INSTRUCTORS ONLY

GI Path Lab 3: Part I

Areas of Concentration

• Adenomas of the colon and rectum

• Carcinomas of the colon and rectum

• The adenoma-carcinoma sequence in the colorectum

• Carcinoid (endocrine or neuroendocrine) tumors of the bowel

• Anal neoplasms

• Polyps of the gut, the colon being the most common site

Upon completion of this exercise, you should be able to:

1. Recognize the entire spectrum of colorectal dysplasias, from the lowest grade that closely caricatures normal to the highest grade that is equivalent to carcinomatous epithelium.

2. Understand the adenoma-carcinoma sequence and how it serves as a model for other dysplasia-carcinoma sequences throughout the gut.

3. Recognize carcinoid tumors of the gut and how they differ from both adenomas and carcinomas.

Slide 90 [WebScope] [ImageScope] and
Slide 91 [WebScope] [ImageScope]

Colonic Adenomas in Familial Adenomatous Polyposis (FAP) and Colonic Carcinoma

In both of these slides, there is neoplastic epithelium that lines tubular structures. First, check the normal crypt epithelium to see what it looks like. It has many goblet cells alternating with squeezed columnar cells, and the nuclei of both cell types are small, uniform, and located at the base of the cells. In contrast, the neoplastic epithelium is different. In Slide 90, from a patient with familial adenomatous polyposis, there are many adenomas of different sizes within the mucosa. In the adenomas, the epithelium tends to be more uniform than in the carcinoma, but both types of epithelium have neoplastic (dysplastic) features. The nuclei are crowded, hyperchromatic, stratified, and take up a greater portion of the cell than they do in normal colonic epithelium. Since there is plenty of normal mucosa for comparison, these differences should be readily apparent. Notice also that the adenomatous epithelium tends to be located near the mucosal surface, with much less adenomatous epithelium appearing toward the base of the mucosa. Most of the adenomatous epithelial cells are tall columnar cells with no obvious differentiation, although there are also scattered dysplastic goblet cells and Paneth cells. The adenomatous tubules are generally uniform. In contrast, the carcinomatous epithelium lines tubules, but make little attempt at uniformity. There is greater stratification of their nuclei, mitotic figures are found readily, and in some places, clusters and strands of undifferentiated epithelial cells invade the stroma. These two slides, therefore, offer excellent comparisons between what pathologists refer to as adenomatous or benign neoplastic or low-grade dysplastic epithelium and carcinomatous or malignant neoplastic or highest grade dysplastic epithelium. It is epithelium of the type in Slide 90 that is considered to be the precursor of the epithelium in Slide 91. In fact, if you carefully examine Slide 91, you will find areas in which the epithelium begins to look more and more like that in Slide 90 with more uniform tubules, less nuclear stratification, and even a few goblet cells. Some adenomas are composed of one or two tubules lined by dysplastic epithelium that closely caricatures normal crypt epithelium. See if you can find them.

1. What are the genetic differences between the two major forms of inherited colorectal cancer?

2. What adenomas are most at risk to develop carcinomatous foci?

3. What is the likelihood that you will develop a colonic adenoma during your lifetime?

4. If you develop such an adenoma, what is the likelihood that it will evolve into a carcinoma?

Slide 199 [WebScope] [ImageScope]

Metastatic Colorectal Carcinoma in Liver

In this slide of liver, there are several separate masses of carcinoma.

1. What type of carcinoma is this? How do you know?

2. What are the usual sites of metastases of colorectal carcinoma?

3. When colorectal carcinoma metastasizes to the liver, is there any treatment for the metastases?

4. What is the differential diagnosis for this type of carcinoma when it occurs in the liver?

Slide 89 [WebScope] [ImageScope]

Small Intestine: Carcinoid Tumor
(Well-Differentiated Endocrine Neoplasm)

This is a typical gastrointestinal tract tumor of endocrine cells composed of nests and cords of uniform cells that look like they could have come from the islets of Langerhans or the pituitary or the parathyroid. They extend from the base of the mucosa through the wall into the mesenteric adipose tissue. These nests are surrounded by very dense collagenized (desmoplastic) stroma that is most impressive in the mesentery. Notice that the bowel is kinked at this point, as a result of the desmoplasia. The most common site of such gastrointestinal endocrine tumors is the appendix where they are usually incidental findings and do not cause any trouble. In the small intestine, the second most common site, they are likely to grow larger, produce symptoms, and even metastasize.

1. What symptoms might this tumor have produced if it were chemically active?

2. What might it have produced if it were chemically inactive?

3. Notice that some of the nests of tumor appear to be in lymphatic spaces. What does this suggest that the most common site of metastasis is likely to be?

The answers to the path lab questions will be posted approximately 48-72 hours after the lab sessions. These are abbreviated answers, not a full discussion of the topics. You can find them in the M2 CTools site resources. In the folder for each sequence the will be a folder called 'Path Lab Resources'