PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
The pattern of spread relates to paravaginal invasion into lateral soft tissues and follows the same criteria as the staging system of cervix uteri (Fig. 47.2; Table 47.2).
PERSPECTIVE AND PATTERNS OF SPREAD
The vagina is a fibromuscular tubular structure about 8 and 10 cm long connecting the uterus to the external female genitals. Vaginal cancer is a rare gynecologic malignancy, constituting only 1% of malignant neoplasms of the female genital tract. Indeed, metastatic involvement of the vagina, particularly by cervical or vulvar carcinoma, occurs much more frequently than primary vaginal cancer. This fact has led to the International Federation of Gynecology and Obstetrics staging system requiring that tumors involving both the vagina and cervix or the vagina and vulva be classified as primary cervical or vulvar carcinoma, respectively.
In the past 30 years, interest has focused on an increased incidence of clear cell adenocarcinoma of the vagina in young women, which, in 1971, was found to be related to the administration of diethylstilbestrol (DES) to their mothers during pregnancy. The incidence of clear cell adenocarcinoma in women exposed prenatally to DES is estimated to be about 1 per 10,000; it has been observed that the risk was greatest for those exposed during the first 18 weeks in utero.
PATHOLOGY
Although, classically, squamous cell cancer arises from its stratified squamous epithelium, it is second in incidence to adenocarcinoma. This is because most common isolated vaginal cancers are most often adenocarcinomas, metastatic often from endometrial malignancies. Of special interest are adenocarcinomas in young women, attributed to the administration of DES to their mothers during pregnancy, particularly in the first 18 weeks in utero. Fortunately, once suspected, these clear cell cancers can be diagnosed in early stages (I and II). A large variety of malignancies can occur and are given in Table 47.1. Sarcoma botryoides occurs mainly in children younger than 5 years of age and is characterized as grape-like clusters (Fig. 47.1). Patterns of spread are given in Fig. 47.2.
• Squamous cell carcinoma accounts for 85% of primary vaginal cancers (most nonkeratinizing), with adenocarcinoma, melanoma, and other histologic subtypes making up the remainder (Table 47.1).
• The majority of nonsquamous vaginal cancers are adenocarcinomas and comprise approximately 5% of primary vaginal tumors; endometrioid, mucinous, papillary, and clear cell variants have been reported. Vaginal adenocarcinomas occur in younger patients than do squamous cell carcinomas, and they usually arise from the Bartholin or Skene submucosal glandular epithelium. Most of these tumors are polypoid or nodular.
Figure 47.1 | Squamous cell cancer. The keratinizing pattern of the tumor is manifested as whorls of keratinized cells (“keratin pearls”) (arrows).
Figure 47.2 | Patterns of spread. A. Sagittal. B. Coronal. In this diagram is a dissection of female peroneum. The vagina is a muscular tumor posterior to trigone of urinary bladder and urethra with rod insert (see also Fig. 47.5A). The cancer is color coded for stage: Tis, yellow; T1, green; T2, blue; T3, purple; and T4, red. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern SIMLAP, Table 47.2.
• Adenoid cystic carcinoma of the vagina is extremely rare. Until 1996, only 45 cases of adenoid cystic carcinoma of Bartholin's gland had been reported in the world literature.
• Neuroendocrine small cell carcinoma may occur in the vagina, either in pure form or associated with squamous or glandular elements. A high proportion show ultrastructural or immunohistochemical evidence of neuroendocrine differentiation. The tumor tends to be aggressive, with a propensity for early spread.
• Sarcoma botryoides occurs primarily in children younger than 5 years old, and it is characterized grossly by a polypoid mass resembling a bunch of grapes and microscopically by crowded rhabdomyoblasts in a distinct subepithelial cambium layer.
• Melanoma accounts for only 3% of vaginal malignancies; it is usually located in the distal third of the vagina. Microscopy demonstrates pleomorphic cells laden with melanin, although pigmentation may be absent in the amelanotic variety. Progression of preexisting melanosis to malignant melanoma of the vagina has been reported.
• Endodermal sinus tumor of the vagina is similar histologically to its ovarian counterpart, with typical Schiller-Duval bodies.
• Most primary malignant lymphomas involving the vagina are the diffuse large cell type, but nodular lymphomas also occur. Characteristically, the mucosa is intact; a submucosal mass is frequently seen. Marker studies are useful in equivocal cases of lymphoma-like lesions.*
*Rubin P, Williams J, eds. Clinical Oncology: A Multidisciplinary Approach for Physicians and Students. 8th ed. Philadelphia: Elsevier, 2001:499–500.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The pattern of spread relates to paravaginal invasion and in lateral soft tissues is stage T2; it follows the same criteria as the staging system of cervix uteri. Thus extension to the pelvic sidewall laterally (stage T3) and anteriorly into the urethra can occur or into the urinary bladder or posteriorly into the rectum (stage T4). Most cancers are squamous cell carcinomas arising from the vaginal mucosa of stratified squamous epithelium (Fig. 47.3).
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The definitions of TNM and the Stage Groupings for this chapter have not changed from the Sixth Edition (Fig. 47.3).
The TNM Staging Matrix allows for identification of Stage Group once T and N stages are determined (Table 47.3).
Cancer of the vagina has four main stages, I to IV, following the T category, and stage IV is divided into IVA (N1) and IVB (M1). There are seven stage groups in total.
VAGINA
Figure 47.3 | TNM staging diagram arranged vertically with T definitions on the left and stage groupings on the right. Vaginal cancers are not common, and if the diagnosis is adenocarcinoma, metastatic uterine cancer should be considered in older women and a search for history of DES administration in younger women. There are four main stages, each with two or three substages. Color bars are coded for stage: stage 0, yellow; I, green; II, blue; III, purple; IV, red; and metastatic disease to viscera and nodes, black.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The isocenter of the vagina is retropubic with inferior extension and is well below the level of the coccyx to the inferior aspect of the pubic bone (Fig. 47.4).
T-oncoanatomy
The T-oncoanatomy is displayed in three planar views in Fig. 47.5. The vagina is a fibromuscular sheath composed of three layers: mucosa, muscle, and adventitia.
• Coronal: The intimate relationship of the urethra in the anterior wall of the vagina is noted.
• Sagittal: The muscle layer is composed of smooth muscle arranged in a circular, then longitudinal direction. The sphincter muscle urethrovaginalis composed of skeletal muscle is at its terminal end, the vestibule.
• Transverse: The pelvic wall is closer to the vagina than at the cervical level, and vaginal cancer becomes fixed earlier.
Figure 47.4 | Orientation of oncoanatomy of the vagina. A. Coronal. B. Sagittal. The anatomic isocenter is at the midline at the floor of the true pelvis at the S4/S5 level.
Figure 47.5 | T-oncoanatomy. A. Coronal. B. Sagittal. C. Transverse axial. The color code for the anatomic sites correlates with the color code for the stage group (Fig. 47.3), patterns of spread (Fig. 47.2), and SIMLAP table (Table 47.2). Connecting the dots of similar colors will provide an appreciation for the 3D oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The upper two thirds of the vaginal tube lymphatics drains into the obturator and hypogastric nodes in the true pelvis. In its lower third, it drains into inguinal nodes and then the external iliac node (Fig. 47.6A; Table 47.4).
The incidence of positive lymph nodes varies with the procedure to identify them: PET (35%), lymph angiograms (42.1%), lymph node dissections (28.6%), bilateral pelvic lymph node dissections (34.5%), and para-aortic lymph node dissection (12.5%).
M-ONCOANATOMY
The adventitia has a rich vascular venous plexus, which attracts metastatic deposits. It is anastomosed to the vesical veins and drains into the internal iliacs similar to the cervix. However, at its inferior vestibule it follows pudendal vessels into the internal iliacs and femorals into the external iliacs (see Fig. 47.6B).
Hematogenis dissemination to distant organs is to lung, then liver and bone. This is a late phenomenon since vaginal cancer usually remains confined to pelvis.
Figure 47.6 | A. N-oncoanatomy. The sentinel nodes are the obturator nodes of the internal iliac chain. B. M-oncoanatomy.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging
Clinical staging involves careful scrutiny and inspection, palpation, and speculum evaluation for vaginal and urethral extension. (If cervix is involved, the staging assigned is similar to that for cervical carcinoma.) (Table 47.5; Fig. 47.7.)
Surgical-pathologic Staging
Pathologic staging can be made if the resection is performed before radiation or chemotherapy. The International Federation of Gynecology and Obstetrics/American Joint Committee on Cancer/International Union Against Cancer vulval T1, T2 criteria are similar to those for other skin cancers, emphasizing the 2-cm size criterion.
Oncoimaging Annotations
Imaging recommendations apply only to advanced unresectable stage III or IV presentations that involve the vagina (Table 47.5).
PROGNOSIS AND CANCER SURVIVAL
CANCER STATISTICS AND SURVIVAL
Female genital system cancers collectively account for 80,000 new cases a year, with uterine corpus exceeding cervix cancer by a factor of four. Both are highly curable, and deaths are relatively low. The major gynecologic killer is ovarian cancer, with 16,000 deaths annually, which exceeds those from the other six primary sites combined.
Survival Rates
The survival rate gains in both cervix uteri and fundus uteri have been incremental. Survival rates of cancer of vagina are poorer than those of cervical cancer. Given that invasive cancers of the gynecologic tract have had a higher baseline—greater than 50% in the 1950s—the gains for all stages are only 15%, or 2% to 3% per decade. As noted, mortality rates have plummeted owing to early detection, especially of cancer of the cervix because it is most often detected in its noninvasive stage. Localized uterine cancers are >90% curable.
Figure 47.7 | Axial CTs of vagina correlate with the T-oncoanatomy transverse section (Fig. 47.5C). Oncoimaging with CT is commonly applied to staging cancers, often combined with positron emission tomography to determine the true extent of primary cancer and involved lymph nodes. (1) Anus. (2) Vagina. (3) Obturator internus muscle. (4) Iliopsoas muscle. (5) Rectus femoris muscle. (6) Tensor fasciae latae muscle. (7) Sartorius muscle. (8) Vastus lateralis muscle. (9) Ischium. UB, urinary bladder.
The cancer survival rates indicate that the gain in survival for uterine corpus and cervix cancers have been modest (14%) over the last five decades. However, most uterine cervix cancers are detected as cancer in situ, and this is not reflected in the figures. Ovarian cancer survival has improved by 22% and, as stated, remains lethal because most cases are detected late due to its insidious onset and the inaccessibility of ovarian nodules to early diagnosis. On the bright side are the high cure and 5-year survival rates for stage I patients with cervical cancer (92%), uterine corpus cancer (96%), and ovarian cancer (95%). Cancer of the vagina has poorer survival rates than cancer of the cervix (Fig. 47.8).
The reported overall 5 year survival for vaginal cancer is approximately 52%, which is 15% poorer than cervix or vulvar cancer. This reflects the advanced stages at presentation and the challenge of treating this cancer. The compilation of 1,671 patients from 12 different sources (1979–2007) is presented in Table 47.6.
Figure 47.8 | Five-year observed survival for carcinoma of the vagina. ( Data from Edge SB, Byrd DR, and Compton CC, et al. AJCC Cancer Staging Manual, 7th edition. New York: Springer, 2010, p. 389.)
