Renal Neoplasia Flashcards
benign renal tumors
- renal papillary adenoma
- oncocytoma
- angiomyolipoma
malignant renal tumors
- renal cell carcinoma
- transitional cell carcinoma
- Wilms Tumor
renal papillary adenoma
*benign
*found in the cortex and arises from papillary or tubular epithelium
*subcapsular and solitary
*measures 15mm or less
*most commonly found at autopsy
*all papillary adenomas are precursors to papillary renal cell carcinoma b/c their histology is similar
*risk factors: ESRD patients
renal oncocytoma - overview
*benign kidney tumor
*arises from the epithelium (specifically the intercalated cells of the collecting duct)
*usually an incidental finding (asymptomatic)
*usually solitary
*can grow in size but rarely invasive or metastatic
*CT or MRI shows a well-circumscribed solid mass containing a central scar
renal oncocytoma - histology
*LM: cells have large eosinophilic (PINK) granular cytoplasm with large nuclei
*EM: numerous, prominent mitochondria
angiomyolipoma - overview
*benign renal tumor; hamartoma
*disorganized mass of normal tissue consisting of:
1. thick walled blood vessels (“angio”)
2. varying amounts of smooth muscle-like cells (“myo”)
3. adipose tissue (“lipo”)
*genetic disease that may be related: tuberous sclerosis
angiomyolipoma - risk factors
*solitary AMLs are found in the general population
*women tend to have more & larger AML lesions compared to men
*pregnancy increases risk for rupture & hemorrhage
*associated with TUBUROUS SCLEROSIS
angiomyolipoma - clinical manifestations
*hemorrhage (from intra-tumoral or retroperitoneal bleeding)
*symptoms of mass effect: abdominal or flank masses, flank tenderness, HTN, renal function impairment
*development and growth of angiomyolipomas = most common cause of death in patients with tuberous sclerosis complex
tuberous sclerosis complex (TSC) - overview
*autosomal dominant genetic syndrome
*defined by an inactivating/loss of function mutation of a tumor suppressor gene, either:
1. TSC 1 on chromosome 9 (encodes hamartin protein)
2. TSC 2 on chromosome 16 (encodes tuberin protein); more severe manifestations
*TSC1 and TSC2 are natural tumor suppressor genes, so when mutated/inactivated → unopposed activity of mTOR pathway → cell proliferation
treatment of angiomyolipomas in tuberous sclerosis complex (TSC)
*mTOR inhibitors (ex. sirolimus, everolimus) are effective in reducing the volume of target angiomyolipomas
angiomyolipomas in tuberous sclerosis complex (TSC) - clinical manifestations
*hamartomas of multiple organs (kidneys, brain, heart, lungs, skin)
*specific renal manifestations:
-renal angiomyolipomas
-renal cysts
-renal cancers
*skin manifestations: angifibromas of face, Ash leaf patch, Shagreen patch
renal cell carcinoma - characteristics
*acquired vs. hereditary
*85% of renal cancers in adults
*occur most often in the 6th to 8th decades of life
*arise from renal tubular epithelium
renal cell carcinoma - risk factors
*tobacco abuse (2x the risk)
*male gender
*obesity
*HTN
*exposure to carcinogens
*ESRD
*patients with acquired renal cysts
renal cell carcinoma - clinical manifestations
*painless (therefore often detected incidentally; some present with metastasis to lung or bone)
*triad of hematuria, palpable mass, flank pain
*systemic symptoms: fever, weight loss, night sweats
*paraneoplastic manifestations:
-excess erythropoietin → erythrocytosis
-excess renin → HTN
-excess PTHrP → hypercalcemia
-excess ACTH → Cushing’s syndrome
*symptoms of renal vein thrombosis (edema, left-sided hydrocele)
renal cell carcinoma - paraneoplastic manifestations
*excess erythropoietin → erythrocytosis
*excess renin → HTN
*excess PTHrP → hypercalcemia
*excess ACTH → Cushing’s syndrome
renal cell carcinoma - gross pathology
*involves any portion of kidney, but usually found in the upper pole
*golden yellow/pale mass
*can extend into the renal calyces, pelvis, collecting system, ureter, renal vein
renal cell carcinoma-related renal vein thrombosis
*leads to left varicocele (swelling of left testicle due to enlarged/twisted veins) in 11% of male patients
*this is because left spermatic vein drains into left renal vein (whereas right spermatic vein drains into IVC directly)
*isolated left varicocele should arouse suspicion for an invasive renal tumor
renal cell carcinoma - subtypes
- papillary RCC - gain of function of MET gene
- clear cell RCC (most common variant) - inactivation of VHL gene
renal cell carcinoma - staging
*TNM staging defines anatomic extent of disease
*T = size and involvement of renal vein
*N = spread to regional lymph nodes
*M = metastasis
*stage correlates with prognosis
clear cell renal cell carcinoma - overview
*most common (70-80% of renal cancers)
*originates from cells in the proximal convoluted tubule
*histology: abundant polygonal cells with clear cytoplasm (containing glycogen & lipids); often arranged in a tubular pattern
*associated with inactivation of VHL gene
clear cell renal cell carcinoma - pathogenesis
*caused by loss-of-function of the VHL tumor suppressor gene located on chromosome 3p
*can be hereditary or sporadic
*loss of VHL gene activity → unopposed HIF activity → increased erythropoietin production → increased angiogenesis and proliferation (through increased VEGF and PDGF)
hereditary clear cell renal cell carcinoma: Von Hippel Lindau disease
*autosomal dominant mutation leading to loss of function of the VHL tumor suppressor gene
*75% of patients with VHL disease will develop renal cell carcinoma by age 60
*extra-renal manifestations: hemangioblastoma of the cerebellum and retina, pancreatic cysts
papillary renal cell carcinoma - characteristics
*10-15% of renal cancers
*especially found in dialysis patients with cystic disease
*originates from cells in the proximal convoluted tubules
*papillary growth pattern made of cuboidal cells with interstitial foam cells at the papillary cores
*associated with gain-of-function of MET gene
papillary renal cell carcinoma - pathogenesis
*can be hereditary or sporadic
*gain of function mutation of MET gene → unopposed cell proliferation and invasiveness
renal cell carcinoma - treatment
*smaller focal RCC lesions are usually resected
*radical nephrectomy
*options for management of metastatic disease: immunotherapy, cryoreductive surgery of metastatic lesions, chemotherapy, radiation
*options for medical management: mTOR inhibitors, VEGF antibodies
transitional cell carcinoma - characteristics
*represents 5-10% of kidney tumors
*found in the urinary tract (renal calyces, renal pelvis, ureters, bladders)
*involves cells from the renal pelvis and ureter
transitional cell carcinoma - risk factors
*smoking
*toxins: aniline dyes, arsenic, phenacetin
*cyclophosphamide
*Balkan nephropathy & Chinese herbal nephropathy (aristolochic acid)
transitional cell carcinoma - clinical presentation
*painless hematuria (post-renal obstruction which can lead to hydronephrosis & flank pain)
transitional cell carcinoma - diagnosis
*cystoscopy & biopsy
transitional cell carcinoma - treatment
*surgery
*radiation
*chemotherapy (platinum-based regimen)
transitional cell carcinoma - prognosis
*worse than renal cell carcinoma prognosis because often multifocal and recurrent
Wilms Tumor - characteristics
*most common malignant renal tumor in CHILDREN (usually age 2-5)
*4th most common pediatric malignancy in US
*usually sporadic
*contains a mixture of primitive cells (blastemal, glomeruli, tubules, stromal cells)
Wilms Tumor - pathogenesis
*loss of function mutation of tumor suppressor & transcription genes, most commonly WT1 on chromosome 11
*WT1 encodes DNA-binding transcription factors that are expressed within several tissues (kidneys, gonads, etc)
*Wilms Tumor can be part of other syndromes (WAGR syndrome, Beckwith-Wiedemann syndrome, Denys Drash syndrome)
Wilms Tumor - clinical presentation
*PAINLESS, LARGE, PALPABLE abdominal mass leading to symptoms such as abdominal pain, intestinal obstruction
*hematuria
*hypertension (secondary to excess renin production)
*metastasizes to the lung
Wilms Tumor - treatment & prognosis
*tx: combination nephrectomy & chemo
*prognosis very good
Wilms Tumor - gross anatomy
*large, yellow, solitary, well-circumscribed mass
Wilms Tumor - histology
*triphasic histology that represents different stages of nephrogenesis:
1. BLASTEMAL CELLS: small, tightly packed blue undifferentiated cells
2. stromal cells: fibrocystic or myxoid, less cellular, immature cells
3. epithelial: primitive tubules or glomeruli
WAGR Syndrome & Wilms Tumor
*WAGR Syndrome = Wilms Tumor + Aniridia + Genital abnormalities + mental and motor Retardation
*aniridia = absence of iris (no colored part of eye)
*associated with a large 11p13 deletion that encompasses several contiguous genes, including WT1 and PAX6
