neoplasia 4.pdf

NEOPLASIA IV DR. NADA HAMZA SHAREEF Learning objectives: To understand ▪ Staging of malignant tumor ▪ Grading of malignant tumor ▪ The biological basis for the use of different cancer treatments ▪ The use of tumor markers in diagnosis and monitoring of disease ▪ The value of screening....

NEOPLASIA IV DR. NADA HAMZA SHAREEF Learning objectives: To understand ▪ Staging of malignant tumor ▪ Grading of malignant tumor ▪ The biological basis for the use of different cancer treatments ▪ The use of tumor markers in diagnosis and monitoring of disease ▪ The value of screening.  PREDICTING TUMOUR BEHAVIOUR (Stage ,Grade ) Staging of malignant tumor The staging of solid cancers is based on the size of the primary lesion Its extent of spread to regional lymph node. The presence or absence of blood-borne metastases The major staging system currently in use is American Joint Committee on Cancer Staging AJCC staging system. TNM system T for primary tumor, N for regional lymph node involvement, M for metastases. The primary lesion is characterized as T1 to T4 based on increasing size. TXNo information about the T or cannot be assessed T0 No evidence of a primary tumor Tis carcinoma in situ NX: regional lymph nodes cannot be assessed. N0: No lymph node involvement. N1 to N3 involvement of an increasing number of nodes. M0 no distant metastases, M1 or sometimes M2 reflects the presence and estimated number of metastases. Breast ductal carcinoma T1 : ≤ 2cm) 20mm) T2 : 2 - 5 cm (20-50mm) T3 : ≥ 5cm (50mm) T4: skin and/ or chest wall involved N0 : no axillary nodes involved N1 : Metastasis in 1-3 nodes N2 : Metastasis 4-9 nodes N3 : Metastasis ≥ 10 nodes M0 = no metastases M1 = demonstrable metastases Rectum Primary tumor (pT) T1: tumor invades submucosa (through the muscularis mucosa but not into the muscularis propria) T2: tumor invades muscularis propria T3: tumor invades through the muscularis propria into the pericolorectal tissues T4: T4a: tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum) T4b: tumor directly invades or adheres to other adjacent organs or structures Dukes staging for neoplasms of rectum A - Not extending through muscularis propria >90% 5 yr survival B - Extending through muscularis propria 70% 5 yr survival C - Lymph nodes involved 30% 5 yr survival  Regional lymph nodes (pN) Distant metastasis (pM) N0: no regional lymph node M0: no distant metastasis metastasis by imaging; no evidence of N1: metastasis in 1 - 3 regional tumor in other sites or organs lymph nodes (this category is NOT N2: metastasis in 4 or assigned by pathologists) more regional lymph nodes M1: distant metastasis URINARY BLADDER Regional lymph nodes (pN) Primary tumor (pT) pN0: no regional lymph node pT1: invades lamina propria metastasis pT2a: invades inner half of pN1: metastasis in 1 true muscularis propria pelvic lymph node pT2b: invades outer half of pN2: metastasis in greater muscularis propria than 1 true pelvic lymph node pT3a: microscopically pN3: metastasis in common iliac invades perivesical tissue lymph node pT3b: macroscopically invades perivesical tissue Distant metastasis (pM) pT4a: directly invades pM1a: metastasis in prostatic stroma, seminal vesicles, nonregional lymph node (ex: uterus or vagina caval / aortic, inguinal) pT4b: directly invades pelvic wall or pM1b: metastasis in other abdominal wall distant site  Hodgkin’s Lymphoma (Ann Arbor) I one group of nodes involved II. two separate groups, same side of diaphragm III. nodes involved both sides of diaphragm, plus spleen IV. bone marrow, lung, other sites A- no symptoms B- fever with sweats, itching, weight loss  Grading of malignant tumor Grade is the differentiation of a tumour. Differentiation is how similar the tumour cells look when compared with the cell type of origin. The grading of a cancer attempts to establish some estimate of its aggressiveness or level of malignancy based on the cytological differentiation of tumor cells and the number of mitoses within the tumor.  For most tumors, four grades are used. GRADE I tumors are so well-differentiated that they closely resemble the normal parent cells, whereas GRADE IV tumors are so anaplastic that even the recognition of their cell of origin becomes difficult. GRADES II AND III are intermediate. instead of using a numerical system, some pathologists prefer to indicate that the tumor is well-differentiated, moderately differentiated, poorly differentiated or undifferentiated these designations would correspond to grades I to IV, respectively. G1-WELL DIFFERENTIATED G2-MODERATELY DIFFERENTIATED G3-POORLY DIFFERENTIATED. G4-UNDIFFERENTIATED  Breast Most commonly used system is Elston / Nottingham modification of Scoring Bloom- Richardson system, based on 3 - 5 points: well (a) tumor tubule formation differentiated (grade I) (b) number of mitotic figures in most 6 - 7 points; active areas moderately (c) nuclear pleomorphism differentiated (grade II) 8 - 9 points: poorly Tumor tubule formation:1 point: > 75% differentiated (grade III) of tumor 2 points: 10 - 75% of tumor 3 points: < 10% of tumor  Grade 1 invasive Ductal Carcinoma , BREAST  Grade 3 invasive Ductal Carcinoma , BREAST Moderately differentiated SCC Poorly differentiated SCC Grade I – well differentiated colonic adenocarcinoma 29 Grade II-moderately Poorly differentiated differentiated adenocarcinoma adenocarcinoma Cancer Diagnosis -Fine-Needle aspiration (FNA) -Exfoliative cytology (pap smear) -biopsy -Biochemical markers (PSA, CEA, Alpha-fetoprotein) Tru-cut (core needle biopsy ) The biological basis for the use of different cancer treatments Surgery Radiotherapy Chemotherapy Hormone therapy Others – cancer specific, vaccines Primary Depends on nature of tumor Stage Adjuvant Recurrent / metastases  cientific Researches The surgery It is localized treatment typically attempts to remove the entire mass Radiotherapy This treatment target specific tumors and cluster of cancer cells but it can affect healthy cell in the area generally it has milder effects than chemotherapy Factors Type of radiation Cumulative dose Rate of delivery Target tissues  Biologic Basis of Radiation Therapy Radiation randomly interacts with molecules within the cell, the critical target for cell killing is the (DNA), damage to the cellular and nuclear membranes and other organelles may also be important. Radiation damage is primarily manifested by the loss of cellular reproductive capacity The concept that cell death following radiation exposure may not be manifested until several cell divisions later has clinical relevance, such that tumors associated with very slowly proliferating cancers may persist for months and appear histologically viable. cells and tissues of the body and their tumors vary in their capacity to sustain Injury: Phase of cell cycle Repair mechanisms Oxygenation  SENSITIVITY High – Lymphoma – Leukaemia – Seminoma Fairly high – Squamous carcinomas Moderate – GI, breast Low – sarcoma Chemotherapy This is the most common treatment. It utilizes a mix of chemicals that are toxic for cancer cells , it kill also healthy cells like : hair ,bone marrow, lymphocytes and others. So it can be very hard to the body. Drugs used have effects at particular stages of the cell cycle. Effects depend on tumour cells being in cell cycle. Also have an effect on rapidly dividing cells eg. bone marrow Chemotherapy Cyclophosphamide- can act on cells in G1, S phase and mitosis. Vincristine - can block cells entering cell cycle and act on mitosis Methotrexate - acts on cells in S phase HORMONE THERAPY Detection of hormone receptor. Ex: detection of estrogen receptors in breast cancer treated with hormonal therapy drugs lowering the level of estrogen or block estrogen receptors. Herceptin : is a type of targeted anticancer therapy called a monoclonal antibody,targeting HER-2 receptors in breast cancer with amplification/overexpression of High estrogen receptors ER Negative ER c-erbB-2/neu/HER-2  GENERAL Promotive and Preventive 1. Lifestyle Modification 2. Nutritional management 3. Screening 4. Early detection  SCREENING 1. Male and female- Occult Blood, CXR, and DRE 2. Female-, Mammography and Pap’s Smear 3. Male- DRE for prostate, Testicular self-exam The value of screening Cancer screening aims to detect cancer before symptoms appear, ( pre-malignant, non invasive and early invasive cancers ) to improve prognosis and increase survival rate. Its benefits including in terms of cancer prevention, early detection and subsquent treatment.  Cancer screening is not indicated unless life expectancy is greater than 5 years and the benefit is uncertain over the age of 70 years. Not useful for rare cancer. Screening recommendations depend on individual risk, those with high risk receiving earlier and more frequent than low risk people Include : Cervical cancer screening. Breast cancer screening. Colorectal cancer screening. Prostate cancer screening.  Cervical Relies on cytological examination of smears to detect “early” changes - dysplasia Factors include – -age range screened 21-29 every 3 year pap test alone. After 30 years old most prefered screen is co test(HPV test ) every 5 years till age of 65 years. population at risk more frequent (annually) -adequate smear, criteria of adequacy checked by cytotechnologist -cytological examination by cytopathologist  Breast Aims to identify invasive cancers before they can be felt (10-15 mm in size ) and DCIS Relies on mammography > 40 years Mammography Breast screening program Easier to detect lesions in the breasts of older women Women between 50-70 years invited every 3 years. Currently being extended 3 years either side (47-73) How can we improve prognosis? Identify “at risk” groups familial occupational Detect at an earlier stage cervix breast Prevention