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RCC Tables

Types of RCC

Tumor Type	% all RCC	Cellular origin	Nuggets (mainly prognosis)
Clear cell	70-80%	Proximal tubule	Aggressive behavior Responds to targeted therapy
Papillary Type I	5-10%		Good prognosis
Papillary Type II			Worse prognosis than Type I
Chromophobe	3-5%	Intercalated cells of collecting duct	Sarcomatoid has worse prognosis
Clear cell papillary	5%		Good prognosis with indolent behavior Seen in VHL and ESRD
Collecting duct (Bellini)	< 1%	Collecting duct	Poor prognosis May respond to chemo
Renal medullary		Collecting duct	Poor prognosis Usually seen in sickle cell patients
HLRCC-associated		-	Early metastasis Poor prognosis
SDH-associated			Occur in young adults
MiT Family (Xp11 and t(6;11)			40% pediatric RCC
Acquired cystic-disease-associated			Seen in ESRD and ACD patients Good prognosis
Multilocular cystic clear cell			Mass with multiple cysts Almost uniformly benign
Tubulocystic			Favorable prognosis
Mucinous tubular and spindle cell			Favorable prognosis
Hybrid oncocytic chromophobe			Generally good prognosis Seen in Birt-Hogg-Dube
Sarcomatoid differentiation	1-5%	Variant seen in most RCC	Indicates worse prognosis
Sarcomatoid differentiation
Unclassifed	1-5%	Unclear	Poor prognosis Aggressive behavior

Familial RCC Syndromes

Syndrome	Gene/Chromosome	Type of RCC	Associated Findings	Management
Von-Hippel Lindau (VHL)	VHL (3p25)	Clear cell (may be multifocal)	Renal cysts Hemangioblastomas Retinal angiomas Pheochromocytoma Epididymal cystadenomas	If < 3cm - active surveillance If > 3cm - nephron sparing surgery
Hereditary Papillary Renal Carcinoma	MET (7q31)	Type I Papillary (multiple, bilateral)	None
Birt Hogg Dube (BHR)	FLCN (17p11)	Chromophobe	Oncocytoma Renal cysts Cutaneous fibrofolliculomas Lung cysts Spontaneous pneumothorax
Cowden Syndrome	PTEN (10q23)	Clear cell Chromophobe Type I papillary	Mucocutaneous lesions Facial trichilemmomas Breast tumors Epithelial thyroid cancer
Hereditary Leiomyomatosis RCC (HLRCC)	FH (1q42-43)	Type II Papillary Collecting Duct	Cutaneous leiomyomas Uterine leiomyomas	Surgical excision with wide margins
Succinate dehydrogenase deficiency RCC	SDHB (qp36) SDHC (1q23) SDHD (11q23)	Clear cell Chromophobe Type II papillary	Oncocytoma Paragangliomas Papillary thyroid cancer
Tuberous Sclerosis	TSC1 (9q34) TSC2 (16p13)	Clear cell	Angiomyolipoma Oncocytoma Polycystic kidneys Cardiac rhabdomyomas Cutaneous angiofibromas Lymphangiomyomatosis Seizures Autism	AML: surveillance (< 3cm), everolimus (3-5cm), surgery/embolization (> 5cm) RCC: surgery (> 3cm)

Diagnosis

Presentation

• Classic triad: flank pain + renal mass + hematuria, seen in < 5% patients - > 60% RCC diagnosed incidentally
• Paraneoplastic syndromes: hypercalcemia, hypertension, polycythemia, anemia, weight loss, fever
• Stauffer syndrome: non-metastatic hepatic dysfunction (3-20% prevalence), normalizes in 60-70% cases after nephrectomy

Initial Imaging

• Options: CT/MR w/ + w/o contrast to assess enhancement, consider contrast-enhanced US if unable to undergo CT/MR
• Enhancement: > 15-20 HU with CT, > 20% with MR
• No fat density: intralesion fat likely angiomyolipoma
• Perirenal hematoma: may have underlying malignancy in > 50% cases, reimage in 2-3 months to assess after resolution
• Complexity profiles: RENAL nephometry score, PADUA score, C-index - useful for predicting complexity of surgical resection

Complete the Workup

• Labs: obtain baseline CMP (assess baseline GFR), CBC, UA (assess proteinuria)
• Chest imaging: obtain CXR, or CT chest (if pulmonary symptoms or abnormal CXR)
• Genetics evaluation: recommended if ≤ 45yo, bilateral masses, multifocal masses, personal or family (first/second degree relative) history of renal mass syndrome (even if no one has had renal masses)
• MR indications (after CT): locally advanced disease, equivocal vein involvement, or contrast allergies
• IVC thrombus: MR is best (chest + abdomen), CT may be equivalent, TEE can be considered
• Brain imaging: only if neurologic symptoms, IVC thrombus, or metastatic disease
• Bone scan: only if bone pain or elevaed alkaline phosphatase
• Nephrology referral: GFR < 45, diabetic w/ CKD, proteinuria, or anticipated GFR < 30 after treatment

When to Biopsy

• Accuracy: sensitivity 97.5%, specificity 96.2%, PPV 99.8%, NPV 63% (20-37% missed cancer diagnosis), biopsy nondiagnostic rate 14% (will find cancer on repeat biopsy), perform core biopsy (not fine-needle aspiration)
• Indications: renal mass is thought to be metastatic, inflammatory, infectious, or hematologic
• Young/healthy: no need for biopsy if patient opts for surgery, but can consider if patient wants observation
• Old/frail: no need for biopsy if planning on observing
• Metastatic sites: preferentially biopsy metastatic lesion, consider renal biopsy if considering palliative/cytoreductive nephrectomy
• Biopsy risks: hematoma (5%), significant pain (1%), hematuria (1%), pneumothorax (0.6%), transfusion (0.4%), tumor seeding rare (no reported cases in modern literature with modern biopsy techniques)

Non-RCC Tumors

Sarcoma

• 1-2% all renal malignancies
• Do not obey normal tissue planes, may require en bloc resection
• Neoadjuvant XRT may reduce risk of positive margins

Leukemia/Lymphoma

• Rarely presents as primary renal lesion
• Imaging findings: retroperitoneal lymphadenopathy, multiple distinct renal masses, spenomegaly, lymphadenopathy in other areas of the body
• Obtain biopsy to confirm diangosis
• Treat with chemo (R-CHOP) +/- XRT, not surgery

Metastatic disease

• 12% cancer patients have renal metastases
• Most common primaries: leukemia/lymphoma, lung, breast, stomach, colon, cervix, melanoma
• Biopsy indicated if unclear whether primary RCC or metastatic lesion
• Nephrectomy rarely indicated

Benign renal tumors

Renal Cysts

• Seen in up to 10% population
• Indications for intervention: pain, infection, HTN, hemorrhage, rupture
• Management: aspiration, decortication, resection, sclerotherapy, embolization, nephrectomy (partial/radical)

Bosniak Renal Cyst Classification

Bosniak Class	Findings	% Malignancy	Plan
I	Water density Homogenous wall No septa, calcifications, or enhancement	0-2%	No follow-up required
II	Few septations with possible enhancement Fine calcifications No obvious enhancement	0-18%	No follow-up
IIF	Multiple septations Perceived wall/septal enhancmenets Calcifications without enhancement No obvious enhancement	3-18%	Repeat imaging to assess stability
III	Thickened/irregular walls/septations with measurable enhancement	33-50%	Observation, excision, ablation
IV	Complex cystic mass Enhancing nodular components "clearly malignant"	75-93%	Surgery

Oncocytoma

• Most common benign renal mass (up to 25% masses < 3cm)
• Can occasionally present with perirenal fat and renal vein invasion
• Association with RCC: ~10% contain RCC, impossible to distinguish on imaging from RCC
• Imaging: may show hypervascularity, central scar, but non-definitive
• Renal biopsy: PPV only 67%, not recommended
• Differential: compare histology for chromophobe RCC, CK7 rarely positive in oncocytoma
• Management: can consider observation, growth rate slower than for chromophobe RCC (average 0.14mm/yr vs 0.38mm/yr)

Angiomyolipoma

• Composed of dysmorphic blood vessels, smooth muscle, and adipose tissue
• More common with tuberous sclerosus or lymphangiomyomatosis
• Wunderlich syndrome: spontaneous retroperitoneal hemorrhage, seen in 15% AMLs
• Diagnose with presence of macroscopic fat (HU -15-20) on CT/MR
• Fat-poor AML: seen in 4-14%, difficult to differentiate from RCC
• MR imaging: recommended in women < 55yo to confirm/rule out AML
• Management: observation if < 4cm and asymptomatic, embolization for active hemorrhage or > 4cm, surgery as last resort (but less surveillance required), consider everolimus if TS

Other masses

• Papillary adenoma: small (< 0.5cm) usually incidentally found in nephrectomy specimens, possible precursor to papillary RCC
• Metanephric adenoma: possibly mature form of Wilms tumor, enhance less than normal renal parenchyma, diagnosis usually confirmed after resection
• Cystic nephroma: appears similar to Wilms tumor, no blastemal/embryonal components
• Mixed epithelial/stromal tumor: associated with estrogen replacement, present as cystic mass
• Leiomyoma: appear similar to chromophobe RCC, usually hyperdense and homogenous enhancement
• Hemangioma: associated with Klippel-Trenaunay and Struge-Weber
• Lymphangioma: abnormal lymphatics create dilated cystic masses, may present with obstruction, HTN, hematuria, and cyluria, can treat with aspiration, sclerosis, excision
• Juxtaglomerular cell tumor (reninoma): presents with hyperaldosteronism, rare cause of HTN, treat w/ partial nephrectomy, 10% have persistent HTN after resection
• Renomedullary interstitial cell tumor: very small (< 5mm) usually incidentally diagnosed

Pseudotumors

• Examples: hypertrophied column of Bertin, fetal lobation, dromedary hump, hilar lip/uncus, nodular compensatory hypertrophy
• Imaging: CT renal mass protocol, DMSA renal scan (normal uptake)