GRADING AND STAGING OF TUMORS
Dr.Ashraf Abdelfatah Deyab
Assistant Professor of Pathology
Faculty of Medicine
Almajma’ah Univeristy
Goals
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.
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Grading-Histologic alterations
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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
Histologic alterations observed in
tumor progression
Sapp, Eversole, & Wysocki (2004). Contemporary oral and maxillofacial pathology, 2nd ed. St. Louis: Mosby, p.
181
WELL?
(pearls)
MODERATE?
(intercellular bridges)
POOR?
(WTF!?!)
GRADING for Squamous Cell Ca.
ADENOCARCINOMA GRADING
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
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
Staging – TNM
system
• Size, in cm, of the tumor (T)
• Involvement of lymph nodes (N)
• Presence or absence of distant metastasis
(M)
Staging – “T”
Size of primary tumor (T) in cm
TX
No information available on primary tumor
T0
No evidence of primary tumor
Tis
Carcinoma in situ at primary site
T1
Tumor less than 2 cm
T2
Tumor 2-4 cm in diameter
T3
Tumor greater than 4 cm
T4
Tumor has invaded adjacent structures
Staging – “N”
Lymph node involvement (N)
NX
Nodes not assessed
N0
No 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
N3
Node or nodes greater than 6 cm
Staging – “M”
Distant metastasis (M)
MX
Distant metastasis not assessed
M0
No distant metastasis
M1
Distant metastasis is present
TNM
Staging
System
Stage
TNM 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
IV
T4 N0 M0
T4 N1 M0
Any T N2 M0
Any T N3 M0
Any T Any N M1
morbidity and mortality
• metastases
• rupture into major vessels
• compression of vital organs
• organ failure
• infection
LABORATORY DIAGNOSIS OF CANCER
• Histologic and Cytologic Methods.
• Immunohistochemistry.
• Flow Cytometry.
• Molecular Diagnosis-Molecular
Profiles of Tumors.
• Tumor Markers
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
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
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
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:
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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.
TUMOR MARKERS
• HORMONES: (Paraneoplastic Syndromes)
• “ONCO”FETAL: AFP- liver HCC& nonseminomatous germ tumor,
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- CEA-ca colon, pancreas, stomach, breast.
ISOENZYMES: PAP- prostate, NSE- SCC lung
PROTEINS: -PSA-prostate tumor.
GLYCOPROTEINS:CA-125- ovarian, CA-19-5colon, 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
Summary
• Stage and grade of tumors indicates
prognosis
• Treatment plans based upon stage and
grade, among other factors
• TNM system used with most cancers
LABORATORY DIAGNOSIS OF CANCER
• Histologic and Cytologic Methods.
• Immunohistochemistry.
• Flow Cytometry.
• Molecular Diagnosis-Molecular
Profiles of Tumors.
• Tumor Markers