1. GRADING AND STAGING OF TUMORS Dr.Ashraf Abdelfatah Deyab Assistant Professor of Pathology Faculty of Medicine Almajma’ah Univeristy

2. Goals

3. Introduction Stage and grade: methods to quantity the aggressiveness of neoplasms to: -Determine prognosis. -Compare treatment outcome of various protocol. Staging reflects the clinical extent of the tumor Grading a tumor reflects its histologic subtype, levels of differentiation, number of mitoses or architectural features..

4. Grading-Histologic alterations Enlarged nuclei and cells Increased nuclear-to-cytoplasmic ratio Hyperchromatic nuclei Pleomorphic (abnormally shaped) nuclei and cells Increased mitotic activity Abnormal mitotic figures Multinucleation of cells Keratin or epithelial pearls Loss of typical epithelial cell cohesiveness

5. Sapp, Eversole, & Wysocki (2004). Contemporary oral and maxillofacial pathology, 2 nd ed. St. Louis: Mosby, p. 181 Histologic alterations observed in tumor progression

6. WELL? (pearls) MODERATE? (intercellular bridges) POOR? (WTF!?!) GRADING for Squamous Cell Ca.

7. ADENOCARCINOMA GRADING

8. Grading-Histologic alterations Generally range from two categories (low grade and high grade) to four categories. Criteria for the grades vary with each form of neoplasia, with descriptive manner. Although histologic grading is useful, however the correlation between histologic appearance and biologic behavior. grading of cancers has proved of less clinical value than has staging

9. Staging The staging of cancers is based on: 1) The size of the primary lesion. 2) Its extent of spread to regional lymph nodes. 3) The presence or absence of blood-borne metastases. The major staging system currently in use is the American Joint Committee on Cancer Staging: Tumor-node-metastasis (TNM) system used for most cancers

10. Staging – TNM system Size, in cm, of the tumor (T) Involvement of lymph nodes (N) Presence or absence of distant metastasis (M)

11. Size of primary tumor (T) in cm TXNo information available on primary tumor T0No evidence of primary tumor TisCarcinoma in situ at primary site T1Tumor less than 2 cm T2Tumor 2-4 cm in diameter T3Tumor greater than 4 cm T4Tumor has invaded adjacent structures Staging – “T”

12. Lymph node involvement (N) NXNodes not assessed N0No clinically positive nodes (not palpable) N1 Single clinically positive ipsilateral (on same side) node less than 3 cm N2 Single clinically positive ipsilateral node 3 to 6 cm; or Multiple ipsilateral nodes with all less than 6 cm; or bilateral or contralateral nodes with none greater than 6 cm N3Node or nodes greater than 6 cm Staging – “N”

13. Staging – “M” Distant metastasis (M) MXDistant metastasis not assessed M0No distant metastasis M1Distant metastasis is present

14. TNM Staging System StageTNM Classification 0 Tis N0 M0 I T1 N0 M0 II T2 N0 M0 III T3 N0 M0 T1 N1 M0 T2 N1 M0 T3 N1 M0 IVT4 N0 M0 T4 N1 M0 Any T N2 M0 Any T N3 M0 Any T Any N M1

15. morbidity and mortality metastases rupture into major vessels compression of vital organs organ failure infection

16. LABORATORY DIAGNOSIS OF CANCER Histologic and Cytologic Methods. Immunohistochemistry. Flow Cytometry. Molecular Diagnosis-Molecular Profiles of Tumors. Tumor Markers

17. Histopathology &cytology Histopathology: Tissue biopsy. Cytology: (exfoliative, BAL, PAP, FNA). Gray zone, mimickers are real challenge. Clinical data in clinician request is crucial. Specimen received should be adequate

18. IMMUNOHISTOCHEMISTRY Helpful in diagnosis & treatment. Categorization of undifferentiated tumors, Leukemias/Lymphomas To determine the Site of origin Hormone Receptors, e.g., ERA, PRA. Detection of molecules that have prognostic or therapeutic significance ERBB2

19. Flow Cytometry. Rapidly quantitatively measure several individual cell characteristics, e.g membrane antigens and the DNA content of tumor cells. Identification and classification of tumors arising from T &B lymphocytes, mononuclear-phagocytic cells

20. Molecular Diagnosis (PCR, FISH, cytogenetic, DNA microarrays ). New established and some emerging: Diagnosis of malignant neoplasms: Prognosis of malignant neoplasms: presence indicate poor prognosis- stratification for therapy Detection of minimal residual disease: KRAS mutations(stool): colon ca. BCR-ABL(BLOOD)-CML Diagnosis of hereditary predisposition to cancer: tumor suppressor genes, including BRCA1, BRCA2, and the RET proto-oncogene.

21. TUMOR MARKERS HORMONES: (Paraneoplastic Syndromes) “ONCO”FETAL: AFP- liver HCC& non- seminomatous germ tumor, - CEA- ca colon, pancreas, stomach, breast. ISOENZYMES: PAP- prostate, NSE- SCC lung PROTEINS: -PSA- prostate tumor. GLYCOPROTEINS:CA-125- ovarian, CA-19-5- colon, pancreas, CA-15-3- breast MOLECULAR: p53, APC, RAS- Colon ca (stoo l+ serum) P53- (urine)- bladder,P53+RAS-LUNG,. Pancrea Immunoglobulin's: Multiple myleoma

22. Summary Stage and grade of tumors indicates prognosis Treatment plans based upon stage and grade, among other factors TNM system used with most cancers

23. LABORATORY DIAGNOSIS OF CANCER Histologic and Cytologic Methods. Immunohistochemistry. Flow Cytometry. Molecular Diagnosis-Molecular Profiles of Tumors. Tumor Markers