Kidney tumor - adult malignancies
Adult renal cell carcinoma
Renal cell carcinoma - general

Author: Sean Williamson, M.D. (see Authors page)

Revised: 8 October 2015, last major update June 2012

Copyright: (c) 2003-2015,, Inc.

PubMed Search: renal cell carcinoma[title]
  • Formerly called hypernephroma due to perceived origin from adrenal gland
  • In US in 2010, were 58,240 new renal cancers and 13,040 deaths; 92% were renal cell carcinoma, 7% renal pelvis carcinoma, 1% Wilms tumor (American Cancer Society Statistics)
  • Usually > 50 years old, 2/3 male, only 1% bilateral
Clinical Features
Risk factors:
  • Renal transplantation, acquired renal cystic disease due to end stage renal disease, cigarette smoking (particularly for renal pelvis tumors), obesity, high blood pressure, treated neuroblastoma

  • 25% present with metastases (lung, bones, lymph nodes, adrenals, liver, brain), sometimes at unusual locations (as seen with melanoma and choriocarcinoma) such as contralateral adrenal gland, anus (Arch Pathol Lab Med 2002;126:856), gallbladder, pancreas (Urol Oncol 2012;30:476)
  • Metastases often solitary and detected years or decades after removal of primary
  • Rarely metastases to bladder (Mod Pathol 1999;12:351) or phalanges (Mod Pathol 1991;4:66)
  • Most common recipient of metastases from another tumor (usually lung)

Familial renal cell carcinoma syndromes

von Hippel-Lindau disease (see clear cell type):
  • Due to germline mutation of VHL gene at chromosome 3p25
  • Renal lesions: renal cysts and clear cell renal cell carcinoma
  • Other organs: Retinal/CNS hemangioblastoma, pheochromocytoma, pancreatic cyst/neuroendocrine tumors

Hereditary papillary renal carcinoma:
  • Due to activating mutation of MET oncogene at chromosome 7q31
  • Autosomal dominant, late onset bilateral papillary renal tumors

Hereditary leiomyomatosis and renal cell carcinoma:
  • Autosomal dominant, familial
  • Due to germline fumarate hydratase mutations
  • Cutaneous or uterine leiomyomas
  • Renal tumors are often papillary with characteristic large nucleus with a very prominent inclusion-like orangiophilic or eosinophilic nucleolus, surrounded by a clear halo
  • Poor prognosis (Am J Surg Pathol 2007;31:1578)

Birt-Hogg-Dubé syndrome:
  • Autosomal dominant with incomplete penetrance
  • Due to germline mutations in BHD gene at chromosome 17p11.2, which codes for folliculin
  • Skin lesions: fibrofolliculomas, trichodiscomas, acrochordons
  • Lung: cysts, spontaneous pneumothorax
  • Renal tumors variable – oncocytoma, clear cell carcinoma, and hybrid oncocytic-chromophobe tumors with areas of clear cells (Am J Surg Pathol 2002;26:1542)

Tuberous sclerosis:
  • Mutations in TSC1 and TSC2 genes via an alternate pathway not involving VHL mutations (Mod Pathol 2002;15:205)
  • Multiple, bilateral angiomyolipomas (or epithelioid angiomyolipoma)
Radiology description
  • Image-guided biopsy of solitary small renal masses increasingly utilized for treatment planning, since pathology cannot be predicted by clinical features (Am J Clin Pathol 2008;130:560, Hum Pathol 2005;36:1309)
  • "Great mimic" due to associated paraneoplastic syndromes of Cushing’s syndrome, gynecomastia, hypercalcemia, hypertension, leukemoid reaction, polycythemia, Stauffer syndrome (hepatomegaly with hepatic dysfunction), systemic amyloidosis, polyneuromyopathy
  • Most tumors are detected incidentally due to increased use of imaging; historically were large (10 cm) at diagnosis
  • "Classic" clinical features of costovertebral pain, palpable mass and hematuria are now present in only 10%
Radiology images

MRI shows massive extension into inferior vena cava (arrows)

Prognostic Factors
  • Radical nephrectomy, partial nephrectomy for small peripheral tumors (5-25% of patients may have multifocal tumors)
  • Cure possible even with extension into renal vein, inferior vena cava and right atrium
  • Chemotherapy and radiation traditionally considered ineffective; however, increasing interest in interferon and anti-angiogenic agents (sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab, pazopanib)
  • Excision of solitary metastases is often effective
  • Occasionally regresses without treatment (as seen with germ cell tumors, melanoma, neuroblastoma)
  • 5 year survival: 68% (all histologic types and stages), varies from 60-80% in stage I vs. 5% in stage IV, lower for renal pelvis carcinoma (51%) compared to renal cell carcinoma (70%)
Gross Description
  • Well-circumscribed, centered on cortex, may bulge/distort kidney contour
  • Often extends into renal vein or vena cava, renal sinus invasion common in large tumors
  • May have satellite nodules, often hemorrhage, necrosis, calcification and cystic change causing variegated appearance
Gross Images

Tumor less than
3 cm

Arising in adult-type
polycystic renal

Diffusely infiltrative

Massive tumor extension
into renal vein and inferior
vena cava

Retrograde extension of tumor
down the left internal spermatic
vein into the spermatic cord

Metastases to small intestine

Nodal metastases

Micro Description
Micro Images

Cutaneous metastases:
H&E and CD10

Neuroendocrine carcinoma is less
well differentiated than carcinoid

Courtesy of Dr. Semir Vranic

Virtual Slides

Various images

Cytology Description
  • 25% sensitive for bladder washings/urine, higher for retrograde brushing
  • FNA helpful to differentiate cyst from carcinoma or to confirm recurrence
  • High false positive rate for FNAs in one study (Arch Pathol Lab Med 2002;126:670)
  • Benign renal tubular epithelial cells may be sampled, mimicking carcinoma
  • Tumor cells have abundant cytoplasm that is vacuolated, fluffy or granular, usually with indistinct cell borders (but chromophobe renal cell carcinoma has distinct borders)
  • Tumor nuclei have variable atypia, irregular contours, haphazard orientation with abnormal chromatin, variably prominent nucleoli
  • Renal tubular cells have well defined cell borders, homogenous cytoplasm, round, regular and orderly nuclei
  • Important features to distinguish from other neoplasms include heterogeneous cell population, small cytoplasmic vacuoles and hemosiderin deposits (Arch Pathol Lab Med 2005;129:1017)
Cytology Images

Normal kidney glomerulus and renal tubular cells

Cells in alveolar arrangement demonstrate vacuolated cytoplasm, vesicular nuclei, prominent nucleoli

Positive Stains
Most commonly used:
Other positive stains:
  • Kidney-specific cadherin, N-cadherin, CD15
  • Occasionally vimentin (25%), S100 (5%), PSA in tumor associated vasculature only (Mod Pathol 2008;21:727)
Negative Stains
Differential Diagnosis
Additional References