What is metaplasia?
Reversible change in which one adult cell type is replaced by another cell type.
What is Dysplasia. [TU 2054]
- Normal cells may become cancer cells. Before cancer cells form in tissues of the body, the cells go through abnormal changes called hyperplasia and dysplasia. In hyperplasia, there is an increase in the number of cells in an organ or tissue that appear normal under a microscope. In dysplasia, the cells look abnormal under a microscope but are not cancer.
Response evaluation criteria in solid tumours (RECIST guideline)?
Evaluation of target lesions
Complete Response (CR): Disappearance of all target lesions. reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease
- Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions
- Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
Criteria is different for non target lesions
International System of Units (SI) Unit and Common Unit Terminology?
- -- // SI Units // Common Units
- Radioactivity // becquerel (Bq) // curie (Ci)
- Absorbed Dose // gray (Gy) // rad
- Dose Equivalent // sievert (Sv) // rem
- Exposure // coulomb/kilogram (C/kg) // roentgen (R)
1 Gy = 100 cGy (Centigray)
The Knudson hypothesis, also known as the two-hit hypothesis or multiple-hit hypothesis, is the hypothesis that cancer is the result of accumulated mutations to a cell's DNA.
Knudson suggested that multiple "hits" to DNA were necessary to cause cancer. In the children with inherited retinoblastoma, the first insult was inherited in the DNA, and any second insult would rapidly lead to cancer. In non-inherited retinoblastoma, two "hits" had to take place before a tumor could develop, explaining the age difference.
Contraindications of irradiations
- • Systemic scleroderma*
- • Active systemic lupus erythematosus*
- • Prior radiation to breast or chest wall
- • Severe pulmonary disease
- • Severe cardiac disease (if tumor is left-sided)• Inability to lie supine
- • Inability to abduct arm on affected side
- • p53 mutation†
Mantle field radiation?
Rarely used today, mantle field radiation is a type of radiation treatment used for Hodgkin’s lymphoma that helped boost cure rates in the 1960s.Radiation was delivered to a large area of the neck, chest and armpits to cover all the main lymph node areas in the upper half of the body. A part of the lungs, heart and the shoulders were shielded from the radiation beam to reduce the side effects.
Discuss the importance of preoperative staging in malignancy with an example. [TU 2057,59,60/12]
What is tumor angiogenesis. How do you use angiogenesis inhibitors in cancer therapy. [TU 2062/12]
Short note on Paraneoplastic syndromes. [TU 2062,64,67,68/5]
Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease.
In a broad sense, these syndromes are collections of symptoms that result from substances produced by the tumor, and they occur remotely from the tumor itself. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature.
Although fever is the most common presentation, several clinical pictures may be observed, each of which specifically simulates more common benign conditions. These syndromes vary from dermatomyositis-polymyositis to Cushing syndrome to the malignant carcinoid syndrome.
Hodgkins and non-hodgkins lymphoma?
Short note on Optical biopsy. [TU 2073]
- Endoscopic diagnosis currently relies on the ability of the operator to visualize abnormal patterns in the image created by light reflected from the mucosal surface of the gastrointestinal tract. Advances in fiber optics, light sources, detectors, and molecular biology have led to the development of several novel methods for tissue evaluation in situ. The term “optical biopsy” refers to methods that use the properties of light to enable the operator to make an instant diagnosis at endoscopy, previously possible only by using histological or cytological analysis.
- Such advanced diagnostic methods go beyond standard endoscopic techniques by offering improved image resolution, contrast, and tissue penetration and providing biochemical and molecular information about mucosal disease.
“Optical biopsy,” are nondestructive in situ assays of mucosal histopathologic states using light that can provide instantaneous tissue assessment. All methods of optical imaging collect backscattered photons from the mucosa. Conventional endoscopy observes reflected visible light (400–700 nm) from the mucosal surface.
- Primary goals include:
- (1) targeting premalignant mucosa for removal by biopsy,
- (2) grading and staging cancer progression, and
- (3) reducing the risk of physical biopsy.
- Optical Biopsy Methods -
- Fluorescence endoscopy
- Optical coherence tomography
- Confocal microscopy
- Light-scattering spectroscopy
- Raman spectroscopy
- Molecular beacons
- Clinical End Points for Optical Biopsy in the Gastrointestinal Tract -
- Minimize number of target biopsies and frequency of surveillance
- Detect and localize high-grade dysplasia in Barrett’s esophagus
- Identify neoplasia beneath neosquamous esophageal mucosa
- Assess depth of tumor invasion for possible mucosal resection
- Preoperative identification of tumor margins
- Evaluate effectiveness of pharmacological therapy
- Detect and localize dysplasia in the setting of ulcerative colitis
- Distinguish adenomatous from hyperplastic polyps
- Avoid biopsy in patients with bleeding diatheses
- Surveillance of polypectomy and mucosal resection site
- Differentiate malignant and benign ulcers and strictures
Short note on Frozen section. [TU 2072/6, 68/2]
- The frozen section procedure is a pathological laboratory procedure to perform rapid microscopic analysis of a specimen. It is used most often in oncological surgery.
- Section are prepared quickly by histological examination by freezing the tissue. The section should should be thin and without water crystals.
- It it important procedure for quick diagnosis.
- Uses -
- - Quick diagnosis
- - Study the margins of cancer
- - Enzyme histochemistry
- - Immunohistochemistry
- - Detection of lipid
- - Some molecular procedures
- Disadvantages -
- - Morphology is distorted
- - Cellular details are not well seen,
- - Staining is not very good
- - Some specials stains cannot be performed
- Handling of the specimen -
- - Tissue must reach histopathology lab immediately.
- - To avoid tissue being dry, it should be kept in saline. Do not use formalin.
- - Thickness - 3-4mm, so that freezing is quick.
- Procedure - The key instrument for cryosection is the cryostat, which is essentially a microtome inside a freezer. The usual histology slice is cut at 5 to 10 micrometres. The surgical specimen is placed on a metal tissue disc which is then secured in a chuck and frozen rapidly to about –20 to –30 °C. The specimen is embedded in a gel like medium called OCT (Optimal Cutting Temperature Compound) and consisting of poly ethylene glycol and polyvinyl alcohol.
- Subsequently it is cut frozen with the microtome portion of the cryostat, the section is picked up on a glass slide and stained (usually with hematoxylin and eosin, the H&E stain).
Short notes on chemical carcinogens. [TU 2063/2]
A carcinogen is any substance, radionuclide, or radiation that can induce conversion of target cells into the neoplastic cells.
- Types -
- - Direct acting carcinogens - these require no metabolic activation
- - Indirect acting - require metabolic activation to act as carcinogens, therefore they are called as procarcinogens, e.g Naphthylamine
- Common chemical carcinogens are -
- - Vinyl chloride - Hemangiosarcoma, liver
- - Benzene - Leukemia, Hodgkin's lymphoma
- - Benzidine
- - Beryllium and its compounds - Lung,
- - Cadmium and its compounds, Prostate
- - Chromium
- - Cadmium
- - Arsenic and its compounds - Lung, Skin
- - Asbestos - Lungs,
- - Asbestosis, Gastrointestinal tract, Pleural Mesothelioma, Peritoneal Mesothelioma
- - Nickel - Nose, Lung
- - Cyclophosphamide
- - Ethylene oxide - Leukemia,
- - Radon and its decay products - Lung
[@ VC suffered from Blood CANCER]
What are tumor suppressor genes. List important tumor suppressor genes involved in human neoplasm. [TU 2065/12]
Short note on Tumor suppression gene. [TU 2073/7]
- Repression of genes that are essential for the continuing of thecell cycle.
- Coupling the cell cycle to DNA damage. As long as there isdamaged DNA in the cell, it should not divide.
- If the damage cannot be repaired, the cell shouldinitiate apoptosis (programmed cell death)
- Some proteins involved in cell adhesion prevent tumor cells from dispersing, block loss of contact inhibition, and inhibit metastasis.These proteins are known as metastasis suppressors.
Categories of tumor suppressor genes?
Caretaker genes: Maintain the integrity of the genome by repairing DNA damage. e.g BRCA1, BRCA2, MSH2
Gatekeeper genes: Inhibit the proliferation or promote the death of cells with damaged DNA. e.g - p53, RB, APC
Name tumor suppressor genes.
Define oncogenes. Discuss in brief their importance in diagnostic and prognostic index. [TU 2063/2]
- Oncogens are cancer susceptibilty genes. Protooncogens are normal genes that are present in normal cells are involved in normal growth and development.
- Under certain circumstances, due to effect of certain process (mutagens, carcinogens, viruses, irradiation, genetic predisposition), these are converted to oncogens.
- Mechanism -
- 1. Point mutation - most common. e.g - mutation in one of the ras gene like hras, kras, nras
- 2. Gene amplification
- 3. Chromosomal rearrangement. e.g Burkitt's lymphoma, Philadelphia chromosome
- 4. Insertional mutagenesis
What is proto-oncogenes. Mention the common proto-oncogenes involved in colorectal cancers. [TU 2067/2]
- Proto-oncogenes are genes that produce proteins that promote cellular growth and proliferation. Mutations in proto-oncogenes typically produce a gain of function and can be caused by mutation in only one of the two alleles. After mutation, the gene is called an oncogene.
- Overexpression of these growth-oriented genes contributes to the uncontrolled proliferation of cells associated with cancer. The products of oncogenes can be divided into categories.
- I. Growth factors
- 1. Platelet Derived Growth factor
- - sis
- 2. Fibroblast growth factor
- - hst-1
- - int-2
- II. Involved in signal transduction:
- 1. Genes producing Tyrosine kinase:
- - Abl – CML,
- - Erb-B2 – breast, ovarian,
- - Ret- MEN 2A, 2B
- [@ Although still Able, Erb Retired because he was tired (Tyred), AbL for Leukemia, ErB for Breast, ReT for Thyroid]
- 2. Serine-Threonine kinases
- - Ras: colon carcinoma
- III. Nuclear regulatory protein:
- - Myc [L-myc: Lungs; N-myc: Neuroblastoma; C-myc: Burkitt's]
- - Jun
- - Fos
- IV. Cell cycle control
- - Bcl-1
- - Cyclin D
- - Mdm-2
- - CDK4 (cyclin dependent kinases)
Short note on APC gene. [TU 2072]
- Implicated in familial adenomatous polyposis coli and most sporadic colorectal cancers
- APC binds to and inhibits the function of β-catenin
- β-catenin activates certain transcription factors that activatesseveral genes including myc and cyclin D
- Mutant APC is unable bind β-catenin to down regulate its activity
- Situated at the short arm of the chromosome 17
- Mutated in most of the cancer cases
- Normal functions p53
- - It can activate DNA repair proteins when DNA has sustained damage.
- - It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for longenough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).
- - It can initiate apoptosis, the programmed cell death, if DNA damage proves to be irreparable.
- - P53 level raise in cells with sustained cell damage, until the damage is repaired or cell undergoes apoptosis
- - Prevents propagation of possibly mutated cells - Called “the guardian of the genome”
- p53 Gene - P53 can lost its function by:
- Non-sense mutation or mis-sense mutation
- Complex of normal p53 and mutant p53 inactivating the function of normal allele
- Binding of normal p53 to viral oncoproteins
Short notes of BRCA 1 & 2 genes. [TU 2068/2]
- Brest(BR) cancer(CA) susceptibility genes, also incriminated in some ovarian cancers
- Involved in G1 check point
- Block entry of cell into S phase, particularly by inducing CDK inhibitor p21
- Promote DNA repair by binding to RAD51
Describe the present concept of the etiology of neoplasia.
Define metastasis of malignant tumor.
List two common sites of metastasis of prostatic tumor and breast tumor. [TU 2056]
Short note on ALP. [TU 2070/6]
Alkaline phosphotase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecule including neucleotides, proteins and alkaloids.
The process of removing the phosphate group is called dephosphorylation.
ALP present in all tissues but it is particularly concentrated in liver, bile duct, kidney, bones, placenta, intestinal mucosa.
Normal value - 53-128 u/l.
- Clinical significance -
- • To detect Liver disease, Bone disorders, biliary obstruction and cancer.
- • In conditions affecting the liver (e.g,hepatitis) damaged liver cells releases increase amounts of ALP in to the blood.
- • To detect biliary obstruction (blocked bile duct)because ALP is especially high in the edges of cells that join to form bile ducts. If one or more of them are obstructed.
- • Any condition that affects bone growth or causes increased activity of bone cells can affect ALP levels in the blood.
- • To detect cancers that have spread to
- • To diagnose Paget's disease that causes malformed bones.