4. STAGING AND CLASSIFICATION SYSTEMS
The classification and morphology of UTUC and bladder carcinoma are similar . However because of the difficulty in adequate sample acquisition, it is often difficult to distinguish between non-invasive papillary tumours , flat lesions (carcinoma in situ [CIS]), and invasive carcinoma. Therefore, histological grade is often used for clinical decision making as it is strongly associated with pathological stage .
4.2. Tumour Node Metastasis staging
The tumour, node, metastasis (TNM) classification is shown in Table 1 . The regional lymph nodes (LNs) are the hilar and retroperitoneal nodes and, for the mid- and distal ureter, the pelvic nodes. Laterality does not affect N classification.
4.3. Tumour grade
In 2004 and 2016, the WHO and the International Society of Urological Pathology published a new histological classification of UCs which provides a different patient stratification between individual categories compared to the older 1973 WHO classification [77,78]. In 2022, an update of the 2004/2016 WHO grading classification was published without major changes . These guidelines are still based on both the 1973 and 2004/2016 WHO classifications since most published data use the 1973 classification .
Table 1: TNM classification 2017 for upper tract urothelial cell carcinoma 
TNM classification 2017 for upper tract urothelial cell carcinoma
T - Primary tumour
Primary tumour cannot be assessed
No evidence of primary tumour
Non-invasive papillary carcinoma
Carcinoma in situ
Tumour invades subepithelial connective tissue
Tumour invades muscularis
(Renal pelvis) Tumour invades beyond muscularis into peripelvic fat or renal parenchyma
Tumour invades adjacent organs or through the kidney into perinephric fat
N - Regional lymph nodes
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single lymph node 2 cm or less in the greatest dimension
Metastasis in a single lymph node more than 2 cm, or multiple lymph nodes
M - Distant metastasis
No distant metastasis
TNM = Tumour, Node, Metastasis (classification).
4.4. Molecular classification of UTUCs
A number of studies focussing on molecular classification have been able to demonstrate genetically distinct groups of UTUC by evaluating DNA, RNA and protein expression. Five different molecular subtypes with different gene expression, tumour location and outcome have been identified, but, as yet, it is unclear whether these subtypes will respond differently to treatment and therefore, these subtypes have limited use in daily practice .