Renal System-Renal Tumors By Leonard

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Renal System-Renal Tumors by Leonard

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Renal System-Renal Tumors by Leonard

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nephroblasomta... age of diagnosis, clinical presentation, prognosis, and treatment

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aka Wilms Tumor

Malignant pediatric tumor of the kidneys comprised of embryonal nephrogenic elements

blast=immature

Clinical
98% occur before age 10; peak 1-3 yo
Accounts for 85% of pediatric renal neoplasms
-lung metastases are common

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It's a triphasic neoplasm, so what does that mean?

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-three possible types of tissue constituents in varying proportions

1.Blastema: small densely packed cells with little cytoplasm; grow in nests or cords (trabeculae)
2.Epithelium: abortive tubules and glomeruli
3.Stroma: spindle cells of varying differentiation
Undifferentiated; skeletal muscle (most common), cartilage

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What is the Rule of 5's?

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-Accounts for ~ 5% of childhood cancers
-5% bilateral
-5% multicentric
-5% anaplastic (histopathologic feature) – worse prognosis

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What three syndromes are associated with Wilms?

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Beckwith-Wiedeman
-Organomegaly, hemihypertrophy
-WT2 gene mutation; 5% develop Wilms tumor

WAGR syndrome (Wilms-aniridia-genital anomaly-retardation)
WT1 gene mutation
33% develop Wilms tumor

Denys-Drash syndrome
-Glomerulonephritis, male pseudohermaphroditism (gonadal dysgenesis), Wilms
-WT1 gene mutation ~ 90% develop Wilms tumor

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Typical clinical presentation(s)
Prognosis
Treatment

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Typical clinical presentation(s)
-Abdominal mass, Abdominal pain, intestinal obstruction, hematuria

Prognosis
-Poor prognostic features (anaplasia; age > 2 yo; large size)
-80-90% overall cure rate; few develop second neoplasms

Treatment
-Nephrectomy plus chemotherapy

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Wilms Tumor - Pathogenesis

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Loss of or mutation in tumor suppressor genes on chromosome 11 (11p13 – 11p15.5)
-WT1 gene protein regulates transcription of growth-promoting genes (e.g., IGF-2)
-WT2 gene product also interacts with growth promoting factors

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Most common renal tumor of infancy

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Congenital Mesoblastic Nephroma
-Tumor composed of spindled cells with varying resemblance to immature tissues from mesoderm (e.g., smooth muscle, cartilage)

5-10% recur or metastasize (usually by 1 yo)
Recurrence from incomplete resection
Metastases are rare: lungs, brain, rarely bone

Treatment
Resection (nephrectomy) with wide margins; chemotherapy if resection is incomplete

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For papillary adenoma and carcinoma, what is important about the neoplasm?

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Tumor size separates papillary adenoma from carcinoma
≤0.5 cm = adenoma; >0.5 cm = papillary renal cell carcinoma

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Clinical and morphological features of Renal Papillary Adenoma

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Clinical:
-Most common renal tubular epithelial neoplasm
--Found in ~ 33% of cases of acquired cystic renal disease (e.g., from hemodialysis)
--Autopsy studies: found in ~ 15% of autopsy cases
-Asymptomatic; are incidentally discovered

Morphologic features
-Well circumscribed, nonencapsulated
-Generally subcapsular

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Renal Oncocytoma clinical and pathology and DDx

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Clinical
Accounts for ~ 5% of resected renal neoplasms
M:F = 2:1; median age 60-65 yo
No recorded deaths from metastases (benign)
Imaging studies may show central scar within lesion

Pathology
Well circumscribed, tan/yellow/mahogany brown
Typically solitary; average size = 6 cm
Central stellate scar (~ 1/3)
Ddx: renal cell carcinoma, chromophobe variant

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Angiomyolipoma clinical and pathological

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A mesenchymal tumor, ~1% neoplasms

Histogenesis: perivascular epithelioid cell
Usually solitary; multifocality suggests tuberous sclerosis
-Autosomal dominant neurocutaneous disorder
LM: mixture of mature adipose tissue, spindled cells with smooth muscle features, and thick-walled blood vessels
May involve veins and regional lymph nodes
-Indicative of multifocal growth and not metastases
May coexist with other renal neoplasms (RCC, oncocytoma)

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Associated with several hereditary disorders of angiomyolipoma

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-Tuberous sclerosis
-von Recklinghausen disease (NF1)
-von-Hippel Lindau syndrome
-Autosomal dominant polycystic kidney disease

Although benign, fatality may result from
-Massive hemorrhage
-Renal failure from significant loss of functional renal parenchyma

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Describe the role of the VHL gene product in the pathogenesis of RCC, particularly clear cell RCC

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Role of VHL gene (3p25) – mutation at this locus seen in >90% of cases
-VHL protein part of ubiquitin ligase complex (targets proteins for degradation); VHL gene acts as a tumor suppressor gene
--VHL gene product mutation causes constitutive activity of protein targets, which results in high levels of pro-angiogenic factors (e.g., VEGF) and cell growth factors (highly vascular tumors)

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What's the most common malignant renal neoplasm in adults?

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Renal Cell Carcinoma (RCC)

-Arise from renal tubular / collecting duct epithelium
-Accounts for ~ 85% of diagnosed renal cancers among adults
~ 2/3 are men; >50 yo; only ~ 1% are bilateral
-Bilaterally strongly suggestive of underlying syndrome

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Classic Triad of clinical symptoms for RCC?

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classic triad of:
-flank pain,
-palpable mass, and
-hematuria

Seen in only ~ 10% cases
Tumors typically detected incidentally

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Most common form of RCC, and prognosis

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Clear Cell RCC

Conventional / classic type
Previously known as hypernephroma since tumor microscopic features resembles adrenal gland)
Accounts for ~ 70% of adult renal cancers

Approximately 50% die of disease

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Second most common type of RCC

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Papillary RCC

Accounts for ~ 10-15% of RCC
Hereditary tumors: germline mutation in c-met gene (rare)
Associated with ESRD (“dialysis kidneys”)
More often multiple than any other type of RCC
By definition: > 0.5 cm
Typically present at early tumor stage
Significantly better prognosis than clear cell RCC

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Chromophobe RCC, prognosis, ddx

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Presents typically at a low stage; prognosis is good – fewer than 10% die of disease
-Most patients are cured by nephrectomy

Ddx includes clear cell RCC and oncocytoma

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How do you determine prognosis of RCCs

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Tumor stage
T – size of primary tumor; extent of invasion beyond kidney
N – presence of metastases to regional lymph nodes
M – distant metastasis

Nuclear grade (Fuhrman grade): 1 – 4
Size, contour, size of nucleoli

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Chronic renal failure requiring longstanding hemodialysis

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Angiomyolipoma

or papillary rcc

(which is right?)

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A prominent central stellate scar grossly seen within a round, well-circumscribed tan/brown tumor that distorts the lower pole of the kidney

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Renal Oncocytoma

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A 38-year-old man with sickle cell disease

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Renal Medullary Carcinoma

Very rare, very aggressive
-Fewer than 500 cases reported; all have been African-American or Mediterranean
-Die within 4-6 months of diagnosis, resistant to chemotherapy

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An invasive urothelial carcinoma in the urinary bladder

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Renal Urothelial Carcinomas
-Neoplasms of transitional cell epithelium (TCC)
-Accounts or ~ 5% of primary renal neoplasms
-Arise where urothelium is located (Calyces, Pelvis (most common intrarenal location))
-Carcinogenic “field effect” (tobacco, chemicals, chronic injury/irritation)
-Histologic grade (low grade, high grade) and presence of invasion
-Typically have an exophytic, papillary growth patter, though may be inverted
--Carcinomas with a flat (low) growth tend to be more aggressive

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Worst prognosis of typical RCC subtypes

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Collecting Duct Carcinoma:
Rare; <0.1% of RCC
50-66% die within first 2 years following diagnosis
Worst prognosis of typical RCC subtypes
Typically presents as painless gross hematuria
50% have coexisting urinary bladder urothelial carcinoma