STAGING AND GRADING OF TUMORS

GUIDE-DR.J.K.KUDRIMOTI

• Neoplasia is defined as abnormal mass of tissue,the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after ceasation of the stimuli which evoked the change.

• Neoplasias are classified as benign or malignant.• Histology provides a definitive diagnosis and also

allows grading and assessment of spread (staging) in cases of malignant tumors.

• Histological diagnosis requires biopsy which may be either incisional or excisional.

• Incisional biopsy-Removal of small portion of tumor.This is for tumors that are thought to be inoperable .This includes endoscopic biopsy, core needle biopsy, fine needle aspiration biopsy.

• Excisional biopsy-This is the most important type of biopsy which allows to assess the extent of spread.

• Grading and staging are 2 systems to determine prognosis and choice of treatment after a malignant tumor is detected.

• These two methods of evaluating malignant tumors (grading and staging) are based on different parameters.

• The curability of a tumor usually is inversely proportional to the tumor burden, which is indicated by the stage and grade of the tumor.

Staging-Staging is defined as the extent of disease evaluated by a variety of noninvasive and invasive diagnostic tests and procedures.

Stage can be assesed by 3 ways –by clinical examination, investigations and by pathologic examination of the tissue removed.

Types of staging-There are two types- a) Clinical staging is based on physical examination, radiographs,

isotopic scans, CT scans, and other imaging procedures; b)Pathologic staging takes into account information obtained

during a surgical procedure,1.intraoperative palpation, 2.resection of regional lymph nodes and/or3. tissue adjacent to the tumor, and inspection and biopsy of organs

commonly involved in disease spread.

• Pathologic staging includes histologic examination of all tissues removed during the surgical procedure.

• Knowledge of the predilection of particular tumors for spread to adjacent or distant organs helps direct the staging evaluation.

• Information obtained from staging is used to define the extent of disease either as localized, as exhibiting spread outside of the organ of origin to regional but not distant sites, or as metastatic to distant sites.

• Staging systems-2 important staging systems currently followed are-TNM staging and AJC staging.

• The most widely used system of staging is the TNM (tumor, node, metastasis) system originally developed by Pierre Denoix in France in 1940 and adopted by the International Union Against Cancer and the American Joint Committee on Cancer (AJCC) in 1950s.

• During the 1990s the importance of TNM staging of cancer was heightened by the mandatory requirement that Commission on Cancer-approved hospitals use the UICC or AJCC TNM system as the major language for cancer reporting.

• General rules of the TNM system- The TNM system is an expression of the anatomic extent of the

disease and is based on the assessment of 3 components:as T-The extent of primary tumor . N-The absence or presence and extent of regional

lymph node metastasis. M-The absence or presence of distant metastasis.• Definitions of TNM-• Primary tumor-(T)- Tx-Primary tumor cannot be assesed. T0-No evidence of primary tumor. Tis-Carcinoma in situ. T1,T2,T3,T4-Increasing size and/or local extent of primary

tumor.

• Regional lymph nodes-(N)- Nx-Regional lymph nodes cannot be assesed. N0-No regional lymph node metastasis. N1,N2,N3-Increasig involvement of regional lymph nodes. Direct extension of the primary tumor into a lymph node is classified

as lymph node metastasis. Metastasis in any lymph node other than regional is classified as

distant metastasis.• Distant metastasis-(M)- Mx-Distant metastasis cannot be assesed. M0-No distant metastasis. M1-Distant metastasis. For pathologic Stage grouping ,if sufficient tissue to evaluate the

highest T and N categories has been removed for pathological examination ,M1 may be either clinical(cM1) or pathologic(pM1).If only the metastasis has had microscopic confirmation the classification is pathoilogic and the stage is pathologic.

Stage grouping-The various permutations of T, N, and M scores (sometimes including tumor histologic grade G) are then broken into stages, usually designated by the roman numerals I through IV.

AJC staging-( American Joint Committee Staging)-divides all cancers into stage 0 to 4 and takes into account all 3 components of the preceeding system in each stage.

Significance of staging-1.Tumor burden increases and curability decreases with

increasing stage. 2.Staging serves to estimate the chances of survival in the

individual patient.3.It helps to compare the results of treatment in different

institutions.

• Some cancers, like squamous cell carcinomas of the uterine cervix, are staged by the clinical examination alone; for others, like transitional cell carcinomas of the bladder and adenocarcinomas of the large bowel, the stage is determined on the basis of the findings in the resected specimens.

In both cases, there is an excellent correlation with the prognosis.

Other staging systems- Other anatomic staging systems are used for some tumors,

e.g., Dukes classification for colorectal cancers, FIGO(International Federation of Gynecologists and

Obstetricians ) classification for gynecologic cancers, Ann Arbor classification for Hodgkin's disease.1

• The staging of bladder neoplasms, devised by Jewett, is as follows:

stage A, invasion of submucosa,five-year survival rate of 53.7 percent;

stage BI, superficial half of the muscle, 52.6 percent; stage B2, deep half of muscle, 28.6 percent; and

stage C,perivesical tissues, 17.9 percent.• Large bowel cancers are staged,according to Dukes, as:

stage A, tumor restricted to the wall of the bowel, with a five-year survival rate of 90 percent;

stage B, with invasion through the wall into the peritoneum or perirectal fat, 65 percent; and

stage C, with regional lymph node metastases, 20 percent.

• Staging of melonomas of the skin has shown to correlate very closely with incidence of lymph

node metastasis and patient survival,whether it is done with the Clark or by measuring the maximum thickness of the tumor in millimeters, as recommended by Breslow.

In the series of Holmes et al. metastatic lymph nodes were present in 32 percent of Level III cases and in over 65 percent of Levels IV and V cases.

Drawbacks of staging- Certain tumors cannot be grouped on the basis of anatomic

considerations. For example, hematopoietic tumors such as leukemia,

myeloma, and lymphoma are often disseminated at presentation and do not spread like solid tumors. For these tumors, other prognostic factors have been identified.

• Grading-Grading is defined as the macroscopic and microscopic degree of differentiation of the tumor.

• Cancers can be graded grossly and microscopically.• Gross features like exophytic or fungating appearance are

indicative of less malignant growth than diffusely infiltrating tumors.

• However grading is largely based on 2 important histologic features-the degree of anaplasia and rate of growth.

• Based on these features cancers are categorised from grade 1 as the most differentiated to grade 3 ,4 as the most undifferentiated or anaplastic.

• Many systems of grading have been proposed but the one described by Borders for dividing squamous cell carcinoma into 4 grades depending upon degree of differentiation is followed for other malignant tumors as well.

• When grading a tumor, the pathologist is referring to the appearance of the tumor cells, specifically to their degree of anaplasia.

• Von Hanseman and Borders were leaders in popularizing this approach.

• 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.

• Borders grading is as follows- 1-Well differentiated(<25% anaplastic cells) 2-Moderately differentiated (25-50 %) 3-Moderately differentiated (50-75%) 4-Poorly differentiated or anaplastic (>75%) • This is reported as: Gx-Grade cannot be assesed. G1-Well differentiated G2-Moderately differentiated G3-Poorly differentiated. G4-Undifferentiated

• However grading of tumors has several shortcomings.

• It is subjective and the degree of differentiation may vary from one area of tumor to the other.

• If different areas of a given neoplasm show different grades of malignancy, the tumor should be graded according to the more undifferentiated area (prostatic cancer being an exception).

• Because of this focal variation in the degree of differentiation, the grade assigned to a small biopsy of a tumor may not always be representative of the whole neoplasm.

• Therefore it is common practice to grade cancers in descriptive terms (eg-well differentiated undifferentiated, keratinising non keratinising ,etc) rather than giving the tumors grade numbers.

• Grading has no prognostic value in certain types of cancers, such as ofmelanoma the skin, and in others it is of questionable value.

• Grading of salivary malignancies is not standardised and may vary according to histologic type.In some instances histologic type defines grade;for eg-myoepithelial carcinoma and basal cell adenocarcinoma are low grade while salivary duct carcinoma is usually high grade.

• In some tumors, such as transitional cell carcinoma of the urinary bladder, the grading has a direct relationship to the prognosis. The five-year survival rate of Grade I tumors is 80 percent, whereas for Grade III neoplasms it is only 20%.

• In the central nervous system, grading is useful for astrocytomas, but not for ependymomas or oligodendrogliomas.

• In bone sarcomas, grading is of value for chondrosarcomas, since the five year survival rate is 78 percent for the well-differentiated tumors, 53 percent for the moderately differentiated and only 22percent for the poorly differentiated ones.

• Grading is of no value for osteosarcomas, except for some distinct subtypes of this tumor.

• Gleason has shown a remarkable correlation between a five grade system of prostatic carcinoma and patient survival.

• Other grading systems used- 1. Scarff Bloom Richardson Grading system for Ca breast based

on degree of tubule formation , nuclear grade and mitotic rate.Points are asigned to each parameter. The histologic grade is determined by summing the points.

2. Albores Saavedra grading system for papillary intraductal carcinomas of pancreas is based on nuclear typia and mitotic figures.

3. Because of poor correlation of cytologic features ,pattern of growth and biologic behavior in most endocrine tumors they are not graded.

4. No grading is currently available for Ca parathyroid. 5.Gleasons grading system is used for prostate Ca which

proposes that Ca prostate may show one or several of 5 histologic patterns. Gleasons score has prognostic significance.

• Fuhran nuclear grade is used to grade kidney tumors.