Campbell Malignant Renal Tumors 2021 Flashcards
Strongest predictors of malignancy in a renal mass (2)
Male sex
Increasing tumor size
___ imaging provides the most accurate characterization of renal masses while assessing for locally advanced features and intra-abdominal metastases and readily excludes angiomyolipoma by identifying intralesional fat.
Multiphasic, cross-sectional imaging
CT and magnetic resonance imaging (MRI) are the most widely used and studied
CT: Enhancement ___ HU is indicative of RCC, but does NOT preclude ___.
MRI: Enhancement ___ with IV gadolinium contrast is suggestive of RCC, helpful for masses ___ cm.
Greater than 15 to 20 Hounsfield units (HU)
Does not preclude benign histology
MRI: > 20% enhancement
masses < 2 cm
Solid massess with areas of ___ indicative of fat are diagnostic for ___.
< -20 HU
AML
Ultrasound criteria for simple cysts
Smooth cyst wall
Round or oval shape
No internal echoes
Through-transmission with strong acoustic shadowing posteriorly
Imaging option for:
Complex cyst or solid mass, with significant contrast allergy
MRI with or without gadolinium
Imaging option for:
Complex cyst or solid mass, no significant contrast allergy, eGFR > 45 or 30-45
Dedicated renal CT with and without contrast or MRI with and without gadolinium
(if eGFR 30-45, add periprocedural hydration)
Imaging option for:
Complex cyst or solid mass, no significant contrast allergy, eGFR < 30
Noncontrast CT or MRI without gadolinium
Ultrasound or CEUS
Uncommon but potentially serious complication with MRI + gadolinium
Nephrogenic systemic fibrosis (NSF)
most common:
- PXs on dialysis, with CKD stage 4 and 5
- Significant acute kidney injury
- Patients receiving multiple doses of gadolinium-based contrast agents
Gadolinium should only be used with eGFR ___
> 30 mL/min
Bosniak I
Water density
Homogeneous, hairline thin wall No septa
No calcification
No enhancement
0% risk of malignancy
Surveillance not necessary
Bosniak II
Few hairline septa in which “perceived” enhancement may be present Fine calcification or short segment of slightly thickened calcification in
wall or septa
No unequivocal enhancement
Hyperdense lesion: ≤3 cm, well marginated, with no unequivocal enhancement
Minimal risk of malignancy
Surveillance not necessary
Bosniak IIF
Multiple hairline thin septa
Minimal smooth wall thickening
“Perceived” enhancement of wall or septae may be present Calcification may be thick or nodular but must be without enhancement Generally well marginated
No unequivocal enhancement
3%–5% risk of malignancy
IF with: Hyperdense lesion: >3 cm or totally intrarenal with no enhancement
5%-10% risk of malignancy
Periodic surveillance
Bosniak III
“Indeterminate,” thickened irregular or smooth walls or septa in which measurable enhancement is present
50% risk of malignancy
Surgical excision
Bosniak IV
Clearly malignant lesions that can have all the criteria of category III but also contain enhancing soft-tissue components
75-90% risk of malignancy
Surgical excision
Clear cell and papillary variants arise from the ____.
Chromophobe and collecting duct carcinoma arise from the ____.
Clear cell and papillary: PCT
Chromophobe and collecting duct carcinoma: DCT
Most generally accepted environmental risk factor for RCC
Tobacco exposure
** All forms of tobacco use have been implicated, and risk increases with cumulative dose or pack-years
RCC risk factors
Tobacco exposure
Obesity
Hypertension
Familial form of clear cell RCC: ____. Its major manifestations include: ___
von Hippel-Lindau (VHL) disease
RCC (50% of patients with VHL)
Pheochromocytoma
Retinal angiomas
Hemangioblastomas of the brainstem, cerebellum, or spinal cord
** Highly vascular tumors can lead to substantial morbidity
VHL protein and RCC
VHL keeps HIF levels low through ubiquitin-mediated degradation
Inactivation of VHL gene –> accumulation of HIFs (esp. HIF-2alpha–> Increased VEGF expression –> pronounced neovascularity in clear cell RCC
Second most common histologic subtype of RCC
Papillary RCC
Prompt surgical management is recommended for patients with ___, due to aggressive tumor behavior vs. other familial RCC syndromes.
HLRCC
- develop cutaneous and uterine leiomyomas and type 2 papillary RCC
- often solitary and unilateral, and they are more likely to be aggressive than other forms of familial RCC
Shares features with HLRCC, early onset (< 40 years old), bilateral, multifocal, often with pheochromocytomas and head and neck paragangliomas
Succinate Dehydrogenase Renal Cell Carcinoma (SDHRCC)
Cutaneous fibrofolliculomas
Lung cysts
Spontaenous pneumothoraces
Distal nephron-derived renal tumors
Birt-Hogg-Dube syndrome
** include: chromophobe RCC, oncocytomas, and hybrid oncocytic tumors that exhibit features of both of these entities
PTEN tumor suppressor gene
34% lifetime risk of RCC
10% risk of epithelial thyroid carcinomas
Usually papillary histology
Cowden Syndrome
AML Cortical tubers Subependymal nodules Subependymal giant cell astrocytomas (SEGA) Pulmonary lymphangiofibromas Multifocal, bilateral, large Typically clear cell histology
Tuberous sclerosis complex (TSC)
Contributes to RCC chemorefractory nature:
Energy-dependent efflux pumps for hydrophobic cytotoxic compounds
** BUT: cisplatin is not extruded by these proteins, so there must be other chemotherapy resistance mechanisms
mTOR inhibitors
Temsirolimus
Everolimus
- Efficacious in patients where TKIs have failed
- mTOR pathway leads to increased expression of HIFs and other growth-promoting and potentially tumorigenic sequelae
Multicentricity is found in ___ of cases, is more common in association with ___.
10-20%
Papillary RCC and familial RCC
All RCCs are ___ derived from ___ cells.
All RCCs are, by definition, ADENOCARCINOMAS, derived from RENAL TUBULAR EPITHELIAL cells.
Originates from proximal tubule Aggressive Hypervascular tumor Typically well- circumscribed, lobulated, golden yellow tumor VHL-associated Chromosome 3p deletions 70-80% of RCC
Clear cell RCC
Proximal tubule Hypovascular Fleshy tumor with fibrous pseudocapsule Basophilic cells, low-grade nuclei HPRC, altered MET proto-oncogene status in 81% 5-10% of RCC
Papillary RCC Type 1
Proximal tubule Hypovascular Fleshy tumor with fibrous pseudocapsule Eosinophilic cells, high grade nuceli HPRC, Fumarate hydratase gene mutation in HLRCC 5-10% of RCC
Papillary RCC Type 2
Intercalated cells of collecting duct “Plant cells” with pale cytoplasm, perinuclear clearing or “halo,” nuclear “raisins,” and prominent cell borders BHD syndrome TP53 and PTEN mutations Folliculin gene mutation
Chromophobe RCC
ESRD and VHL Good prognosis Low-grade clear epithelial cells in linear papillae VHL disease ~5% of RCC
Clear cell papillary RCC
Collecting duct Poor prognosis Complex highly infiltrative cords within inflamed stroma Firm, centrally located tumor Multiple chromosomal losses RARE <1%
CA of the collecting ducts of Bellini
Collecting duct Dismal prognosis Poorly differentiated cells, lacelike appearance Extensive hemorrhage and necrosis Sickle-cell trait association
Renal medullary carcinoma
Metastasizes early Extremely poor prognosis Hypovascular HLRCC FH mutation
HLRCC associated RCC
Young adults, SDH mutation
HIF-VEGF pathway
Vacuolated eosinophilic or clear cells
Solitary lesion
Succinate-dehydrogenase deficient renal carcinoma
Children and young adults: 40% of pediatric RCC
Clear cells with papillary architecture; variable histo
Well-circumscribed, tan-yellow
MiT family translocation RCC
T1a
Organ-confined ≤4.0 cm
T1b
Organ-confined >4.0 cm to 7.0 cm
T2a
Organ-confined >7.0 to 10.0 cm
T2b
Organ-confined >10.0 cm
T3a
Invasion of pelvicalyceal system
Invasion of perinephric or renal sinus fat
Extension into renal vein or branches
T3b
Extension into IVC below diaphragm
T3c
Extension into IVC above diaphragm or invasion of IVC wall
T4
Direct adrenal involvement Locally advanced (invasion beyond Gerota fascia)
N1
Regional LN involvement
M1
Systemic metastasis
___ is the premier study for invasion into adjavent structures and evaluation and staging of IVC thrombus
MRI
Metastatic workup should include:
Chest radiograph Abdominal and pelvic CT or MRI Liver function tests Bone scintigraphy (for elevated alk phos, bone pain, or poor performance status) Chest CT (if abnormal CXR findings)
No longer recognized as a distinct histologic subtype of RCC: ___ and ___
Sarcomatoid and rhabdoid differentiation
** Spindle cell histology, positive staining for vimentin, infiltrative growth pattern, aggressive local and metastatic behavior, and poor prognosis
Classic triad (a.k.a. “too late triad”)
Gross hematuria
Palpable abdominal mass
Flank pain
** The classic triad of flank pain, gross hematuria, and palpable abdominal mass is now rarely seen. This is fortunate because this constellation of findings almost always denotes advanced disease and some refer to it as the “too late triad.”
MOST COMMON paraneoplastic syndrome in RCC
Elevated ESR
** The most common of these syndromes is elevated erythrocyte sedimentation rate, which accounts for more than 50% of identified paraneoplastic syndromes.
Management of paraneoplastic hypercalcemia
Vigorous hydration
Furosemide
Bisphosphonates (zoledronic acid 4 mg IV q4weeks)
Denosumab therapy if no response to zoledronic)
Hypertension in RCC mechanism
Increased production of renin
Encasement of the renal artery or branches – renal artery stenosis
Polycythemia from EPO production
AV fistula within the tumor
In general, treatment of paraneoplastic syndromes requires ___ except for ___.
Surgical excision
Hypercalcemia: treated medically
The SINGLE MOST IMPORTANT prognostic factor for RCC
Pathologic stage
** Lymph node involvement is associated with 5- and 10-year survival rates of 5% to 30% and 0 to 5%, respectively
Factors favoring active surveillance in RCC
Elderly
Life expectancy <5 years High comorbidities
Excessive perioperative risk Frailty (poor functional status) Patient preference for AS Marginal renal function
Tumor size <3cm
Tumor growth <5mm/year Non-infiltrative
Low complexity Favorable histology
RCC surgical principles:
LND for ___.
Adrenalectomy for ___.
Minimally invasive
considered when ___.
LND for clinically concerning regional lymphadenopathy.
Adrenalectomy for intraop/imaging findings of invasion or metastasis of adrenal
Min invasive when it would not compromise oncologic, functional and perioperative outcomes.
Radical nephrectomy generally preferred only if ALL of these criteria are met:
- High tumor complexity and PN would be challenging even in experienced hands
- No preexisting CKD or proteinuria; and
- Normal contralateral kidney and new baseline GFR will likely be >45 mL/ min/1.73 m2.
Thermal ablative therapies include: ___ and ___
For management of stage ___ renal masses smaller than ___ cm.
Cryosurgery Radiofrequency ablation (RFA)
cT1a
< 3.0 cm
Complete and reliable tissue necrosis with cryoablation is con- sistently achieved only at temperatures of ___ or lower.
Iceball must extend beyond visible margins of tumor.
−19.4°C
Stage I IVC thrombus
I: adjacent to the ostium of the renal vein
Stage II IVC thombus
II: extending up to the lower aspect of the liver and below the hepatic veins
Stage III IVC thrombus
III: involving the intrahepatic portion of the IVC but below the diaphragm
Stage IV IVC thrombus
IV: extending above the diaphragm
