Kidney tumor
Adult renal cell carcinoma
Renal cell carcinoma - general


Topic Completed: 1 April 2017

Revised: 17 September 2019

Copyright: 2003-2019, PathologyOutlines.com, Inc.

PubMed Search: Renal cell carcinoma [title]

Nicole K. Andeen, M.D.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Andeen NK, Tretiakova M. Renal cell carcinoma - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytumormalignantrcc.html. Accessed December 7th, 2019.
Definition / general
  • Adult renal cell carcinoma (RCC)
Essential features
  • Sixteenth 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, ninth most common cancer in men (214,000 cases) and fourteenth 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 tumor 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 versus 5% in stage IV, lower for renal pelvis carcinoma (51%) compared with 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

Contributed by Debra Zynger, M.D.

pT2b

pT3a

pT4



AFIP images
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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

Contributed by Maria Tretiakova, M.D., Ph.D.

RCC metastatic to stomach

RCC metastatic to bronchus

RCC metastatic to duodenum



Images hosted on other servers:
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Granulomas - contributed by 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

AFIP images
  

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
Differential diagnosis
Gross differential diagnosis
Multilocular cystic renal neoplasm of low malignant potential
  • "Neoplasm composed entirely of numerous cysts, the septa of which contain individual or groups of clear cells without expansile growth" (WHO 2016) clear cells have low grade nuclei (ISUP 1 or 2)
  • Multicystic with no expansile growth / solid nodules

Cystic clear cell papillary renal cell carcinoma
  • Linear arrangement of nuclei away from basal membrane
  • Coexpression of CK7 & CAIX (cup shaped positivity)

Clear cell renal cell carcinoma with cystic degeneration
  • An extensively cystic / necrotic tumor may still exhibit aggressive behavior even if only rare identifiable tumor cells (Am J Surg Pathol 2000;24:988)
  • Hemorrhage, necrosis, thick irregular cyst wall, may be papillary / pseudopapillary, may have large areas of solid architecture or few residual tumor cells.

Clear cell renal cell carcinoma originating in a benign cyst
Acquired cystic disease associated renal cell carcinoma
  • Most common kidney tumor in patients with end stage renal disease and acquired cystic disease
  • Characterized by abundant calcium oxalate crystals and variable morphology: papillary, solid, eosinophilic and clear cell-like areas

Tubulocystic renal cell carcinoma
  • Sponge-like, composed of small to intermediate size cysts
  • Usually enlarged nuclei and ISUP grade 3 nucleoli
  • Shares cytogenetic abnormalities with papillary RCC (trisomy 7 / 17)

Cystic nephroma (in adult)
  • Multiloculated benign tumor with cysts lined by flat to hobnailed epithelial cells separated by fibrous septa containing paucicellular or ovarian-like stroma; no septal nodules of clear cells
  • Part of a spectrum of renal epithelial and stromal tumors that includes mixed epithelial and stromal tumor (Am J Surg Pathol 2009;33:72, Am J Surg Pathol 2007;31:489)
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