PERSPECTIVES, PATTERNS OF SPREAD, AND PATHOLOGY
The staging is similar to that for most skin cancers; both size and depth of invasion are the critical criteria.
PERSPECTIVE AND PATTERNS OF SPREAD
Cancers of external female genitalia arise in a variety of anatomic sites and are difficult to recognize and identify because of their location. A predisposing factor is human papilloma virus (HPV); HPV16 is the most common variety and requires cofactors such as herpes simplex virus to complete the induction neoplastic process. Vulval cancers are uncommon—slightly greater than 1% of all gynecologic cancers, with approximately 4,000 new cases a year, 20% of which may result in death. The majority occur in the labia majora and minora (70%) and 10% to 15% in the clitoris, with other sites being infrequent. Ten percent of vulvar cancers are too extensive to determine site of origin, and 5% are multifocal. The most common symptoms are vulval pruritus and bleeding or spotting, but otherwise these are asymptomatic.
The spread patterns are similar to those of other skin cancers, appearing as surface lesions that fail to heal and gradually spread superficially and then in depth (Fig. 48.2, Table 48.2). The rich lymphatics of the perineum result in lymph node enlargement in the groin, which can be unilateral or bilateral.
PATHOLOGY
The external genitalia are lined by stratified squamous epithelium and lead to squamous cell carcinomas (90%). In addition, there are numerous secretory glands (Skene's and Bartholin's) that may give rise to adenocarcinomas. Preinvasive changes such as Bowen's disease or Paget's disease with erythroplasia or leukoplasia may be the earliest sign of disease. Melanomas account for a few percent of most series (Table 48.1; Fig. 48.1).
Figure 48.1 | Squamous cell carcinoma of vulva. A. The tumor is situated in an extensive area of lichen sclerosus (white). B. Small nests of neoplastic squamous cells, some with keratin pearls, are evident in this well-differentiated tumor.
Figure 48.2 | Patterns of spread. The cancer is color coded for stage: Tis and T0, 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, i.e., SIMLAP, Table 48.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The staging is similar to that for most skin cancers; both size and depth of invasion are the critical criteria: T1, 2 cm; and T2, >2 cm; with modification in stage I for depth of invasion: 1a, 1 mm; and 1b, >1 mm. T3 has superior spread into the vagina or urethra, and T4 has reached more deeply to the bladder or rectum. Lymph nodes are simply categorized as N1, unilateral, or N2, bilateral. When extensive, cancerous infiltration of the entire perineum may occur with recurrent cancers that are incompletely treated.
The staging criteria have remained stable (Fig. 48.3).
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The definition of TNM and the Stage Grouping for this chapter have changed for the Seventh Edition and reflect new staging criteria adopted by the International Federation of Gynecology and Obstetrics (FIGO) (2008) (Fig. 48.3).
FIGO uses the classification T2/T3. This is defined as T2 in TNM.
FIGO uses the classification T4. This is defined as T3 in TNM.
The TNM staging matrix allows for identification of stage group once T and N stages are determined (Table 48.3).
VULVA
Figure 48.3 | TNM staging diagram arranged vertically with T definitions on the left and stage groupings on the right. Vulva cancers are most resectable when detected as stage I or II lesions; stage III requires radical vulvectomy with inguinal node dissection, often bilaterally. There are four main stages, with two substages for stages II and IV. 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 THREE-PLANAR ONCOANATOMY
The orientation three-planar anatomy shows the vulvar isocenter is at the level of the perineum (Fig. 48.4).
T-oncoanatomy
The T-oncoanatomy is displayed in three planar views in Fig. 48.5:
• Coronal: The labia majora and labia minora are folds of skin with varying degrees of fat covered by stratified squamous epithelium, and covered with hair on the external surface labia majora but devoid of hair on the inner, smooth surface. The male homolog for the labia majora is the scrotum.
• Sagittal: The vestibule is the space surrounded by the labia minora. The clitoris is located between the labia minora and is the homolog to the erectile bodies of the male penis containing numerous capillaries and autonomic nerve fibers.
• Transverse: The urethra and crus of the clitoris are shown anteriorly at the vestibule of the vagina.
Figure 48.4 | Orientation of oncoanatomy of the vulva. The anatomic isocenter is at the midline at the vestibule of the vulva. A. Coronal. B. Sagittal.
Figure 48.5 | T-oncoanatomy. A. Inferior. B. Sagittal. C. Transverse axial. The color code for the anatomic sites correlates with the color code for the stage group (Fig. 48.3), patterns of spread (Fig. 48.2), and SIMLAP table (Table 48.2). Connecting the dots in similar colors will provide an appreciation for the three-dimensional oncoanatomy. **FIGO T4 in the TNM is T3.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The femoral and inguinal nodes are the first station sentinel nodes, and spread into the external iliac pelvic nodes follows. If the cancer invades the vagina or bladder, the obturator and internal iliac nodes are at risk (Fig. 48.6A; Table 48.4).
Since 1970, the overall incidence of lymph node metastases is approximately 30%. The relationship of clinical stage to the incidence of positive lymph nodes is shown in Table 48.4B. Based on an extensive review of the literature from 1975–1989, from 10 different sources, the depth of stromal invasion is a robust determinant of lymph node involvement (Table 48.4C).
Metastases to pelvic nodes are uncommon, the overall frequency is approximately 9%; approximately 20% of vulvar cancers with positive inguinal nodes have positive pelvic nodes. Clinical evaluation of inguinal/femoral lymph nodes prove to be inaccurate in 25–30% of patients.
Compared with surgical staging, the percentage of error in clinical staging increases from 18% in stage I to 44% in stage IV. Generally patients with negative lymph nodes have an excellent prognosis, regardless of the size of the primary tumor. Survival depends on the number of positive nodes, therefore stage IIIABC and stage IVA are a very heterogeneous group of patients.
M-ONCOANATOMY
The perineal veins drain into the femoral/inguinal, then the external iliac veins to inferior vena cava or internal pudendal veins into internal iliac veins to inferior vena cava (Fig. 48.6B). Lung is the target organ for metastases.
Figure 48.6 | A. N-oncoanatomy. The sentinel nodes are the femoral and inguinal nodes; however, with deep invasion of vagina or pelvic organs, such as bladder or anus, deeper pathways are opened. B. M-oncoanatomy. The venous drainage is via internal pudendal vein into the internal iliac veins to the vena cava and right heart.
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 the cervix is involved, the staging is assigned similar to that for cervical carcinoma (Table 48.5; Fig. 48.7).
Surgical–pathologic Staging
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 criteria are similar to those for other skin cancers, emphasizing the 2-cm size criterion.
Oncoimaging Annotations
Imaging recommendations apply only to adnexal unresectable stage III or IV presentations that involve the vagina.
PROGNOSIS AND CANCER SURVIVAL
CANCER STATISTICS AND SURVIVAL
Female genital system cancers collectively account for 80,000 new cases per 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 that from the other six primary sites combined. Vulvar cancers are detected in early localized stages I-II yielding excellent survival rates of 98% and 85%, respectively (Fig. 48.8). As aforementioned survival decreases as lymph nodes become involved. Patients with negative lymph nodes have survival rates of approximately 81% which decrements to 13% when four or more nodes are positive. In Table 48.6, the five year survival rate, as a function of lymph node status is presented.
Figure 48.7 | Axial CTs of female pelvis correlate with the T-oncoanatomy transverse section (Fig. 48.5C). 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.
Figure 48.8 | Five-year survival rates for vulva cancer. ( Edge SB, Byrd DR, and Compton CC, et al. AJCC Cancer Staging Manual, 7th edition. New York: Springer, 2010.)
SECTION 6
Generalized Anatomic
Primary Sites
