Deep dive into oncopathology and genetic disorders relevant to ENT. Essential for Year 5 medical students preparing for their end-semester exams.
SECTION A: MBPA 3412 (ONCOPATHOLOGY) Question 1: Define the following terms (5 Marks) a. Pleomorphism Variation in size and shape of cells and their nuclei within a tumor. It is a characteristic feature of malignant neoplasms indicating lack of uniformity. b. Anaplasia Lack of cellular differentiation in malignant tumors. Cells lose their specialized features and resemble primitive cells with marked pleomorphism, abnormal nuclei, increased mitoses, and high nuclear-to-cytoplasmic ratio. c. Dysplasia Disordered growth with abnormal cells showing loss of uniformity and architectural orientation. It is a precancerous condition confined within epithelium without basement membrane invasion. Classified as mild, moderate, or severe. d. Oncogenes Mutated or overexpressed genes that promote cancer development. Derived from normal proto-oncogenes that regulate cell growth. Examples include RAS, MYC, and HER2. Act dominantly requiring only one mutated allele. e. Differentiation The extent to which tumor cells resemble their normal counterparts morphologically and functionally. Well-differentiated tumors resemble normal tissue with better prognosis; poorly differentiated tumors show little resemblance with worse prognosis. --- Question 2: Discuss the grading and staging of tumours (20 Marks) INTRODUCTION Grading and staging are two essential systems for assessing tumors. Grading evaluates microscopic features and biological behavior, while staging determines anatomical extent of disease. Both are crucial for treatment planning and prognosis. TUMOR GRADING Grading is based on cytologic differentiation and mitotic activity, assessing how closely tumor cells resemble normal cells. Principles of Grading: - Evaluates degree of differentiation - Assesses number of mitoses - Examines nuclear pleomorphism - Looks at architectural patterns Grading Systems: Universal System: - Grade I (G1): Well-differentiated, resembles normal tissue - Grade II (G2): Moderately differentiated, intermediate features - Grade III (G3): Poorly differentiated, little resemblance to normal - Grade IV (G4): Undifferentiated/anaplastic, no resemblance to normal Specific Grading Systems: - Gleason score for prostate cancer (scores 2-10) - Nottingham system for breast cancer (scores 3-9) - Fuhrman grade for renal cell carcinoma (grades 1-4) Significance: - Higher grade indicates more aggressive behavior - Correlates with prognosis and survival - Guides treatment intensity - Well-differentiated tumors have better outcomes TUMOR STAGING Staging determines anatomical extent of tumor spread. The most widely used system is the TNM classification. TNM Classification: T (Primary Tumor): - TX: Primary tumor cannot be assessed - T0: No evidence of primary tumor - Tis: Carcinoma in situ - T1-T4: Increasing size and local extent of primary tumor N (Regional Lymph Nodes): - NX: Nodes cannot be assessed - N0: No regional lymph node metastasis - N1-N3: Increasing involvement of regional lymph nodes M (Distant Metastasis): - M0: No distant metastasis - M1: Distant metastasis present Stage Groupings: After TNM assessment, tumors are assigned overall stages: - Stage 0: Carcinoma in situ - Stage I: Localized tumor, small size - Stage II: Larger tumor or limited local spread - Stage III: Extensive local and regional spread - Stage IV: Distant metastasis present Other Staging Systems: - FIGO staging for gynecologic cancers - Ann Arbor staging for lymphomas - Clark and Breslow for melanomas - Dukes staging for colorectal cancer Clinical vs Pathological Staging: - Clinical staging (cTNM): Based on physical examination, imaging, and biopsies before treatment - Pathological staging (pTNM): Based on surgical specimens and pathological examination, more accurate Significance of Staging: - Most important prognostic factor - Determines treatment protocols - Essential for comparing treatment outcomes - Allows standardized communication between clinicians - Stage I has best prognosis; Stage IV has worst - Guides surveillance strategies COMPARISON: GRADING VS STAGING COMBINED SIGNIFICANCE Both grading and staging together provide comprehensive tumor assessment. A high-grade, early-stage tumor may behave differently from a low-grade, advanced-stage tumor. Treatment decisions consider both parameters. CONCLUSION Grading and staging are complementary systems essential for cancer management. Staging provides the anatomical roadmap of disease extent and is the primary determinant of prognosis, while grading offers insight into tumor biology and aggressiveness. Together, they guide treatment selection, predict outcomes, and facilitate clinical research. --- SECTION B: MBPA 3413 (GENETIC DISORDERS) Question 1: Define the following terms (5 Marks) a. Genetic Refers to conditions or traits that are inherited through genes passed from parents to offspring. Genetic disorders result from mutations in DNA sequence that can be transmitted through generations. b. Congenital Present at birth, regardless of cause. Congenital conditions may be genetic (inherited) or acquired during fetal development due to environmental factors like infections, drugs, or teratogens. Not all congenital disorders are genetic, and not all genetic disorders are congenital. c. Multigenic disorders Also called multifactorial or polygenic disorders. Caused by interactions between multiple gene variants (polymorphisms) and environmental factors. Examples include diabetes, hypertension, and most common diseases. Each gene contributes a modest effect. d. Single nucleotide polymorphisms (SNPs) Variations in DNA sequence where a single nucleotide (base pair) differs between individuals. SNPs occur at least in 1% of the population and are the most common type of genetic variation. They contribute to individual differences and susceptibility to diseases. e. t(9;22)(q34;q11) Reciprocal translocation between chromosomes 9 and 22. The long arm (q) of chromosome 9 at region 3, band 4 exchanges material with the long arm of chromosome 22 at region 1, band 1. This creates the Philadelphia chromosome associated with chronic myeloid leukemia, producing the BCR-ABL fusion gene. --- Question 2: Discuss transmission patterns of single-gene disorders (20 marks) INTRODUCTION Single-gene disorders, also called Mendelian disorders, result from mutations in a single gene. They follow predictable inheritance patterns first described by Gregor Mendel. Understanding these patterns is crucial for genetic counseling and predicting disease risk in families. CLASSIFICATION Single-gene disorders are classified based on: - Chromosomal location (autosomal vs X-linked) - Expression pattern (dominant vs recessive) This gives four main patterns: autosomal dominant, autosomal recessive, X-linked recessive, and X-linked dominant. 1. AUTOSOMAL DOMINANT (AD) DISORDERS Characteristics: - Only one mutated allele needed for disease expression - Affected individuals are usually heterozygotes - Both males and females equally affected - Vertical transmission pattern (multiple generations affected) Inheritance Pattern: - Affected parent × Normal parent:50% offspring affected - 50% offspring normal - Affected individuals usually have one affected parent - Disease does not skip generations (except with incomplete penetrance) Special Features: - Variable expressivity: Same mutation causes different severity in different individuals - Incomplete penetrance: Not all with mutation show disease - New mutations common in some disorders - Age-dependent expression in many disorders Examples: - Familial hypercholesterolemia - Huntington disease - Marfan syndrome - Neurofibromatosis - Achondroplasia - Adult polycystic kidney disease Pedigree Features: - Multiple generations affected - Male-to-male transmission possible - Both sexes equally affected - Affected individual usually has affected parent 2. AUTOSOMAL RECESSIVE (AR) DISORDERS Characteristics: - Two mutated alleles required for disease expression - Affected individua