In oncology, staging represents the anatomical extension of the tumour and provides a standardised way of defining the size and spread of the tumour at the time of its diagnosis.
Staging is fundamental in oncology, as it provides the information necessary for the choice of therapy, to define the prognosis, to assess the results of treatment, to exchange information among the various cancer centres and to facilitate research. This implies that veterinarians who manage oncological patients must become accustomed to collecting and recording data on staging, as this provides the minimum information database necessary to approach each specific case.
THE TNM SYSTEM
The Tumour, Node, Metastasis (TNM) staging system is universally accepted to define the extension of a tumour; it is based on the clinical and, if possible, histological examination of the neoplasm.
The TNM staging system is based on three elements:
- T (tumour) = extension of the primary tumour (Fig. 1and Fig. 2)
- N (node) = presence or absence of spread to regional lymph nodes (Fig. 3)
- M (metastasis) = presence or absence of distant metastases (Fig. 4and Fig. 5).
A number is added to the T, N and M to indicate the extension of the neoplasm (a higher number indicates greater extension of the disease):
- T: T1, T2, T3, T4
- N: N0, N1, N2, N3
- M: M0, M1
In the presence of multiple tumours (of the same histotype) in the same subject, the tumour is staged on the basis of the one with the greatest extension, indicating within brackets the number of tumours present, e.g. T3 (2).
CLINICAL STAGE
Having defined the T, N and M, it is then possible to define the clinical stage. The clinical stage is a condensation of the T, N and M categories and ranges from 0 (in situ tumour) to IV/V (presence of distant metastases).
The goal of this stratification is to ensure that stages are homogeneous in terms of survival. In addition, the subdivision of patients according to clinical stage enables non-anatomical prognostic factors to be evaluated as a function of specific anatomical stages and a comparison of the importance of non-anatomical factors with the extension of the tumour. Once the clinical stage has been determined, it must remain unchanged within the patient’s clinical records.
GENERAL CRITERIA
T (Tumour)
- Tx: primary tumour cannot be evaluated
- T0: no evidence of primary tumour
- Tis: carcinoma in situ
- T1, T2, T3, T4: increase in size and/or local extension of the primary tumour
N (Node)
- Nx: regional lymph nodes cannot be evaluated
- N0: no regional lymph node involvement
- N1, N2, N3: increasing involvement of regional lymph nodes (e.g. N3 indicates fixed, typically non-resectable lymph nodes)
The sentinel lymph node is the first station which drains the lymph originating from the primary tumour. Within the TNM system, the following denominations are used when assessing the sentinel lymph node:
- Nx(sn): sentinel lymph node cannot be evaluated
- N0(sn): no sentinel lymph node involvement
- N1(sn): involvement of sentinel lymph node
M (Metastasis)
- Mx: distant metastasis cannot be evaluated
- M0: no distant metastasis
- M1: distant metastasis present
The site of the metastasis is indicated within brackets:
- lung metastasis: PUL
- bone metastasis: OSS
- liver metastasis: HEP
- brain metastasis: BRA
- lymph node metastasis: LYM
- bone marrow metastasis: MAR
- pleural metastasis: PLE
- peritoneal metastasis: PER
- adrenal metastasis: ADR
- skin metastasis: SKI
- other metastasis: OT
CLINICAL AND PATHOLOGICAL STAGING
Clinical staging (cTNM) is based on the clinical examination and on specific instrumental tests (which vary depending on the type of neoplasm present) to characterize the T and the N. cTNM is also named pre-treatment staging. The instrumental tests used for staging the patient include traditional radiology (direct and contrast-enhanced examinations), ultrasonography, computed tomography, magnetic resonance imaging and scintigraphy.
Pathological staging (pTNM) is based on the evidence acquired before treatment, modified or integrated with further evidence resulting from surgery and from the subsequent histopathological examination. pTNM is also named post-treatment or post-surgical staging.
The pathological assessment of T is based on surgical resection of the primary tumour or on the specific biopsy necessary to ascertain the highest pT class.
The pathological assessment of N is based on lymph node resection, in order to exclude any metastasis to regional lymph nodes (pN0) or to ascertain the highest pN class.
The pathological assessment of M is based on microscopic evaluation.
cTNM and pTNM are irreplaceable points of reference: the clinical stage is essential to select therapy and assess its effects, while the pathological staging provides precise data for predicting the prognosis, deciding on the necessary adjuvant therapy and analysing results.
ADDITIONAL SYMBOLS
- m: indicates the presence of multiple tumours
- y: indicates that staging was done during or after the start of multimodal therapy
- r: indicates a tumour relapse after a disease-free interval
- a: indicates that the staging was done for the first time at autopsy
CERTAINTY OF INFORMATION
The certainty factor, or factor C, reflects the validity of the staging information based on the diagnostic methodology used:
- C1: evidence from standard diagnostic means
- C2: evidence from special diagnostic means
- C3: evidence based upon surgical exploration, including cytology and/or histology
- C4:evidence based upon surgical removal of the tumour and histopathology
- C5: evidence based on autopsy
SPECIAL CONDITIONS
Lymphoma
- Stage I: involvement limited to a single lymph node or to lymphoid tissue of a single organ (including the cranial mediastinum).
- Stage II: regional involvement of several lymph nodes, with or without tonsillar involvement.
- Stage III: generalised lymph node involvement.
- Stage IV: involvement of the liver and/or spleen, with or without generalised lymph node involvement (stage I-III).
- Stage V: involvement of the bone marrow, blood and/or other extra-nodal organs (gastrointestinal tract, skin, kidneys, lungs with or without pleural effusion, only pleural effusion if not secondary to lymphadenopathy, eyes, pericardium, spinal cord), with or without the other stages.
Subclassification: each stage is further classified into subclasses “a” or “b”, indicating the absence or presence, respectively, of general symptoms or hypercalcaemia.
Mast cell tumour
- Stage 0: solitary skin lesion, excised without requiring a radical approach, with no involvement of lymph nodes.
- Stage I: solitary skin lesion with no involvement of lymph nodes or distant metastasis.
- Stage II:solitary skin lesion with involvement of lymph nodes.
- Stage III: multiple skin lesions or presence of a large, infiltrating tumour, with or without involvement of lymph nodes. No evidence of distant metastasis.
- Stage IV: presence of any lesion with distant metastases (including blood or bone marrow involvement).
Subclassification: each stage is further classified into subclasses “a” or “b”, indicating the absence or presence, respectively, of general symptoms.
Suggested readings
- Ehrhart EJ, Powers BE: The pathology of neoplasia. In: Withrow & MacEwen’s Small Animal Clinical Oncology, Withrow SJ and Vail DM (eds), Saunders Elevier, 2007: 54-67.
- Owen LM: TNM Classification of tumors in domestic animals. Geneva, World Health Organization, 1980.
- Sobin LH: TNM: principles, history, and relation to other prognostic factors. Cancer, 91: 1589, 2001.
- Sobin LH, Wittekind CH (a cura di), TNM Classification of Malignant Tumors. UICC (International Union Against Cancer), VI edizione, 2002.
- Sobin LH: TNM: evolution and relation to other prognostic factors. Semin Surg Oncol, 21: 3, 2003.
- Sobin LH: TNM, 6th edition: new developments in general concepts and rules. Semin Surg Oncol, 21: 19, 2003.