Pathology 13 – Colon Cancer

Non-neoplastic polyps:
Hyperplastic polyps, juvenile polyps, inflammatory polyps, hamatomatous polyps, Peutz-Jegners polyps, lymphoid polyps

Classification of neoplastic polyps:
Arise as the result of epithelial proliferation and dysplasia, precursors of carcinoma. 5% of Americans have them, make up ~10% of epithelial polyps

Tubular/pedunculated adenomas appearance:
Mosty tubular glands, recapitulating mucosal topology, slender stalks, raspnerry-like heads, stalk covered by normal colonic mucosa, head composed of neoplastic epithelium – branching glands, tall hyperchromatic disorderly cells

Villous adenomas appearance:
Villous projections, larger, velvety cauliflower-like masses projecting above mucosa – frond-like villi form extensions of mucosa covered by dysplastic, disorderly/piled-up columnar epithelium

Tubulovillous adenomas appearance:
Mixture of tubular and villous, broad mix of tubular and villous areas

Secile serrated adenomas appearance:
Serrated epithelium lining the crypts

Prevalence of tumors:
20-30% before 40, 40-50% after 60

Factors affecting malignancy in tumors:
Maximum diameter of polyp (size), histologic architecture, severity of epithelial dysplasis

APC Pathway in Colon cancer development:
Chromosomal instability associated with stepwise accumulation of mutations in a number of oncogenes and tumor suppressor genes. Germ-line or somatic mutations of cancer suppressor genes (APC) first hit. Methylation abnormalities in activation of normal alleles second hit. Protoncogenes mutations (adenoma) K-RAS – homozygous loss of additional cancer suppressor genes, overexpression of COX-2 – additional mutations, gross chromosomal alterations (carcinoma)

Mismatch Repair Pathway in colon cancer development:
Characterized by genetic lesions in DNA mismatch repair genes. Germline or somatic mutations of mismatch repair genes – alteration of second allele by LOH, mutation or promoter methylation – microsatellite instability/mutator phenotype – sessile serrated adenoma – accumulated mutations in genes that regulate growth, differentiation and/or apoptosis – carcinoma

Clinical features colon carcinoma:
Asymptomatic for years. Coecal and R colonic: fatigue, weakness, iron deficiency anaemia. L colonic: occult bleeding, changes in bowel habit, cramp, LLQ discomfort

Gross morphology of colon carcinoma:
Proximal colon – polypoid, exophytic masses, extend along one wall of cecum and ascending colon. Distal colon: annular, encircling lesions, produce “napkin ring” contractions of bowel and narrowing of lumen. Both directly penetrate bowel wall over time and may appear as firm masses on serosal surface

Histology of colon carcinoma:
Adenocarcinomas that range from well-differentiated to undifferentiated, anaplastic masses. Many tumors produce mucin which is secreted into lumen or interstitium – facilitate extension of cancer

TNM Staging:
T0 = none evident
Tis = in situ (limited to mucosa)
T1 = invasion of lamina propria or submucosa
T2 = invasion of muscularis propria
T3 = invasion through muscularis propria into subserosa or non-peritoneal perimuscular tissue
T4 = invasion of other organs or structures
N0 = none evident
N1 = 1-3 positive pericolic nodes
N2 = 4+ positive pericolic nodes
M0 = none evident
M1 = any distant metastasis

Adenomas:
Those >50 have 1+ adenoma in GIT, 1% become malignant. Most common site in sigmoid and ascending colon

Invasive adenocarcinoma of sigmoid colon - annular obstruction with infiltration of the wall, 3 involved mesenteric nodes, partially exophytic carcinoma, craggy mass - solid, whiteish, irregular, not well encapsulated, fungating, large, completely obstructing lumen (dilation above)
Invasive adenocarcinoma of sigmoid colon – annular obstruction with infiltration of the wall, 3 involved mesenteric nodes, partially exophytic carcinoma, craggy mass – solid, whiteish, irregular, not well encapsulated, fungating, large, completely obstructing lumen (dilation above)

Histology of tumor at edge - well differentiated carcinoma, normal mucosa on right, invading malignant glands extending downwards on the left beneath the normal mucosa
Histology of tumor at edge – well differentiated carcinoma, normal mucosa on right, invading malignant glands extending downwards on the left beneath the normal mucosa

Histology of tumor deeper layers – invading adenocarcinoma with irregular glands showing hyperchromacticity, nuclear crowding and loss of polarity, mucous lakes due to glandular obstruction, serosal surface bottom left corner

Dukes Staging Classification:
A – limited to mucosa
B – penetrating the wall, negative lymph nodes (B1 partial invasion of muscularis propria, B2 total invasion of MP)
C – penetrating the wall, positive lymph nodes
D – distant metastatic spread. Metastases to liver 1st – portal circulation

Perirectal lymph node – mesenteric lymph node, invading adenocarcinoma with residual lymphoid tissue on far left, irregular glands with cytological features of malignancy in the subcapsular zone. Well differentiated adenocarcinoma of the rectum

Adenocarcinoma of Ascending Colon - usually exophytic circumferential tumor, adenomatous polyps (up middle and L), no obstruction, may present with bleedinf per rectum, fungating, cauliflower-like, malignancy extends through to the serosa. Bile salts reabsorbed in coecum, deficiency of fat-soluble vitamins
Adenocarcinoma of Ascending Colon – usually exophytic circumferential tumor, adenomatous polyps (up middle and L), no obstruction, may present with bleedinf per rectum, fungating, cauliflower-like, malignancy extends through to the serosa. Bile salts reabsorbed in coecum, deficiency of fat-soluble vitamins

Tubular adenoma - thin stalk and lobulated head, normal mucosa at base on R, dysplastic/carcinoma insitu in top centre, may become invasive should be removed
Tubular adenoma – thin stalk and lobulated head, normal mucosa at base on R, dysplastic/carcinoma insitu in top centre, may become invasive should be removed

Sessile tubular adenoma - broad stalk, normal mucosa each side, inflammation congestion, superficial ulceration, carcinoma in situ, may become invasive
Sessile tubular adenoma – broad stalk, normal mucosa each side, inflammation congestion, superficial ulceration, carcinoma in situ, may become invasive

Transverse colon - on L villous adenoma, in middle invasive carcinoma, on R tubular carcinoma
Transverse colon – on L villous adenoma, in middle invasive carcinoma, on R tubular carcinoma

Deep aspect of transvere colon tumor - poorly differentiated adenocarcinoma, penetration of the muscularis propria by poorly formed glands showing cytological features of malignancy
Deep aspect of transvere colon tumor – poorly differentiated adenocarcinoma, penetration of the muscularis propria by poorly formed glands showing cytological features of malignancy

Gross calf vessels - propagating thrombus, DVT, long, worm-like clot
Gross calf vessels – propagating thrombus, DVT, long, worm-like clot

Histology DVT - valve crosses lumen in middle (line), Lines of Zahn - formed by fibrin and platelet aggregations on L middle
Histology DVT – valve crosses lumen in middle (line), Lines of Zahn – formed by fibrin and platelet aggregations on L middle

Predisposing factors DVT (pulmonary embolism):
Post-op immobilisation, prolonged bed rest for debilitating illness, childbirth

DVT in lung - abnormal area wedge-shaped, black (thrombosed haemorrhage), pulmonary infarct causes necrosis, bleeds, clots. DVT from vascular stasis, hyper-coagulability and endothelial damage. DVT complications - fragment, dislodge, emboli, complete obstruction
DVT in lung – abnormal area wedge-shaped, black (thrombosed haemorrhage), pulmonary infarct causes necrosis, bleeds, clots. DVT from vascular stasis, hyper-coagulability and endothelial damage. DVT complications – fragment, dislodge, emboli, complete obstruction

Pulmonary embolis - large, folded saddle-like embolus, occluded pulmonary trunk and L,R pulmonary arteries, pulmonary valve below the embolus, embolus straddles bifurcation of pulmonary arteries
Pulmonary embolis – large, folded saddle-like embolus, occluded pulmonary trunk and L,R pulmonary arteries, pulmonary valve below the embolus, embolus straddles bifurcation of pulmonary arteries

Leave a Reply

Your email address will not be published. Required fields are marked *