SLIDE 2, APPENDIX, ACUTE APPENDICITIS
38 Appendix, LP: Acute appendicitis, ulceration of mucosal surface.
39 Appendix, HP: Acute appendicitis, inflammatory exudate with many neutrophils.
40 Appendix, Gross: Normal appendix on right, note shiny serosa. Acute appendicitis on left, with serosal hyperemia and fibrinopurulent exudate (friable, tan-yellow, dull).
CLINICAL HISTORY: A 16 year old girl began having periumbilical pain. By the following morning she was experiencing anorexia, nausea and vomiting and the pain was now in the right lower quadrant. Examination by her physician revealed deep tenderness at McBurney's point and a low fever. A CBC revealed a leukocytosis with a left shift. The patient was taken to surgery and the appendix was removed.
GROSS: The appendix appeared slightly swollen and there was minimal fibrinous exudate over the appendiceal tip. On cut section the mucosa was hyperemic and edematous.
MICROSOCPIC:
SCAN AND LOW POWER: Identify the normal layers of the appendix and concentrate on the mucosa. In most slides the mucosa is congested, edematous and focally ulcerated at one of the angles of the lumen.
MEDIUM AND HIGH POWER: Examine the ulcerated area and notice that the mucosa contains many neutrophils in the area of mucosal necrosis. In most slides the inflammation is limited to the mucosa or submucosa without extension through the muscularis propria. Examine the serosa to determine if there is a fibrinous exudate (amorphous or smudgy pink material on the serosal surface).
QUESTIONS:
1. What is the pathogenesis of acute appendicits?
Obstruction of the appendiceal lumen by fecaliths, kinks or structures, or lymphoid hyperplasia result in accumulation of secretions with luminal distention. This is followed by venous compression and chronic passive congestion which leads to ischemia of the mucosa that allows invasion of the mucosa by bacteria from the appendiceal lumen. This results in a vicious cycle with more vascular compromise.
2. The symptoms in this patient were classic. When would the symptoms likely to be different?
In the very young and the very old. Also if the appendix rupture the distention is relieved the the abdominal pain often lessens temporarily and is known as the "treacherous calm" of Dieulafoy.
3. What are possible complications?
Perforation and pylephlebitis
4. What would be your differential diagnosis in a patient with right lower quadrant pain?
mesenteric lymphadenitis, systemic viral infection, acute salpingitis, ectopic pregnancy, "mittelschmerz", meckel's diverticulum.
Slide 44
COLON, ADENOCARCINOMA
31 Colon (slide 44) LP Adenocarcinoma invading into muscularis propria
32 Colon LP Adenocarcinoma at junction with uninvolved mucosa. Note invasion beneath the mucosa and compare the nuclei of the carcinoma to the nuclei of the normal mucosa.
33 Colon HP Adenocarcinoma. Note cribriform pattern (glands that are back to back without intervening stroma). Also note other features of malignancy.
34 Colon Gross Adenocarcinoma with the gross napkin ring pattern or apple core pattern. Note how narrow the lumen becomes in the area of the carcinoma. The mucosa is nodular and erythematous in this region. It may be ulcerated.
CLINICAL HISTORY: A 62 year old woman who had noted weakness and a change in her bowel habits saw her physician after passing bright red blood in her stool. Rectal exam revealed no palpable mass but the stool tested positive for occult blood. A complete blood count revealed a hypochromic, microcytic anemic. A barium enema and sigmoidoscopy identified an ulcerated mass in the sigmoid colon and a biopsy confirmed the presence of adenocarcinoma.
GROSS: A 20 cm segment of colon had a constricted area at 5 cm from the distal resection margin. The bowel proximal to this segment was dilated. Opening the colon revealed an excavated, infiltrating tumor with a raised peripheral margin. The tumor measured 4 cm in greatest diameter with narrowing of the colonic lumen.
MICROSCOPIC:
SCAN AND LOW POWER: Compare the normal mucosa at either end of the colon section to the tumor. Note the glandular spaces in the tumor, and note the marked complexity of some of the glands with papillary folding or back to back glands. Also note that the tumor infiltrates through the muscularis mucosa and submucosa into the muscularis propria. Identify the fibrous tissue reaction to the tumor.
MEDIUM AND HIGH POWER: The tumor again can be seen to the composed of glands lined by tall columnar cells with enlarged hyperchromatic nuclei with occasional prominent nucleoli. Compare the size of the tumor nuclei to the normal colonic goblet cell nuclei. Mitoses are frequent in the tumor. The tumor is surrounded by fibrosis containing a scattering of lymphocytes.
Questions:
1. What lesion probably preceded this patient's carcinoma? An adenomatous polyp. The vast majority of colon carcinomas arise in preexisting neoplastic polyps. The frequency of malignant change varies with the size of polyp: < 1% in polyps < 1 cm, 10% of polyps between 1-2 cm, up to 45% of villous adenomas > 2 cm in diameter
2. Is this type of cancer common? Yes, 2nd most common visceral cancer in the U. S.
3. What etiologic factors may have been involved in this tumors development? Dietary factors such as low content of nonabsorbable vegetable fiver, high content of refined carbohydrates, and high fat content. These factors may alter bacterial flora of stool which then degrade bile salts to produce potential carcinogens which have prolonged contact with bowel mucosa because of increase transit time.
4. Where are colon carcinomas commonly found? 25% rectum, 25% sigmoid, 50% rest of colon, esp cecum and ascending colon
5. Are lymph node metastases possible in this patient? Yes. Lymph node metastases are uncommon until the carcinoma has penetrated the muscularis propria, and are common when the carcinoma reaches the serosa. Since this patients carcinoma has invaded the muscularis propria, but not reached the serosa the likelihood of lymph node metastases is somewhere in between.
6. a. How would this tumor be classified if the lymph nodes were not positive? b. If lymph nodes were positive?
c. If there were distant metastases?
a. B1, penetrates the muscularis propria, but not through it.
b. C1, B1 tumors with mets to regional lymph nodes
c. D, Distant metastases
A is when the tumor is confined to the mucosa and B2 is tumors that invade through the muscularis propria into the serosa but without lymp node or distant mets.
C2 is a B2 tumor with lymph node metastases
7. Read and understand the clinical correlation.
CLINICAL CORRELATION:
Adenocarcinoma of the colon and rectum is a very common cancer in both men and women in the United States. The symptoms depend upon the anatomical location of the lesion. In the right colon it tends to grow in a fungating fashion. The symptoms are weakness and fatigue. There is anemia and occult blood in the stools. In the left colon, tumors tend to encircle the bowel causing change in bowel habits. The presenting symptom in the sigmoid colon and rectum may be the passage of blood. The survival rate depends on the extent of local invasion and the presence of metastases. The degree of differentiation of the tumor is also important. The overall 5-year survival rate for all stages is 35-49%.
SLIDE 45, COLON, PEDUNCULATED ADENOMATOUS POLYP, MAINLY TUBULAR
29 Colon Gross Pedunculated adenomatous polyps with their narrow stalks (most likely tubular adenomas).
26 LP Colon, adenomatous polyp. Note how blue the slide appears because of the closely spaced pseudostratified, large nuclei. Some of the polyp is formed of glands and some of finger like projections or villi.
27 Same HP Shows pseudostratification of large nuclei.
28 Colon HP Stalk of polyp showing relatively normal epithelium for comparison.
CLINICAL HISTORY: A 45 year old white man was found to have guaic positive stools on a routine check up. Colonoscopy identified a polyp in the sigmoid colon which was removed.
GROSS: A 1 cm polypoid lesion with a narrow stalk was bisected for histologic evaluation.
MICROSCOPIC:
SCAN AND LOW POWER: At low power identify the normal colonic wall in which the epithelium contains numerous goblet cells. Identify the stalk that consists of mucosa and submucosa and projects above the normal mucosa to form the polyp. Notice that the polyp epithelium appears darker blue than that of the normal colonic epithelium. Most of the polyp mucosa forms tubules, but some areas of finger like stroma are covered by epithelium forming villus areas.
MEDIUM AND HIGH POWER: Compare the mucosa of the normal colon to that of the polyp. Note that the epithelial cells of the polyp have nuclei that are enlarged, crowded and in many areas appear to be pseudostratified even out to the surface of the polyp. Also notice that the number of mitoses the polyp epithelium is much higher than in the crypts of the normal epithelium.
Comment: In a few slides there is a separate focus of polyp in which the glands are back to back and epithelium in which there is marked nuclear atypia and loss of nuclear polarity indicating a focus of carcinoma. Most slides do not have this finding.
QUESTIONS:
1. Is this a neoplastic or non-neoplastic polyp? Name some non-neoplastic polyps.
Neoplastic--adenomatous polyps including both tubular adenomas and villous or papillary adenomas are neoplastic
Hyperplastic polyps which have serrated infoldings of epithelium, normal crypt configuration and nuclei at the base of the crypts
Hamartomatous polyps such as Peutz-Jegher polyps or juvenile polps.
Lymphoid polyps (focal lymphoid hyperplasia)
Pseudopolyps
2. What is the importance of adenomatous polyps?
Their relationship to colon carcinoma. The larger the polyp the more likely it is to have undergone malignant change. Up to 45% of larger bulky villous adenomas > 2 cm will have carcinomas in them.
3. What type of hereditary intestinal polyposis syndrome would have numerous polyps like the one in this slide?
Familial polyposis which is autosomal dominant. The colon becomes covered with thousands of polyps and if untreated the patients dies of carcinoma of the colon in the 3rd or 4th decade.
Gardners syndrome which is also autosomal dominant and has adenomatous polyps in colon (fewer than familial), but also in stomach and/or duodenum. Also an increased risk of colon carcinoma. Other features are osteomas of facial and skull bones, dental anomalies, fibromas lipomas, and multiple epidermoid cysts of the skin.
4. Which polyposis syndromes do not have adenomatous polyps?
Peutz-Jeghers syndrome which is autosomal dominant and has melanosis of lips, buccal mucosa and digits. The polyps are hamartomatous and rarely undergo malignant change.
Juvenile polyposis syndrome has multiple juvenile polyps involving stomach and small intestine (with or without colon involvement) composed of epithelium indigenous to the site but disorganized with cystic dilation of the glandular structure and fibroblastic stroma with inflammatory cells. Some have associated malignancies and some die at young age.
SLIDE 46, UNKNOWN CASE FOR GASTROINTESTINAL LAB
58 Small Intestine LP Crohn's disease. Thickened small intestine with chronic inflammation extending into muscularis propria.
59 Small Intestine LP Crohn's disease. Fibrosis and chronic inflammation extending into serosa (transmural inflammation). While granulomatous inflammation is not clearly identified in this case, it is often present and is a helpful histologic feature.
60 Small Intestine HP Crohn's disease. Focus showing chronic inflammation and fibrosis.
61 Small Intestine Gross Crohn's disease. Encroachment of mesenteric fat over the bowel surface.
62 Small Intestine Gross Crohn's disease. Shows segmental involvement and marked thickening of the bowel wall characteristic of Crohn's disease. Note dilatation of the proximal small intestine, secondary to obstruction from the narrowed segment, is difficult to see.
63 Small Intestine Gross Crohn's disease. Note the markedly thickened, stiff wall (garden hose appearance) that has resulted from the transmural inflammation and fibrosis. Tooth picks are required to hold the lumen open.
64 Small Intestine Gross Crohn's disease. Cross section of inflammatory mass formed of loops of small bowel fibrosed together.
CLINICAL HISTORY: The patient was a 28 year old white woman, who for the past 8 years, had recurrent episodes of diarrhea, abdominal pain, and fever. She had developed an abdominal mass and intestinal obstruction requiring partial bowel resection.
GROSS: The specimen consisted of a 20 x 15 cm mass of intestine which was tightly bound together by adhesions. The bowel was very thick and the lumen was nearly obliterated in one are leading to the obstruction. Mucosal ulceration was noted and pus oozed from loculated abscesses in the dense fibrous tissue between loops of bowel. Fat encompassed the entire circumference of the bowel.
QUESTIONS:
1. Is the organ large or small intestine and how do you know?
Villi are present, even though they are somewhat distorted. Also the muscularis propria, where it is intact, has two broad layers (the outer longitudinal layer is not aggregated into taenia).
2. What are the histologic features which are present?
There is transmural inflammation and fibrosis in all slides. The inflammatory cells are predominantly mononuclear but some eosinophils are present, and in some slides there are neutrophils in the fistula tract. The epithelium does not reveal loss of mucin. Some slides have foci of loose collections of macrophages, but no definite granulomas are present. The nerve branches are prominent.
3. What is your diagnosis and what do you base it on?
Crohn's disease, based on the gross and histology.
4. Why do you think the patient was obstructed?
Fibrous adhesions 2nd to the IBD causing kinking in the bowel loops.
5. What other lesions may cause obstruction in the colon?
Carcinomas are the most common cause. Infarcts may also cause mechanical obstruction.