Malignant neoplasms are among the leading causes of death in recent US statistic: death from malignancy is currently only second to cardiovascular diseases. As an aspiring medical professional, you will find cancer in nearly every clinical field. As widely varied as tumors can be, characterization through staging and grading is virtually universally applicable. Both indicators help to make statements regarding prognosis and treatment. Here you will learn the appropriate terminology, and how to classify and differentiate between them.

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Grading is understood as the histological assessment of tumor cells according to their state of differentiation.Differentiation in microscopic appearance of tumor cells determine the numbering of grade. Based on the resemblance and differentiation of tumor cells with normal healthy cells, they are grouped into four types. Well differentiated tumors (low grade) generally have a better prognosis than poorly differentiated tumors (high grade).

 G1  Well differentiated, close similarity to original tissue (“low grade“)
 G2  Fairly differentiated malignant tissue (intermediate grade)
 G3  Poorly differentiated malignant tissue (High grade)
 G4 Undifferentiated malignant tissue; the original tissue which gave rise to the tumor can only be determined by immuno-histochemical evaluation or not at all (high grade)
 G9  Cannot gauge level of differentiation (undetermined grade)

Aside from a few exceptions, grading is performed on all types of tumors: prostate tumors receive histologic assessment according to the GLEASON-Score, breast tumors are assessed by Nottingham grading system while brain tumors have their own WHO classification.

Tumor Grade is evaluated by visual and microscopic examination of tumor cells during a surgery or biopsy.

Note: Grading describes the grade of the histologic change of tumor tissue with the neighboring healthy tissue


Staging of tumor can be defined as the size and extent of the overgrowth that spread throughout the body. Stage of tumor is evaluated by different laboratory tests such as x-rays, ultrasound, CT scan, etc. Solid tumors are usually classified by using the TNM system. This system of classification has been administered by the UICC (Union Internationale Contre le Cancer) since the 50s and is regularly updated.

The three letters (T, N and M) stand for the separate categories: tumor (size and extent of primary tumor), node (involvement of neighboring lymph nodes) and status of metastases respectively.

Primary tumor (T) Tx: Measurement of primary tumor cannot be done

T0: Absence of primary tumor

T1–4: Assignment of various stages occurs according to specific tumor, taking into account different criteria such as size (diameter), invasive depth, infiltration of neighboring tissue and organs

Involvement of lymph nodes (N) Nx: Involvement of neighboring lymph nodes cannot be assessed

N0: No involvement of neighboring lymph nodes

N1–3: Number and localization of involved lymph nodes developing cancer

Distant metastases (M) Mx: Distant metastases cannot be assessed

M0: No metastases

M1: Distant metastases observed

An example of tumor description according to TNM classification could be T1N0M0. This would mean that the tumor has only moderate localized spread, does not affect any lymph nodes and there are no distant metastases.

Lower case letters which precede the TNM code help to provide additional information. For example, ”a” means that a tumor was discovered by means of an autopsy, ”c” advises of clinical diagnosis, ”p” specifies confirmation of stage through pathological evaluation, ”y” means previous neo-adjuvant therapy, and ”r” indicates reoccurrence.

TNM system is further divided into following five stages to illustrate the staging of tumor:

Stage 0 There is marked growth of abnormal cells in the tissue not spreading to neighboring tissue but they have potential to develop into tumor, are also termed as carcinoma in situ
Stage I, Stage II, Stage III Assignment of various stages occurs according to specific tumor, taking into account different criteria such as size (diameter), invasive depth, infiltration of neighboring tissue
Stage IV Metastasis to different organs

The combination of all three categories finally determines the tumor stage. The criteria for staging is specifically defined according to tumor type and is based on the statistical analysis of stage-specific prognosis and corresponding treatment options.

Staging is a routine part of tumor diagnostics since it has considerable influence on the course of the treatment. Important diagnostic procedures involved for the detection of stages of tumor involve radiological modalities such as ultrasound, CT and x-ray (determination of tumor size and local spread, lymph node involvement as well as distant metastases), nuclear medicine, and tissue sampling for histological, immuno-histochemical and/or cytological examination

Note: Staging describes the totality of all indicated examinations which are necessary to determine malignant tumor spread. Observations are described by TNM classification and assigned to a specific stage.  

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