TUMORS OF THE ANAL CANAL
The anal canal is the terminal portion of the large intestine. It is divided into three zones: the upper (covered with rectal mucosa), the middle (partially covered with a transitional mucosa),
and the lower (covered by stratified squamous mucosa). The tumors located in this anatomic location are designated as carcinoma of the anal canal. Patterns of differentiation
include a basaloid pattern, squamous cell carcinoma, and adenocarcinoma.
Anal canal carcinoma with basaloid differentiation is a tumor populated by immature proliferative cells derived from the basal layer of a stratified squamous epithelium. These tumors may
occur sporadically and be uniform in their histologic features. Alternatively, basaloid differentiation may be a component of a tumor that exhibits more genuine squamous cell
differentiation and/or the mucin vacuole-containing features of adenocarcinoma. All such tumors remain classified as anal canal carcinoma.
Pure squamous cell carcinomas of the anal canal are closely associated with chronic HPV infection. Some rare cases are also related to immunosuppression, as encountered in renal
transplantation and in AIDS patients. As with the genital tract, chronic HPV infection of the anal canal often causes precursor lesions such as condyloma acuminatum, squamous epithelium
dysplasia, and carcinoma in situ.
Pure adenocarcinoma of the anal canal is often the extension of rectal adenocarcinoma. Rarely, other tumors may arise from the anal canal, notably Paget disease, small-cell carcinoma,
The appendix is an underdeveloped residuum of the otherwise voluminous cecum. The adult appendix averages 6 to 7 cm in length, is partially anchored by a mesenteric extension from the
adjacent ileum, and has no known function. The appendix has the same four layers as the remainder of the gut and possesses a colonic-type mucosa. A distinguishing feature of this organ
is the extremely rich lymphoid tissue of the mucosa and submucosa, which in young individuals forms an entire layer of germinal follicles and lymphoid pulp. This lymphoid tissue
undergoes progressive atrophy during life to the point of complete disappearance in advanced age. In the elderly the appendix, particularly the distal portion, sometimes undergoes fibrous
Diseases of the appendix loom large in surgical practice; appendicitis is the most common acute abdominal condition the surgeon is called on to treat. Appendicitis is one of the best-known
medical entities and yet may be one of the most difficult diagnostic problems to confront the emergency physician. A differential diagnosis must include virtually every acute process that
can occur within the abdominal cavity, as well as some emergent conditions affecting organs of the thorax.
Inflammation in the right lower quadrant was considered a nonsurgical disease of the cecum (typhlitis or perityphlitis) until Fitz recognized acute appendicitis as a distinct entity in 1886.
Appendiceal inflammation is associated with obstruction in 50% to 80% of cases, usually in the form of a fecalith and, less commonly, a gallstone, tumor, or ball of worms (oxyuriasis
vermicularis). Continued secretion of mucinous fluid in the obstructed viscus presumably leads to a progressive increase in intraluminal pressure sufficient to cause eventual collapse of the
draining veins. Ischemic injury then favors bacterial proliferation with additional inflammatory edema and exudation, further embarrassing the blood supply. Nevertheless, a significant
minority of inflamed appendices have no demonstrable luminal obstruction, and the pathogenesis of the inflammation remains unknown.
At the earliest stages, only a scant neutrophilic exudate may be found throughout the mucosa, submucosa, and muscularis propria. Subserosal vessels are congested, and often there is a
modest perivascular neutrophilic infiltrate. The inflammatory reaction transforms the normal glistening serosa into a dull, granular, red membrane; this transformation signifies early acute
appendicitisfor the operating surgeon. At a later stage, a prominent neutrophilic exudate generates a fibrinopurulent reaction over the serosa ( Fig. 17-66 ). As the inflammatory process
worsens, there is abscess formation within the wall, along with ulcerations and foci of suppurative necrosis in the mucosa. This state constitutes acute suppurative appendicitis. Further
appendiceal compromise leads to large areas of hemorrhagic green ulceration of the mucosa and green-black gangrenous necrosis through the wall, extending to the serosa, creating acute
gangrenous appendicitis,which is quickly followed by rupture and suppurative peritonitis.
The histologic criterion for the diagnosis of acute appendicitis is neutrophilic infiltration of the muscularis propria. Usually, neutrophils and ulcerations are also present within the mucosa.
Since drainage of an exudate into the appendix from alimentary tract infection may also induce a mucosal neutrophilic infiltrate, evidence of muscular wall inflammation is requisite for the
Figure 17-66Acute appendicitis. The inflamed appendix shown below is red, swollen, and covered with a fibrinous exudate. For comparison, a normal appendix is shown above.
Figure 17-67Mucinous cystadenocarcinoma of the appendix, with spread into the immediate periappendiceal tissues.
1. DeNardi FG, Riddell RH: The normal esophagus. Am J Surg Pathol 15:296, 1991.
2. Hornby PJ, Abrahams TP, Partosoedarso ER: Central mechanisms of lower esophageal sphincter control. Gastroenterol Clin North Am 31:S11, v–vi, 2002.
3. Rittler M, Paz JE, Castilla EE: VATERL: an epidemiologic analysis of risk factors. Am J Med Genet 73:162, 1997.
4. Hirano I: Pathophysiology of achalasia. Curr Gastroenterol Rep 1:198, 1999.
5. Richter JE: Oesophageal motility disorders. Lancet 358:823, 2001.
6. Weiss S, Mallory G: Lesions of cardiac orifice of the stomach produced vomiting. JAMA 98:1353, 1932.
7. Shaheen N, Ransohoff DF: Gastroesophageal reflux, Barrett esophagus, and esophageal cancer: scientific review. JAMA 287:1972, 2002.
8. Spechler SJ: Clinical practice. Barrett's esophagus. N Engl J Med 346:836, 2002.
9. Sbarbati A, et al: Ultrastructural phenotype of "intestinal-type" cells in columnar-lined esophagus. Ultrastruct Pathol 26:107, 2002.
10. Haggitt RC: Pathology of Barrett's esophagus. J Gastrointest Surg 4:117, 2000.
11. Jankowski JA, et al: Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154:965, 1999.
12. Souza RF: Molecular and biologic basis of upper gastrointestinal malignancy—esophageal carcinoma. Surg Oncol Clin N Am 11:257, 2002.
13. Kok TC, et al: No evidence of known types of human papillomavirus in squamous cell cancer of the oesophagus in a low-risk area. Rotterdam Oesophageal Tumour Study Group. Eur J
Cancer 33:1865, 1997.
14. Lam AK: Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol 33:71, 2000.
15. Jenkins GJ, et al: Genetic pathways involved in the progression of Barrett's metaplasia to adenocarcinoma. Br J Surg 89:824, 2002.
16. Croft J, et al: Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization. Eur J Gastroenterol Hepatol 14:1179,
17. Hanby AM, et al: The mucous neck cell in the human gastric corpus: a distinctive, functional cell lineage. J Pathol 187:331, 1999.
18. Kojima M, et al: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656, 1999.
19. Owen DA: Gastritis and carditis. Mod Pathol 16:325, 2003.
20. Moss SF, Sood S: Helicobacter pylori. Curr Opin Infect Dis 16:445, 2003.
21. Tomb JF, et al: The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539, 1997.
22. Blaser MJ, Atherton JC: Helicobacter pylori persistence: biology and disease. J Clin Invest 113:321, 2004.
23. Covacci A, Rappuoli R: Helicobacter pylori: after the genomes, back to biology. J Exp Med 197:807, 2003.
24. Backert S, et al: Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer. Infect Immun 72:1043,
25. Furuta T, et al: Interleukin 1b polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. Gastroenterology 123:92,
26. Solnick JV, Schauer DB: Emergence of diverse Helicobacter species in the pathogenesis of gastric and enterohepatic diseases. Clin Microbiol Rev 14:59, 2001.
27. Toh BH, van Driel IR, Gleeson PA: Pernicious anemia. N Engl J Med 337:1441, 1997.
28. Sandler RS, et al: The burden of selected digestive diseases in the United States. Gastroenterology 122:1500, 2002.
29. Chan FK, Leung WK: Peptic-ulcer disease. Lancet 360:933, 2002.
30. Prinz C, Hafsi N, Voland P: Helicobacter pylori virulence factors and the host immune response: implications for therapeutic vaccination. Trends Microbiol 11:134, 2003.
31. Ming SC: Cellular and molecular pathology of gastric carcinoma and precursor lesions: a critical review. Gastric Cancer 1:31, 1998.
32. Abraham SC, et al: Sporadic fundic gland polyps: common gastric polyps arising through activating mutations in the b-catenin gene. Am J Pathol 158:1005, 2001.
33. Wingo PA, et al: Long-term trends in cancer mortality in the United States, 1930–1998. Cancer 97:3133, 2003.
34. Normark S, et al: Persistent infection with Helicobacter pylori and the development of gastric cancer. Adv Cancer Res 90:63, 2003.
35. Kelley JR, Duggan JM: Gastric cancer epidemiology and risk factors. J Clin Epidemiol 56:1, 2003.
36. Powell SM: Stomach cancer. In: Vogelstein B, Kinzler W (eds): The Genetic Basis of Human Cancer, 2nd Edition. New York: McGraw-Hill, 703, 2002.
37. Naumann M, Crabtree JE: Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis. Trends Microbiol 12:29, 2004.
38. El-Rifai W, Powell SM: Molecular biology of gastric cancer. Semin Radiat Oncol 12:128, 2002.
39. Connolly EM, Gaffney E, Reynolds JV: Gastrointestinal stromal tumours. Br J Surg 90:1178, 2003.
40. Duffaud F, Blay JY: Gastrointestinal stromal tumors: biology and treatment. Oncology 65:187, 2003.
41. Heinrich MC, et al: PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708, 2003.
42. Demetri GD, et al: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472, 2002.
43. Fellermann K, Stange EF: Defensins—innate immunity at the epithelial frontier. Eur J Gastroenterol Hepatol 13:771, 2001.
44. Gewirtz AT, et al: Intestinal epithelial pathobiology: past, present and future. Best Pract Res Clin Gastroenterol 16:851, 2002.
45. Bordeaux MC, et al: The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease. EMBO J 19:4056, 2000.
46. Martucciello G, et al: Pathogenesis of Hirschsprung's disease. J Pediatr Surg 35:1017, 2000.
47. Newgreen D, Young HM: Enteric nervous system: development and developmental disturbances-part 2. Pediatr Dev Pathol 5:329, 2002.
48. Bates MD, Deutsch GH: Molecular insights into congenital disorders of the digestive system. Pediatr Dev Pathol 6:284, 2003.
49. Guerrant RL, et al: Magnitude and impact of diarrheal diseases. Arch Med Res 33:351, 2002.
50. Goodgame RW: Viral causes of diarrhea. Gastroenterol Clin North Am 30:779, 2001.
51. Yu D, Kuipers JG: Role of bacteria and HLA-B27 in the pathogenesis of reactive arthritis. Rheum Dis Clin North Am 29:21, 2003.
52. Jones SL, Blikslager AT: Role of the enteric nervous system in the pathophysiology of secretory diarrhea. J Vet Intern Med 16:222, 2002.
53. Faruque SM, Albert MJ, Mekalanos JJ: Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. Microbiol Mol Biol Rev 62:1301, 1998.
54. Randazzo PA, et al: Molecular aspects of the cellular activities of ADP-ribosylation factors. Sci STKE 2000:RE1, 2000.
55. Borriello SP: Pathogenesis of Clostridium difficile infection. J Antimicrob Chemother 41 (suppl) C:13, 1998.
56. Procop GW: Gastrointestinal infections. Infect Dis Clin North Am 15:1073, 2001.
57. Katz DE, Taylor DN: Parasitic infections of the gastrointestinal tract. Gastroenterol Clin North Am 30:797, 2001.
58. Caplan MS, Jilling T: New concepts in necrotizing enterocolitis. Curr Opin Pediatr 13:111, 2001.
59. Pardi DS: Microscopic colitis. Mayo Clin Proc 78:614, 2003.
60. Cohen J, West AB, Bini EJ: Infectious diarrhea in human immunodeficiency virus. Gastroenterol Clin North Am 30:637, 2001.
61. Cruz-Correa M, et al: Endoscopic findings predict the histologic diagnosis in gastrointestinal graft-versus-host disease. Endoscopy 34:808, 2002.
62. Cipolla G, et al: Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res 46:1, 2002.
63. Farrell RJ, Kelly CP: Celiac sprue. N Engl J Med 346:180, 2002.
64. Catassi C, Fasano A: New developments in childhood celiac disease. Curr Gastroenterol Rep. 4:238, 2002.
65. Green PH, Jabri B: Celiac disease. Lancet 362:383, 2003.
66. Marth T, Raoult D: Whipple's disease. Lancet 361:239, 2003.
67. Bentley SD, et al: Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei. Lancet 361:637, 2003.
68. Podolsky DK: Inflammatory bowel disease. N Engl J Med 347:417, 2002.
69. Mowat AM: Anatomical basis of tolerance and immunity to intestinal atigens. Nat Rev Immunol 3:331, 2003.
70. Bouma G, Strober W: The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3:521, 2003.
71. Hugot JP, et al: Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599, 2001.
72. McKay DM: Intestinal inflammation and the gut microflora. Can J Gastroenterol 13:509, 1999.
73. Dubinsky MC, et al: Clinical utility of serodiagnostic testing in suspected pediatric inflammatory bowel disease. Am J Gastroenterol 96:758, 2001.
74. Bansi DS, Chapman RW, Fleming KA: Prevalence and diagnostic role of antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Eur J Gastroenterol Hepatol 8:881,
75. Greenson JK: Dysplasia in inflammatory bowel disease. Semin Diagn Pathol 2002;19:31.
76. McKenna BJ, Appelman HD: Dysplasia can be a pain in the gut. Pathology 34:518, 2002.
77. Chen R, et al: DNA fingerprinting abnormalities can distinguish ulcerative colitis patients with dysplasia and cancer from those who are dysplasia/cancer-free. Am J Pathol 162:665,
78. Eaden JA, Abrams KR, Mayberry JF: The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526, 2001.
79. Miyaki M, Kuroki T: Role of Smad4 (DPC4) inactivation in human cancer. Biochem Biophys Res Commun 306:799, 2003.
80. Burgart LJ: Colorectal polyps and other precursor lesions. Need for an expanded view. Gastroenterol Clin North Am 31:959, 2002.
81. Bienz M: Apc. Curr Biol 13:R215, 2003.
82. Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med 348:919, 2003.
83. Kinzler KW, Vogelstein B: Lessons from hereditary colorectal cancer. Cell 87:159, 1996.
84. Jass JR: Pathogenesis of colorectal cancer. Surg Clin N Am 82:891, 2002.
85. Knudson AG: Two genetic hits (more or less) to cancer. Nat Rev Cancer 1:157, 2001.
86. Kinzler KW, Vogelstein B: Colorectal tumors. In: Kinzler KW, Vogelstein B (eds): The Genetic Basis of Human Cancer, 2nd Edition. New York: McGraw-Hill 583, 2002.
87. Wynter CV, et al: Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut 53:573, 2004.
88. Bader S, et al: MBD1, MBD2, and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers. Oncogene 22:3506, 2003.
89. Taketo MM, Takaku K: Gastro-intestinal tumorigenesis in Smad4 mutant mice. Cytokine Growth Factor Rev 11:147, 2000.
90. Rudolph KL, et al: Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28:155, 2001.
91. Jemal A, et al: Cancer statistics, 2002. CA Cancer J Clin 52:23, 2002.
92. Wei EK, et al: Comparison of risk factors for colon and rectal cancer. Int J Cancer 108:433, 2004.
93. Lieberman DA, et al: Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 290:2959, 2003.
94. Imperiale TF: Aspirin and the prevention of colorectal cancer. N Engl J Med 348:879, 2003.
95. Parsonnet J, Isaacson PG: Bacterial infection and MALT lymphoma. N Engl J Med 350:213, 2004.
96. Matczak E: Human papillomavirus infection: an emerging problem in anal and other squamous cell cancers. Gastroenterology 120:1046, 2001.
97. Goede AC, Caplin ME, Winslet MC: Carcinoid tumour of the appendix. Br J Surg 90:1317, 2003.
98. Stancu M, et al: Genetic alterations in goblet cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors. Mod Pathol 16:1189, 2003.
99. Reynolds PA, et al: Identification of a DNA-binding site and transcriptional target for the EWS-WT1 (+KTS) oncoprotein. Genes Dev 17:2094, 2003.
Date: 2016-04-22; view: 417