PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
Because of invasion and fissures depending on location, these cancers are intersphincteric, extrasphincteric, or transphincteric, tunneling through perianal sphincter and fat to skin surface perianally (fistula-in-anus)
PERSPECTIVE AND PATTERN OF SPREAD
To understand the transformation to different malignancies in the anus and anal canal, its embryology is pivotal. The dentate line represents the junction between endoderm and ectoderm. Innervation blood supply and lymphatics vary accordingly. Proximal to the dentate line are autonomic nerves, sympathetic and parasympathetic versus somatic. Pain above the dentate line is perceived much less than that below it, where biopsies require anesthesia. The seventh edition of the American Joint Committee on Cancer (AJCC) AJCC Cancer Staging Manual details diagrammatically the anus and anal canal and portrays lymphatic drainage as a function of the primary location; it is discussed in the N-oncoanatomy section. Anal cancers provide new evidence for the role of immunosuppression and viral infections in carcinogenesis. Of the 5,000 new patients expected annually, there is a bioassociation with condylomata (human papilloma virus and human immunodeficiency virus, with a higher incidence of anal cancer in homosexuals with acquired immunodeficiency syndrome) The anal canal is a transitional zone marked by the pectinate line, or mucocutaneous junction. The two predominant histologic types of anal carcinoma are variants of squamous cell cancers. Basaloid (cloacogenic) cancers arise at this junction, whereas more typical epidermoid cancers occur on the skin. The epicenter of the cancer determines its origin. According to the AJCC, cancers are anal tumors if their epicenter is ≤2 cm from the pectinate line; otherwise, they are rectal cancers with epicenters? >2 cm proximal to the dentate line.
Anal sphincter preservation with radiochemotherapy is the standard of treatment for most patients with anal cancers. In fact, the application of similar treatment regimens to rectal and esophageal cancers has improved their survival outcomes with normal tissue and organ conservation. Size of tumor determines the staging categories rather than depth of invasion, similar to the skin cancer classification
Note: It is important is to recognize the anatomic differences in males versus females as to surrounding structures. In the male, there are solid structures above the anal canal, that is, prostate, penis crura, and urethra, whereas in the female, the vaginal tube and vulva separate the urethra. Thus, different SIMLAP tables are provided (Fig. 33.1; Table 33.2).
PATHOLOGY
The anal canal is a transitional zone marked by the pectinate line, or mucocutaneous junction. The two predominant histologic types of anal carcinoma are variants of squamous cell cancers. Basaloid (cloacogenic) cancers arise at this junction, whereas more typical epidermoid cancers occur on the skin (Table 33.1).
Figure 33.1 | Patterns of spread for anal cancer are color coded for T stage. A. Male. B. Female. 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, i.e., SIMLAP Table 33.2A/B.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The anatomy reflects the spread pattern. There is an importan distinction between cancers of the anal canal (extending from the rectum to the pectinate line) and cancers on the perineal aspect of the anus to the pectinate line. Anal margin lesions are distal to the anal verge, where hair -bearing skin occurs. Cancers of the anal canal are of greater concern because they are more likely to invade the rectal sphincters and open more pathways of spread deep into the pelvis via lymphatics and hemorrhoidal veins.
The TNM staging of anal cancer has not changed. Primary anal cancers are staged based on size of the cancer rather than depth. However, it should be noted that direct invasion of the rectal wall or anal and rectal sphincter invasions are T3 and T4 cancers. Evidence of an adjacent organ, such as vagina, urethra, or bladder, is required.
Generally, there is no overarching principle or context design for the digestive system (gastrointestinal tract) or major digestive glands (MDGs). Stages are frequently expanded to six by subdividing stages into A and B. The T and N categories are assigned to a stage grouping, specifically for division of stage into more (a) versus less (b) favorable groupings. This occurs at different stages for different sites. Specificall, this site has a similar pattern of T stage progression as N stage progression, with T3/T4 = N1; stage III is divided into A/B/C (i.e., IIIA = T3, IIIB = T4); and IIIC is N1.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
• The definitions of TNM and the stage groupings for thi chapter have not changed from the sixth edition (Fig. 33.2).
• The descriptions of both the boundaries of the anal canal and anal carcinomas have been clarified
• The collection of the reported status of the tumor for the presence of human papilloma virus is included.
The TNM Staging Matrix is color coded for identification o Stage Group once T and N stages are determined (Table 33.3).
ANUS
Figure 33.2 | TNM staging diagram presents a vertical arrangement with color bars encompassing TN combinations showing progression. Anal cancers are very chemoradiation sensitive, and response and survival rates are high, with anal preservation. Stage 0, yellow; I, green; II, blue; III, purple; IV, red; and IV (metastatic), black. Definitions of TN on left and stage grouping o right.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The anatomic isocenter for the anus is below the coccyx in line with the pubic bone and femoral heads and is readily identifie on physical examination (Fig. 33.3).
T-oncoanatomy
Orientation views are presented in Fig. 34.3 and three-planar views in Fig. 34.4A–C. The T -oncoanatomy is displayed in three planar views. A: Coronal. B: Sagittal. C: Transverse axial (Fig. 33.4 Male [A,B,C]; Female [A,B,D]). The terminal portion of the digestive system has a complex anatomy and is best viewed as follows:
• Coronal: Defines the anorectal line, the columns of Morgagni, and the pectinate line at the mucocutaneous junction. The anal canal extends from the dentate or pectinate line to the hair-bearing skin.
• Sagittal: It offers views of the various spaces of the perineopelvic region: perianal, postanal, superficial and deep and submucosal and presacral.
• Transverse: Differentiates the anatomy of the female and male pelvises. The axial views relate the female and male genitalia to the anus.
Figure 33.3 | Orientation and overview of oncoanatomy. The anatomic isocenter for the anus is below the coccyx in line with the pubic bone and femoral heads and is readily identified on physical examination. A. Coronal. B.Sagittal.
Figure 33.4 | T-oncoanatomy. Connecting the dots. Structures are color coded for cancer stage progression. The color code for the anatomic sites correlates with the color code for the stage group (Fig. 33.2) and patterns of spread (Fig. 33.1) and SIMLAP table (Table 33.2). Connecting the dots in similar colors will provide an appreciation for the 3D oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The nodal drainage again depends on which side of the pectinate line the anal cancer has its epicenter. For cancers of the anal verge, the lymphatic drainage is into inguinal nodes and then external iliac nodes. For cancers of the anal canal, particularly involving the rectum, the drainage is into internal iliac nodes. Both external and internal iliac nodes eventually drain into the common iliacs and para-aortic nodes (Fig. 33.5A; Table 33.4).
New diagrams in the seventh edition of the AJCC Manual portray lymph nodes at risk as a function of advancement.
N1 represents perirectal nodes in the presacral area.
N2 represents unilateral inguinal nodes with Ts below the dentate line or unilateral iliac and obturator nodes above the dentate line.
N3 can be combinations of N1 and N2 and include the following:
A. Perirectal/inguinal unilateral nodes
B. Bilateral internal iliac nodes
C. Bilateral internal iliac and inguinal nodes
Regional Lymph Nodes
Lymphatic drainage and nodal involvement of anal cancers depend on the location of the primary tumor. Tumors above the dentate line spread primarily to the anorectal, perirectal, and paravertebral nodes, whereas tumors below the dentate line spread primarily to the superficial inguinal nodes
The regional lymph nodes are as follows:
Perirectal
Anorectal
Perirectal
Lateral sacral
Internal iliac (hypogastric)
Inguinal
Superficia
All other nodal groups represent sites of distant metastasis.*
M-ONCOANATOMY
The venous drainage varies and is related to whether the primary is above or below the dentate line (DL) (Fig. 33.5B).
• Above the DL, the drainage is via the middle and superior rectal veins, placing liver metastases as the target organ.
• Below the DL, drainage is to inferior rectal vein and anastomosis to superficial inguinal/femoral vein branches an then into external iliacs; lung metastases can occur via inferior vena cava.
*Preceding passage from Edge SB, Byrd DR, Compton CC, et al., AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 166.
Figure 33.5 | A. N-oncoanatomy. Sentinel nodes of the anus are inguinal nodes. B. M-oncoanatomy. The anus and inferior portion of the rectum drain via the inferior and middle rectal veins, into the internal iliac veins, and then into the common iliacs and inferior vena cava. Thus, lung metastases are more common in this site as compared to other sites in the gastrointestinal system.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Clinical staging is commonly used because effective chemoradiation regimens have allowed for cure with anal sphincter preservation. The imaging tools, such as endorectal magnetic resonance imaging (EMRI) and endoluminal ultrasound (EUS), are most useful for assessing deeper invasion, especially to pelvic structures such as bladder and rectum, and to vagina and uterus when the cancer is extensive (see Table 33.5; Fig. 33.6).
Pathologic Staging
The surgically resected anus and associated lymph nodes removed are assessed. Tumor extension and location of both primary and nodes should be documented. Accurate radial margins should be marked and recorded and are defined as th surgically dissected surface adjacent to the deepest point of tumor invasion beyond the wall of the anus. The completeness of resection depends on the clearing of the deepest point of invasion: R0, complete; R1, microscopic; and R2, macroscopic.
Oncoimaging Annotations
• Computed tomography is useful for advanced stages and deeper invasion of surrounding structures.
• EUS and EMRI are valuable to assess depth of wall penetration.
Figure 33.6 | Axial CTs of femoral head and neck and pubis levels correlate with the T-oncoanatomy transverse section (Figure 33.4C,D). Oncoimaging with CT is commonly applied to staging cancers, often combined with PET to determine true extent of primary cancer and involved lymph nodes. A. Female. (correlates with Fig. 33.4D). 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. B. Male. (correlates with Fig. 33.4C). 1. Prostate. 2. Rectum. 3. Obturator internus muscle. 4. Spermatic cords.
PROGNOSIS AND CANCER SURVIVAL
PROGNOSIS
The limited number of prognostic factors are listed in Table 33.6.
CANCER STATISTICS AND SURVIVAL
The digestive system, or gastrointestinal tract, which includes MDGs, accounts for 275,000 new patients annually, with colon and rectum responsible for >50%, or about 140,000 new diagnoses annually. Approximately half of these patients eventually die of these cancers. MDG cancers as a group are more lethal; only a handful of patients become long-term survivors. Fortunately, colon and rectal cancers are the most common, with the majority of patients becoming 5-year survivors (63%) responding to chemoradiation programs, often with the sparing of the rectal sphincter with conservative surgery. Anal cancers are the most responsive to chemoradiation (5-fluorouracil and cisplatin), eliminating the need for surgery. The 5-year survival rate is >90%, with anal sphincter preservation. This regimen has been proven to be very effective in clinical trials and to result in more long-term survivors, which is currently reflected in the literature. Live, bile duct, and pancreatic cancers are among the poorest in terms of survival, which is often measured in months rather than years.
Specificall, the anus accounted for approximately 5,000 new cancer cases and 720 cancer deaths (14%). Survival rates vary as a function of stage, with T1, T2 at 75% to 14% and T3, T4 at 40% to 60%.
Figure 33.7 | A. Five-year survival for squamous anal cancer. B. Five-year survival for nonsquamous anal cancer. Patient outcome stratified by AJCC stage group and tumor histolog (squamous vs. nonsquamous types). (Data from Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual, 7th ed. New York: Springer, 2010, p. 167.)
SECTION 4
Male Genital Tract and Urinary System Primary Sites
