Part I Answers for GI I laboratory, 2/21/2001
1 Stomach (slide 9) LP Chronic gastric ulcer: gastric wall with ulcer base showing all four layers of chronic ulcer.
2 Stomach (slide 9) MP Same.
3 Stomach Gross Benign chronic gastric ulcer: note sharp margins, flat relatively clean ulcer base and folds that radiate from the ulcer margin, location on the lesser curvature in the antrum at the fundopyloric junctional mucosa (precepitous proximal and sloping distal border not clearly seen).
4 Stomach Gross Penetrating gastric carcinoma: note nodularity of the base and the thickened nodular or rolled margins and that the rugae or folds do not radiate to the edge of the ulcer in most areas.
5 Stomach, gross: Multiple acute peptic ulcers: multiple, small black ulcers located in the body and fundus.
QUESTIONS, SLIDE 9:
1. What is the pathogenesis of chronic peptic ulcers?
Acid-peptic digestion of the alimentary tract is the immediate cause (no acid-no ulcer). However, there are many factors that interact either to stimulate secretion of acid such as endocrine (gastrin), neural (vagus n), or paracrine (histamine), that decrease the normal cellular defenses such as NSAIDs and H. pylori, that change gastric motility or blood flow to increase the susceptibility of the stomach or duodenum to ulcer, or that decrease bicarbonate (in duodenal ulcer patients). There is increased susceptibility of junctional mucosa (particulary fundopyloric, and pyloroduodenal).
2. What is the typical pathologic anatomy of chronic peptic ulcer?
GU--lesser curvature and antrum, DU-- within 2 cm of pylorus
1-2 cm in diameter, usually single
GU--precipitous proximal border and sloping distal border with radial converging rugae
Fused muscularis mucosae with muscularis propria
Layers:
Granular debris and fibrinopurulent exudate
Fibrinoid necrosis
Granulation tissue
Dense fibrous tissue
3. Compare the differences between a duodenal ulcer and gastric ulcer.
4. What are the typical clinical features of a chronic peptic ulcer?
Major symptom is pain. Intermittent gnawing or burning epigastric pain 1-4 hours after eating relieved by food or antacids.
5. What are some complications of chronic peptic ulcer?
hemorrhage 25%, perforation 10%, pyloric obstruction 10%, or from therapy such as alkalosis, stomal ulcer, or dumping syndrome.
6. How are acute peptic ulcers different from chronic peptic ulcers?
If involve only mucosa then is called and erosion or if penetrate through muscularis mucosa to submucosa then is called an ulcer. Multiple, shallow, more frequent in fundus. May occur as linear erosions in esophagus just above cardia. Causes are different (although acid is required) and include shock, steroids, and Curlings (burns), Cushing's (brain diseases), esophageal ulcers require reflux. Necrosis and hyperemia with slight acute inflammation in base and heal without scarring. May bleed and rarely perforate, may cause epigastric pain. NOT A PRECURSOR TO CHRONIC PEPTIC ULCERS.
SLIDE 116, STOMACH, DIFFUSE INFILTRATING ADENOCARCINOMA (LINITIS PLASTICA)
7 Stomach (slide 116) LP Linitis Plastica: mucosa showing the normal glands spread apart and not reaching the muscularis mucosa.
8 Stomach (slide 116) HP Many signet ring cells (individual malignant glandular cells) in mucosa replacing the normal mucosa. Note the few benign glands present and how benign appearing the individual malignant cells appear.
9 Stomach (slide 116) LP Focus where carcinoma infiltrates as cords of cells (remember epithelial cells usually show cohesion, such as these foci. But in linitis plastica, the poorly differentiated carcinoma tends to infiltrate as individual cells).
10 Stomach (slide 116) HP Same as 9. 11 Stomach Gross Linitis plastica or diffusely infiltrating carcinoma, note leather bottle appearance.
11 Stomach, Gross: Linitis plastica or diffusely infiltrating carcinoma, note leather bottle appearance.
CLINICAL HISTORY: A 75 year old man was admitted for workup of an unexplained 25 pound weight loss. Physical examination revealed a cachectic man. Radiographic examination revealed a greatly thickened stomach wall with loss of normal motility. At laparoscopy the stomach was found to be diffusely thickened, stiff and relatively inflexible- the classic "leather bottle" appearance.
GROSS: The wall of the stomach measured over a centimeter in thickness and was very firm. No definite nodules were identified, but the mucosa was diffusely thickened and focally hemorrhagic. On cut section the layers of the gastric wall were indistinct.
MICROSCOPIC:
SCAN AND LOW POWER: Begin at the mucosa and notice that it is thickened and that the architecture of the normal mucosa is disrupted, especially in the lower half of the mucosa. Then normal glands are spread apart or are completely replaced by relatively small cells. The thickened submucosa is fibrotic and contains too many nuclei. The muscularis propria is also thickened and has irregular bands of fibrous tissue which also contain too many nuclei.
MEDIUM AND HIGH POWER: Examine the mucosa and notice that the tumor cells disrupting the normal glands have their nuclei pushed to one side by foamy or granular pale pink cytoplasm. The nuclei of many of these signet ring cells is only slightly larger than the nuclei of the numerous lymphocytes and plasma cells that are also present. Similar cells are found scattered in the fibrotic submucosa and the fibrous reaction in the muscularis propria. In some areas, the tumor cells form cords or tiny clusters indicating their epithelial nature. In some areas the nuclei are somewhat larger with clumping and clearing of the chromatin and an irregular nuclear membrane with thickening and thinning indicating malignancy. However, in much of the tumor the cells are very difficult to differentiate from macrophages. These cells are secreting mucin which makes their cytoplasm foamy and would stain positively with a mucicarmine stain which can aid in the diagnosis in difficult cases.
QUESTIONS, SLIDE 116:
1. How are ulcers related to gastric carcinoma?
DU ulcers and acute peptic ulcer are not related.
Probably < 1% of chronic GU become malignant
2. What are factors with a strong relationship to gastric carcinoma?
1. Severe chronic atrophic gastritis with intestinal metaplasia
2. Pernicious anemia (chronic atrophic gastritis occurs).
3. H. pylori may be associated in some cases.
4. Environmental factors are important
Gastric carcinoma is the most common fatal cancer worldwide, but has been decreasing in incidence in the U. S.
3. What histologic type of carcinomas usually occur in the stomach?
Poorly differentiated adenocarcinoma. Grossly the tumors may be penetrating, fungating or diffusely infiltrative (linitis plastica).
4. What is the patients prognosis?
Grim, overall 5 year survival < 10 %
SLIDE 117, APPENDIX, CARCINOID TUMOR
13 Appendix (slide 117) LP Carcinoid tumor: Mucosa replaced by rosettes and nests of tumor.
14 Appendix (slide 117) HP Carcinoid tumor: note rosettes, solid cords, uniformity of cells and lack of mitoses.
15 Appendix (slide 117), Gross, Carcinoid: yellowish-white tumor replacing mucosa and filling lumen. Note rim of gray-white muscularis propria.
CLINICAL HISTORY:
This 28 year old Harvard anthropologist had an unilateral salpingo-oophorectomy for ovarian torsion and had an incidental appendectomy.
GROSS: The appendix was unremarkable externally and on sectioning the mucosa was somewhat thickened and yellowish-tan in the distal tip.
MICROSCOPIC:
SCAN AND LOW POWER: The mucosa has been completely effaced by a tumor composed of rosettes, nests, and cords or ribbons and festoons of dark blue cells.
MEDIUM AND HIGH POWER: Notice the monotony of the tumor cells which have uniform hyperchromatic, oval to round nuclei and modest amounts of cytoplasm. The cells either cluster together in cords, nests or form rosettes. Notice the lack of mitoses.
Clinical correlation: Carcinoid tumors are frequently incidental findings in appendices removed for either acute appendicitis or as an incidental procedure.
Questions slide 117:
1. Where do most carcinoids occur?
60-80% are found in the appendix or terminal ileum, but they can be found in any site of GI tract from the esophagus on down and in many other organs such as lung, biliary tract, ovary and pancreas.
2. What cell type do carcinoid tumors arise from?
Progenitor cells that develop features of argentaffin cells (neuroendocrine cells).
3. Is this patient likely to have metastases?
No. Most carcinoid tumors of the appendix are small (as was this one) and rarely metastasize.
Small intestinal tumors < 1 cm rarely metastasize, 1-2 cm, 50% mets, and > 2 cm 80% metastasize.
4. Is this patient likely to have carcinoid syndrome?
No. Since carcinoid syndrome is generally found in patients who have widespread metastatic lesions usually including liver, carcinoids of the appendix rarely cause the syndrome. Carcinoid syndrome results from peptides or biogenic amines secreted by tumor such as serotonin and kallikrein which the liver inactivates from abdominal carcinoids which drain into the portal system. When there are extensive metastases to the liver or lung the secretory products can get into the circulation via hepatic vein branches without being inactivated. Carcinoid syndrome is most commonly associated with small intestinal carcinoids (18%).
Carcinoid syndrome includes cutaneous flushing, diarrhea, bronchospasm, brawny edema of lower limbs, personality changes, subendocardial fibrosis, and may terminate with right-sided CHF.
Diagnosed by increased levels of 5-hydroxyindolactetic acid in the 24 hour urine.
SLIDE 75, PAROTID, BENIGN MIXED TUMOR, PLEOMORPHIC ADENOMA
22 Parotid (slide 75), LP: Benign mixed tumor or pleomorphic adenoma, note variability, stroma and glands.
23 Parotid (slide 75), MP: Glands and cords of epithelial cells, spindle shaped myoepithelial cells, and stroma.
24 Parotid, Gross: Benign mixed tumor or pleomorphic adenoma. Note well circumscribed appearance, and remember pseudopodia of tumor extend into surrounding parenchyma.
CLINICAL HISTORY: A 47 year old woman saw her physician for a slowly enlarging, nonpainful mass in front of her left ear. She was not sure how long it had been present, but she had first noticed it 4 months earlier. On examination the mass was firm and easily movable. The mass was surgically removed.
GROSS: The tumor was rubbery, roughly spherical and appeared grossly to be well circumscribed. The cut surface was grayish white with small grayish blue translucent foci.
MICROSCOPIC:
SCAN AND LOW POWER: Notice the normal parotid gland consisting of serous acini with adipose tissue intermixed. Notice that the gland appears well circumscribed in most areas, but that a few small fingers or foci of the tumor extend irregularly beyond the circumscribed bulk of the tumor. Notice the presence of both epithelial and mesenchymal elements. Notice that some areas of the tumor is very blue and amorphous with few cells (myxoid), while the paler blue areas contain more evenly distributed cells within lacunae (cartilaginous). Notice that cords, tubules (epithelial component), and individual stellate and fusiform cells (myoepithelial cells) are scattered irregularly throughout the tumor.
MEDIUM AND HIGH POWER: Examine the very blue myxoid areas and the cartilaginous areas under higher magnification. Also examine the epithelial cords and tubules and the myoepithelial cells. Notice the lack of mitoses.
Questions, slide 75:
1. Is this tumor common and where are most of them found?
Commonest salivary gland tumor, 75% of all salivary gland tumors. 80% occur in the parotid (superficial part).
2. Do these tumors become malignant?
Yes, rarely in long standing tumors. Clinically is sudden enlargement in a tumor which has been present for many years.
3. What is the treatment of choice in these neoplasms?
Complete excision with a surrounding rim of normal salivary gland. Otherwise recurrence is common because of the pseudopods of tumor which extend beyond the pseudocapsule seen grossly. If recurs is very difficult to treat.