1. Neoplasia 7 Dr. Hiba Wazeer Al Zou’bi

2. Clinical aspects of neoplasia Both malignant and benign tumors may cause problems because of (1) location and impingement on adjacent structures (2) functional activity such as hormone synthesis or the development of paraneoplastic syndromes (3) bleeding and infections when the tumor ulcerates through adjacent surfaces (4) symptoms that result from rupture or infarction (5) cachexia or wasting

3. CLINICAL ASPECTS OF NEOPLASIA 1- Location is crucial in both benign and malignant tumors: a. A small pituitary adenoma can destroy the surrounding normal gland, giving rise to hypopituitarism. b. Benign and malignant colon tumors can ulcerate and cause hemorrhage and in addition can cause obstruction.

4. 2. Cancer Cachexia - Progressive loss of body fat and lean body mass, accompanied by weakness, anorexia, and anemia - There is some correlation between the size and extent of spread of cancer and the severity of cachexia - Cachexia is not caused by the nutritional demands of the tumor. - Cachexia results from the action of soluble factors than reduced food intake; such as TNF (produced from tumor cells or host). - TNF suppresses appetite and inhibits the action of lipoprotein lipase, inhibiting the release of free fatty acids from lipoproteins - There is no satisfactory treatment for cancer cachexia other than removal of the underlying tumor.

5. 3- Paraneoplastic Syndromes Cannot be readily explained by local or distant spread of the tumor or by the elaboration of hormones native to the tissue of origin of the tumor. 10% to 15% of patients with cancer

6. Most common syndromes are hypercalcemia (PTHrP), Cushing syndrome(ACTH), and nonbacterial thrombotic endocarditis. Occurs in lung, pancreatic and breast cancers and hematologic malignancies. It should be noted that hypercalcemia resulting from bone metastases is not a paraneoplastic syndrome. Sometimes one tumor induces several syndromes concurrently such as bronchogenic carcinoma.

7. Grading and staging of cancer Grading of a cancer - Establish some estimate of tumor aggressiveness or level of malignancy based differentiation and the number of mitosis. -The cancer may be classified as grade I, II, III, or IV, in order of increasing anaplasia. - Criteria for the individual grades vary with each form of neoplasia

8. Staging of cancers is based on : a. The size of the primary lesion b. The spread to regional lymph nodes c. The presence or absence of metastases - This assessment usually is based on clinical and radiographic examination (CT and MRI) and in some cases surgical exploration

9. -Two methods of staging are currently in use: 1- TNM system (T, primary tumor; N, regional lymph node involvement; M, metastases) T1, T2, T3, and T4 describe the increasing size of the primary lesion N0, N1, N2, and N3 indicate progressively advancing node involvement M0 and M1 reflect the absence and presence of distant metastases 2- AJC (American Joint Committee) system. cancers are divided into stages 0 to IV, incorporating the size of primary lesions and the presence of nodal spread and of distant metastases. - Staging has proved to be of greater clinical value when compared with grading.

10. Diagnosis of cancer History & clinical examination -Symptoms: What the health care worker learns from talking to the patient. - Signs: Physical examination of patient e.g. A mass may be palpable or visible, fever…etc

11. Radiographic techniques – X ray – CT scan – MRI – Ultrasound Laboratory tests – CBC, LFT, KFT, stool for occult blood, blood sugar…….etc

12. Histologic methods: -Biopsy of tissue: Needle core biopsy, Endoscopic Biopsy, or open surgical biopsy -Excision of the whole mass - Frozen Section (Rapid technique) H&E, Special stains e.g. ( PAS, CONGO RED, PERL’s stains) or by IMMUNOHISTOCHEMICAL stains

13. Cytological methods: (Study of cells) 1- Fine needle aspiration (FNA): - Used most commonly with readily palpable lesions affecting the breast, thyroid, lymph nodes, and salivary glands - Modern imaging techniques permit extension of the method to deeper structures, such as the liver, pancreas, and pelvic lymph nodes. - Use of this diagnostic modality obviates surgery and its attendant risks

14. 2- Cytologic (Papanicolaou) smears - Investigate many forms of suspected malignancy, such as cervical carcinoma. - Identification of tumor cells in abdominal, pleural, joint, and cerebrospinal fluids

15. Immunocytochemistry - Detection of cytokeratin by specific monoclonal antibodies labeled with peroxidase points to a epithelial origin of tumor. - Detection of prostate-specific antigen (PSA) in metastatic deposits by immunohistochemical staining allows definitive diagnosis of a primary tumor in the prostate. - Immunocytochemical detection of estrogen receptors allows prognostication and directs therapeutic intervention in breast cancers.

16. Electron Microscopy: - Study the intracellular structures: desmosomes, neurosecretory granules, etc…

17. Flow cytometry: - Used in the classification of leukemias and lymphomas. - In this method, fluorescent antibodies against cell surface molecules and differentiation antigens are used to obtain the phenotype of malignant cells.

18. Tumor Markers -Biochemical assays for tumor-associated enzymes, hormones, and other tumor markers in the blood. - Cannot be utilized for definitive diagnosis of cancer, but they can be useful screening tests and in some instances have utility in quantitating the response to therapy or detecting disease recurrence. PSA, used to screen for prostatic adenocarcinoma Carcinoembryonic antigen (CEA), elaborated by carcinomas of the colon, pancreas, stomach, and breast Alpha fetoprotein: Hepatocellular carcinomas All of these markers can be produced in a variety of non- neoplastic conditions as well.

19. Molecular diagnosis: - Methods used include:  PCR (Polymerase Chain Reaction)  FISH (Fluorescent In Situ Hybridization) -Used for diagnosis to detect gene rearrangement, translocations, amplifications…etc -For prognosis - Detection of residual disease in chronic myeloid leukemia (BCR-ABL) Diagnosis of hereditary predisposition to cancer e.g BRCA-1 in breast cancer Useful in TARGETED THERAPY