Gastrointestinal Pathology Case Studies Part II

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Gastrointestinal Pathology Case Studies Part II
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CASE 1

• Clinical History
• A 31 year old woman has a 10 year history of
  intermittent, bloody diarrhea. Radiographic
  studies and sigmoidoscopy revealed a friable,
  ulcerated mucosa extending to the splenic flexure
  (Slide 1.1). The descending with sigmoid colon
  and rectum were resected. The gross specimen
  shown in Slide 1.2 is from another case with even
  more severe disease, in which the ulceration
  extends nearly to the ileocecal valve. On closer
  inspection (Slide 1.3) the mucosa is completely
  eroded away, except for reddish "pseudopolyps".
  Microscopic examination shows diffuse mucosal
  ulceration, with several ulcers extending to the
  muscularis propria. The intervening mucosa shows
  misshapen, distorted crypts with occasional crypt
  abscesses (Slides 1.4 and 1.5).

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Slide 1.1These views on endoscopy reveal the
typical friable, erythematous mucosa with
diminished haustral folds.
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Slide 1.2The gross specimen shown here is from
another case with even more severe disease, in
which the ulceration extends nearly to the
ileocecal valve.
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Slide 1.3On closer inspection, grossly the
mucosa is completely eroded away, except for
reddish "pseudopolyps". The radiographic view
below is from a barium enema (not typically
performed nowadays when colonoscopy can define
the location of lesions and provide opportunity
for biopsy) that reveals a coarsely granular
mucosal pattern.
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Slide 1.4Microscopic examination shows diffuse
mucosal ulceration, with several ulcers extending
to the muscularis propria.
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Slide 1.5At higher power, the intervening mucosa
shows misshapen, distorted crypts with occasional
crypt abscesses.
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Questions

• What are the major differential diagnoses?
• What is the diagnosis here?
• What is the course of this disease and what kinds
  of complications can develop?

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CASE 1 Ulcerative Colitis

• What are the major differential diagnoses? The
  history suggests inflammatory bowel disease. The
  major differential diagnoses are ulcerative
  colitis and Crohn's disease. Given the
  chronicity, an infectious cause is unlikely.
• What is the diagnosis here? The gross appearance
  of a continuous mucosal involvment of the colon,
  starting from the rectum, along with microscopic
  ulceration of the mucosa, is most typical for
  ulcerative colitis.
• What is the course of this disease and what kinds
  of complications can develop? The typical course
  is relapsing disease--flareups with intervening
  quiescent periods of months to years. Slightly
  more than half of patients have fairly mild
  disease that can be well-managed by medical
  means. About 1/4 of patients may develop a
  fulminant colitis. The long-term risk is colonic
  adenocarcinoma, which may be multifocal.

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CASE 2

• Clinical History
• A 27 year old man has had recurrent attacks of
  abdominal pain, diarrhea, and low-grade fever. He
  also developed steatorrhea. Colonoscopy revealed
  erythema and erosions of the terminal ileum
  (Slide 2.1). Radiographic studies demonstrated an
  enteroenteric fistula that bypassed much of the
  small intestine, which was the cause of the
  malabsorption and steatorrhea (Slide 2.2). He was
  taken to surgery where a portion of small
  intestine was resected. The gross specimen shows
  an area in which the small intestinal serosa is
  reddened, the wall is thickened, the lumen
  narrowed, and the mucosa ulcerated (Slide 2.3).
  The microscopic section shows small intestine
  with extensive mucosal ulceration, transmural
  chronic inflammation, fibrosis, and granulomas
  (Slides 2.4 and 2.5).

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Slide 2.2On colonoscopy, there were no lesions
of the colon, but the appearance of the terminal
ileum with erythema and erosions is seen here.
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Slide 2.2The abdominal CT scan views seen here
demonstrate enteroenteric fistula formation in a
case of Crohn's disease. Loops of small bowel
converge because of adhesions resulting from the
transmural inflammation. The panel above is
without contrast and the panel below with
contrast.
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Slide 2.3The gross specimen shows an area in
which the small intestinal serosa is reddened,
the wall is thickened, the lumen narrowed, and
the mucosa ulcerated.
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Slide 2.4Microscopically at low power, the small
intestine has extensive mucosal ulceration,
transmural chronic inflammation, fibrosis, and
granulomas.
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Slide 2.5Microscopically at high power, the
granulomas are evident. No infectious agents can
be demonstrated in these granulomas.
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Questions

• What is the diagnosis?
• Could the patient also have colonic involvement?
• What is the course of this disease and what kinds
  of complications can develop?

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CASE 2 Crohn's Disease

• What is the diagnosis? This is Crohn's disease,
  typified by discontinuous small bowel disease
  which microscopically is transmural and
  demonstrates granulomas.
• Could the patient also have colonic involvement?
  Yes, about half of patients with small intestinal
  Crohn's disease will also have colonic Crohn's
  disease.
• What is the course of this disease and what kinds
  of complications can develop? The course
  typically involves intermittent flareups with
  intervening asymptomatic periods of weeks to
  months. Compications of the inflammation include
  fibrosis with stricture leading to obstruction,
  fistulas to other loops of bowel or to bladder or
  skin, and malabsorption. Extraintestinal
  manifestations of Crohn's disease include
  erythema nodosum, ankylosing spondylitis,
  migratory polyarthritis, and sacroilitis. There
  is a slightly increased risk for small or large
  bowel carcinoma, but this risk is far less than
  that in ulcerative colitis.

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CASE 3

• Clinical History
• Following heart transplantation for idiopathic
  dilated cardiomyopathy, this 40 year old female
  developed rejection, as shown on endomyocardial
  biopsy. Her immunosuppressive therapy was
  increased. She then developed bacterial and
  fungal sepsis. She was treated with antimicrobial
  therapy, including clindamycin. She patient then
  developed diarrhea. A colonoscopy was performed
  (Slide 3.1). A colectomy was performed, and the
  surface of the colon showed diffuse reddening
  with an overlying friable tan-green exudate
  (Slide 3.2). The microscopic section of colon
  shows surface mucosal erosions with overlying
  fibrinopurulent exudate (Slides 3.3 and 3.4).

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Slide 3.1On colonoscopy can be seen an extensive
tan-green exudate over the mucosa.
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Slide 3.2The surface of the colon shows diffuse
reddening with an overlying friable tan-green
exudate.
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Slide 3.3At low power microscopically, the colon
shows surface mucosal erosions with overlying
fibrinopurulent exudate.
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Slide 3.4At high power microscopically, the
colon shows surface mucosal erosions with
overlying fibrinopurulent exudate.
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Questions

• What is the diagnosis?
• What laboratory test was done that helped to make
  the diagnosis?
• What is the pathogenesis of this lesion?

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CASE 3 Pseudomembranous Colitis

• What is the diagnosis? This is pseudomembranous
  colitis. In some cases the small intestine can
  also be involved to produce pseudomembranous
  enterocolitis.
• What laboratory test was done that helped to make
  the diagnosis? An assay for C. difficile was done
  and was positive.
• What is the pathogenesis of this lesion? This
  disease is produced by mucosal injury from the
  toxin of Clostridium difficile. C. difficile is a
  normal gut commensal organism that can overgrow
  with broad spectrum antibiotic therapy
  (clindamycin, lincomycin, ampicillin, etc.) and
  lead to extensive mucosal injury. Overgrowth of
  other organisms such as Candida and
  Staphylococcus can produce similar findings.

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CASE 4

• Clinical History
• A 45 year old man was found to have a stool
  positive for occult during a routine physical
  examination. A colonoscopy was performed and a
  1.3 cm diameter polypoid lesion on a short stalk
  was found in the descending colon, along with a
  smaller 0.5 cm polyp in the sigmoid region (Slide
  4.1). Both were resected. The gross photograph
  shows another case of a patient with several of
  these lesions (Slide 4.2). Another patient with a
  different gross appearance is shown in slide 4.3.
  The microscopic section demonstrates the polyp
  removed at colonoscopy at low power (Slide 4.4)
  that consists of closely packed tubular glands
  lined by cells with depleted cytoplasmic mucin
  and hyperchromatic, stratified nuclei and
  occasional mitoses (Slide 4.5).

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Slide 4.1The colonoscopic views of the smaller
and larger polyps are seen here.
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Slide 4.2The gross lesion here is from another
case of a patient with several of these lesions.
The barium enema view below demonstrates a
colonic polyp. The head of the polyp is partially
obscured by the pool of barium contrast in which
it rests.
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Slide 4.3Another patient with a similar disease
but different gross appearance is shown here.
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Slide 4.4Seen here microscopically at low power
is one of the polyps.
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Slide 4.5Seen here microscopically at higher
power, the polyp at the right consists of closely
packed tubular glands lined by cells with
depleted cytoplasmic mucin and hyperchromatic,
stratified nuclei and occasional mitoses. Compare
with the normal colonic mucosa at the left.
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Questions

• What is the diagnosis?
• This is thought to be a precursor for what
  lesion?
• Name a syndrome in which the patient has hundreds
  of these polyps (A gross photograph of such a
  patient is shown in Slide 4.4).
• Name a syndrome that not only has hundreds of
  these polyps, but also has osteomas, desmoids,
  and other extracolonic manifestations.

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CASE 4 Tubular Adenoma

• What is the diagnosis? These are benign tubular
  adenomas (adenomatous polyps).
• This is thought to be a precursor for what
  lesion? This is thought to be a precursor for
  adenocarcinoma. Polyps greater than 2 cm have a
  greater chance for containing adenocarcinoma.
  Over time, more genetic "hits" occur in the
  neoplasm to drive transformation to malignancy.
• Name a syndrome in which the patient has hundreds
  of these polyps (A gross photograph of such a
  patient is shown in Slide 4.4). The syndrome is
  familial polyposis coli, with an autosomal
  dominant inheritance pattern. Colectomy is
  performed to prevent development of
  adenocarcinomas.
• Name a syndrome that not only has hundreds of
  these polyps, but also has osteomas, desmoids,
  and other extracolonic manifestations. The
  syndrome is Gardner syndrome, also with an
  autosomal dominant inheritance pattern, but with
  variable expression. These patients are also at
  risk for development of gastrointestinal tract
  adenocarcinomas.

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CASE 5

• Clinical History
• A 44 year old male emergency medical technician
  has been feeling fatigued for months. He just
  doesn't have the same level of energy he used to
  have. He remembers that he had experienced an
  episode of jaundice about 10 years ago, but that
  resolved and he had been healthy since. A CBC
  reveals that he is not anemic. A chemistry panel
  reveals normal serum electroytes, but he has an
  elevated alanine aminotransferase of 132 U/L and
  aspartate aminotransferase of 113 U/L. He has a
  total bilirubin of 1.3 mg/dL with direct
  bilirubin of 0.8 mg/dL. His total protein is 5.4
  g/dL with albumin of 2.9 g/dL. A liver biopsy is
  performed.

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Slide 5.1The gross appearance of another liver
with this process is shown here. What is
abnormal?
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Slide 5.2The medium power appearance of the
liver is shown here. How has the architecture
been altered?
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Slide 5.3The medium power appearance of the
liver is seen here. What is happening to the
hepatocytes (arrows)?
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Slide 5.4The gross appearance of the liver seen
here illustrates a complication of this disease
process.
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Slide 5.5The gross appearance of the liver seen
here illustrates another complication of this
disease process.
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Questions

• What is suggested by the clinical laboratory and
  biopsy findings?
• What is the differential diagnosis?
• Further History
• A hepatitis panel revealed the following
• TestResult
• Hepatitis A antibodies, total Positive
• Hepatitis A, IgM Negative
• Hepatitis B surface antigen Positive
• Hepatitis B surface antibody Negative
• Hepatitis B core antibody Positive
• Hepatitis C antibody Negative
• How do you explain these additional laboratory
  findings?
• What complications of this disease are
  illustrated by slides 5.5 and 5.6?

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CASE 5 Hepatitis B Infection with Chronic
Hepatitis

• What is suggested by the clinical laboratory and
  biopsy findings? Hepatitis. Slide 5.1 shows a
  typical gross appearance of a liver with ongoing
  hepatitis, with necrosis and lobular collapse
  seen as areas of hemorrhage and irregular furrows
  and granularity on the cut surface. Slide 5.2
  demonstrates a mononuclear inflammatory cell
  infiltrate that extends from portal areas and
  disrupts the limiting plate of hepatocytes which,
  in Slide 5.3 are seen to be are undergoing
  necrosis ("ballooning degeneration") with a small
  round Councilman body. This is the so-called
  "piecemeal" necrosis of chronic active hepatitis.
• What is the differential diagnosis? Viral
  hepatitis is the most likely diagnosis. Hepatitis
  A is generally a mild, self-limited illness.
  Hepatitis B and C can produce more chronic
  disease. The latter two agents are more commonly
  parenterally acquired (transfusion of blood
  products, penetrating injuries in the health care
  setting, injection drug use, vertical
  transmission from mother to fetus) while
  hepatitis A is more often acquired via fecal-oral
  contamination. However, an identifiable risk may
  not be found in all cases.
• How do you explain these additional laboratory
  findings? The hepatitis A tests suggest that he
  has IgG antibodies from a remote, not current
  infection. The hepatitis B surface antibody is
  negative, though a positive value should be found
  in a person who received a hepatitis B
  vaccination. With chronic liver disease from
  hepatitis B, the surface antigen and core
  antibody are typically positive. The histologic
  findings are consistent with chronic hepatitis B.
  If a person with hepatitis B clears the
  infection, then hepatitis B surface antibody
  appears.
• What complications of this disease are
  illustrated by slides 5.4 and 5.5? The
  complications are those of chronic liver disease.
  In about two-thirds of patients, hepatitis B
  produces a subclinical disease. About 20 develop
  a clinically apparent hepatitis. About 5 to 10
  go on to chronic hepatitis with both fibrosis and
  inflammation. The fibrosis can proceed to a
  macronodular cirrhosis. In this setting, the risk
  for hepatocellular carcinoma is increased. The
  fibrosis can proceed to a macronodular cirrhosis
  (slide 5.5). In this setting, the risk for
  hepatocellular carcinoma (slide 5.6) is increased.

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CASE 6

• Clinical History
• A 63 year old man sought medical help because of
  increasing abdominal girth over many months along
  with a recent episode of vomiting blood. Serum
  chemistries showed sodium 120, potassium 4.2,
  chloride 99, bicarbonate 20, glucose 75, total
  protein 6.2, albumin 1.9, total bilirubin 5.0,
  AST 190, ALT 123, and protime 18 seconds (normal
  12). A gross photograph (Slide 6.1) shows how his
  liver and spleen would appear. The microscopic
  section is also representative of his liver. It
  shows a diffusely disorganized architecture with
  nodules of hepatocytes with focal cholestasis and
  surrounded by fibrous bands with bile duct
  proliferation (Slides 6.2 and 6.3). At high
  magnification, globular eosinophilic material is
  seen in some hepatocytes (Slide 6.4).

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Slide 6.1This is how his liver and spleen would
appear. The shrunken, nodular appearance of the
liver and the enlarged spleen are both seen in
the abdominal MRI scan below.
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Slide 6.2There is portal fibrosis and marked
macrovesicular steatosis (fatty change) at low
power.
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Slide 6.3There are nodules of regenerating
hepatocytes surrounded by dense fibrous bands
seen here microscopically at low power.
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Slide 6.4At high magnification, globular
eosinophilic material is seen in some
hepatocytes.
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Questions

• What is the diagnosis? What do the clear vacuoles
  in the hepatocytes represent? What is the clumped
  eosinophilic material seen in some of the swollen
  hepatocytes?
• What is the probable etiology?
• Correlate the clinical and laboratory findings in
  this patient.
• What are potential complications of this disease?

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CASE 6 Alcoholic Liver Disease

• What is the diagnosis? What do the clear vacuoles
  in the hepatocytes represent? What is the clumped
  eosinophilic material seen in some of the swollen
  hepatocytes? This is cirrhosis. It can be further
  classified as a micronodular cirrhosis on the
  basis of the size of the nodules (lt5 mm). The
  vacuoles are of fat from fatty change. The
  clumped eosinophilic material is Mallory's
  hyaline.
• What is the probable etiology? Given the above
  findings, the most probable etiology is
  alcoholism.
• Correlate the clinical and laboratory findings in
  this patient. Patients with cirrhosis can develop
  portal hypertension with esophageal varices,
  which may explain the hematemesis. Liver failure
  from cirrhosis can lead to hypoalbuminemia,
  hypoprothrombinemia, and ascites.
• What are potential complications of this disease?
  Complications leading to morbidity and mortality
  include gastrointestinal hemorrhage, hepatic
  coma, infection (pneumonia, peritonitis), renal
  failure with hepatorenal syndrome, and
  hepatocellular carcinoma.

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CASE 7

• Clinical History
• A 40 year old woman developed increasingly severe
  abdominal pain over a two day period. In the
  emergency room, physical examination demonstrated
  board-like rigidity of the abdomen with extreme
  tenderness. A radiograph of the abdomen
  demonstrated dilated loops of bowel, several
  radiopaque gallstones in the gallbladder, but no
  free air. The total bilirubin was 3.8, AST 25,
  ALT 30, albumin 3.5, total protein 5.8, glucose
  120, calcium 7.8, phosphorus 3.3, and lipase
  2,250. The gross photograph depicts the process
  (Slide 7.1). The microscopic section shows
  extensive necrosis with acute inflammation and
  fat necrosis (Slides 7.2 and 7.3).

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Slide 7.1The pancreas is seen grossly. It is
enlarged because of edema and hemorrhage. In the
abdominal CT scan view below, there is decreased
enhancement of the swollen pancreas as a result
of the edema, hemorrhage, and fat necrosis.
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Slide 7.2Microscopically at medium power, there
is extensive hemorrhage and fat necrosis.
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Slide 7.3Microscopically at medium power, there
is extensive inflammation with neutrophils and
fat necrosis.
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Slide 7.4A cystic space in the lesser sac lined
by inflamed, necrotic tissue is seen here. In the
abdominal CT scan view below, this cystic area
appears with a low attenuation liquefied center,
involving the tail of the pancreas, that appears
to interdigitate with accentuated gastric rugal
folds of the stomach filled with bright contrast.
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Questions

• What is the diagnosis?
• What is the probable etiology?
• What is the course and what are the possible
  complications? (One complication is pictured in
  slide 7.4).

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CASE 7 Acute Pancreatitis

• What is the diagnosis? This is acute
  pancreatitis.
• What is the probable etiology? Probably
  gallstones were the cause, since these were seen
  on x-ray, and there is no history of alcoholism.
  Less common causes for acute pancreatitis include
  hypertriglyceridemia, trauma, viral infections,
  and drugs.
• What is the course and what are the possible
  complications? (One complication is pictured in
  slide 7.4). Acute pancreatitis is a medical
  emergency, and patients can die from it. It often
  resolves without sequelae. With chronic
  pancreatitis, pancreatic pseudocysts can develop
  (as shown in slide 7.4). Repeated bouts of acute
  pancreatitis can lead to chronic pancreatitis.
  Severe chronic pancreatitis often has an etiology
  of alcoholism. Loss of enough pancreas so that
  islets as well as acinar parenchyma are destroyed
  is not common, so diabetes mellitus is a rare
  complication.

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CASE 8

• Clinical History
• A 40 year old woman was told that she had
  "hepatitis" when she recently tried to donate
  blood. She is asymptomatic and denies intravenous
  drug abuse or any known exposure to individuals
  with hepatitis. On laboratory testing, the
  hepatitis C antibody test is positive, and her
  serum is positive for hepatitis C viral RNA by
  PCR. Her hepatitis A IgG and IgM are negative.
  Tests for hepatitis B are negative. A liver
  biopsy is performed.

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Slide 8.1The low power appearance of the liver
is shown here. How has the architecture been
altered?
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Slide 8.2The medium power appearance of the
liver is seen here.
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Slide 8.3The high power microscopic appearance
of the liver is seen here.
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Questions

• What is the microscopic appearance?
• In the old nomenclature of chronic hepatitis,
  what would this be?
• What are risk factors for her disease?
• What are complications of this disease?

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CASE 8 Hepatitis C Infection with Chronic
Hepatitis

• What is the microscopic appearance? Hepatitis.
  Slide 8.1 shows a high stage with extensive
  fibrosis and progression to macronodular
  cirrhosis, as evidenced by the large regenerative
  nodule. In slides 8.2 through 8.3 extensive
  inflammation are prominent, and there is some
  steatosis as well (steatosis is not a usual
  feature of hepatitis B).
• What is the significance of these findings? The
  extent of the liver injury suggests a high stage
  (fibrosis progressing to cirrhosis) and high
  grade (significant inflammation). The older
  terminology with chronic persistent hepatitis
  (CPH) and chronic active hepatitis (CAH) have
  largely been abandoned. We now ascribe an
  etiology for the liver disease and then grade
  (degree of inflammation) and stage (degree of
  fibrosis) on a scale of 1 to 4. A lower grade
  and stage with hepatitis B suggest that
  progression to cirrhosis is less likely. However,
  even mild changes with hepatitis C do not
  guarantee that cirrhosis will not occur. The
  presence of hepatitis C antibody is not
  protective either.
• What are risk factors for her disease? In many
  cases (a third to a half) there is no obvious
  risk factor. Risk factors in some cases of
  hepatitis C and are the same as those for
  hepatitis B, because both are spread
  parenterally. Unlike hepatitis B, there is
  usually no acute episode associated with
  hepatitis C, and there is a greater tendency for
  hepatitis C to become chronic.
• What are complications of this disease? In about
  85 of patients, hepatitis C goes on to chronic
  liver disease. About 15 of cases resolve.
  Fulminant hepatitis is quite rare. The fibrosis
  can proceed to a macronodular cirrhosis. In this
  setting, the risk for hepatocellular carcinoma is
  increased.

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CASE 9

• Clinical History
• A 45 year old male has become increasingly short
  of breath over the past year. He has also noted a
  darker color to his skin, even though he has a
  job in a bank and does not go out in the sun
  much. He has worsening joint pain, but no joint
  deformity. His physician notes a firm liver edge
  on physical examination, but no abdominal pain or
  masses. A stool guaiac is negative. Laboratory
  findings include sodium 148 mmol/L, potassium
  4.2 mmol/L, chloride 97 mmol/L, CO2 24 mmol/L,
  urea nitrogen 19 mg/dL, creatinine 1.2 mg/dL,
  glucose 178 mg/dL, total protein 5.9 g/dL,
  albumin 3.4 g/dL, alkaline phosphatase 30 U/L,
  AST 43 U/L, ALT 40 U/L, and total bilirubin 0.8
  mg/dL. The gross appearance of organs of a
  patient at autopsy with the same underlying
  condition are shown in Slide 9.1.

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Slide 9.1The gross appearance of the liver,
pancreas, and lymph nodes are shown here.
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Slide 9.2A liver biopsy is shown here with HE
stain. What has accumulated in the hepatocytes?
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Slide 9.3The liver biopsy is shown here with a
special stain. What is it?
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Slide 9.4Many persons as they age accumulate
more of the pigment shown here. What is it?
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Slide 9.5The appearance of this particular
pigment is abnormal. What is it?
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Slide 9.6What complication has developed in this
liver?
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Questions

• What underlying condition do you suspect?
• What laboratory test finding in his history given
  above is most significant?
• What other laboratory test on his serum would be
  abnormal?
• What special stain would you perform on a liver
  biopsy?
• What other pigments could be present in liver?

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More Questions

• What complication will develop in the liver if he
  is untreated?
• Describe the pathologic findings that you expect
  to be present in this patient.
• What diseases may produce the gross and
  microscopic findings in the liver as seen in this
  case?

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CASE 9 Hemochromatosis

• What underlying condition do you suspect? The
  dark brown color of the organs in Slide 9.1
  suggests excessive iron deposition--hemochromatosi
  s
• What laboratory test finding in his history given
  above is most signficant? The elevated serum
  glucose is consistent with diabetes mellitus.
• What other laboratory test on his serum would be
  abnormal? The serum ferritin is a measure of iron
  stores. This patient's serum ferritin was 7800
  ng/mL (normal 7 - 340).
• What special stain would you perform on a liver
  biopsy? Slide 9.2 demonstrates brown, granular
  pigment in the hepatocytes consistent with
  hemosiderin, and this is confirmed with the iron
  stain in Slide 9.3 (Perl's iron stain, with
  Prussian blue reaction).
• What other pigments could be present in liver?
  Slide 9.4 demonstates light brownish-yellow
  lipochrome (lipofuscin) pigment, which is a
  "wear-and-tear" pigment that accumulates with
  aging, but it has no pathologic effect on liver
  function. Slide 9.5 demonstrates cholestasis with
  bile pigment distending small bile ducts and
  canaliculi this is abnormal. In parts of the
  world where malaria is endemic, brown to black
  malarial pigment, seen as small grains, may
  collect in liver, particularly in Kupffer cells.

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CASE 9 Hemochromatosis

• What complication will develop in the liver if he
  is untreated? There is extensive bridging portal
  fibrosis with nodular regeneration seen in Slide
  9.6 (also with iron stain). The pattern of
  cirrhosis with hemochromatosis is typically
  micronodular.
• Describe the pathologic findings that you expect
  to be present in this patient. The iron
  deposition can occur in many tissues. However,
  some organs are affected more than others. Iron
  accumulation in the heart leads to an
  infiltrative cardiomyopathy, which explains the
  heart failure in this case. Pancreatic iron
  deposition leads to "bronze diabetes" and
  explains the hyperglycemia in this case. Patients
  may also have polyarthritis. Of course, the
  hepatic hemochromatosis leads to cirrhosis and
  liver failure. Deposition of iron in skin
  produces the darker pigmentation noticed in
  light-skinned persons.
• What diseases may produce the gross and
  microscopic findings in the liver as seen in this
  case? Persons with anemia from ineffective
  erythropoiesis that can be seen with thalassemias
  can absorb excessive iron. Persons with
  refractory anemias requiring chronic transfusion
  therapy will also accumulate excessive iron.
• This patient has hereditary hemochromatosis. It
  is inherited as an autosomal recessive trait, and
  the HFE gene is closely linked to the HLA locus
  on chromosome 6. HFE is homologous to class I MHC
  molecules. Genetic studies suggest that this
  mutation arose in a Celtic population in Europe
  60 to 70 generations ago. A single mutation, a
  substitution of cystine to tyrosine at amino acid
  282, is responsible for most cases. Treatment is
  removal of iron by phlebotomy. Family members
  also need to be screened to identify affected
  members before tissue damage develops.

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CASE 10

• Clinical History
• A 56 year old woman has a routine physical
  examination performed by her physician, and the
  only abnormal finding is a positive stool occult
  blood test. She is referred to a
  gastroenterologist for a colonoscopy. Laboratory
  findings include a CBC that shows WBC count
  7760/uL, Hgb 12.1 g/dL, Hct 35.2, MCV 84 fL, and
  platelet count 209,000/uL. Following colonoscopy
  with biopsy, a laparotomy with segmental
  resection of the colon is performed.

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Slide 10.1These views on colonoscopy demonstrate
a large mass with an irregular, eroded surface.
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Slide 10.2Though a barium enema is not often
performed and not needed along with colonoscopy,
this example demonstrates the "napkin ring"
encirclement of the bowel by the lesion.
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Slide 10.3This abdominal CT scan illustrates the
appearance of the lesion. No other lesions are
noted.
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Slide 10.4This is the gross appearance of the
lesion following laparotomy and segmental
resection of the colon.
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Slide 10.5The low power microscopice appearance
of the lesion is seen here as it interfaces with
normal colonic mucosa at the left.
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Slide 10.6The nature of the lesion is
illustrated at high magnification. Note that it
resembles colonic glands, but that there is
crowding and stratification of the hyperchromatic
and pleomorphic nuclei.
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Questions

• What is your diagnosis?
• What do the laboratory test findings in this
  history suggest?
• If the lesion extends into the pericolonic fat,
  what is the Duke's stage?
• Is there a genetic basis for this condition?

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CASE 10 Colonic adenocarcinoma

• What is your diagnosis? Adenocarcinoma of the
  colon, moderately differentiated.
• What do the laboratory test findings in this
  history suggest? She has an iron deficiency
  anemia from chronic blood loss as a result of
  bleeding from the adenocarcinoma.
• If the lesion extends into the pericolonic fat,
  what is the Duke's stage? This is Duke's stage B.
  If the lesion were confined to the wall of the
  bowel, then it would be stage A. If lymph node
  metastases were present, it would be stage C.
• Is there a genetic basis for this condition? At
  her age, such a lesion is unlikely to be an
  inherited genetic disorder such as familial
  polyposis with the APC gene or hereditary
  non-polyposis colon carcinoma (HNPCC). However,
  even sporadic colon carcinomas contain mutations
  that have collected over years as there is a
  progression from normal mucosa to adenoma to
  carcinoma. Such "hits" can include APC (a tumor
  suppressor gene), abnormal mismatch repair genes
  (exhibiting microsatellite instability), k-ras
  (an oncogene), and p53 (a tumor suppressor gene)

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Remember this one!
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• Can you believe it?
• This is Pathology Case Study 17 of 17
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  rotations to go!
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  in the coming year and in your future career!
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