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

Author: Nicole K. Andeen, M.D. (see Authors page)
Editor: Maria Tretiakova, M.D.

Revised: 12 April 2017, last major update April 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Renal cell carcinoma [title]
Cite this page: Renal cell carcinoma - general. PathologyOutlines.com website. http://pathologyoutlines.com/topic/kidneytumormalignantrcc.html. Accessed April 30th, 2017.
Definition / general
  • Adult renal cell carcinoma (RCC)
Essential features
  • 16th most common cause of death from cancer worldwide; estimated 143,000 deaths from kidney cancer in 2012 (WHO 2016)
  • See subtypes: Kidney tumor
Terminology
  • Historic synonyms: nephrocellular carcinoma, Grawitz tumor, hypernephroma (due to perceived origin from adrenal gland)
Epidemiology
  • Incidence: worldwide as of 2012, 9th most common cancer in men (214,000 cases) and 14th most common in women (124,000 cases) (WHO 2016)
  • Approximately 2:1 male: female ratio
  • Approximately 70% of new cases occur in countries with high socioeconomic development
  • RCC incidence varies widely from region to region with the highest rates in the Czech Republic and North America
  • In the United States, there are ~ 64,000 new cases and almost 14,000 deaths from RCC each year (CA Cancer J Clin 2017;67:7)
Sites
  • Kidney
Pathophysiology
  • Various molecular pathways
Etiology
  • Risk factors: obesity, smoking, hypertension, acquired cystic kidney disease due to end stage renal disease, occupational exposure to trichloroethylene, treated neuroblastoma
  • Genetic susceptibilities estimated to account for 2 - 4% (WHO 2016)
  • Usually > 50 years old
Hereditary Renal Cell Tumors
    von Hippel-Lindau syndrome
    • Autosomal dominant, due to germline mutation of VHL gene at chromosome 3p25
    • Renal lesions: renal cysts and clear cell renal cell carcinoma (Clear cell renal cell carcinoma)
    • Associated with bilateral or multiple renal cell carcinomas in 50% (eMedicine - Von Hippel-Lindau Syndrome)
    • Other organs: hemangioblastomas of cerebellum and retina, cysts of pancreas, liver and kidney, clear cell tumors of other sites, papillary cystadenoma of epididymis, pheochromocytoma

    Hereditary papillary renal cell carcinoma
    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 eosinophilic nucleolus (HLRCC)

    Familial papillary thyroid carcinoma

    Hyperparathyroidism-jaw tumour syndrome

    Birt-Hogg-Dubé syndrome
    • Autosomal dominant with incomplete penetrance
    • Due to germline mutations in BHD gene at chromosome 17p112, 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, Hybrid oncocytic / chromophobe tumor, Oncocytoma)

    Tuberous sclerosis
    Constitutional chromosome 3 translocations
Diagnosis
Radiology description
  • "Classic" clinical features of costovertebral pain, palpable mass and hematuria are now present in only 10%
  • Most tumors are detected incidentally due to increased use of imaging; historically were large (10 cm) at diagnosis
  • "Great mimic" due to associated paraneoplastic syndromes of Cushing syndrome, gynecomastia, hypercalcemia, hypertension, leukemoid reaction, polycythemia, Stauffer syndrome (hepatomegaly with hepatic dysfunction), systemic amyloidosis, polyneuromyopathy
Prognostic factors
  • WHO / International Society of Urologic Pathology (ISUP) Grading for Clear Cell and Papillary RCC:
    • Grade 1: nucleoli inconspicuous or absent at 400x (objective magnification 40x)
    • Grade 2: nucleoli prominent at 400x
    • Grade 3: nucleoli prominent at 100x magnification
    • Grade 4: extreme nuclear pleomorphism, multinucleated giant cells, sarcomatoid or rhabdoid change
  • Staging
  • Histologic subtype: Kidney tumor
Treatment
  • Resection (partial or radical nephrectomy)
  • Depends on subtype
  • Chemotherapy and radiation traditionally considered ineffective; however, increasing use of interferon,cytokine IL2,antiangiogenic agents and immunotherapy (sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab, pazopanib, nivolumab)
  • 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 RCC (70%)
Handling and Staging Guide
    (from Am J Surg Pathol 2013;37:1469)
  • Perinephric fat invasion: either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia
  • Renal sinus invasion: when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma or if it involves any endothelium lined spaces within the renal sinus If uncertain, at least 3 blocks of the tumor renal sinus interface should be submitted
  • Renal vein margin: margin is positive only when adherent tumor is visible microscopically at the actual margin If there is a submitted separately as “caval thrombus” take 2 or more sections to look for adherent caval wall tissue
  • Uninvolved renal parenchyma: should be sampled, distant from tumor, for underlying renal disease
  • Lymph nodes: should be sought but are found in < 10% of radical nephrectomy specimens
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
Gross images
Images hosted on PathOut server:

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Tumor less than 3 cm

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Arising in adult-type polycystic renal disease

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Diffusely infiltrative

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Massive tumor extension
into renal vein and inferior
vena cava


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Metastases to small intestine

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Nodal metastases

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

Microscopic (histologic) images

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Neuroendocrine carcinoma is less
well differentiated than carcinoid



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Cutaneous metastases: H&E and CD10

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Courtesy of Dr. Semir Vranic

Cytology description
  • Tumor cells have abundant cytoplasm that is vacuolated, fluffy or granular, usually with indistinct cell borders (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)
  • High false positive rate for FNAs in one study (Arch Pathol Lab Med 2002;126:670)
Cytology images
Images hosted on PathOut server:

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



Images hosted on other servers:

Normal kidney glomerulus
and renal tubular cells

Positive stains