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Learning Modules ❯ Genitourinary

The Challenges in the Diagnosis of Transitional Cell Carcinoma of the Kidney: Optimizing Lesion Detection

The Challenges in the Diagnosis of Transitional Cell Carcinoma of the Kidney: Optimizing Lesion Detection

M. Yasrab, MD; Felipe Lopez-Ramirez, MD; Satomi Kawamoto, MD; Linda C. Chu, MD; Elliot K. Fishman, MD
Johns Hopkins Hospital

 

Teaching Points

  • While the majority of urothelial carcinoma (UC, also called transitional cell carcinoma) develop in the urinary bladder, upper tract urothelial carcinoma (UTUC) of the kidney and ureter prove to be a challenging diagnosis because lesions are often small and can mimic other pathologies
  • Multidetector computed tomography urography (CTU) is the mainstay imaging modality of choice for diagnosis and workup
  • Detection of UTUC is dependent on proper scan protocols as well as scan display (MPR, MIP, VRT)
  • UTUC have a range of CTU appearances from infiltration of a calyx to infiltration of the kidney, to focal filling defects to calyceal amputation
  • UTUC can be confused with other renal tumors as well as renal inflammatory disease
  • Early detection is critical for outcome and attention to spread of disease including multifocal disease will be addressed

 

Background & Demographics

  • <2 cases per 100,000 population in developed countries
  • UTUC form 5-7% of all urothelial cancers and 10-15% of all kidney tumors
  • Renal pelvis is 2nd most common site of UC after bladder, and 2/3 of all UTUC
  • UC are multifocal and UTUC are more aggressive than bladder counterparts
    • Up to 50% of patients with UTUC will develop a metachronous bladder UC
    • Up to 4% of patients with a bladder UC will develop a UTUC
  • Major risk factors include smoking, alcohol, occupational carcinogens (aniline dyes) and medication toxicity (e.g., cyclophosphamide)
  • Increasingly found incidentally, but most patients present with gross/microscopic hematuria or flank pain due to obstructive hydronephrosis in up 30% of cases
  • Seen mostly in patients older than 60 years and 2-3 times more common in men
  • 85% papillary type, often slow-growing and low-stage
  • 15% solid, flat type, often aggressive and higher stage at presentation
    • (Rouprκt et al., 2023), (Yu et al., 2021), (Fojecki et al., 2019), (Ali et al., 2019), (Raman et al., 2012), (Margulis et al., 2009), (Kirkali and Tuzel, 2003), (Buckley et al., 1996)

     

    Workup & Prognostication

    • CTU is the preferred modality for tumor staging + detecting metastases
    • Flexible ureteroscopy with biopsies
    • Staging and grading are the most important prognostic factors, however difficult preoperatively
    • The European Association of Urology propose a low and high-risk stratification to guide treatment
    • Kidney-sparing surgery in low-risk disease to radical nephroureterectomy  in more advanced disease, with or without chemotherapy
    • Low-risk UTUC defined as (all present):
      • Size <2 cm
      • Unifocal disease
      • Low-grade cytology/biopsy
      • No invasive features on CTU
    • High-risk UTUC is defined as (any present):
      • Size >2 cm
      • Multifocal disease
      • Hydronephrosis
      • High-grade cytology/biopsy or subtype histology
      • (History of) radical cystectomy

     

    CTU Protocol & Optimization

    • Both American College of Radiology (ACR) Appropriateness Criteria and American Urological Association (AUA) guidelines recognize CTU as the imaging modality of choice for adults presenting with hematuria
    • Ideally:
      • Maximize distension and opacification of the collecting systems in the delayed excretory phase (for UC)
      • Achieve sufficient sensitivity for other causes of hematuria, including calculi and renal cell carcinoma (RCC)
    • CTU achieves a pooled sensitivity of 92% (CI 0.85–0.96) and specificity of 95% (CI 0.88–0.98)
    • Sensitivity decreases to 89% for lesions <5 mm and 40% for lesions <3 mm
      • Flat lesions are even more difficult to diagnose

     

    • Phases in renal imaging include non-contrast (for renal calculi, HU of homogenous renal mass), arterial phase/corticomedullary, venous phase/nephrogenic, and delayed phase/excretory
    • CTU protocol typically includes non-contrast, nephrographic and excretory phases (per ACR)
      • Arterial phase can help to detect enhancing small UTUC
    • Two protocols in use for CTU: single bolus (more common) and split bolus (see next slide)
      • Triple bolus technique is rarely used in clinical practice
    • Dual-energy or photon-counting CT to create virtual non-contrast images 
    • Axial source images, multiplanar reformats (MPR), 3D postprocessing
    (Janisch et al., 2020), (Ali et al., 2019), (Kawamoto et al., 2008)

    Renal Transitional Cell Carcinoma

     

    Single Bolus

    100-120 mL of IV contrast at 4-5 mL/s → Arterial phase (30-35 sec) → Venous phase (60-70 sec) → Excretory phase (5–8 min)
    • Pros: maximal distension of the collecting system achieved as all the contrast is injected at once, more sensitive for RCCs than split bolus technique (arterial phase helpful to detect small enhancing UTUC and to differentiate subtypes of RCC)
    • Cons: increased radiation dose*
    Split Bolus

    50 mL of IV Contrast → Additional 80 mL of IV contrast at 5 min → Combined nephrographic and excretory phase images at 7 min
    • Pros: lower radiation dose due to lower number of acquisitions
    • Cons: suboptimal distension of the collecting system due to fraction of contrast excreted at a time, decreased sensitivity for detection of subtle lesions (particularly RCC)
    *Most institutes employ the single bolus technique, particularly due to use of MDCT that allows radiation dose reduction

    (Fojecki et al., 2019), (Ali et al., 2019), (Raman and Fishman, 2018) (Kawamoto et al., 2008)

     

    3D Postprocessing & Cinematic Rendering (CR)

    • Virtual ureteroscopy via 3D postprocessing can enhance detection of subtle urothelial thickening, especially in obstructed systems
    • Traditional postprocessing techniques include Maximal intensity projection (MIP) and 3D volume rendering (VRT)
    • 3D CR uses global illumination and path tracing models, whereby numerous light rays propagate through volumetric data to generate photorealistic images
      • Natural lighting effects, such as (reflection or scatter) are simulated as photons interact with the dataset
      • Improves depth and shape perception, allowing better evaluation of complex anatomical structures and spatial relationships
      • Clearer visualization of anatomy, improving diagnostic accuracy and providing valuable insights for surgical planning


    3D CR demonstrating invasive high-grade bladder UC and synchronous low-grade UTUC in left upper calyces (case revisited in later slides)
    (Rowe et al., 2019), (Ali et al., 2019), (Raman et al., 2012)
    Renal Transitional Cell Carcinoma

     

    Optimization

    • Smaller intraluminal neoplasms are obscured by dense contrast in the renal collecting system with standard soft-tissue window settings, so use of wide window settings can help increase detection
    • Techniques to maximize distension:
      • Oral or intravenous hydration
        • Similarly improves distention and dilutes contrast; we use oral hydration in our practice
        • Typically, 100–250 mL of saline administered IV as a bolus or 500-1000 mL per oral prior to the study
      • Use of diuretics (Lasix) (low evidence)
        • Small dose of 10–20 mg improves excretion into the collecting systems and subsequent distention + dilutes contrast entering excretory system, allowing detection of subtle sites of urothelial thickening or nodularity
      • Abdominal compression/compression belt (low evidence)
      • Imaging in prone position (low evidence)
      • Log-rolling (low evidence)

     

    UTUC Cases & CTU Features

    • Classical findings include:
      • Urothelial thickening and enhancement
      • Focally dilated calyx
      • “Amputated” calyx (irregularity and destruction of a calyx)
      • Central solid mass in the renal pelvis that expands centrifugally, compressing renal sinus fat
      • Infiltrative hypodense mass
    • Larger infiltrating UTUCs can mimic:
      • Infiltrating renal cell carcinoma
      • Lymphoma
      • Metastases
      • Xanthogranulomatous pyelonephritis
    • We will showcase a series of UTUC cases with a diverse range of presentations, followed by notable mimickers and distinguishing features

     

    UTUC as urothelial thickening on CTU

    1. Proximal ureter urothelial thickening extending into the renal pelvis

    Renal Transitional Cell Carcinoma

    2. Distal ureter urothelial thickening

    Renal Transitional Cell Carcinoma

    3. Proximal collecting system urothelial thickening

    Renal Transitional Cell Carcinoma

     

    UTUC as enhancing mass involving the calyces on CTU

    4. Multifocal enhancing UTUCs in left renal collecting system: lower pole calyces (blue arrow), renal pelvis (yellow arrow) and proximal ureter (white arrow)
    Invasive, high-grade UTUC, pT1

    Renal Transitional Cell Carcinoma

     

    5. Enhancing lesion within the inferior left renal collecting system + patchy urothelial thickening of the left ureter
    Invasive, high-grade UTUC, pT1

    Renal Transitional Cell Carcinoma

    6. Infiltrating soft tissue surrounding the lower pole right infundibulum with upper pole caliectasis
    High-grade UTUC on cytopathology

    Renal Transitional Cell Carcinoma

     

    7. Invasive high-grade bladder UC with left upper pole renal collecting system mass consistent with synchronous UTUC
    Noninvasive, low-grade

    Renal Transitional Cell Carcinoma

     

    UTUC involving the renal pelvis
on CTU

    8. Enhancing tumor at the left renal pelvis extending to the ureteropelvic junction + Irregular urothelial thickening
    Noninvasive, high-grade papillary UTUC

    Renal Transitional Cell Carcinoma

     

    9. Solid mass in the right renal pelvis

    Renal Transitional Cell Carcinoma

     

    10. Polypoid lesion within the left renal pelvis
    Noninvasive, low-grade papillary UTUC

    Renal Transitional Cell Carcinoma

     

    11. Enhancing left renal pelvis wall thickening or enhancing renal pelvis mass with central necrosis
    Metastatic, high-grade papillary UTUC

    Renal Transitional Cell Carcinoma

     

    12. Lobulated enhancing filling defect within the left renal pelvis
    Low-grade, papillary UTUC

    Renal Transitional Cell Carcinoma

     

    UTUC as infiltrative mass on CTU

    13. Mass-like Infiltration in the right renal pelvis

    Renal Transitional Cell Carcinoma

     

    14. Large left renal hypoenhancing infiltrative mass involving renal sinus, invading pelvis, and encasing interpolar arteries + tumor thrombus in renal vein
    Invasive, high-grade UTUC with focal squamous differentiation, pT3

    Renal Transitional Cell Carcinoma

    15. Enhancing soft tissue mass in the R collecting system and ureter causing obstruction
    Noninvasive, low-grade papillary UTUC

    Renal Transitional Cell Carcinoma

     

    16. Infiltrating enhancing mass in the left collecting system of the upper pole, extending into the left renal pelvis + mass effect on the focally narrowed ureteropelvic junction
    Invasive, high-grade UTUC, pT3

    Renal Transitional Cell Carcinoma

     

    17. Infiltrating heterogenous mass in the left upper kidney involving the central sinus fat and collecting system with an  exophytic nodule + lung metastases
    Metastatic, high-grade UTUC

    Renal Transitional Cell Carcinoma

    18. Large upper and mid left renal infiltrative heterogeneously enhancing mass extending to the renal pelvis and proximal left ureter, invading vein, and encases segmental artery
    Metastatic, high-grade UTUC

    Renal Transitional Cell Carcinoma

     

    19. Infiltrative left renal pelvic mass which expands the hilum and secondarily involves renal parenchyma
    High grade papillary UTUC on cytopathology

    Renal Transitional Cell Carcinoma

     

    Multifocal UTUC on CTU

    20. Small hyperdense and enhancing soft tissue nodular filling defects in upper pole and mid-kidney calyces of the right kidney
    + Subcentimeter hyperdense filling defect in the ureter
    + Additional nodule along bladder wall
    All lesions were noninvasive, low-grade papillary UC

    Renal Transitional Cell Carcinoma

     

    21. Diffuse nodular thickening of right renal pelvis extending to upper ureter + New defects in upper and mid ureter (blood clot vs. drop metastasis) + Enhancing bladder lesion
    Noninvasive, low-grade papillary UTUC

    Renal Transitional Cell Carcinoma

     

    22. Ill-defined soft tissue mass in left upper pole calyces + New mass arising from left renal pelvis + metastatic lesion to left ureter
    High-grade UTUC on biopsy

    Renal Transitional Cell Carcinoma

     

    23. Soft tissue nodularity within right renal collecting system, ureter and at the right ureterovesical junction + Lung mets
    Metastatic, high-grade UTUC

    Renal Transitional Cell Carcinoma

    24. Enhancing mass in the lower pole of the right kidney communicating with collecting system + Bilobed tumor in distal right ureter + Bladder wall lesion
    High-grade UTUC on biopsy

    Renal Transitional Cell Carcinoma

     

    Infiltrative Lesions that are Mimics of UTUC on CT

    • qRenal cell carcinoma (RCC)
    • Renal lymphoma
    • Renal sarcoma/plasmacytoma
    • Metastases to the kidney
    • Acute pyelonephritis
    • Renal contusion
    • Radiation therapy
    • IgG4 Renal disease
    • Xanthogranulomatous pyelonephritis
    1. Candidiasis mimicking UTUC

    Renal Transitional Cell Carcinoma

     

    2. Clear Cell RCC (ISUP nucleolar grade 3) presenting as a multilobular partially exophytic enhancing mass in the right kidney lower pole, invading the lower pole calyx with a filling defect and amputation of calyces, mimicking UTUC with a large exophytic component

    Renal Transitional Cell Carcinoma

     

    RCC vs. UTUC

    UTUC:
    • Homogenous enhancement
    • Central point of origin in the pelvis or collecting system
    • Focal filling defects
    • Centrifugal expansion or invasion of the kidney
    • Preserve reneiform shape while compressing or displacing renal sinus fat
    RCC:
    • Heterogenous enhancement
    • Variable in shape and size
    • Variable foci of calcification
    • Cystic/necrotic changes
    (Ali et al., 2019), (Raza et al., 2012)

    Renal Transitional Cell Carcinoma

     

    3. RCC presenting as a hypoenhancing infiltrative lesion centered in the upper pole of the right kidney, mimicking UTUC

    Renal Transitional Cell Carcinoma

     

    4. Oncocytic neoplasm presenting as well-defined enhancing mass in the medial interpolar region of the right kidney, extending to the renal hilum with mild mass effect on the renal collecting system, mimicking UTUC

    Renal Transitional Cell Carcinoma

     

    5. Marginal zone lymphoma presenting as a lobulated enhancing mass within the left renal collecting system, extends to hilum and para-aortic region mimicking UTUC

    Renal Transitional Cell Carcinoma

     

    6. Mildly enhancing left lower pole soft tissue mass encasing the proximal ureter and causing moderate hydronephrosis + filling defects in collecting system, raising suspicion for UTUC vs. papillary RCC vs. proteinaceous debris: biopsy returned fibrous tissue with lymphoplasmacytic infiltrate, subsequently Erdheim-Chester diagnosed

    Renal Transitional Cell Carcinoma

     

    7. High density enhancing mass expanding and filling the right renal pelvis, extending into the right lower pole and midpole calyces, and invading into the lower pole cortex with foci of calcifications concerning for UTUC vs. blood clot with neovascularization: biopsy and uteroscopy returned benign findings of acute and chronic inflammation with no evidence for neoplasm

    Renal Transitional Cell Carcinoma

     

    Pearls & Pitfalls

    • Low T-stage tumors (Ta–T2) often show symmetric/asymmetric wall thickening with no spiculation into peripelvic or periureteric fat, as opposed to advanced stage tumors (T3) that have a more infiltrative morphology with hypoenhancement, as seen in our cases
      • Although most small UTUCs detected via MDCT urography are low-grade, imaging cannot consistently predict tumor type, growth pattern, or grade
      • MDCT urography can sometimes miss small neoplasms due to poor opacification/distension of ureteral segments
      • Microscopic peritumoral invasion or reactive interstitial changes on CT can lead to understaging or overstaging of UTUC
    • The presence of hydronephrosis in UTUC has been shown to be independent predictor for pT2 and high-grade disease on pathology (Chung et al., 2024)
    • When presenting as a large infiltrating renal tumor, UTUC can mimic renal cell carcinoma, lymphoma, or metastasis and vice versa
    • Focal (or occasionally diffuse) wall thickening or nodule/mass should raise concern for malignancy, though benign entities like infection can mimic malignancy
    • Blood clots are completely intraluminal and do not attach to the wall, helping distinguish them from tumors, and like other benign entities including sloughed papillae and fungus balls, and they do not enhance on post-contrast images

     

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