Neoplasia Overview

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Questions and Answers

What distinguishes neoplasia from hyperplasia?

Neoplasia does not produce new tissue.

Neoplasia is reversible.

Neoplasia involves multiple origin cells.

Neoplasia exhibits monoclonality. (correct)

What does clonality indicate in relation to neoplastic cells?

They exhibit variable ratios of active isofoms.

They are derived from a single mother cell. (correct)

They have diverse isoforms from multiple parent cells.

They are randomly obtained from both parents.

In females, how is the G6PD isoform ratio normally maintained?

Only one isoform is present in all cells.

One isoform is inactivated randomly by lyonization. (correct)

Both isoforms are active in all cells.

Isoforms are equally expressed in all tissues.

What is the normal kappa to lambda light chain ratio in healthy B cells?

3:1 Signup and view all the answers

Which characteristic defines malignant tumors?

Ability to invade locally. Signup and view all the answers

What type of neoplastic change occurs when the kappa to lambda ratio exceeds 6:1?

Monoclonal disturbance. Signup and view all the answers

What are examples of benign tumors and their malignant counterparts?

Papilloma; Carcinoma. Signup and view all the answers

Which of the following is a leading cause of death in adults?

Cancer. Signup and view all the answers

What is a characteristic feature of malignant tumors?

High mitotic activity with atypical mitosis Signup and view all the answers

Which of the following best describes well-differentiated cancers?

They resemble normal parent tissue. Signup and view all the answers

What is the purpose of serum tumor markers?

They are useful for screening and monitoring treatment response. Signup and view all the answers

Which grading of cancer indicates it resembles normal tissue the most?

Well differentiated Signup and view all the answers

Which feature is NOT characteristic of benign tumors?

High mitotic activity Signup and view all the answers

What does the 'M' in the TNM staging system refer to?

Metastasis Signup and view all the answers

Which characteristic is a hallmark of malignant tumors?

Disorganized growth Signup and view all the answers

What type of staining is used to help classify difficult tumors?

Immunohistochemical staining Signup and view all the answers

Which oncogene is associated with Burkitt lymphoma?

c-MYC Signup and view all the answers

What role does the p53 gene play in tumor formation?

It induces apoptosis when DNA repair fails. Signup and view all the answers

How does the Rb protein regulate the cell cycle?

By binding and holding E2F transcription factor. Signup and view all the answers

What characteristic is typical of malignant tumors?

Infiltrative behavior Signup and view all the answers

Which of the following factors is typically produced by tumor cells to promote angiogenesis?

VEGF Signup and view all the answers

What is a consequence of Bcl2 overexpression in follicular lymphoma?

Stabilization of mitochondrial membrane Signup and view all the answers

What is the role of telomerase in cancer cells?

It helps maintain telomere length. Signup and view all the answers

In what way does cancer avoid immune surveillance?

By downregulating MHC class I. Signup and view all the answers

Which mutation leads to familial retinoblastoma?

Germline mutation of the Rb gene Signup and view all the answers

What drives oncogenesis in gastrointestinal stromal tumors (GISTs)?

Point mutation in the KIT gene Signup and view all the answers

Which cell adhesion molecule is typically downregulated in cancer invasion?

E-cadherin Signup and view all the answers

Which of the following conditions leads to increased risk for cancer?

Immunodeficiency states Signup and view all the answers

Which of the following is NOT a characteristic of benign tumors?

Rapid growth Signup and view all the answers

Which result correlates with a mutation in the p53 gene?

Propensity for multiple cancers Signup and view all the answers

Which type of cancer is most commonly associated with lung carcinoma?

Mesothelioma Signup and view all the answers

What is the primary goal of cancer screening methods?

To identify dysplasia before it progresses to cancer Signup and view all the answers

What initiates the formation of cancer in stem cells?

Damage to DNA that overcomes repair mechanisms Signup and view all the answers

Which agent is classified as a chemical carcinogen that can lead to liver cancer?

Aflatoxins Signup and view all the answers

Which type of mutation is associated with the unregulated growth of cells through the activation of oncogenes?

Gain-of-function mutations Signup and view all the answers

Which protein regulates the cell cycle at the G1 to S phase transition?

p53 Signup and view all the answers

What is the role of proto-oncogenes in cellular growth?

They are essential for cell growth and differentiation Signup and view all the answers

Which common screening method detects cervical dysplasia?

Pap smear Signup and view all the answers

What type of cancer is commonly associated with high-risk HPV subtypes?

Cervical cancer Signup and view all the answers

Which of the following cancer types is most commonly screened by the PSA test?

Prostate cancer Signup and view all the answers

Which factor is known to disrupt key regulatory systems in cancer development?

Mutations in DNA Signup and view all the answers

Which genetic event is associated with a loss of function of p53, leading to increased cancer risk?

Mutations in tumor suppressor genes Signup and view all the answers

Which category does 'ras' belong to within the oncogene framework?

Signal transducer Signup and view all the answers

What common environmental source is recognized for contributing to skin carcinoma?

UVB sunlight Signup and view all the answers

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Study Notes

Neoplasia

Neoplasia is unregulated, irreversible, new tissue growth, distinct from hyperplasia and repair.
Monoclonal: Neoplastic cells originate from a single parent cell.
Clonality Determination:
Glucose-6-phosphate dehydrogenase (G6PD) isoforms: Different isoforms exist (e.g., G6PDA, G6PD8, G6PDc), inherited one frgom each parent. Females randomly inactivate one isoform per cell. The normal ratio in cells is 1:1 (e.g., 50% of cells have G6PD A' and 50% G6PD8). This 1:1 ratio is maintained in polyclonal hyperplasia, whereas only one isoform characterizes monoclonal neoplasia.
Androgen receptor isoforms are also useful for assessing clonality; located on the X chromosome.
Immunoglobulin (Ig) light chain phenotype (B lymphocytes): B cells express either kappa or lambda light chains. The normal ratio is kappa:lambda=3:1. This ratio is maintained in polyclonal hyperplasia, but increases to >6:1 or inverts (e.g., 1:3) in monoclonal lymphoma.
Tumor types: Neoplastic tumors can be benign or malignant.
Benign tumors: Localized, non-metastatic.
Malignant tumors (cancer): Invade locally and can metastasize.
Tumor nomenclature: Based on tissue lineage and benign/malignant status (e.g., adenoma vs. adenocarcinoma).

Epidemiology of Cancer

Cancer: Second leading cause of death in adults and children.
Adult causes (leading to death): 1) Cardiovascular disease; 2) Cancer; 3) Cerebrovascular disease.
Child causes (leading to death): 1) Accidents; 2) Cancer; 3) Congenital defects.
Common cancers (adult incidence): Breast/prostate, lung, colorectal.
Common cancer causes of death (adult): Lung, breast/prostate, colorectal.

Cancer Screening

Cancer develops from a single mutated cell.
Multiple divisions (doubling time) occur before detectable symptoms. Each doubling leads to increased mutations.
Late detection cancers have more divisions and mutations; poorer prognosis.
Screening goals detect precancerous changes (dysplasia) or cancers before symptoms.
Common screening methods:
Pap smear (cervical dysplasia).
Mammography (breast cancer, in situ or invasive).
PSA and DRE (prostate cancer).
Hemoccult test and colonoscopy (colon cancer, adenomas).

Carcinogenesis

Cancer formation: DNA damage in stem cells initiates the process. DNA damage overcomes repair but is not immediately lethal.
Carcinogens: Agents that damage DNA, increase cancer risk (chemicals, oncogenic viruses, radiation).
DNA mutations disrupt regulatory systems:
Proto-oncogenes: Essential for cell growth/differentiation. Mutation creates oncogenes leading to uncontrolled growth. Categories include growth factors, receptors, signal transducers, nuclear regulators and cell cycle regulators.
Tumor suppressor genes: Regulate cell growth, decrease tumor formation (e.g., p53, Rb).
p53: Regulates cell cycle from G1 to S. DNA damage → slows cycle, upregulates repair enzymes. No repair possible → apoptosis. p53 upregulates BAX, disrupts Bcl2, cytochrome c leaks to initiate apoptosis Knudson two-hit hypothesis, both copies required for tumor formation.
Rb: Also regulates G1 to S phase. Rb "holds" E2F transcription factor, releases when phosphorylated. Rb mutation creates constitutively free E2F = uncontrolled growth. Both copies of Rb gene require mutation for tumor formation. Knudson two-hit hypothesis, both copies needed for tumor formation.
Regulators of apoptosis (e.g., Bcl2). Normal cells = prevents apoptosis; mutated cells = promote apoptosis as DNA cannot be repaired. Bcl2 stabilizes mitochondrial membrane inhibiting the release of cytochrome C. Bcl2 overexpression in Follicular lymphoma is a significant event as translocation t(14;18) places Bcl2 gene near an Ig heavy-chain locus leading to overexpression; this further stabilizes mitochondrial membrane prohibiting apoptosis, B cells accumulate in the germinal centers of the lymph node causing an eventual buildup into lymphoma.
Other important features of tumor development:
Telomerase: Necessary for cell immortality. Normal = telomere shortening, ultimately cell senescence. Cancer cells have upregulated telomerase.
Angiogenesis: New blood vessel formation is needed for tumor survival & growth
Immune evasion: Tumor cells avoid immune system surveillance. Mutations can cause abnormal proteins, expressed on MHC class I. CD8+ T cells target & destroy cells. Tumor cells can downregulate MHC class I expression. Immunodeficiency increases cancer risk.

Tumor Progression

Tumor invasion & spread: Accumulation of mutations.
Epithelial tumors: Normally attached by adhesion molecules like E-cadherin. Mutation leads to dissociation.
Tissue invasion: Tumor cells attach to laminin, destroy basement membrane via collagenases. Cells attach to fibronectin in the extracellular matrix = local spread.
Routes of metastasis:
Lymphatic spread: Common in carcinomas. Initial spread to regional draining lymph nodes.
Hematogenous spread: Predominantly in sarcomas. Also in renal, hepatocellular cancers; Follicular carcinoma of thyroid; and choriocarcinoma.
Body cavity seeding: Common in ovarian carcinoma. Involves the peritoneum causing "omental caking."

Clinical Characterisitcs of Tumors

Benign tumors: Slow growth, well-circumscribed, distinct borders; mobile.
Malignant tumors: Rapid growth, poorly circumscribed, infiltrative, fixed to surrounding tissues.
Diagnosis requires biopsy/excision
Histologic features: Well-differentiated benign tumors (organized, uniform nuclei, low nuclear:cytoplasmic ratios, low mitosis). Poorly differentiated malignant tumors (disorganized growth, nuclear pleomorphism, high nuclear:cytoplasmic ratios, high atypical mitosis).
Immunohistochemistry: Characterizes difficult-to-classify tumors.
Serum tumor markers: Proteins released into serum from tumors. Useful for screening, monitoring treatment,/recurrence. Elevated levels require biopsy.
Grading: Microscopic assessment of differentiation (how much cancer resembles parent tissue). Low/Well diff. better prognosis than high/poor diff.
Staging: Assessment of size and spread. Uses TNM system (T-tumor, N-lymph nodes, M-metastasis). TNM staging important prognostic factor.

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Description

This quiz covers the fundamentals of neoplasia, including the differences between neoplasia, hyperplasia, and repair. It also explores the significance of clonality determination through various isoforms and immunoglobulin phenotypes. Test your knowledge on tumor types and the characteristics of neoplastic growth.