Path: GI Tumors Flashcards
What are some of the genetic events in the development of epithelial tumors of the colon?
Inherited or early acquired APC/HNPCC gene mutation Methylation of DNA Activation of KRAS Loss of DCC Loss of p53
Describe histological progression of adenocarcinoma of colon
Normal==>Adenomatous poly (low grade to high grade)==>Carcinoma
Describe histological features of adenocarcinoma of colon (4)
Large cigar shaped nuclei
Less cytoplasm
Picket fence, high located nuclei
Nuclear overlap
What are the polyp types that can progress to invasive carcinoma? (6)
Adenomatous Sessile serrated Familial adenomatous polyposis (FAP) HNPCC Peutz Jeghers polyps Juvenile polyps
What is the difference between hyperplasic polyps and sessile serrated adenomas?
Hyperplasic polyps: Left-sided, benign
Sessile serrated: Right sided, associated with tumor development via BRAF changes
Describe histological appearance of hyperplasia polyps
Serrated (saw-tooth) surface epithelium involving 2/3 of luminal part of crypt
Basal portion shows normal crypt base
Describe the histological appearance of sessile serrated adenoma
Serrated surface epithelium involving entire crypt
Crypt base is dilated without dysplastic epithelium
What are mutations of sessile serrated adenomas that lead to invasive adenocarcinoma? (5)
DNA methylation (92%)
BRAF (80%)
APC/KRAS (
Familial Adenomatous Polyposis: Describe genetics and risk for carcinoma
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
What is Lynch Syndrome? (HNPCC)
Autosomal dominant disorder of DNA mismatch repair genes
Increases risk of GI and non-GI cancers but has lower #polyps than FAP
Describe Peutz Jeghers syndrome:
What kind of polyps occur?
What is the loci of mutation and what additional mutations occur in carcinogenesis?
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
What is a sign of Peutz Seghers syndrome?
Pigmentation of lips
Describe histological appearance of a Peutz Jegher polyp
Arborizing smooth muscle fibers
Lobulated intestinal glands
Hamartomatous architecture
What is risk of developing cancer from Peutz Jeghers Syndrome? IS it limited to just colon cancer?
53% of PJS patients develop noncutaneous cancers
50% colon cancer
Also sertoli cell tumor, sex cord stromal tumor
Describe gross appearance of a juvenile polyp
Large hemorrhagic polyp with cystic cut surface
Describe the histological appearance of a juvenile polyp
Large cysts lined by intestinal glands
Inflammatory cells in lamina propria between glands
If dysplasia: nuclear overlap, decrease in cytoplasm, nuclear pleomorphism
Describe pattern of an invasive carcinoma on imaging
“Apple core lesion”==>Stenotic area
What are important factors for pathologic evaluation of colon cancer? (3)
TNM grading
Histological grading (well differentiated or poorly?)
Tumor margins
Describe the epidemiology of GI neuroendocrine tumors:
Incidence, location
Rare; annual incidence of 1-2/100k
2% of all GI tumors
Appendix>ileum, rectum
Appendix and rectum behave mostly benign
Describe heritable associations with pathogenesis of neuroendocrine tumors: (4)
MEN-1
ZE-syndrome
NF1
FAP
Describe the epidemiology of appendiceal neuroendocrine tumors: Prevalence, age, sex, size
1/3 of GI NETs
Average age ~20yr younger than for other NETs
Women>M
Majority localized to appendix and are small
Describe the histological appearance of neuroendocrine tumors
“Jigsaw appearance”
Densely packed cells in nests with salt/pepper appearance
NO pleomorphism or overlap
IHC Stain of neuroendocrine cells
Ki-67
Chromagranin
What are factors for predicting outcome of neuroendocrine tumors? (4)
Size of tumor
Depth of invasion
Proliferative activity (mitoses/Ki-67)
Location
What is histological appearance of GIST?
“school of fish” – wavy spindle cells with irregular pleomorphic nuclei
What are mutations of GIST?
Kit (85%)
PDGFRA (10%)
Where are GISTs observed?
All parts of GI tract, but majority in stomach (60-70%) with some in small intestine (25-35%)
How do you differentiate between malignant/benign GIST? (3)
Malignant:
>5 mitoses
>5cm
Necrosis
How does gross mucinous cystic neoplasm appear in appendix?
Dilated tip with mucin-filled lumen
Describe histological appearance of mucinous cystic neoplasms:
Adenoma or carcinomatous epithelium with diffuse proliferation (not a polyp)
What is abdominal mutinous carcinomatosis? What does it lead to?
Presence of mucin-producing adenoacarcinoma in abdominal cavity– leads to pseudomyxoma peritonei (presence of mucin in abdominal cavity)
What are the types of malignant tumors of the rectum/anus? (4)
Adenoacarcinoma
Leiomyosarcoma
Lymphoma
Anal canal squamous cell carcinoma
What are the transitions in the histology of the anal canal that are associated with the development of squamous cell carcinoma?
Viral changes related to HPV lead to increasing dysplasia and eventually carcinoma
What is most common presentation for small bowel adenoma?
Ampulla of Vater
