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Polyps
 Most common in colon but may occur in esophagus, stomach, or small intestine
 Most, if not all, begin as small elevations of mucosa; sessile (flowers and leaves that grow directly from stem
without a stalk); polyps with stalks are pedunculated
 In general, classified as non-neoplastic or neoplastic in nature; most common neoplastic polyp is adenoma (has
potential to progress to cancer); non-neoplastic polyps can be further classified as inflammatory,
hamartomatous, or hyperplastic
Inflammatory Polyps
 Polyp that forms as part of solitary rectal ulcer syndrome
 Patients present with clinical triad of rectal bleeding, mucus discharge, and inflammatory lesion of anterior
rectal wall; underlying cause is impaired relaxation of anorectal sphincter that creates sharp angle at anterior
rectal shelf and leads to recurrent abrasion and ulceration of overlying rectal mucosa
 Inflammatory poly may ultimately form as result of chronic cycles of injury and healing
o Entrapment of polyp in fecal stream leads to mucosal prolapse
 Distinctive histologic features are those of typical inflammatory polyp with superimposed mucosal prolapse and
include lamina propria fibromuscular hyperplasia, mixed inflammatory infiltrates, erosion, and epithelial
hyperplasia
Hamartomatous Polyps
 Occur sporadically; tumor-like growths composed of mature tissues normally present at site in which they
develop; rare, but important to recognize because of associated intestinal and extra-intestinal manifestations
and possibility that other family members affected
 Juvenile polyps – focal malformations of mucosal epithelium and lamina propria
o May be sporadic or syndromic
o Vast majority occur in children under 5
o When present in adults, they are inflammatory polyps (identical to these though)
o Majority of juvenile polyps located in rectum and most present with rectal bleeding
o In some cases, prolapse occurs and polyp protrudes through anal sphincter
o Sporadic juvenile polyps usually solitary lesions (retention polyps)
o Individuals with autosomal dominant syndrome of juvenile polyposis have 3-100 hamartomatous polyps
and may require colectomy to limit chronic and sometimes severe hemorrhage associated with polyp
ulceration
o Minority of patients also have polyps in stomach and small bowel
o Pulmonary arteriovenous malformations are recognized extra-intestinal manifestation of syndrome
o Polyps typically pedunculated, smooth-surfaced, reddish lesions with characteristic cystic spaces
apparent after sectioning; cysts are dilated glands filled with mucin and inflammatory debris
 Remainder of polyp composed of lamina propria expanded by mixed inflammatory infiltrates
o Muscularis mucosa may be normal or attenuated
o Mutations in pathways that regulate cellular growth cause autosomal dominant juvenile polyposis
 Most common mutation identified is SMAD4 (encodes cytoplasmic intermediate in TGF-β
signaling pathway); BMPR1A (kinase in TGF-β superfamily) may be mutated in other cases
 Mutations account for fewer than ½ patients
o Dysplasia occurs in small proportion of juvenile polyps
o Juvenile polyposis syndrome associated with increased risk of colonic adenocarcinoma
 Peutz-Jeghers syndrome – rare autosomal dominant syndrome; presents at median age of 11 with multiple GI
hamartomatous polyps and mucocutaneous hyperpigmentation (dark blue to brown macules around mouth,
eyes, nostrils, buccal mucosa, palmar surfaces of hands, genitalia, and perianal region)
o Lesions similar to freckles but distinguished by presence in buccal mucosa
o Polyps can initiate intussusception (telescoping bowel), which is occasionally fatal
o Associated with increased risk of cancers of colon, pancreas, breast, lung, ovaries, uterus, and testicles,
as well as other unusual neoplasms such as sex cord tumors
o Germline heterozygous loss-of-function mutations in gene LKB1/STK11 present in ½ of individuals with
familial Peutz-Jeghers syndrome as well as subset of patients with sporadic Peutz-Jeghers syndrome
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LKB1/STK11 – kinase that regulates cell polarization, growth, and metabolism
Function of second normal copy often lost through somatic mutation in cancers (LKB1/STK11 is
tumor suppressor gene)
o GI adenocarcinomas arise independently of hamartomatous polyps (harmartomas not preneoplastic
precursor lesions)
o Polyps most common in small intestine, though they may occur in stomach and colon, and with much
lower frequency, bladder and lungs
 Grossly, polyps are large and pedunculated with lobulated contour
 Histologic exam has characteristic arborizing network of CT, smooth muscle, lamina propria, and
glands lined by normal-appearing intestinal epithelium
 Arborization and presence of smooth muscle intermixed with lamina propria helpful in
distinguishing polyps of Peutz-Jeghers syndrome from juvenile polyps
o Morphology can overlap with that of sporadic hamartomatous polyps, so presence of multiple polyps in
small intestine, mucocutaneous hyperpigmentation, and positive family history are key to diagnosis
o Detection of LKB1/STK11 mutations helpful diagnostically in patients with polyps who lack
mucocutaneous hyperpigmentation; absence of LKB1/STK11 mutations doesn’t exclude the diagnosis
o Because of increased risk of cancer, routine surveillance of GI tract, pelvis, and gonads recommended
 Cowden syndrome and Bannayan-Ruvalcaba-Riley syndrome – autosomal dominant hamartomatous polyp
syndromes associated with loss-of-function mutations in PTEN (gene encoding lipid phosphatase that inhibits
signaling through PI3K/AKT pathway)
o PTEN – well-characterized tumor suppressor; also mutated in small number of those with juvenile
polyposis; multiple syndromes associated with mutations sometimes grouped as “PTEN hamartoma
syndrome”
o Cowden syndrome – characterized by macrocephaly, intestinal hamartomatous polyps, and benign skin
tumors, typically trichilemmomas, papillomatous papules, and acral keratoses
 Variety of other lesions derived from all 3 embryologic layers, including subcutaneous lipomas,
leiomyomas, and hemangiomas also occur
 Patients don’t have increased risk of GI malignancy, but they are predisposed to breast
carcinoma, follicular carcinoma of the thyroid, and endometrial carcinoma
o Bannayan-Ruvalcaba-Riley syndrome – mental deficiencies and developmental delays and lower
incidence of neoplasia than Cowden syndrome
o Both above syndromes have GI hamartomatous polyps, lipomas, macrocephaly, hemangiomas, and in
males, pigmented macules on glans penis
 Cronkhite-Canada syndrome – nonhereditary and most often develops in individuals over 50 years of age
o Clinical symptoms include diarrhea, weight loss, abdominal pain, and weakness
o Most characteristic features is presence of hamartomatous polyps of stomach, small intestine, and
colorectum histologically indistinguishable for juvenile polyps
o Nonpolypoid intervening mucosa shows cystic crypt dilatation and lamina propria edema and
inflammation
o Associated abnormalities include nail atrophy and splitting, hair loss, and areas of cutaneous
hyperpigmentation and hypopigmentation
o Cause unknown and no specific therapies available
o Supportive nutritional therapy alleviates cachexia and anemia, can occasionally induce remission
o As many as 50% of cases fatal
Hyperplastic Polyps
 Colonic hyperplastic polyps – common epithelial proliferations typically discovered in 50s and 60s
 Result from decreased epithelial cell turnover and delayed shedding of surface epithelial cells, leading to piling
up of goblet cells and absorptive cells
 Don’t have malignant potential; chief significance is that they must be distinguished from sessile serrated
adenomas (histologically similar lesions that have malignant potential)
 Epithelial hyperplasia can occur as nonspecific reaction adjacent to or overlying any mass or inflammatory lesion
and, therefore, can be a clue to presence of adjacent, clinically important lesion
 Most commonly found in left colon; smooth, nodular protrusions of mucosa, often on crests of mucosal folds
o May occur singly but more frequently multiple, particularly in sigmoid colon and rectum
 Histologically, composed of mature goblet and absorptive cells
 Delayed shedding of cells leads to crowding that creates serrated surface architecture that is morphologic
hallmark of these lesions
Neoplastic Polyps
 Any neoplastic mass of GI tract may produce mucosal protrusion (polyp); includes carcinoid tumors, stromal
tumors, lymphomas, and metastatic cancers from distant sites
 Most common and clinically important neoplastic polyps are colonic adenomas (benign polyps that are
precursors to majority of colorectal adenocarcinomas)
 Adenomas – intraepithelial neoplasms that range from small, often pedunculated polyps to large sessile lesions
o No gender preference; present in nearly 50% of adults in Western world by age 50
o Precursors to colorectal cancer, so that’s why all adults in U.S. recommended to undergo surveillance
colonoscopy by age 50
o Those with family history at higher risk for developing colon cancer earlier in life
 Colorectal adenoma characterized by presence of epithelial dysplasia; prevalence of colorectal adenomas
correlates with that of colorectal carcinoma and distributions of adenomas and adenocarcinoma in colon similar
 Regular surveillance colonoscopy and polyp removal reduces incidence of colorectal adenocarcinoma
o Majority of adenomas do not progress to become adenocarcinoma
o No tools to distinguish between those that will and those that won’t undergo malignant transformation
o Most adenomas clinically silent, with exception of large polyps that produce occult bleeding and anemia;
rare villous adenomas cause hypoproteinemic hypokalemia by secreting large amounts of protein and
potassium
 Typical adenomas – can be pedunculated or sessile, with surface of both types having texture resembling velvet
or raspberry due to abnormal epithelial growth pattern
o Cytologic hallmark of epithelial dysplasia is nuclear hyperchromasia, elongation, and stratification; often
accompanied by presence of large nucleoli, eosinophilic cytoplasm, and reduction in number of goblet
cells; epithelium fails to mature as cells migrate from crypt to surface
o Pedunculated adenomas have slender fibromuscular stalks containing prominent blood vessels derived
from submucosa; usually covered by non-neoplastic epithelium, but dysplastic epithelium sometimes
present
 Adenomas classified as tubular, tubulovillous, or villous based on architecture
o Tubular adenomas tend to be small, pedunculated polyps composed of small rounded or tubular glands
o Villous adenomas often larger and sessile and covered by slender villi; contain foci of invasion more
frequently than tubular adenomas
o Tubulovillous adenomas have mixture of tubular and villous elements
o Architecture alone doesn’t increase cancer risk when polyp size considered
 Sessile serrated adenomas overlap histologically with hyperplastic polyps, but are more commonly found in right
colon; lack typical cytologic features of dysplasia present in other adenomas (still potential for malignancy)
o Histologic criteria include serrated architecture throughout full length of glands, including crypt base,
associated with lateral growth and crypt dilation
o Serrated architecture typically confined to surface of hyperplastic polyps
 Intramucosal carcinoma – when dysplastic epithelial cells breach basement membrane to invade lamina propria
or muscularis mucosa
o Because lymphatic channels absent in colonic mucosa, intramucosal carcinoma has little or no
metastatic potential and complete polypectomy effective therapy
o Invasion beyond muscularis mucosa, including into submucosal stalk of pedunculated polyp, constitutes
invasive adenocarcinoma and carries risk of spread to other sites
 Histologic grade of invasive component, presence of vascular or lymphatic invasion, and
distance of invasive component from margin of resection must be considered in planning further
therapy
 Invasive adenocarcinoma in polyp requires resection
 Most colorectal adenomas are benign lesions, but small proportion may harbor invasive cancer at time of
detection; size is most important characteristic that correlates with risk of malignancy
o High-grade dysplasia is risk factor for cancer in individual polyp (but not other polyps in same patient)
Familial Syndromes
 Familial adenomatous polyposis (FAP) – autosomal dominant disorder in which patients develop numerous
colorectal adenomas as teenagers; caused by mutations of adenomatous polyposis coli (APC) gene
o At least 100 polyps necessary for diagnosis of classic FAP; several thousand may be present
o Growths are morphologically indistinguishable from sporadic adenomas
o Flat or depressed adenomas prevalent, and microscopic adenomas (only 1-2 dysplastic glands)
frequently observed in otherwise normal-appearing mucosa
o Colorectal adenocarcinoma develops in all untreated patients, often before age 30
o Prophylactic colectomy is standard therapy for individuals carrying APC mutations; prevents colorectal
cancer, but patients remain at risk for neoplasia at other sites (adenomas may develop adjacent to
ampulla of Vater or in stomach)
o Associated with congenital hypertrophy of retinal pigment epithelium (generally detected at birth and
can be adjunct to early screening)
 Specific APC mutations associated with development of other manifestations (Gardner
syndrome and Turcot syndrome)
 Gardner syndrome families have osteomas of mandible, skull, and long bones; epidermal cysts,
desmoid tumors, thyroid tumors, and dental abnormalities (unerupted and supernumerary
teeth)
 Turcot syndrome – rarer than Gardner; characterized by intestinal adenomas and tumors of
CNS; 2/3 of patients with Turcot syndrome have APC gene mutations and develop
medulloblastomas; remaining 1/3 have mutations in one of several genes involved in DNA repair
and develop glioblastomas
o Some patients with APC loss have mutations of base-excision repair gene (MUTYH)
o Certain APC and MUTYH mutations associated with attenuated forms of FAP, characterized by delayed
polyp development, presence of fewer than 100 adenomas, and delayed appearance of colon cancer,
often to ages 50+
 Hereditary non-polyposis colorectal cancer (HNPCC) – also known as Lynch syndrome; familial clusters of
cancers in colorectum, endometrium, stomach, ovary, ureters, brain, small bowel, hepatobiliary tract, and skin
o Colon cancers tend to occur at younger ages than sporadic colon cancers and often located in right colon
o Caused by inherited mutations in genes that encode proteins responsible for detection, excision, and
repair of errors that occur during DNA replication
 Majority of cases involve MSH2 and MLH1
 Autosomal dominant; when second copy lost through mutation or epigenetic silencing, defects
in mismatch repair lead to accumulation of mutations up to 1000x faster than normal, mostly in
regions containing short repeating DNA sequences (microsatellite DNA)
o Human genome contains 50,000-100,000 microsatellites, prone to undergo expansion during DNA
replicatin and represent most frequent site of mutations in HNPCC
Adenocarcinomas
 Adenocarcinoma of colon is most common malignancy of GI tract and is major cause of morbidity and mortality
worldwide
 Small intestine is uncommon site for benign and malignant tumors; among malignant small intestine tumors,
adenocarcinomas and carcinoid tumors have roughly equal incidence, followed by lymphomas and sarcomas
 Colorectal adenocarcinoma represents 15% of all cancer-related deaths and is second only to lung cancer
o Incidence peaks at 60-70 years of age; fewer than 20% of cases occur before age 50
o Males affected slightly more than females
 Dietary factors most closely associated with increased colorectal cancer rates are low intake of unabsorbable
vegetable fiber and high intake of refined carbs and fat
o Reduced fiber content leads to decreased stool bulk and altered composition of intestinal microbiota;
change may increase synthesis of potentially toxic oxidative by-products of bacterial metabolism, which
would be expected to remain in contact with colonic mucosa for longer periods of time as result of
reduced stool bulk
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Deficiencies of vitamins A, C, and E, which act as free-radical scavengers, may compound damage caused
by oxidants
o High fat intake enhances hepatic synthesis of cholesterol and bile acids, which can vbe converted into
carcinogens by intestinal bacteria
Aspirin or other NSAIDs have protective effect; some NSAIDs cause polyp regression in FAP patients in whom
rectum was left in place after colectomy
o Mediated by inhibition of COX-2 (highly expressed in 90% of colorectal carcinomas and 40-90% of
adenomas); COX-2 necessary for production of PGE2 (promotes epithelial proliferation, particularly after
injury); COX-2 expression regulated by TLR4, which recognizes lipopolysaccharide and is overexpressed
in adenomas and carcinomas
Combination of molecular events that lead to colonic adenocarcinoma is heterogeneous and includes genetic
and epigenetic abnormalities; at least 2 distinct genetic pathways described (APC/β-catenin pathway associated
with WNT and classic adenoma-carcinoma sequence and microsatellite instability pathway associated with
defects in DNA mismatch repair)
o Both pathways involve stepwise accumulation of multiple mutations, but genes involved and
mechanisms by which mutations accumulate differ
o Epigenetic events (most common is methylation-induced gene silencing) may enhance progression along
both pathways
Classic adenoma-carcinoma sequence – accounts for as much as 80% of sporadic colon tumors; typically includes
mutation of APC early in neoplastic process
o Both copies of APC gene must be functionally inactivated, either by mutation or epigenetic events, for
adenomas to develop
o APC is key negative regulator of β-catenin (component of WNT signaling pathway)
 APC protein normally binds to and promotes degradation of β-catenin
 With loss of APC function, β-catenin accumulates and translocates to nucleus, where it activates
transcription of genes, such as those encoding MYC and cyclin D1, which promote proliferation
o During proliferation, additional mutations develop, including activating mutations in KRAS (promote
growth and prevent apoptosis)
o Neoplastic progression associated with mutations in tumor suppressor genes such as those encoding
SMAD2 and SMAD4, which are effectors of TGF-β signaling, which normally inhibits cell cycle
o Tumor suppressor p53 mutated in 70-80% of colon cancers, but uncommonly affected in adenomas (p53
mutations occur at late stages of tumor progression)
 Loss of function of p53 and other tumor suppressor genes often caused by chromosomal
deletions, so chromosomal instability is hallmark of APC/ β-catenin pathway
o Tumor suppressor genes may be silenced by methylation of CpG-rich zone (CpG island; 5’ region of some
genes that frequently includes promoter and transcriptional start site)
o Expression of telomerase increases as lesions become more advanced
In patients with DNA mismatch repair deficiency due to loss of mismatch repair genes, mutations accumulate in
microsatellite repeats (microsatellite instability)
o While mutations generally silent because microsatellites typically in noncoding regions, some
microsatellite sequences located in coding or promoter region of genes involved in regulation of cell
growth, such as those encoding type II TGF-β receptor and pro-apoptotic protein BAX
o Because TGF-β inhibits colonic epithelial cell proliferation, type II TGF-β receptor mutants can contribute
to uncontrolled cell growth, while loss of BAX may enhance survival of genetically abnormal clones
o Mutations in oncogene BRAF and silencing of distinct groups of genes due to CpG island
hypermethylation common in cancers that develop through DNA mismatch repair defects
 KRAS and p53 not typically mutated
o Combination of microsatellite instability, BRAF mutation, and methylation of specific targets, such as
MLH1, is signature of this pathway of carcinogenesis
Third group of colon cancers with increased CpG island methylation in absence of microsatellite instability also
exists; many of these tumors harbor KRAS mutations, but p53 and BRAF mutations uncommon
o p53 mutations common in colon cancers that don’t display CpG island methylator phenotype
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Morphology can’t reliably predict underlying molecular events that led to carcinogenesis, but certain
correlations associated with mismatch repair deficiency and microsatellite instability
o Molecular alterations common in sessile serrated adenomas
o Invasive carcinomas with microsatellite instability can be recognized by absence of
immunohistochemical staining for mismatch repair proteins or by molecular genetic analysis of
microsatellite sequences
 Important to identify those with HNPCC because of implications of genetic counseling, elevated risk of second
malignancy of colon and other organs, and (in some settings) differences in prognosis and therapy)
 Adenocarcinomas distributed approximately equally over the entire length of the colon
o Tumors in proximal colon often grow as polypoid, exophytic masses that extend along one wall of largecaliber cecum and ascending colon; rarely cause obstruction
o Carcinomas in distal colon tend to be annular lesions that produce napkin-ring constrictions and luminal
narrowing, sometimes to point that obstruction occurs
o Both forms grow into bowel wall over time and may be palpable as firm masses
o Most tumors composed of tall columnar cells that resemble dysplastic epithelium found in adenomas
o Invasive component of tumors elicits strong stromal desmoplastic response responsible for
characteristic firm consistency
o Some poorly differentiated tumors form few glands; others may produce abundant mucin that
accumulates in intestinal wall (associated with poor prognosis)
o Tumors may be composed of signet-ring cells similar to those in gastric cancer; others may display
features of neuroendocrine differentiation
 Colorectal cancers develop insidiously and may therefore go undetected for long periods
o Cecal and other right-sided colon cancers most often called to clinical attention by appearance of fatigue
and weakness due to iron deficiency anemia
o Left-sided colorectal adenocarcinomas may produce occult bleeding, changes in bowel habits, or
cramping in LLQ
o Mucinous histologies associated with poor prognosis, but 2 most important prognostic factors are depth
of invasion and presence or absence of lymph node metastases (form core of TNM [tumor-nodesmetastasis] classification and staging system)
o Some patients with small numbers of metastases do well for years following resection of distant tumor
nodules; metastases may involve regional lymph nodes, lungs, and bones, but as a result of portal
drainage of colon, liver is most common site of metastatic lesions
o Rectum doesn’t drain via portal circulation, and carcinomas of anal region that metastasize often
circumvent liver
Tumors of the Anal Canal
 Anal canal divided into thirds: upper zone lined by columnar rectal epithelium; middle third by transitional
epithelium; and lower third by stratified squamous epithelium
o Carcinomas of anal canal may have typical glandular (normal epithelium of upper third) or squamous
(normal epithelium of lower third) patterns of differentiation
 Basaloid differentiation pattern present in tumors populated by immature cells derived from basal layer of
transitional epithelium
o When entire tumor displays basaloid pattern, called cloacogenic carcinoma
o Basaloid differentiation may be mixed with squamous or mucinous differentiation
 Pure squamous cell carcinoma of anal canal frequently associated with HPV infection (causes precursor lesions
such as condyloma accuminatum)
Hemorrhoids
 Affect about 5% of general population and develop secondary to persistently elevated venous pressure within
hemorrhoidal plexus; most frequent predisposing influences are straining at stool because of constipation and
venous stasis of pregnancy
 Variceal dilations of anal and perianal venous plexuses form collaterals that connect portal and caval venous
systems, thereby relieving venous hypertension
o Collateral vessels in inferior hemorrhoidal plexus located below anorectal line (external hemorrhoids)
o
Collaterals that result from dilation of superior hemorrhoidal plexus in distal rectum are internal
hemorrhoids
 Histologically, hemorrhoids consist of thin-walled, dilated, submucosal vessels that protrude beneath anal or
rectal mucosa; in exposed position, they are subject to trauma and tend to become inflamed, thrombosed, and
(in course of time) recanalized; superficial ulceration may occur
 Often present with pain and rectal bleeding, particularly bright red blood seen on toilet tissue
o Except for pregnant women, hemorrhoids rarely encountered in persons under 30
o May develop as result of portal hypertension, where implications are more ominous
o Hemorrhoidal bleeding not generally a medical emergency and can be treated by sclerotherapy, rubber
band ligation, or infrared coagulation
o Extensive or severe internal or external hemorrhoids may be removed surgically by hemorrhoidectomy
Acute Appendicitis
 Appendix is normal true diverticulum of cecum prone to acute and chronic inflammation
 Acute appendicitis most common in adolescents and young adults, but may occur in any age group
 Lifetime risk for appendicitis is 7%; males affected slightly more than females
 Diagnosis can be difficult to confirm preoperatively and may be confused with mesenteric lymphadenitis (often
secondary to unrecognized Yersinia infection or viral enterocolitis), acute salpingitis, ectopic pregnancy,
mittelschmerz, and Meckel diverticulitisd
 Acute appendicitis initiated by progressive increases in intraluminal pressure that compromise venous outflow
o In 50-80% of cases, acute appendicitis associated with over luminal obstruction, usually caused by small
stone-like mass of stool (fecalith) or less commonly gallstone, tumor, or mass of worms (oxyuriasis
vermicularis)
o Ischemic injury and stasis of luminal contents (favor bacterial proliferation) trigger inflammatory
responses including tissue edema and neutrophilic infiltration of lumen, muscular wall, and
periappendiceal soft tissues
 In early acute appendicitis, subserosal vessels congested; modest perivascular neutrophilic infiltrate within all
layers of wall
o Inflammatory reaction transforms normal glistening serosa into dull, granular, erythematous surface
o Diagnosis requires neutrophilic infiltration of muscularis propria
o Although mucosal neutrophils and focal superficial ulceration often present, they aren’t specific markers
of acute appendicitis
o In more severe cases, prominent neutrophilic exudate generates serosal fibrinopurulent reaction
o As process continues, focal abscesses may form within wall (acute suppurative appendicitis)
o Further appendiceal compromise leads to large areas of hemorrhagic ulceration and gangrenous
necrosis that extends to serosa creating acute gangrenous appendicitis, often followed by rupture and
suppurative peritonitis
 Early acute appendicitis produces periumbilical pain that ultimately localizes to RLQ, followed by nausea,
vomiting, low-grade fever, and mildly elevated peripheral WBC count
o Classic physical finding is McBurney’s sign (deep tenderness located 2/3 of distance from umbilicus to
right ASIS (McBurney’s point))
o Signs and symptoms often absent, creating difficulty in clinical diagnosis
o In some cases, retrocecal appendix may generate right flank or pelvic pain, while malrotated colon may
give rise to appendicitis in LUQ
o In some cases, peripheral leukocytosis may be minimal or so great that other causes considered
 Diagnosis of acute appendicitis in very young or very old problematic, since other causes of abdominal
emergencies prevalent in these populations, and very young and old also more likely to have atypical clinical
presentations
o Removing normal appendix preferred to delayed resection of diseased appendix, given significant
morbidity and mortality associated with appendiceal perforation
 Other complications include pyelophlebitis (inflammation of veins of renal pelvis), portal venous thrombosis,
liver abscess, and bacteremia
Tumors of the Appendix
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Most common tumor is carcinoid; usually discovered incidentally at time of surgery or exam of resected
appendix; most frequently involves distal tip of appendix, where it produces solid bulbous swelling
o Intramural and transmural extension may be evident, but nodal metastases infrequent, and distant
spread exceptionally rare
 Conventional adenomas or non-mucin-producing occur in appendix and may cause obstruction and enlargement
that mimics acute appendicitis
 Mucocele – dilated appendix filled with mucin; may be obstructed appendix containing inspissated mucin or be
a consequence of mucinous cystadenoma or mucinous cystadenocarcinoma
o In mucinous cystadenocarcinoma, invasion through appendiceal wall can lead to intraperitoneal seeding
and spread
o In women, resulting peritoneal implants may be mistaken for mucinous ovarian tumors
 In most advanced cases, abdomen fills with tenacious, semisolid mucin (pseudomyxoma peritoneii;
disseminated intraperitoneal disease); can be held in check for years by repeated debulking, but in most
instances, follows inexorably fatal course
Peritoneal Cavity
 Peritoneal cavity houses abdominal viscera and is lined by single layer of mesothelial cells that cover visceral and
parietal surfaces and are supported by thin layer of CT to form peritoneum
 Tumors less common than inflammatory or infectious process, but tumors can carry grave prognosis
Inflammatory Disease
 Peritonitis may result from bacterial invasion or chemical irritation and most often due to
o Leakage of bile or pancreatic enzymes, which produces sterile peritonitis
o Perforation or rupture of biliary system that evokes highly irritating peritonitis, usually complicated by
bacterial superinfection
o Acute hemorrhagic pancreatitis, associated with leakage of pancreatic enzymes and fat necrosis;
globules of fat may be found in peritoneal fluid; damage to bowel wall may allow bacteria to spread to
peritoneal cavity, leading to frank suppurative exudate after 24-48 hours
o Foreign material, including that introduced surgically, that induces foreign body-type granulomas and
fibrous scarring
o Endometriosis, which causes hemorrhage into peritoneal cavity, where it acts as irritant
o Ruptured dermoid cysts release keratins that invoke intense granulomatous reaction
o Perforation of abdominal viscera
 Bacterial peritonitis – occurs when bacteria from GI lumen released into abdominal cavity, typically following
perforation; occurs most commonly as complication of acute appendicitis, peptic ulcer, cholecystitis,
diverticulitis, and intestinal ischemia
o Acute salpingitis, abdominal trauma, and peritoneal dialysis are other potential sources of
contaminating bacteria
o Although E. coli, streptococci, S. aureus, enterococci, and C. perfringens implicated most often, virtually
any bacteria can be associated with bacterial peritonitis
 Spontaneous bacterial peritonitis develops in absence of obvious source of contamination; uncommon disorder
seen most often in patients with cirrhosis and ascites (10% of cirrhosis/ascites patients)
o Children, particularly those with nephrotic syndrome, may develop spontaneous bacterial peritonitis
o Organisms identified most often are E. coli and pneumococci
 Normally glistening serosal and peritoneal surfaces become dull and lusterless, and serous or slightly turbid fluid
begins to accumulate in 2-4 hours of infection
o As infection progresses, creamy suppurative material (may be extremely viscous) accumulates
o Volume of fluid varies and may be localized by omentum and viscera to small area or may fill abdominal
cavity
o Exudate may collect around liver to form subhepatic and subdiaphragmatic abscesses
 Cellular inflammatory response composed primarily of dense collections of neutrophils and fibrinopurulent
debris that coat viscera and abdominal wall; reaction usually remains superficial and doesn’t penetrate deeply
o Tuberculous peritonitis – typically studs serosal and peritoneal surfaces with small, pale granulomas;
penetrates deeply
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Inflammatory process can heal either spontaneously or as result of therapy; may resolve completely or undergo
organization into fibrous adhesions or become walled off in abscesses that may persist (potentially serving as
new sources of infection) or heal
Sclerosing retroperitonitis – also known as idiopathic retroperitoneal fibrosis or Ormond disease; characterized
by dense fibrosis that may extend to involve mesentery
Cysts – may develop in abdominal cavity and frequently attached to peritoneum
o Can be large enough to present as palpable abdominal masses
o Develop from blind lymphatic channels, foregut or hindgut diverticulae that pinch off during
development, urogenital ridge or its derivatives, walled-off infections, or as sequela of pancreatitis
(pseudocysts)
Tumors
 Most tumors malignant and can be divided into primary and secondary forms
 Primary tumors arising from peritoneal lining are mesotheliomas similar to tumors of pleura and pericardium
o Almost always associated with significant asbestos exposure
o Histopathologic diagnosis can be difficult; differential diagnosis includes metastatic adenocarcinoma
(distinguished from mesothelioma using variety of immunohistochemical markers)
o Rarely, primary benign and malignant soft-tissue tumors develop within peritoneum and
retroperitoneum
 Most common of these is desmoplastic small round cell tumor – aggressive tumor that occurs in
children and young adults; characterized by reciprocal chromosomal translocation that results in
fusion of genes associated with Ewing sarcoma (EWS) and Wilms tumor (WT1)
 Morphologically, tumor bears resemblance to Ewing sarcoma and related tumors
 Secondary tumors of peritoneum quite common; in any form of advanced cancer, direct spread to serosal
surface or metastatic seeding (peritoneal carcinomatosis) may occur
o Most common tumors producing diffuse serosal implants are ovarian and pancreatic adenocarcinoma
o Appendiceal mucinous carcinomas may produce pseudomyxoma peritoneii
o Any intra-abdominal malignancy, as well as wide variety of tumors of extra-abdominal origin, may
spread to peritoneum