Características

• Urothelial Cancers: facts
  - Make up 10-15% of all renal tumors
  - 90% are transitional cell carcinomas, 9% are squammous cell carcinoma and 1% are mucinous adenocarcinoma
  - Average age is 6-7th decade of life
  - Male to female ratio is 3-1
  - 40% of patients with upper tract TCC will develop metachronous TCC of the lower urinary tract

• TCC Staging

  • Localized

    • Patients with localized disease may be classified into three groups:

      • Group 1: Low-grade tumor confined to the urothelium without lamina propria invasion (papilloma grade I transitional cell cancer).

      • Group 2: Grade I–III carcinomas without demonstrable subepithelial invasion or focal microscopic invasion or papillary carcinomas with carcinoma in situ and/or carcinoma in situ elsewhere in the urothelium.

      • Group 3: High-grade tumors that have infiltrated the renal pelvic wall or renal parenchyma or both but remain confined to the kidney. Infiltration of muscle in the upper tract may not be associated with as much potential for distant dissemination as appears to be the case for bladder cancer.

  • Regional

    • • Group 4: Extension of tumors beyond the renal pelvis or parenchyma and invasion of peripelvic and perirenal fat, lymph nodes, hilar vessels, and adjacent tissues

  • Metastatic

    • • Spread of the tumor to distant tissues.

• “Our data is in line with the known epidemiologic characteristics of UTUC. CT imaging is the preferred imaging modality as also recommended by guidelines. Diagnostic URS (ureteroscopy) gained a stronger position, however, in almost half of patients a definitive treatment decision was made without complete endoscopic information. Only one-third of patients with UTUC are currently treated with kidney sparing surgery.”
  Contemporary patterns of presentation, diagnostics and management of upper tract urothelial cancer in 101 centres: the Clinical Research Office of the Endourological Society Global upper tract urothelial carcinoma registry, 
  Baard, Joyce et al.
  Current Opinion in Urology: July 2021 - Volume 31 - Issue 4 - p 354-362

• “The major risk factors for urothelial carcinoma of the upper urinary tract include male gender, increasing age, cigarette smoking and tobacco use, phenacetin abuse, exposure to certain chemicals and drugs (such as cyclophosphamide), chronic hydronephrosis, and a history of prior recurrent or severe urinary tract infections..”
  Upper and Lower Tract Urothelial Imaging Using Computed Tomography Urography 
  Siva P. Raman, MD*, Elliot K. Fishman
  Urol Clin N Am 45 (2018) 389–405

• “Urothelial cancer (UC) constitute up to 10% of neoplasms of the upper urinary tract. UC occurs most frequently in the extrarenal part of the renal pelvis, followed by the infundibulocaliceal region. When manifesting as an infiltrative pattern, UC expands out of the renal pelvis into the parenchyma with distortion of the normal renal corticomedullary architecture with preservation of the reniform shape, which is not typically the case in RCC -  Nota : RCC de alto grau com padrão sarcomatoide por exemplo podem ter esse caráter mais infiltrativo, assim como os tumores de ducto coletor e os medulares 

• Urothelial Cancers: CT Findings
  - Single or multiple sessile filling defects that compress the renal sinus fat
  - Pelvicaliceal irregularities (stricture like)
  - Focal or diffuse mural thickening
  - Caliceal amputation
  - Tumor filled distended calices

• Transitional Cell Carcinoma: Differential Diagnosis
  - Large TCC’s may look similar to
  --- Infiltrating renal cell carcinoma (aggressive RCC /medular/ ducto coletor)
  --- Lymphoma
  --- Metastases
  --- Xanthogranulomatous pyelonephritis

• “The most common imaging manifestation of transitional cell carcinoma in the ureters is urothelial thickening, particularly focal thickening or a short-segment ureteral stricture. Similar to other sites in the urinary tract, diffuse or bilateral urothelial thickening in the ureters is unlikely to represent malignancy, and is much more likely to represent an ascending urinary tract infection (particularly when associated with diffuse bladder wall thickening secondary to cystitis).”

• “As with other portions of the urinary tract, transitional cell carcinomas in the ureter are often hypovascular, making it critical that the field of view includes the entirety of the ureters during the arterial phase acquisition. Any focal or irregular urothelial hyperenhancement should raise concern for malignancy, and, in some instances, there may be associated tumor neovascularity.”

• “ The hallmark of TCC is multiplicity and recurrence. Nearly 2-4% of patients with bladder cancer develop upper tract TCC, but 40% of patients with upper tract TCC develop bladder cancer.”
  
  

• Ureteral TCC
  - 2,290 patients and 700 deaths in 2008
  - Can occur anywhere in the ureter
  --- Distal ureter lesions account for ¾ of cases
  --- Unfortunately, distal ureter is the most difficult to consistently distend and visualize well.
  - Ureter rarely involved by lymphoma and metastatic disease (breast, GI, prostate, cervix, and RCC)

• Ureteral TCC: Imaging Findings
  - Urothelial thickening
  - Abnormal urothelial enhancement
  --- Particularly when asymmetric, focal, and in conjunction with thickening
  - Ureteral calcification
  - Periureteral fat stranding
  - Discrete filling defect or mass
  - Look for site of transition and proximal hydronephrosis & hydroureter

• Mimics on Imaging
  - Lymphoma
  - Metastatic disease
  --- Breast cancer, GI tract malignancies, prostate cancer, cervical cancer
  - Infiltrating variants of RCC
  - Xanthogranulomatous Pyelonephritis (XGP)

• Infiltrative Renal Lesions on CT
  - Renal cell carcinoma
  - Urothelial tumor (TCC)
  - Renal lymphoma
  - Renal sarcoma/plasmacytoma/metastasis
  - Acute pyelonephritis
  - Renal contusion
  - Radiation therapy
  - IgG4 Renal disease 

-Metastatic disease (Breast cancer, GI tract malignancies, prostate cancer, cervical cancer)

• “In conclusion, this study revealed the radiologic characteristics of IgG4-related lesions involving the upper urinary tract compared with those of urothelial carcinoma. CT findings suggestive of IgG4-related upper urinary tract lesions in comparison with urothelial carcinoma are bilateral and have longer urinary tract involvement; extramural growth pattern; ill-defined margins; a gradual enhancement pattern in the dynamic CT study; aortic involvement; and fat stranding in the paraaortic space, presacral space, or pelvic wall areas. IgG4-related disease can also manifest as unilateral lesions, which could appear similar to those of urothelial carcinoma and be difficult to differentiate.”
  CT Findings of Upper Urinary Tract Lesions in IgG4-Related Disease: Comparison With Urothelial Carcinoma
  Minobu Kamo et al.
  AJR 2020; 215:406–412

• - An infiltrative renal pelvic UCC should be considered when a central, poorly marginated mass extending into the adjacent parenchyma is seen at imaging, especially if an additional lesion is identified in the urinary tract.
  - The combination of infiltrative renal masses in the presence of bulky perinephric disease, widespread lymphadenopathy, splenomegaly, and bilateral involvement is suggestive of lymphoma. In many cases, patients have an established diagnosis of lymphoma at the time of imaging.
  Infiltrative Renal Malignancies: Imaging Features, Prognostic Implications, and Mimics
  Sweet DE et al.
  RadioGraphics 2021; 41:0000–0000

• “Bilaterality (p < 0.0001), an extramural growth pattern (p < 0.0001), a greater number of affected segments (p = 0.04), and a gradual dynamic enhancement pattern (p < 0.001) were significantly more frequent in patients with IgG4-related disease. With regard to extraurinary findings, paraaortic fat stranding (p = 0.03), presacral fat stranding (p < 0.001), fat stranding of the pelvic walls (p < 0.001), and aortic involvement (p < 0.001) were seen more frequently in patients with IgG4-related disease; on the other hand, there was no statistically significant difference in terms of frequency of pancreatic involvement. Hydronephrosis and renal involvement were seen more frequently in patients with urothelial carcinoma, although the difference was not statistically significant.”
  CT Findings of Upper Urinary Tract Lesions in IgG4-Related Disease: Comparison With Urothelial Carcinoma 

• “Urothelial carcinoma of the upper urinary tract (renal collecting system and ureter) is a relatively uncommon malignancy, accounting for 5–7% of urothelial tumors and up to 10–15% of all renal tumors. The exact incidence of upper urinary tract urothelial carcinoma is difficult to assess, given its rarity; about 2290 Americans were diagnosed with ureteral urothelial carcinoma, and nearly 700 patients died from it in 2008 . The renal pelvis is the most commonly involved site in the UUT , and is second to the urinary bladder in overall incidence of urothelial carcinoma.”
  
  Upper urinary tract urothelial carcinoma on multidetector CT: spectrum of disease
  
  Osama Ali1 · Elliot Fishman1 · Sheila Sheth1
  
  Abdominal Radiology https://doi.org/10.1007/s00261-019-02173-2

• Multifocality is a key feature in urothelial carcinoma warranting long-term surveillance. Up to 40% of patients with UUT urothelial carcinoma will develop a metachronous tumor in the urinary bladder, usually within the first 2 years following surgical resection, and this is typically seen more with ureteric tumors than with renal pelvic tumors. Approximately, 2–9% of patients with urothelial carcinoma of the urinary bladder have a metachronous upper tract urothelial carcinoma.
  
  Upper urinary tract urothelial carcinoma on multidetector CT: spectrum of disease
  
  Osama Ali1 · Elliot Fishman1 · Sheila Sheth1
  
  Abdominal Radiology https://doi.org/10.1007/s00261-019-02173-2

• “When the ureter is affected, the most commonly involved segment is the distal third (73%), followed by the mid ureter (24%), and proximal ureter (3%). Bilateral ureteral involvement occurs in 2–5% of cases . Approximately, 11–13% of patients with upper tract urothelial carcinoma develop metachronous upper tract tumors. Patients usually present with microscopic or gross hematuria, flank pain, or renal colic. However, up to 20% of lesions are detected incidentally or during surveillance imaging for a known urothelial tumor in the urinary bladder.”
  
  Upper urinary tract urothelial carcinoma on multidetector CT: spectrum of disease
  
  Osama Ali · Elliot K. Fishman · Sheila Sheth
  
  Abdominal Radiology https://doi.org/10.1007/s00261-019-02173-2

• “Papillary forms of urothelial carcinoma in the upper urinary tract, which accounts for up to 85% of urothelial carcinomas, are cytologically and histologically similar to their urinary bladder counterpart. These tumors are usually low-stage and superficial, with frondlike morphology, and tend to have a slow growth rate with a relatively indolent course. Solid, flat tumors, accounting for approximately 15% of cases, tend to be more aggressive with a higher stage at presentation.
  Upper urinary tract urothelial carcinoma on multidetector CT: spectrum of disease
  Osama Ali · Elliot K. Fishman · Sheila Sheth
  Abdominal Radiology https://doi.org/10.1007/s00261-019-02173-2

• CTU tends to perform well in differentiating early stage from advanced-stage tumors; however, it is not that accurate in dif- ferentiation among early-stage tumors (Ta, T1, and T2).”
  Upper urinary tract urothelial carcinoma on multidetector CT: spectrum of disease
  Osama Ali · Elliot K. Fishman · Sheila Sheth
  Abdominal Radiology https://doi.org/10.1007/s00261-019-02173-2 

• “Diffuse bladder wall thickening is very unlikely to represent malignancy, and most often represents infectious cystitis or an artificially thickened bladder wall caused by bladder decompression. However, the presence of focal or asymmetric bladder wall thickening should always raise concern for malignancy, and should prompt further evaluation with cystoscopy.”

  Upper and Lower Tract Urothelial Imaging Using Computed Tomography Urography
Raman SP, Fishman EK
Radiol Clin North Am 2017 Mar;55(2):225-241.

• “Accordingly, some sites of subtle urothelial thickening may be more apparent on the arterial phase images as a result of associated hypervascularity and enhancement. In general, any type of urothelial thickening, when focal, should raise concern for malignancy, with many ureteral tumors showing irregular, nodular soft tissue thickening, rather than circumferential or smooth wall thickening.”

  Upper and Lower Tract Urothelial Imaging Using Computed Tomography Urography
Raman SP, Fishman EK
Radiol Clin North Am 2017 Mar;55(2):225-241.

• 
  

• “The presence of focal wall thickening or a discrete nodule/mass should raise concern for the presence of malignancy anywhere in the upper or lower urinary tract and should prompt further evaluation with direct visualization. Nevertheless, there are multiple benign entities that could potentially mimic findings of malignancy. In particular, urothelial thickening is a common finding, and, when bilateral and diffuse throughout the collecting systems, is much more likely to be the sequela of infection, rather than tumor, particularly when the wall thickening is smooth and regular.”
  
  
Upper and Lower Tract Urothelial Imaging Using Computed Tomography Urography
Raman SP, Fishman EK
Radiol Clin North Am 2017 Mar;55(2):225-241.

• “Urothelial carcinoma of the upper urinary tract (including the intrarenal collecting systems, renal pelvis, and ureters) is uncommon, although the renal pelvis is probably the second most common location for urothelial carcinoma following the bladder. Although exact numbers are difficult to obtain for the incidence of upper urinary tract tumors given their rarity, it is thought that roughly 2300 patients in the United States were diagnosed with transitional cell carcinoma of the ureter (with 700 deaths) in 2008. Upper tract tumors account for only 5% of all urothelial carcinomas and 15% of all renal tumors.”

  
  Upper and Lower Tract Urothelial Imaging Using Computed Tomography Urography 
Siva P. Raman, Elliot K. Fishman 
Radiol Clin N Am - (2016)

• Transitional Cell Carcinoma
  - Roughly 2300 new cases of TCC every year
  - 700 deaths per year
  - 10% of all renal neoplams
  - Men outnumber women 3:1
  - Most common in patients over 60
  - Most commonly presents with hematuria

• Risk Factors
  - Cigarette Smoking
  - Analgesic abuse
  - Chemical carcinogens
  - Aniline dyes
  - Cyclophosphamide therapy
  - Caffeine use (especially with heavy use)

• Intrarenal Collecting System TCC:
  Imaging Findings
  - Urothelial thickening and enhancement
  - Focally dilated calyx
  - “Amputated” calyx
  - Irregularity and destruction of a calyx
  - Infiltrative hypodense mass

• Ureteral TCC
  - 2,290 patients and 700 deaths in 2008
  - Can occur anywhere in the ureter
  - Distal ureter lesions account for ¾ of cases
  - Unfortunately, distal ureter is the most difficult to consistently distend and visualize well.
  - Ureter rarely involved by lymphoma and metastatic disease (breast, GI, prostate, cervix, and RCC)

• Bladder TCC
  - Bladder cancer is the 4th most common malignancy in men and 10th most common malignancy in women
  - 61000 new cases and 13000 deaths each year
  - 90% of bladder cancers are TCC (4% squamous cell carcinoma, 1% adenocarcinoma)
  - 70% are superficial and have relatively good prognoses
  - When metastatic, prognosis is much worse (5% at 2 years)

• Bladder TCC
  - CT is a better modality for the identification of bladder cancer than most radiologists think.
  - “The overall sensitivity, specificity, accuracy, PPV, and NPV for bladder cancer detection were 79%, 94%, 91%, 75%, and 95% for CT urography”
  Sadow CA et al.  Radiology 2008

• Bladder Cancer Enhancement
  - Wide variability in degree of enhancement
  - “17 (85%) of 20 bladder cancers enhanced maximally to approximately 106 HU around the 60 second scan delay and washout out slowly thereafter”
  Kim KK et al.  Radiology 2004.
  - Most bladder TCCs will show early enhancement and will be best visualized in a well-distended bladder with unenhanced urine.
  - Stresses importance of arterial phase imaging through distended bladder
  - Patients should not void for at least 1 hour prior to scan

• Bladder Cancer Imaging Appearance
  - Asymmetric wall thickening
  - Diffuse bladder wall thickening is rarely cancer (i.e. cystitis, bladder outlet obstruction, neurogenic bladder)
  - Focal mass
  - Small filling defect
  - Calcification in bladder wall

• Hematuria
  - Microscopic hematuria has a prevalence of 2.5% in asymptomatic patients
  - Cause for abnormality not found in many patients
  - These patients need further work-up depending on risk factors
  - Macroscopic hematuria much more concerning
  - Risk of malignancy ranges from 3 – 6%
  - Requires evaluation of the upper tracts with CT and bladder with cystoscopy

• Risk Factors for Urologic Malignancies
  - Age > 40
  - Gross hematuria
  - Smoking
  - Obesity
  - Analgesic abuse
  - Chemical carcinogen exposure
  - Occupational exposures
  - Chronic inflammatory conditions of the urinary tract
  - Congenital abnormalities of the urinary tract
  - Pelvic radiation

• “ Nearly 2-4% of patients with bladder cancer develop upper tract TCC. Hence, the surveillance of the upper tract, in which imaging plays a central role, is an important component in the management of TCC.”
  Imaging and Staging of Transitional Cell Carcinoma: Part I, Lower Urinary Tract
  Vikram R et al
  AJR 2009;192:1481-1487

• “ A thorough CT urography examination involves four key phases- unenhanced, arterial, nephrogenic, and excretory- to permit identification of features such as enhancement, excretion, and associated vasculature.”
  Imaging of Urothelial Cancers: What the Urologist Needs to Know
  Lee EK et al.
  AJR 2011; 196:1249-1254

• “ A thorough CT urography examination involves four key phases- unenhanced, arterial, nephrogenic, and excretory- to permit identification of features such as enhancement, excretion, and associated vasculature.”
  Imaging of Urothelial Cancers: What the Urologist Needs to Know
  Lee EK et al.
  AJR 2011; 196:1249-1254

• “ CT urography was more accurate than excretory urography in the detection and localization of upper urinary tract urothelial carcinoma and should be considered as the initial examination for the evaluation of patients at high risk for upper urinary tract urothelial carcinoma.”
  Comparison of CT Urography and Excretory Urography in the Detection and Localization of Urothelial carcinoma of the Upper Urinary Tract
  Jinzaki M et al.
  AJR 2011; 196:1102-1109
   

• Kidney: Transitional Cell Carcinoma of the Kidney: Facts
  - Multiplicity common
  - Distal ureter most common site in the ureter (73%)
  - metastases common to renal vein, IVC and local nodes
  - Tumors may occassionally have fine stippled calcifications

• Kidney: Transitional Cell Carcinoma of the Kidney: Facts
  - 15% of malignant renal tumors
  - More common in men (2-1)
  - Incidences peaks in 7th decade
  - Upper tract TCC occurs in 2% of patient with lower tract disease, but 40% of patients with upper tract disease develop lower tract disease

• "The hallmark of TCC is multiplicity and recurrence. Nearly 2-4% of patients with bladder cancer develop upper tract TCC, but 40% of patients with upper tract TCC develop bladder cancer."