstet Gynecol Surv 1976;31:233. 225. Cramer DW, Cutler SJ. Incidence and histopathology of malignancies of the female genital organs in the United States. Am J Obstet Gynecol 1974;118:443–460. 226.


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Gynecology_Novak. 225. Cramer DW, Cutler SJ. Incidence and histopathology of malignancies of the female genital organs in the United States. Am J Obstet Gynecol 1974;118:443–460. 226. Eddy GL, Singh KP, Gansler TS. Superficially invasive carcinoma of the vagina following treatment for cervical cancer: a report of six cases. Gynecol Oncol 1990;36:376–379. 227. Reddy S, Lee MS, Graham JE, et al. Radiation therapy in primary carcinoma of the vagina. Gynecol Oncol 1987;26:19–24. 228. Kucera H, Langer M, Smekal G, et al. Radiotherapy of primary carcinoma of the vagina: management and results of different therapy schemes. Gynecol Oncol 1985;21:87–93. 229. Houghton CRS, Iversen T. Squamous cell carcinoma of the vagina: a clinical study of the location of the tumor. Gynecol Oncol 1982;13:365–372. 230. Lamoreaux WT, Grigsby PW, Dehdashti F, et al. FDG-PET evaluation of vaginal carcinoma. Int J Radiat Oncol Biol Phys 2005;62:733–737. 231.


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Gynecology_Novak. 230. Lamoreaux WT, Grigsby PW, Dehdashti F, et al. FDG-PET evaluation of vaginal carcinoma. Int J Radiat Oncol Biol Phys 2005;62:733–737. 231. Dalrymple JL, Russell AH, Lee SW, et al. Chemoradiation for primary invasive squamous carcinoma of the vagina. Int J Gynecol Cancer 2004;14:110–117. 232. Eddy GL, Marks RD, Miller MC 3rd, et al. Primary invasive vaginal carcinoma. Am J Obstet Gynecol 1991;165:292–296. 233. Pride GL, Schultz AE, Chuprevich TW, et al. Primary invasive squamous carcinoma of the vagina. Obstet Gynecol 1979;53:218– 225. 234. Kirkbride P, Fyles A, Rawlings GA, et al. Carcinoma of the vagina: experience at the Princess Margaret Hospital (1974–1989). Gynecol Oncol 1995;56:435–443. 235. Perez CA, Grigsby PW, Garipagaoglu M, et al. Factors affecting long-term outcome of irradiation in carcinoma of the vagina. Int J Radiat Oncol Biol Phys 1999;44:37–45. 236.


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Gynecology_Novak. 235. Perez CA, Grigsby PW, Garipagaoglu M, et al. Factors affecting long-term outcome of irradiation in carcinoma of the vagina. Int J Radiat Oncol Biol Phys 1999;44:37–45. 236. Tewari KS, Cappuccini F, Puthawala AA, et al. Primary invasive carcinoma of the vagina: treatment with interstitial brachytherapy. Cancer 2001;91:758–770. 237. Otton GR, Nicklin JL, Dickie GJ, et al. Early-stage vaginal carcinoma—an analysis of 70 patients. Int J Gynecol Cancer 2004;14:304–310. 238. Frank SJ, Thingran A, Levenbach C, et al. Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 2005;62:138–147. 239. Tran PT, Su Z, Lee P, et al. Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 2007;105:641– 649. Ovarian, Fallopian Tube, and Jonathan S. Berek Teri A. Longacre Michael Friedlander


Gynecology_Novak

Gynecology_Novak. Ovarian, Fallopian Tube, and Jonathan S. Berek Teri A. Longacre Michael Friedlander The peak incidence of invasive epithelial ovarian cancer is at about 60 years of age. About 30% of ovarian neoplasms in postmenopausal women are malignant, whereas only about 7% of ovarian epithelial tumors in premenopausal patients are frankly malignant. The average age of patients with borderline tumors is approximately 46 years. Ovarian cancer is associated with low parity and infertility. Because parity is inversely related to the risk of ovarian cancer, having at least one child is protective for the disease, with a risk reduction of 0.3 to 0.4. Oral contraceptive use reduces the risk of epithelial ovarian cancer. Women who use oral contraceptives for 5 or more years reduce their relative risk to 0.5 (i.e., there is a 50% reduction in the likelihood of development of ovarian cancer).


Gynecology_Novak

Gynecology_Novak. Given the false-positive results for both CA125 and transvaginal ultrasonography, particularly in premenopausal women, and the absence of evidence from randomized trials that these tests reduce the mortality of ovarian cancer, these tests should not be used routinely to screen women at risk for ovarian cancer. Most epithelial ovarian cancers are sporadic, but at least 5% to 10% result from inherited susceptibility and are hereditary. Hereditary ovarian cancers, particularly those caused by BRCA1 mutations, occur in women approximately 10 years younger than those with nonhereditary tumors.


Gynecology_Novak

Gynecology_Novak. Most hereditary ovarian cancers result from germline mutations in the BRCA1 and BRCA2 genes. The mutations are inherited in an autosomal dominant fashion, and therefore a full pedigree analysis (i.e., both maternal and paternal sides of the family history for both breast and ovarian cancer) must be carefully evaluated in all patients with epithelial ovarian cancer, and those with fallopian tube cancer and peritoneal cancer. The value of prophylactic salpingo-oophorectomy in these patients is well documented and is the most effective way to reduce risk of these cancers.


Gynecology_Novak

Gynecology_Novak. The importance of thorough surgical staging cannot be overemphasized, because subsequent treatment and prognosis will be determined by the stage of disease. Patients with advanced-stage disease should undergo debulking or cytoreductive surgery to remove as much of the tumor and its metastases as possible, if the patient is medically fit for major surgery. The performance of a debulking operation as early as possible in the course of the patient’s treatment is considered the standard of care for most patients. Most patients have a primary debulking surgery, while a smaller proportion of patients not suitable for initial surgery receive two to three cycles of primary chemotherapy followed by interval debulking surgery.


Gynecology_Novak

Gynecology_Novak. Combination chemotherapy with carboplatin and paclitaxel is recommended for patients with high-risk, low-stage disease. For advanced-stage epithelial ovarian cancer, the choice of intravenous versus intraperitoneal platinum and taxane chemotherapy should be individualized. In the first two decades of life, almost 70% of ovarian tumors are of germ cell origin, and one-third of these are malignant. In contrast to the relatively slow-growing epithelial ovarian tumors, germ cell malignancies grow rapidly. The most common types of malignant germ cell tumors are dysgerminomas, immature teratomas, and endodermal sinus tumors. Preservation of fertility should be standard in most patients. The most effective chemotherapy is bleomycin, etoposide, and cisplatin (BEP). Stromal tumors include granulosa cell tumors, which are low-grade malignancies. In premenopausal women, they can be treated conservatively. Adjuvant chemotherapy is of unproven value.


Gynecology_Novak

Gynecology_Novak. Stromal tumors include granulosa cell tumors, which are low-grade malignancies. In premenopausal women, they can be treated conservatively. Adjuvant chemotherapy is of unproven value. Metastatic tumors to the ovaries are most frequently from the breast and gastrointestinal tract. Fallopian tube carcinomas and peritoneal cancers are treated the same as ovarian cancer, with staging and cytoreductive surgery followed by platinum and taxane chemotherapy.


Gynecology_Novak

Gynecology_Novak. Of all the gynecologic cancers, ovarian malignancies represent the greatest clinical challenge because they have a high mortality. Epithelial cancers are the most common ovarian malignancy, and over two-thirds of patients have advanced disease at diagnosis. Ovarian cancer represents a major surgical challenge, and optimal therapy includes surgical debulking followed by platinum-based combination chemotherapy. It has the highest fatality-to-case ratio of all the gynecologic malignancies. There are nearly 22,000 new cases annually in the United States, and 15,460 women can be expected to succumb to their illness (1). Ovarian cancer is the seventh most common cancer in women in the United States, accounting for 3% of all malignancies and 6% of deaths from cancer in women and almost one-third of invasive malignancies of the female genital organs. Ovarian cancer is the fifth most common cause of death from malignancy in women. A woman’s risk at birth of having ovarian cancer at some point


Gynecology_Novak

Gynecology_Novak. of invasive malignancies of the female genital organs. Ovarian cancer is the fifth most common cause of death from malignancy in women. A woman’s risk at birth of having ovarian cancer at some point in her lifetime is 1% to 1.5% and that of dying from ovarian cancer is almost 0.5% (2).


Gynecology_Novak

Gynecology_Novak. Approximately 90% of ovarian cancers are derived from the coelomic epithelium or mesothelium (2). The cells are a product of the primitive mesoderm, which can undergo metaplasia. A classification of the histologic types of epithelial tumors of the ovary is presented in Table 37.1. Neoplastic transformation can occur when the cells are genetically predisposed to oncogenesis or exposed to an oncogenic agent or both (3). Table 37.1 Epithelial Ovarian Tumors I. Serous Endosalpingeal A. Benign B. Borderline C. Malignant II. Mucinous Intestinal, Endocervical A. B. C. III. A. B. C. IV. A. B. C. V. Brenner Transitional A. Benign B. Borderline (proliferating) C. Malignant VI. A. B. C. VII. Undifferentiated May be anaplastic VIII. Unclassified From Seroy SF, Scully RE, Sobin LH. International histological classification of tumours no. 9. Histological typing of ovarian tumors. Geneva, Switzerland: World Health Organization, 1973, with permission.


Gynecology_Novak

Gynecology_Novak. pattern that resembles epithelium in the lower genital tract (3). For example, serous tumors have an appearance similar to that of the glandular epithelial lining of the fallopian tube, endometrioid tumors resemble proliferative endometrium, and clear cell tumors resemble secretory or gestational endometrium. Mucinous tumors may contain cells that resemble endocervical glands, but more commonly these cells resemble the gastrointestinal epithelium. Transitional (Brenner) tumors are so named because of a resemblance to the epithelium in Walthard rests and bladder urothelium.


Gynecology_Novak

Gynecology_Novak. Although it was believed that epithelial ovarian cancers arise from either the surface epithelium of the ovary or from inclusion cysts within the ovary, there is growing evidence to suggest that many, if not most, high-grade serous carcinomas of the ovary arise from the fimbrial end of the fallopian tube rather than from the ovary (4,5). It is suggested that serous epithelial ovarian cancers be separated into two distinct groups—type I and type II serous tumors—as they differ considerably in the cell of origin, molecular pathogenesis, and their biological behavior (6). Type I tumors include serous borderline tumors and low-grade serous carcinoma; they are genetically stable and are characterized by mutations in KRAS and BRAF. Type II serous tumors are rapidly growing, highly aggressive neoplasms that lack well-defined precursor lesions; most are advanced stage at, or soon after, their inception and many appear to arise in the fimbrial end of the fallopian tube (7). The type II tumors


Gynecology_Novak

Gynecology_Novak. that lack well-defined precursor lesions; most are advanced stage at, or soon after, their inception and many appear to arise in the fimbrial end of the fallopian tube (7). The type II tumors are genetically unstable and harbor p53 mutations.


Gynecology_Novak

Gynecology_Novak. Borderline Tumors An important group of tumors to distinguish is the tumor of low malignant potential, also called the borderline tumor. Borderline tumors are lesions that tend to remain confined to the ovary for long periods, occur predominantly in premenopausal women, and are associated with a very good prognosis (2,3,8–12). They are encountered most frequently in women between the ages of 30 and 50 years, whereas invasive carcinomas occur more often in women between the ages of 50 and 70 years (2). Although uncommon, implants may occur with serous borderline tumors. Such implants are divided into noninvasive and invasive forms. The latter group has a higher likelihood of developing into progressive, proliferative disease in the peritoneal cavity, which can lead to intestinal obstruction and death (2,6). Classification of Epithelial Ovarian Tumors Serous Tumors


Gynecology_Novak

Gynecology_Novak. Classification of Epithelial Ovarian Tumors Serous Tumors Serous tumors are so classified because they resemble tubal secretory cells. Psammoma bodies are frequently found in these neoplasms, and they are made up of concentric rings of calcification. Several hypotheses pertaining to the origin and development of psammoma bodies are proposed, including apoptosis of tumor cells and osteoinductive cytokines produced by macrophages (6). In the wall of the mesothelial invaginations, papillary ingrowths are common, representing the early stages of development of a papillary serous cystadenoma. There are many variations in the proliferation of these mesothelial inclusions. Several foci may be lined with ﬂattened inactive epithelium; in adjacent cavities, papillary excrescences are present, often resulting from local irritants (2).


Gynecology_Novak

Gynecology_Novak. Borderline Serous Tumors Approximately 10% of all ovarian serous tumors fall into the category of a tumor of low malignant potential or borderline tumor (Fig. 37.1), and 50% occur before the age of 40 years. The criteria for the diagnosis of serous borderline tumors are as follows (11): 1. Epithelial hyperplasia in the form of pseudostratification, tufting, cribriform, and micropapillary architecture 2. 3. 4. Absence of destructive stromal invasion (i.e., without tissue destruction) Serous borderline tumors that are composed of an exuberant micropapillary architecture are designated as serous borderline tumors with micropapillary features (Fig. 37.2); these tumors are more frequently bilateral, exophytic, and high-stage than the usual serous borderline tumor.


Gynecology_Novak

Gynecology_Novak. It should be emphasized that up to 40% of serous borderline tumors are associated with spread beyond the ovary, but high-stage disease does not necessarily warrant a diagnosis of carcinoma. The diagnosis of a serous borderline tumor versus serous carcinoma is based on the histologic features of the primary tumor (11). Up to 10% of women with ovarian serous borderline tumors and extraovarian implants may have invasive implants, and these can behave more aggressively (13). The 5-year overall survival for women with invasive implants is about 50% if stringent criteria are applied (10,13–15). Most implants are noninvasive (10,16). In the noninvasive implants, papillary proliferations of atypical cells involve the peritoneal surface and form smooth invaginations (10). In contrast, the invasive implants resemble well-differentiated serous carcinoma and are characterized by atypical cells forming irregular glands with sharp borders. Implants are usually confined to the abdominal cavity and


Gynecology_Novak

Gynecology_Novak. implants resemble well-differentiated serous carcinoma and are characterized by atypical cells forming irregular glands with sharp borders. Implants are usually confined to the abdominal cavity and may be seen in the pelvis, omentum, and adjacent tissues, including lymph nodes, but spread outside the abdominal cavity is rare. Death can occur as the result of intestinal obstruction (16–19).


Gynecology_Novak

Gynecology_Novak. Borderline serous tumors may harbor foci of stromal microinvasion (18). Most patients are young and International Federation of Gynecology and Obstetrics (FIGO) stage I. Stromal microinvasion is increased about ninefold in pregnant women with serous borderline tumors. Figure 37.1 Serous borderline tumor of the ovary. Complex papillary fronds with hierarchical branching are lined with pseudostratified columnar cells. The epithelium and the stroma are clearly separated by a basement membrane, indicating no stromal invasion. Figure 37.2 Serous borderline tumor with micropapillary features. The papillae have a non-hierarchical branching pattern and are lined by a monomorphous population of cells. CHAPTER 37 Ovarian, Fallopian Tube, and Peritoneal Cancer Figure 37.3 Low-grade serous adenocarcinoma of the ovary. Clusters and papillae of malignant cells are in direct contact with fibrous stroma indicative of stromal invasion.


Gynecology_Novak

Gynecology_Novak. Figure 37.3 Low-grade serous adenocarcinoma of the ovary. Clusters and papillae of malignant cells are in direct contact with fibrous stroma indicative of stromal invasion. The presence of stromal microinvasion is associated with lymphovascular space invasion in the primary ovarian tumor (and likely represents a form of true stromal invasion), but it is not associated with an aggressive clinical course, and patients with this finding should be managed in the same way as patients without stromal microinvasion.


Gynecology_Novak

Gynecology_Novak. Serous Carcinomas In malignant serous tumors, stromal invasion is present (2). The grade of tumor is important and needs to be documented. In low-grade serous adenocarcinomas, papillary and glandular structures predominate (Fig. 37.3); high-grade neoplasms are characterized by solid sheets of cells, nuclear pleomorphism, and high mitotic activity (Fig. 37.4). Laminated, calcified psammoma bodies are found in 80% of serous carcinomas. Serous psammocarcinoma is a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. At least 75% of the epithelial nests are associated with psammoma body formation. Patients with serous psammocarcinoma have a protracted clinical course and a relatively favorable prognosis; their clinical course more closely resembles that of high-stage, progressive serous borderline tumor than serous carcinoma.