Gastrointestinal Pathology Case Studies Part II

1. Gastrointestinal Pathology Case Studies Part II

2. 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).

3. Slide 1.1These views on endoscopy reveal the typical friable, erythematous mucosa with diminished haustral folds.

4. 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.

5. 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.

7. Slide 1.4Microscopic examination shows diffuse mucosal ulceration, with several ulcers extending to the muscularis propria.

8. Slide 1.5At higher power, the intervening mucosa shows misshapen, distorted crypts with occasional crypt abscesses.

9. 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?

10. 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.

11. 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).

12. 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.

13. 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.

14. 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.

15. Slide 2.4Microscopically at low power, the small intestine has extensive mucosal ulceration, transmural chronic inflammation, fibrosis, and granulomas.

16. Slide 2.5Microscopically at high power, the granulomas are evident. No infectious agents can be demonstrated in these granulomas.

17. 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?

18. 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.

19. 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).

20. Slide 3.1On colonoscopy can be seen an extensive tan-green exudate over the mucosa.

21. Slide 3.2The surface of the colon shows diffuse reddening with an overlying friable tan-green exudate.

22. Slide 3.3At low power microscopically, the colon shows surface mucosal erosions with overlying fibrinopurulent exudate.

23. Slide 3.4At high power microscopically, the colon shows surface mucosal erosions with overlying fibrinopurulent exudate.

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

25. 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.

26. 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).

27. Slide 4.1The colonoscopic views of the smaller and larger polyps are seen here.

28. 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.

30. Slide 4.3Another patient with a similar disease but different gross appearance is shown here.

31. Slide 4.4Seen here microscopically at low power is one of the polyps.

32. 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.

33. 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.

34. 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.

35. 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.

36. Slide 5.1The gross appearance of another liver with this process is shown here. What is abnormal?

37. Slide 5.2The medium power appearance of the liver is shown here. How has the architecture been altered?

38. Slide 5.3The medium power appearance of the liver is seen here. What is happening to the hepatocytes (arrows)?

39. Slide 5.4The gross appearance of the liver seen here illustrates a complication of this disease process.

40. Slide 5.5The gross appearance of the liver seen here illustrates another complication of this disease process.

41. 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?

42. 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.

43. 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).

44. 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.

46. Slide 6.2There is portal fibrosis and marked macrovesicular steatosis (fatty change) at low power.

47. Slide 6.3There are nodules of regenerating hepatocytes surrounded by dense fibrous bands seen here microscopically at low power.

48. Slide 6.4At high magnification, globular eosinophilic material is seen in some hepatocytes.

49. 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?

50. 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 (<5 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.