Grading Staging And Prognostic Factors Notes

Grading, Staging, And Prognostic Factors

‘Grading’ and ‘staging’ are the two systems to predict tumour behaviour and guide therapy after a malignant tumour is detected. Grading is defined as the gross appearance and microscopic degree of differentiation of the tumour, while staging means the extent of the spread of the tumour within the patient.

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Thus, grading is done on patholologic basis while staging is on clinical grounds.

Grading

Cancers may be graded grossly and microscopically. Gross features like exophytic or fungating appearance are indicative of less malignant growth than diffusely infiltrating tumours. Grading is largely based on 2 important histological features: the degree of anaplasia, and the rate of growth.

Based on these features, cancers are categorised from grade I as the most differentiated, to grade III or IV as the most undifferentiated or anaplastic. Many systems of grading have been proposed for epithelial and mesenchymal tumours.

Epithelial Tumours:

Grading described by Broders for dividing squamous cell carcinoma into 4 grades depending upon the degree of differentiation is followed for other malignant tumours as well. Broders’ grading is as under:

1. Grade I: Well-differentiated (less than 25% anaplastic cells)
2. Grade II: Moderately-differentiated (25-50% anaplastic cells)
3. Grade III: Moderately-differentiated (50-75% anaplastic cells)
4. Grade IV: Poorly-differentiated or anaplastic (more than 75% anaplastic cells)

Soft Tissue Tumours:

The number of pathological grades of soft tissue tumours may vary according to different grading systems: 2-grade system (grade I-II as low and high grade), 3- grade system (grade I, II, III as low, intermediate and high grade) and 4-grade system (grade IIV).

Pathological grading is based on following 3 features:

1. Tumour differentiation or degree of cytologic atypia
2. Mitotic count
3. Tumour necrosis

However, the grading of tumours has several shortcomings. It is subjective and the degree of differentiation may vary from one area of tumour to the other.

Therefore, it is common practice with pathologists to grade cancers in descriptive terms (for example, Well-differentiated, undifferentiated, keratinising, non-keratinising etc) rather than giving the tumours grade numbers.

More objective criteria for histologic grading include modern methods such as:

• Flow cytometry for mitotic cell counts
• Cell proliferation markers by immunohistochemistry
• Image morphometry for cancer cell and nuclear parameters.

Staging

The extent of spread of cancers in a case can be assessed in 3 ways—by clinical examination, by investigations, and by pathologic examination of the tissue removed. Two important staging systems currently followed are: TNM staging and AJC staging.

While TNM and AJC staging systems can be applied for the staging of most malignant tumours, soft tissue tumours are also staged by Enneking’s staging system.

TNM staging:

TNM staging (T for primary tumour, N for regional nodal involvement, and M for distant metastases) was developed by the UICC (Union Internationale Contre Cancer, Geneva).

For each of the 3 components (T, N and M), numbers are added to indicate the extent of involvement as under:

1. T0 to T4: In situ lesion to largest and most extensive primary tumour.
2. N0 to N3: No nodal involvement to widespread lymph node involvement.
3. M0 to M2: No metastasis to disseminated haematogenous metastases

AJCC staging:

American Joint Committee staging divides all cancers into stage 0 to IV, and takes into account all the 3 components of the preceding system (primary tumour, nodal involvement and distant metastases) in each stage.

Enneking’s staging:

This staging system is accepted by most oncologists and is based on the grade and location of the tumour as under:

According to tumour location T1 (intracompartmental) and T2 (extra compartmental)
tumours.

• According to tumour grade G1 (low grade) and G2 (high grade) tumours.
• Accordingly, the stages of soft tissue tumours vary from stage I to stage III as under:

1. 1. Stage I G1 and T1-T2 tumours, but no metastases.
   2. Stage II G2 and T1 -T2 tumours, but without metastases.
   3. Stage III G1 or G2, T1 or T2 tumours, but with metastases.

Currently, clinical staging of tumours does not rest on routine radiography (X-ray, ultrasound) and exploratory surgery but more modern techniques are available by which it is possible to ‘stage’ a malignant tumour by non-invasive techniques. These include the following:

• Modern imaging techniques: Such as computed tomography (CT) and magnetic resonance imaging (MRI) scan based on tissue density for locating the local extent of the tumour and its spread to other organs.
• The availability of positron emission tomography (PET) scan has further overcome the limitation of CT and MRI scan because PET scan facilitates the distinction of benign and malignant tumour on the basis of biochemical and molecular processes in tumours.
• Radioactive tracer studies: In vivo such as the use of iodine isotope 125 bound to specific tumour antibodies is another method by which small number of tumour cells in the body can be detected by imaging of tracer substance bound to specific tumour antigen.

Prognostic Factors

Three cardinal features of malignant tumours are:  Anaplasia, Invasion and Metastasis. Metastasis is a common event in malignant tumours which greatly reduces the survival of the patient.

Evidence has shown that in metastatic tumours, the survival of the host is correlated with some clinical and molecular features of tumours which act as prognostic markers. Although specific markersare given in related chapters, some common prognostic markers are as under:

• Clinical prognostic markers: Size, histologic grade, nodal involvement and vascular invasion by the tumour.
• Molecular prognostic markers:  Molecular markers indicative of poor prognosis in certain specific tumours are as follows:
  • Expression of an oncogene by tumour cells (C-met)
  • CD44 molecule
  • Hormone receptors (ER, PR)
  • Human epidermal growth factor receptor (HER2/neu)
  • Angiogenesis factors and degree of neovascularisation
  • Expression of metastasis-associated gene for nucleic acid (MAGNA) in the DNA fragment in metastasising tumour.
  • Proliferation markers and mitotic index

Grading, Staging, and prognostic Factors:

• Grading of tumours is done on pathologic examination and includes the gross appearance and microscopic degree of differentiation of the tumour (for example, Well differentiated, poorly differentiated).
• Staging of the cancer is clinical, and it means the extent of spread of the tumour within the patient (for example, TNM staging, AJC staging).
• Soft tissue tumours are also staged by Enneking staging that takes into account tumour location(compartment involved) and grade.
• Prognostic parameters vary depending upon the type of tumour. However, a few general prognostic factors are size, grade, regional nodal involvement and distant spread.
• Molecular factors are an expression of certain oncogenes, hormone receptors, mitotic index etc.