Path: GI Tumors

Question 1

What are some of the genetic events in the development of epithelial tumors of the colon?

Answer 1

Inherited or early acquired APC/HNPCC gene mutation
Methylation of DNA
Activation of KRAS
Loss of DCC
Loss of p53

Question 2

Describe histological progression of adenocarcinoma of colon

Answer 2

Normal==>Adenomatous poly (low grade to high grade)==>Carcinoma

Question 3

Describe histological features of adenocarcinoma of colon (4)

Answer 3

Large cigar shaped nuclei
Less cytoplasm
Picket fence, high located nuclei
Nuclear overlap

Question 4

What are the polyp types that can progress to invasive carcinoma? (6)

Answer 4

Adenomatous
Sessile serrated
Familial adenomatous polyposis (FAP)
HNPCC
Peutz Jeghers polyps
Juvenile polyps

Question 5

What is the difference between hyperplasic polyps and sessile serrated adenomas?

Answer 5

Hyperplasic polyps: Left-sided, benign

Sessile serrated: Right sided, associated with tumor development via BRAF changes

Question 6

Describe histological appearance of hyperplasia polyps

Answer 6

Serrated (saw-tooth) surface epithelium involving 2/3 of luminal part of crypt
Basal portion shows normal crypt base

Question 7

Describe the histological appearance of sessile serrated adenoma

Answer 7

Serrated surface epithelium involving entire crypt

Crypt base is dilated without dysplastic epithelium

Question 8

What are mutations of sessile serrated adenomas that lead to invasive adenocarcinoma? (5)

Answer 8

DNA methylation (92%)
BRAF (80%)
APC/KRAS (

Question 9

Familial Adenomatous Polyposis: Describe genetics and risk for carcinoma

Answer 9

Autosomal dominant disease due to mutation in APC gene on 5q21

Results in 100-2500 polyps throughout GI tract with 100% risk of carcinoma in 3rd decade

Question 10

What is Lynch Syndrome? (HNPCC)

Answer 10

Autosomal dominant disorder of DNA mismatch repair genes

Increases risk of GI and non-GI cancers but has lower #polyps than FAP

Question 11

Describe Peutz Jeghers syndrome:
What kind of polyps occur?
What is the loci of mutation and what additional mutations occur in carcinogenesis?

Answer 11

Hamartomatous polyps that occur throughout GI tract

Hamartoma formation is due to somatic loss of 19p13 allele. Dysplasia and carcinoma arise in these hamartomas through the acquisition of genetic alterations in TP53/ß-Catenin

Question 12

What is a sign of Peutz Seghers syndrome?

Answer 12

Pigmentation of lips

Question 13

Describe histological appearance of a Peutz Jegher polyp

Answer 13

Arborizing smooth muscle fibers
Lobulated intestinal glands
Hamartomatous architecture

Question 14

What is risk of developing cancer from Peutz Jeghers Syndrome? IS it limited to just colon cancer?

Answer 14

53% of PJS patients develop noncutaneous cancers
50% colon cancer
Also sertoli cell tumor, sex cord stromal tumor

Question 15

Describe gross appearance of a juvenile polyp

Answer 15

Large hemorrhagic polyp with cystic cut surface

Question 16

Describe the histological appearance of a juvenile polyp

Answer 16

Large cysts lined by intestinal glands
Inflammatory cells in lamina propria between glands
If dysplasia: nuclear overlap, decrease in cytoplasm, nuclear pleomorphism

Question 17

Describe pattern of an invasive carcinoma on imaging

Answer 17

“Apple core lesion”==>Stenotic area

Question 18

What are important factors for pathologic evaluation of colon cancer? (3)

Answer 18

TNM grading
Histological grading (well differentiated or poorly?)
Tumor margins

Question 19

Describe the epidemiology of GI neuroendocrine tumors:

Incidence, location

Answer 19

Rare; annual incidence of 1-2/100k
2% of all GI tumors
Appendix>ileum, rectum
Appendix and rectum behave mostly benign

Question 20

Describe heritable associations with pathogenesis of neuroendocrine tumors: (4)

Answer 20

MEN-1
ZE-syndrome
NF1
FAP

Question 21

Describe the epidemiology of appendiceal neuroendocrine tumors: Prevalence, age, sex, size

Answer 21

1/3 of GI NETs
Average age ~20yr younger than for other NETs
Women>M
Majority localized to appendix and are small

Question 22

Describe the histological appearance of neuroendocrine tumors

Answer 22

“Jigsaw appearance”
Densely packed cells in nests with salt/pepper appearance
NO pleomorphism or overlap

Question 23

IHC Stain of neuroendocrine cells

Answer 23

Ki-67

Chromagranin

Question 24

What are factors for predicting outcome of neuroendocrine tumors? (4)

Answer 24

Size of tumor
Depth of invasion
Proliferative activity (mitoses/Ki-67)
Location

Question 25

What is histological appearance of GIST?

Answer 25

“school of fish” – wavy spindle cells with irregular pleomorphic nuclei

Question 26

What are mutations of GIST?

Answer 26

Kit (85%)

PDGFRA (10%)

Question 27

Where are GISTs observed?

Answer 27

All parts of GI tract, but majority in stomach (60-70%) with some in small intestine (25-35%)

Question 28

How do you differentiate between malignant/benign GIST? (3)

Answer 28

Malignant:
>5 mitoses
>5cm
Necrosis

Question 29

How does gross mucinous cystic neoplasm appear in appendix?

Answer 29

Dilated tip with mucin-filled lumen

Question 30

Describe histological appearance of mucinous cystic neoplasms:

Answer 30

Adenoma or carcinomatous epithelium with diffuse proliferation (not a polyp)

Question 31

What is abdominal mutinous carcinomatosis? What does it lead to?

Answer 31

Presence of mucin-producing adenoacarcinoma in abdominal cavity– leads to pseudomyxoma peritonei (presence of mucin in abdominal cavity)

Question 32

What are the types of malignant tumors of the rectum/anus? (4)

Answer 32

Adenoacarcinoma
Leiomyosarcoma
Lymphoma
Anal canal squamous cell carcinoma

Question 33

What are the transitions in the histology of the anal canal that are associated with the development of squamous cell carcinoma?

Answer 33

Viral changes related to HPV lead to increasing dysplasia and eventually carcinoma

Question 34

What is most common presentation for small bowel adenoma?

Answer 34

Ampulla of Vater