Renal Cell Carcinoma

Todd M. Blodgett, MD

Alex Ryan, MD

Hesham Amr, MD

Key Facts

Terminology

Renal cell carcinoma (RCC), clear cell carcinoma, hypernephroma, renal cancer

Imaging Findings

Iso- or hypermetabolic renal mass ± lymphadenopathy, metastases on FDG PET
Presents most commonly as incidental solid tumor on imaging
Enhancing solitary mass on CT highly suspicious for RCC
Hypervascular mass with enhancement (HU increase by > 20) compared to noncontrast
Enhancement often heterogeneous, particularly larger lesions
FDG PET and RCC
- FDG uptake by RCC, metastases variable
- Sensitivity 60%, specificity ˜ 100% for evaluating primary RCC
- 80-100% specific for bony metastases

Top Differential Diagnoses

Angiomyolipoma (AML)
Renal Oncocytoma
Hemorrhagic Renal Cyst
Transitional Cell Carcinoma (TCC)
Rare Parenchymal TCC (Indistinguishable from RCC)
Lymphoma
Renal Infection or Abscess
Metastatic Disease

Diagnostic Checklist

FDG PET for staging, evaluation of bony metastases
RCC has variable uptake on FDG PET

Graphic shows a typical appearance of a large renal cell carcinoma

with invasion of the renal vein and inferior vena cava

Coronal PET (A), axial CT (B) and fused PET/CT (C) show a relatively non-FDG-avid renal cell carcinoma

TERMINOLOGY

Abbreviations and Synonyms

Renal cell carcinoma (RCC), clear cell carcinoma, hypernephroma, renal cancer

Definitions

Carcinoma of renal tubular epithelium

IMAGING FINDINGS

General Features

Best diagnostic clue
- Iso- or hypermetabolic renal mass ± lymphadenopathy, metastases on FDG PET
- Presents most commonly as incidental solid tumor on imaging
- Enhancing solitary mass on CT highly suspicious for RCC
  - Necrosis, hemorrhage, septae more likely in large masses
Location
- Usually renal cortex
- Often exophytic
- Rarely bilateral (2%) or multicentric (more common in von Hippel-Lindau)
Size: Variable depending on time of diagnosis
Morphology
- 10% calcified, often irregular
- 2-5% cystic

Imaging Recommendations

Best imaging tool
- Combination of CT, ultrasound
  - CECT often shows enhancing lesion; hyperdense benign cysts will not enhance
  - US indicated in patients with nonenhancing hyperdense renal lesions to differentiate cyst from mass
  - If contraindication to contrast, MR superior to CT
- FDG PET and PET/CT not currently covered by Medicare, but may be helpful for staging and restaging
Protocol advice
- For CT: Noncontrast and CECT, thin sections (2.5-5.0 mm), during both corticomedullary and nephrographic phases
  - For PET CT: If only single phase obtained, use later nephrographic phase of contrast enhancement
- Corticomedullary phase (25-70 seconds post-injection)
  - Better visualization of renal vessels; evaluate for renal vein/IVC thrombosis or tumor extension
  - Limited detection of small renal lesions
  - Centrally located tumors commonly mistaken for normal hypoattenuating medulla
- Nephrographic phase (80-180 seconds post-injection)
  - Best imaging of renal medulla masses

CT Findings

NECT
- Solid-tissue-density mass, which distorts normal kidney contour and typically is in the 30-50 HU range
- Can be hyperdense, isodense, or hypodense to surrounding normal kidney
- Heterogeneous mass (hemorrhage and necrosis); high (acute hemorrhage) or low attenuation (chronic)
  - ± Calcifications (10% of cases); amorphous internal (most common), curvilinear (peripheral or central), dense or diffuse calcification
- High density rim may separate mass from adjacent renal tissue (pseudocapsule)
- Rarely contains small areas of fat (-50 to -150 HU)
- Combination of fat and calcification suggests RCC, not renal angiomyolipoma
- Cystic RCC
  - Uni- or multilocular cystic mass with a thick calcification of septa or tumor capsule
  - Septa may enhance on CECT
CECT
- Hypervascular mass with enhancement (HU increase by > 20) compared to noncontrast
  - Enhancement often heterogeneous, particularly larger lesions
- Tumor extension or thrombus in renal vein (23%), inferior vena cava (7%)
- Local extension common
  - Nodal spread typically to para-aortic or aortocaval lymph nodes
- Most common metastatic locations include lung, liver, bone, adrenal, and opposite kidney
- Usually solid, and decreased attenuation suggestive of necrosis often present
- Sometimes presents as predominantly cystic mass with thick septa and wall nodularity
- Nephrographic phase is most sensitive for tumor detection, especially for masses smaller than 3 cm
- Corticomedullary phase required for tumor extension into renal veins
  - Evaluation for hypervascular metastases
- Helical CT improves diagnosis and eliminates respiratory misregistration

Nuclear Medicine Findings

FDG PET and PET/CT for RCC
- Iso- or hypermetabolic renal mass ± lymphadenopathy, metastases
- FDG uptake by primary RCC and metastases is somewhat variable; therefore, PET and PET/CT are more helpful when positive
  - Negative study may represent either a non-FDG-avid RCC or truly negative disease
- Sensitivity 60%, specificity ˜ 100% for evaluating primary RCC
- Excretory FDG in collecting system can mask small RCCs adjacent to collecting system
- 80-100% specific for bony metastases

DIFFERENTIAL DIAGNOSIS

Angiomyolipoma (AML)

Fat attenuation (-30 to -150 HU) fairly specific for this neoplasm
Low FDG uptake
Reliably distinguished from malignancy by CT characteristics

Renal Oncocytoma

Central scar on CT/MR and spoke-wheel pattern of vessels on angiograms suggest oncocytoma; not entirely specific
Cannot confidently differentiate from RCC by PET

Hemorrhagic Renal Cyst

> Water attenuation on CT (˜ 30-70 HU)
Should not enhance when comparing noncontrast and CE series

Transitional Cell Carcinoma (TCC)

Renal pelvis filling defect, narrowing
Urothelial thickening or involvement
Rare parenchymal TCC indistinguishable from RCC

Lymphoma

Typically more diffusely infiltrative than discrete mass

Renal Infection or Abscess

Focal nephritis can appear mass-like
- Short term follow-up helpful
Clinical history and urine analysis often helpful

Metastatic Disease

History essential
Common primary cancers include lung, breast, colon, melanoma, pancreatic
Typically only hypervascular metastases mistaken for RCC

PATHOLOGY

General Features

General path comments
- Staging
  - Stage I: Solid mass ≤ 7 cm, confined to kidney
  - Stage II: > 7 cm but still organ confined; spread to perinephric fat
  - Stage III: Invasion of renal vein or vena cava, involvement of ipsilateral adrenal gland &/or perinephric fat, or spread to one local lymph node
  - Stage IV: Invasion of adjacent organs, more than one local node, or distant metastases
Genetics: Associated with von Hippel-Lindau syndrome (autosomal dominant)
Etiology
- Arise from tubular epithelium
- Bilateral lesions associated with von Hippel-Lindau syndrome, tuberous sclerosis, chronic dialysis
- Other risk factors: Smoking, chemical exposure (diethylstilbestrol and fluoroacetamide)
Epidemiology
- Approximately 2% of adult malignancies (30,000/year in USA)
- Undiagnosed small RCCs found at autopsy even more frequently

Gross Pathologic & Surgical Features

Solid to cystic components with necrosis, hemorrhage, and rarely fat

Microscopic Features

70% clear cell, 13% papillary, 7% granular, 10% other

CLINICAL ISSUES

Presentation

Most common signs/symptoms
- Usually a combination of hematuria (50%), flank pain (40%), &/or flank mass (35%)
- Nearly half of RCCs discovered incidentally
Other signs/symptoms
- Fever, nausea, weight loss
- Rarely, humoral factors such as erythropoietin, renin, parathyroid hormone, or prolactin may cause symptoms