L1 – Colorectal Pathology Flashcards
What are the main pathways in colorectal cancer development?
Colorectal cancer develops via distinct pathways including chromosome instability (CIN), microsatellite instability (MSI), and the serrated neoplasia pathway.
How is colorectal cancer described in terms of heterogeneity?
It is a heterogeneous disease that evolves through stepwise genetic and epigenetic alterations.
What is the worldwide incidence trend of colorectal cancer?
Colorectal cancer shows significant geographical variation with sporadic and familial cases, and its incidence is influenced by lifestyle and dietary factors.
Why is recognising the genetic pathways in colorectal cancer important?
Understanding these pathways aids in diagnosis, prognosis, and may inform targeted therapeutic approaches.
Which risk factors predispose to colorectal carcinoma?
Age, obesity, physical inactivity, alcohol consumption, inflammatory bowel disease, schistosomiasis, and family history of colorectal neoplasia.
How do dietary factors influence colorectal cancer risk?
Diets low in fibre and high in refined carbohydrates and beef increase risk, partly due to longer transit times and bile acid conversion into carcinogens.
What role do polyposis syndromes play in colorectal cancer?
Syndromes such as familial adenomatous polyposis and Lynch syndrome cause early-onset colorectal neoplasia through inherited mutations (e.g. APC, MLH1).
How do genetic abnormalities contribute to the adenoma–carcinoma sequence?
Sequential mutations—starting with APC, then KRAS, TP53 and others—drive the progression from benign adenoma to malignant carcinoma.
What is the definition of a polyp in colorectal pathology?
A polyp is a protuberant growth arising from epithelial or mesenchymal tissues, which may be benign or malignant.
Name the major types of colorectal polyps.
Inflammatory, hamartomatous, neoplastic (e.g. adenomas, adenocarcinomas), and other types such as hyperplastic polyps.
How does a hamartomatous polyp differ from an adenomatous polyp?
Hamartomatous polyps are benign tumour-like lesions containing multiple differentiated tissues, whereas adenomas are neoplastic and can progress to carcinoma.
What is the clinical significance of adenomatous polyps?
Over 95% of colorectal adenocarcinomas arise from adenomatous polyps, making their detection and removal critical.
What genetic changes mark the CIN pathway?
The CIN pathway involves aneuploidy, somatic copy number alterations, and mutations in genes like APC, KRAS, and TP53.
How does the MSI pathway differ from the CIN pathway?
MSI tumours, often seen in Lynch syndrome, result from mutations in DNA mismatch repair genes and are characterised by frequent base pair mutations in microsatellites.
What genetic abnormality is typically associated with serrated polyps?
Activating mutations in the BRAF oncogene are commonly associated with serrated neoplasia.
Why is the order of genetic alterations important in the adenoma–carcinoma sequence?
The sequence of alterations influences the histological progression and potential for invasive cancer development.
How does chronic inflammation, such as in inflammatory bowel disease, promote colorectal carcinogenesis?
Persistent inflammation leads to DNA damage and a microenvironment that favours neoplastic transformation.
How do bile acids contribute to the risk of colorectal cancer?
Bile acids, when converted into secondary carcinogens, can damage the colonic mucosa and promote mutations.
What is the impact of fibre intake on colorectal cancer development?
High fibre diets reduce transit time and dilute potential carcinogens, lowering the risk of neoplastic changes.
How does loss of heterozygosity (LOH) affect tumour suppressor genes in colorectal cancer?
LOH results in the inactivation of key tumour suppressors, removing crucial controls over cell proliferation.
How can molecular testing assist in risk stratification of colorectal polyps?
It identifies mutations (e.g. KRAS, BRAF) that help predict the likelihood of progression to malignancy.
What is the clinical relevance of distinguishing sporadic from familial colorectal cancers?
Familial cases (e.g. Lynch syndrome, FAP) may require early screening and genetic counselling due to their distinct genetic basis.
How does the serrated neoplasia pathway differ morphologically from the traditional adenoma–carcinoma sequence?
Serrated lesions exhibit a saw-tooth epithelial pattern and often progress via BRAF mutations, sometimes more rapidly.
In what way does microsatellite instability (MSI) affect chemotherapy response in colorectal cancer?
MSI-high tumours can respond differently to certain chemotherapies and generally have a distinct prognosis compared with CIN tumours.
What is the primary function of the large bowel?
The large bowel primarily functions in water absorption and the consolidation of fecal material.
Where are colorectal tumors most commonly located?
Colorectal tumors are more commonly found on the left side (descending colon, sigmoid, rectum) but also occur on the right side (ascending colon).
Why do right-sided colorectal tumors often present later than left-sided tumors?
Right-sided tumors tend to grow larger before detection due to the looser consistency of fecal matter in that region.
What is a common symptom associated with right-sided colorectal cancer?
A common symptom of right-sided colorectal cancer is anemia due to chronic occult blood loss.
Why is anemia a key symptom in right-sided colorectal cancer?
Anemia results from prolonged, undetected bleeding in the right colon, often leading to fatigue and pallor.
How does colorectal cancer screening aid in early detection?
Screening detects early-stage lesions, such as polyps or hidden blood in the stool, enabling timely intervention.
What is the histological structure of the bowel mucosa?
The bowel mucosa consists of a single layer of glandular epithelium with crypts for nutrient absorption.
What role do crypts play in the intestinal epithelium?
Crypts generate new epithelial cells, ensuring continuous renewal and maintenance of the intestinal lining.
What are polyps, and how are they classified?
Polyps are protuberant growths in the intestinal lining that can be inflammatory, hamartomatous, or neoplastic.
Why are adenomatous polyps significant in colorectal cancer?
Adenomatous polyps are significant as they can undergo malignant transformation into colorectal cancer.
What is the adenoma-carcinoma sequence?
The adenoma-carcinoma sequence describes the stepwise genetic changes that drive colorectal cancer progression.
Which genetic mutations are commonly involved in colorectal cancer progression?
Key genetic mutations include APC, K-RAS, and TP53, which regulate cell growth and tumor formation.
How do lifestyle and dietary factors influence colorectal cancer risk?
Diets high in fat and low in fiber, obesity, smoking, and a sedentary lifestyle increase colorectal cancer risk.
What hereditary syndromes increase colorectal cancer risk?
Familial adenomatous polyposis (FAP) and Lynch syndrome predispose individuals to early-onset colorectal cancer.
How does the classification of colorectal cancer aid in treatment?
Colorectal cancer classification guides treatment decisions based on tumor stage, grade, and genetic features.
What screening methods are commonly used for colorectal cancer?
Screening methods include fecal occult blood tests (FOBT) and colonoscopy to detect early neoplastic changes.
Why is colonoscopy an important tool in colorectal cancer prevention?
Colonoscopy allows direct visualization and removal of precancerous polyps, preventing cancer progression.
What role does histopathology play in colorectal cancer diagnosis and prognosis?
Histopathology evaluates tumor differentiation, invasion, and molecular markers for diagnosis and treatment planning.
How does colorectal cancer staging impact treatment decisions?
Staging determines whether the tumor is localized, has spread to lymph nodes, or has metastasized, guiding therapy.
What are the primary treatment modalities for colorectal cancer?
Treatment modalities include surgical resection, chemotherapy, radiation, and targeted molecular therapies.
How do targeted therapies improve colorectal cancer outcomes?
Targeted therapies address specific genetic mutations, improving patient outcomes in advanced colorectal cancer.
What is the role of lymphovascular invasion in colorectal cancer prognosis?
Lymphovascular invasion indicates a higher risk of metastasis and worse prognosis in colorectal cancer.
Why is early detection crucial in managing colorectal cancer?
Early detection through screening and intervention significantly improves survival rates.
How does chronic inflammation contribute to colorectal carcinogenesis?
Chronic inflammation, such as in inflammatory bowel disease, leads to DNA damage and a pro-carcinogenic environment.
What histological features distinguish hyperplastic from adenomatous polyps?
Hyperplastic polyps show well-formed glands with serrated epithelium but no dysplasia.
Adenomatous polyps display dysplastic, crowded glands with nuclear atypia.
Adenomas are precancerous, while hyperplastic polyps are typically benign.
Size and location can help differentiate: adenomas often larger and left-sided.
What are the characteristics of high-grade dysplasia in colorectal adenomas?
Marked nuclear atypia and loss of polarity.
Complex glandular architecture with cribriform or back-to-back glands.
Mitotic figures may be numerous and atypical.
Strong predictor of malignant transformation.
What are sessile serrated lesions (SSLs), and why are they clinically important?
SSLs are premalignant polyps with serrated architecture and abnormal crypts.
Often flat and located in the right colon, making detection more difficult.
Associated with BRAF mutations and the serrated neoplasia pathway.
Can progress to MSI-high colorectal cancer.
What histological features suggest invasion in colorectal adenocarcinoma?
Irregular, angulated glands infiltrating desmoplastic stroma.
Loss of glandular architecture compared to adenomas.
Presence of “dirty necrosis” in glandular lumens.
Invasion beyond muscularis mucosae into submucosa or deeper layers.
What are the poor prognostic histological features in colorectal cancer?
Poor differentiation or mucinous/signet-ring histology.
Lymphovascular or perineural invasion.
High tumour budding (individual or small clusters of tumour cells).
Positive resection margins and advanced T/N stage.
What is tumour budding, and what is its prognostic significance in colorectal cancer?
Tumour budding refers to single cells or small clusters at the invasive front.
Indicates epithelial-mesenchymal transition (EMT).
Associated with increased risk of metastasis.
Independent poor prognostic marker.
How is the depth of invasion used in staging colorectal cancer?
T1: Invades submucosa.
T2: Invades muscularis propria.
T3: Invades subserosa/pericolic fat.
T4: Penetrates visceral peritoneum or invades adjacent organs.
Why are sessile serrated polyps more challenging to detect endoscopically?
Often flat and covered by mucous cap.
Located in the right colon with subtle mucosal changes.
Require careful inspection and adequate bowel prep.
Risk being missed, contributing to interval cancers.
What is ‘dirty necrosis’ and in what context is it seen?
Dirty necrosis refers to necrotic debris within glandular lumens.
Characteristic of invasive colorectal adenocarcinoma.
Reflects high cellular turnover and lack of mucosal architecture.
Helps distinguish carcinoma from benign lesions histologically.
What is the significance of perineural invasion in colorectal cancer?
Indicates aggressive tumor behavior.
Associated with higher risk of local recurrence.
Independent adverse prognostic factor.
Seen as tumor cells tracking along nerves histologically.
What is a mucinous adenocarcinoma and how does it differ from conventional adenocarcinoma?
Contains >50% extracellular mucin.
Tumor cells appear to “float” in mucin pools.
Often associated with MSI-high and right-sided location.
Tends to have a worse prognosis and reduced chemo response.
What are signet-ring cells and what is their clinical relevance in colorectal cancer?
Tumor cells with intracytoplasmic mucin displacing nucleus to the periphery.
Indicates an aggressive, poorly cohesive cancer type.
Often associated with peritoneal spread and poor prognosis.
Frequently MSI-high and more common in younger patients.
What defines a T1 colorectal carcinoma arising in a polyp?
Invasion into submucosa but not beyond.
If completely excised and with no adverse features (e.g. poor differentiation, LVI), may not need further surgery.
Important to assess margin clearance and depth of invasion.
Sometimes managed endoscopically if criteria are met.
What is pseudoinvasion in colorectal polyps?
Misplacement of adenomatous glands into submucosa due to mechanical trauma.
Can mimic invasive carcinoma.
Glands retain rounded shape, are surrounded by lamina propria, and lack desmoplastic reaction.
Key to avoid overtreatment.
