GRADING AND STAGING OF

TUMORS & PARANEOPLASTIC

SYNDROME

Shiksha Choytoo

Roll No. 12

22 September 2014

Introduction

Grading and staging are systems

developed to quantify the extent of a

neoplasm in a given case and its clinical

aggressiveness and to compare the end

results of various treatment modalities.

GRADING

Grading

• It is done on two basis:

1. level of differentiation

2. Number of mitotic figures per high power field

• It is done by histopathological exam. By pathologist.

Differentiation

• It is the extent to which the

tumor cells represent their

normal counter part both

morphologically and

functionally.

• Lack of differentiation

is anaplasia.

Mitotic Figure per HPF

• Cell under mitosis are easy

to spot

• The chromosomes are

visible as tangled, dark-

staining threads.

• We call these “mitotic

figures”.

• Helps in grading of tumor.

• The malignancy of tumor can be graded into 4 categories.

• Recommended by the American Joint commission on Cancers and other bodies

GRADES DESCRIPTION

GX Grade cannot be assessed

G1 Well differentiated (Low grade)

G2 Moderately differentiated (Intermediate grade)

G3 Poorly differentiated (High grade)

G4 Undifferentiated (High grade-ANAPLASIA)

Gleason Scale

Grading of CA Prostate

Grading of CA Breast

STAGING

• It is based on

1. Tumor size and/or extent reached

2. Lymph node status

3. presence or absence of metastasis

• It is done by detailed clinical examination, usually along with radiological exam. (x-ray, CT scan, MRI, Ultrasonography)

• Sometimes surgical exploration may be required.

• There are two systems of staging

1. Union for international cancer control (UICC)

The TNM system

2. American Joint Committee on Cancer (AJCC)

• Most medical facilities use the TNM system as their main method for cancer reporting.

TNM System

T • TUMOR SIZE

N • NODAL STATUS

M • +/- METASTASIS

Tumor sizeTUMOR (T) DESCRIPTION

TX Primary tumor cannot be evaluated

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor < 2cm

T2 Tumor 2-5cm

T3 Tumor > 5cm

Eg: CA Prostate

• NOTE

CA in situ

abnormal cells are present but have not spread to neighbouring tissue;

although not cancer, CIS may become cancer

sometimes called preinvasive cancer

Lymph Node Status

LYMPH NOTE STATUS (N) DESCRIPTION

NX Regional lymph nodes cannot be evaluated

N0 No regional lymph node involvement

N1 3 Lymph nodes + Axillary

N2 10 Lymph nodes+

Distant Metastasis (+/-)

METASTASIS DESCRIPTION

MX Distant metastasis cannot be evaluated

M0 No distant metastasis

M1 Distant metastasis is present

Eg: CA Breast

System based on AJCC

STAGE DESCRIPTION

Stage 0 Carcinoma in situ

Stage I

Stage II

Stage III

Higher numbers indicate more extensive disease:

Larger tumor size and/or spread of the cancer beyond

the organ in which it first developed to nearby lymph

nodes and/or tissues or organs adjacent to the location

of the primary tumor

Stage IV The cancer has spread to distant tissues or organs

Importance of grading and

staging

• Helps the doctor plan the appropriate treatment

• Estimates patients’ prognosis trials and comparing the

results of different trials.

• Helps health care providers and researchers exchange

information about patients.

• It also gives them a common terminology for

evaluating the results various treatments

NOTES

• Not all cancers have TNM Designation, eg cancers of spinal

cord and brain ( they are staged according to cell type and

grade)

• Most of the cancers of blood and bone marrow does not

have a clear cut staging system

• Ann Arbor staging classification – lymphomas

• Another staging system, developed by the International

Federation of Gynecology and Obstetrics (FIGO), is used to

stage cancers of the cervix, uterus, vagina, ovary and vulva.

PARANEOPLASTIC

SYNDROME

Definition

Paraneoplastic syndromes are defined as

symptoms complexes occurring in cancer

bearing patients which cannot be explained

on the basis of

• Local spread

• Distant spread

• Elaboration of hormone belonging to that

particular site from the tumor arose.

Significance

• May be the 1st manifestation of occult neoplasm

• It may mimic metastatic disease and confuse treatment

• It may be a serious clinical manifestation that prove fatal

Paraneoplastic syndromes can be grouped into the following 4 categories:

• Endocrinopathies

• Neurological

• Musculocutaneous

• Vascular and hematological

Endocrinopathies

CLINICAL SYNDROME

UNDERLYINGCANCER

CAUSAL MECHANISM

Cushing Syndrome •Small cell CA lung•Pancreatic cancer

Production of ACTH or ACTH like substances

SIADH- Syndrome of inappropriate ADHsecretion

•Small cell CA lung•Intracranial neoplasm

Ectopic ADH or atrialNatriuretic hormone

Hyper calcemia •Squamous cell CA lung•CA Breast•Renal cell CA•Ovarian CA•Adult T cell LL

Production of parathomone related peptide, TGF-alpha,TNF-alpha, IL-1

Hypoglycemia •Fibrosarcoma•Hepatocellular CA

Production of insulin and insulin like substance

Carcinoid Syndrome •Bronchial CA•Pancreatic Cancer•Gastric cancer

•Serotonin•Bradykinin

Polycythemia Renal Cell CA Erythropoetin

Nerve and Muscle Syndm.CLINICAL SYNDROME

UNDERLYINGCANCER

CAUSAL MECHANISM

Myesthenia gravis likes syndrome

Bronchogenic CA Immunological

Disorders of CSN & PNS CA Breast

DERMATOLOGICAL DISORDERSAcanthosis Nigricans

•Gastric CA•CA Lung•Uterine CA

Immunological & secretion of epidermal GF

Dermatomyositis CA LungCA Breast

Immunological

OSSEOUS,ARTICULARAND SOFT TISSUE CHANGES

Hypertropic osteoarthritis and clubbing of finger

Bronchogenic CA Unknown

Vascular & Hematological Changes

CLINICAL SYNDROME

UNDERLYINGCANCER

CAUSAL MECHANISM

Venous thrombosis or migratonisthrombophlebitis

•Pancreatic cancer•Bronchogenic CA•Mucin secreting adenocarcimoma

Tumor products and mucin activated clotting pathway

DIC Acute promylocyticleukemia

Muccin activated coagulation cascade

NBTE ( Non bacterial

endocarditis)

Disceminated/ Advanced CA

Anemia Thymic neoplasm Unknown

OTHERSNephrotic syndrome

Various cancers Deposition of tumor antigens & antibodies or immune complexes

References

• Class Notes

• Robbins and Cotran- pathology textbook

• Internet

• Wikipedia

Thank you