Tumors of Kidney and Urinary Tract Flashcards
Renal Neoplasms
• Benign tumors
♦ Renal papillary adenoma
♦ Angiomyolipoma
♦ Oncocytoma
• Malignant tumors
♦ Renal cell carcinoma
♦ Wilms tumor
♦ Urothelial (transitional cell) carcinoma of renal pelvis
Renal Papillary Adenoma
- Common (up to 22% of patients at autopsy)
- Gross findings
a. Small (less than or equal to 1.5 cm)
b. Pale yellow-gray, discrete, well circumscribed nodule in the cortex
i. May be multiple - Microscopic findings
a. Papillary or tubular architecture
b. Bland, cuboidal nuclei without atypia (low grade)
i. No obvious nucleoli, mitoses or significant pleomorphism
c. Well circumscribed, but no capsule or desmoplastic response - Behavior
a. Benign – no metastasis or progression
Renal Papillary Adenoma
Angiomyolipoma
- Relatively rare tumor. Most cases are sporadic, not associated with genetic syndrome. 2. Minority of cases associated with tuberous sclerosis (brain lesions causing epilepsy/mental retardation, skin abnormalities, variety of benign neoplasms)
a. 25-50% of patients with tuberous sclerosis have angiomyolipoma - Usually benign behavior, rarely metastasizes
a. Patients may have spontaneous hemorrhage of tumor - Gross findings
a. Variable appearance
– Tan to brown, may have areas of hemorrhage and yellow adipose tissue
- Microscopic findings
a. Composed of variable amounts of blood vessels, smooth muscle and fat
Angiomyolipoma
Angiomyolipoma
Angiomyolipoma
Oncocytoma
- Represents 5-15% of all primary renal tumors
- Benign behavior
- Gross findings
a. Solid, mahogany brown
b. May have a central scar
c. May be large (tumors up to 12 cm reported) - Microscopic findings
a. Nests of cells with abundant granular eosinophilic cytoplasm and bland nuclei (no significant atypia, necrosis or mitoses)
i. Cells contain numerous mitochondria
Oncocytoma
Oncocytoma
Renal Cell Carcinoma
- Origin from renal cortical tubules; account for 85% of primary renal malignancies
- Biologic behavior related to:
a. Tumor size - Tumors less than 3 cm in diameter rarely metastasize; tumors over 3 cm diameter may metastasize
b. Pathologic stage – Penetration through renal capsule, involvement of surrounding perinephric fat, invasion into vascular structures, and lymph node metastases are all associated with worse prognosis
c. Tumor grade – Higher grade = more aggressive behavior - Clinical features:
a. Affects adults (usually older than 50 years); males more commonly affected than females
b. Classic triad of symptoms: (Seen only in 10% of cases)
i. Costovertebral angle pain
ii. Palpable mass
iii. Hematuria (most common symptom, often microscopic)
c. Paraneoplastic syndrome: Polycythemia (due to secretion of erythropoietin)
d. 25% of patients have metastases at time of diagnosis (most often to lung or bone; ~ 10% metastasize to the opposite kidney)
e. Localized Disease Treatment: Surgical
i. Radical nephrectomy
– Removal of entire kidney and surrounding perinephric fat up to Gerota’s fascia (large tumors, or tumors extending outside of the kidney)
ii. Partial nephrectomy – Indicated for some tumors <7 cm and confined to kidney
a. Partial nephrectomy is “nephron sparing” and better choice for patients with underlying kidney disease to preserve renal function
f. Metastatic Disease Treatment: Chemotherapy - Most RCC does not respond to standard chemotherapy
i. Newer agents directly target VEGF, tyrosine kinases, mTOR
ii. Immunotherapy – IL-2, interferon-alpha (significant side effects)
g. Prognosis – Depends on Stage. 5 year survival:
i. Stage I (< 7cm, confined to kidney) - 95%
ii. Stage II (> 7cm, confined to kidney) – 82%
iii. Stage III (Renal vein invasion or in perinephric fat) – 64%
iv. Stage IV (lymph node or distant metastases) – 23%
4. Frequent cytogenetic abnormalities in renal cell carcinoma:
a. Clear-cell carcinoma: chromosome 3p deletion
i. Often includes loss of the Von Hippel-Lindau tumor suppresser gene
ii. May result in promotion of tumor angiogenesis through activation of VEGF
b. Papillary carcinoma: trisomy chromosome 7
i. May include mutation of MET proto-oncogene, which encodes a tyrosine kinase receptor for hepatocyte growth factor
5. Pathology
a. Gross findings: Nodular mass, frequently bright yellow, with areas of hemorrhage and necrosis
b. Microscopic findings:
i. Clear cell carcinoma (70-80%): Cells have clear cytoplasm (containing lipid and/or glycogen), arranged in nests and sheets along delicate fibrovascular network
a. May have bland nuclear features, except for highgrade tumors.
ii. Papillary carcinoma (10-15%): Cuboidal or low columnar cells arranged in papillary formations, may have prominent macrophages, often multifocal.
iii. Others: Chromophobe carcinoma, Collecting duct carcinoma, Xp11 translocation carcinoma
6. Pattern of spread
a. Invasion through renal capsule into perinephric fat
b. Invasion of renal vein with proximal spread along inferior vena cava (may spread by this route up into right atrium of the heart)
c. Lymph node metastases: Renal hilum, para-aortic
d. Distant metastases: Adrenal gland, liver, lungs, brain
Renal Cell Carcinoma
Renal Cell Carcinoma
Renal Cell Carcinoma - Clear Cell Type
Renal Cell Carcinoma - Clear Cell Type
Renal Cell Carcinoma - Papillary
Renal Cell Carcinoma - Papillary
Renal Cell Carcinoma - Chromophobe
Renal Cell Carcinoma Grades
RCC - Sarcomatoid Dedifferentiation
RCC - Sarcomatoid Dedifferentiation
Wilms Tumor (Nephroblastoma)
- Malignant renal tumor of children (generally 2-5 years old); 4th most common pediatric malignancy in United States
- Chromosomal abnormality: Most common is mutation of a portion of short arm of chromosome 11 that codes for the WT1 gene (Wilms tumor associated gene)
a. Germline WT1 mutations are associated with several genetic syndromes:
i. WAGR syndrome: Wilms tumor, aniridia, genital anomalies and mental retardation
ii. Denys-Drash syndrome: Wilms tumor, gonadal dysgenesis, early-onset nephropathy leading to renal failure - Clinical features
a. Usually presents as abdominal mass
i. One of three important intra-abdominal mass-lesion malignancies of infancy/childhood (the others being hepatoblastoma of liver and neuroblastoma of adrenal)
b. Other symptoms: Abdominal pain, hematuria, intestinal obstruction, hypertension
c. 5-10% bilateral tumors
i. Patients with bilateral Wilms present earlier
ii. Often caused by germline mutation in Wilms tumorpredisposing genes
d. Treatment:
i. May include combined surgical, radiation therapy and chemotherapy
e. Prognosis: Depends on tumor stage, and histologic appearance - presence/absence of anaplasia (see below)
i. Favorable histology (no anaplasia)
– 4 year survival 80- 90%
ii. Unfavorable histology (anaplastic)
– 4 year survival varies from 80% (stage I) to 50% (stage IV)
- Pathology
a. Gross findings: Nodular, gray to gray-white, soft, fleshy mass
b. Microscopic findings: Represents malignancy of primitive renal blastema, with epithelial and stromal components (triphasic pattern)
i. Primitive blastema - Small, dark, undifferentiated cells
ii. Epithelial component - Abortive tubules and glomeruli
iii. Stroma - May have heterologous elements (cartilage, muscle, bone)
c. Anaplasia: Specifically defined in Wilms tumor by presence of tumor cell pleomorphism, hyperchromatic nuclei and abnormal mitotic figures
i. Anaplasia is a poor prognostic indicator; correlates with more aggressive behavior due to resistance to chemotherapy
d. Nephrogenic rests: Clusters of primitive cells seen in the renal parenchyma adjacent to Wilms tumors; may be a precursor lesion
i. Present in up to 40% of unilateral Wilms, and 100% of bilateral Wilms tumor patients
Wilms Tumor
Wilms Tumor
Wilms Tumor - Anaplasia
Additional Malignant Renal Tumors of Childhood
- clear cell carcinoma
- rhabdoid tumor
Urothelial Carcinoma
- Origin in urothelium lining the renal pelvis
- Clinical features:
a. Represents 5-10% of primary renal tumors
b. Occurs in adults
c. Frequently associated with urothelial carcinoma or dysplasia elsewhere in the urinary system, particularly in the bladder (“field effect” of carcinogenesis)
i. 50% of patients may have pre-existing or concomitant bladder tumor
d. Patients present with hematuria, urinary obstruction, hydronephrosis, flank pain
i. Often comes to clinical attention earlier vs renal cell carcinoma due to location and tendency to cause obstructive symptoms - Pathology
a. Gross findings
i. Papillary – Exophytic mass with papillary fronds
ii. Flat lesion – Reddened or granular appearance
b. Microscopic findings
i. Papillary – Papillary fronds with vascular cores lined by a proliferation of malignant urothelial cells
ii. Flat – No papillary growth pattern, cells show malignant features (high N:C ratios, hyperchromasia, pleomorphism), disordered maturation
iii. Cytology of neoplastic cells ranges from relatively bland (low-grade) to very malignant (high grade)
- Low grade lesions: Rarely invade (but may recur)
- High grade lesions: Often invade
c. Appearance similar to urothelial carcinoma in ureter and urinary bladder - Behavior and prognosis
a. Infiltrates adjacent calyces and renal parenchyma
b. Prognosis – depends on grade, depth of penetration through urothelial wall, presence/absence of metastases
Urothelial Carcinoma
Normal Urothelium
Normal Renal Pelvis
Papillary Urothelial Carcinoma
Papillary Urothelial Carcinoma Low Grade
Papillary Urothelial Carcinoma High Grade
Papillary Urothelial Carcinoma - in situ
Papillary Urothelial Carcinoma Invasive
Papillary Urothelial Carcinoma Invasive High Grade
Papillary Urothelial Carcinoma Ureter
Urinary Bladder Neoplasms
I. Incidence
A. Bladder cancer accounts for 5% of cancers and 3% cancer deaths in US
B. Higher incidence in males
- Urothelial carcinoma: Male:female ratio of 3:1; Squamous cell carcinoma: Male:female ratio of 3:2
C. 80% of patients are between 50 and 80 years
II. Epidemiology and Pathogenesis
A. Cigarette smoking
- Most important factor, increases risk by 3 to 7 fold
- Associated with 50-80% of all bladder cancers
B. Chemical carcinogens: 2-naphthylamine and related arylamines
C. Infectious agents
- Schistosoma haematobium – Parasite; associated with squamous cell carcinoma
a. Endemic areas – Egypt, Sudan
D. Other risk factors: Cyclophosphamide, long-term analgesic use, radiation exposure
III. Clinical Diagnosis
A. Signs and symptoms: Hematuria, dysuria
B. Goal: Early detection and treatment
- Cystoscopy with biopsy
- Urine cytology
a. Best for detection of high grade malignancy
b. Difficult to distinguish low grade carcinoma from reactive urothelium
IV. Neoplasms – Classification
A. Benign bladder tumors (rare)
- Leiomyoma - Most common
- Urothelial papilloma (benign, very rare)
B. Malignant bladder tumors (more common)
- Urothelial carcinoma – 90% of all bladder tumors; both papillary and flat lesions with similar gross and microscopic features as renal pelvis, as discussed above (section D3) a. Papillary lesions
i. Urothelial neoplasm of low malignant potential
ii. Papillary urothelial carcinoma, low grade aa. 10% risk of invasion iii. Papillary urothelial carcinoma, high-grade aa. 80% risk of invasion
b. Flat lesions
i. Dysplasia (low grade, no risk of invasion)
ii. Carcinoma in situ (CIS) (high-grade) aa. Increased risk for progression to invasive carcinoma - Squamous cell carcinoma
a. Represents 3-7% of all malignant bladder tumors
b. Arise in a background of squamous metaplasia, usually associated with chronic inflammation/infection
c. Well known association with schistosomiasis
d. Morphologic appearance similar to squamous cell carcinoma occurring elsewhere
e. Treatment – Radical cystectomy - Adenocarcinoma (rare)
a. Similar appearance to colonic adenocarcinoma
b. May arise from urachal remnant
c. Treatment – Radical cystectomy +/- radiation - Small cell carcinoma (SCC) (rare, aggressive)
a. Poorly differentiated appearance (scant cytoplasm, high N:C ratios)
b. Similar in appearance and behavior to pulmonary small cell carcinoma
c. Treatment
i. Localized disease - Aggressive combined modality (chemotherapy + radical cystectomy and/or radiation)
ii. Disseminated disease – Systemic chemotherapy - Sarcomas (rare)
a. Embryonal rhabdomyosarcoma – Malignant tumor of urinary bladder in children
b. Leiomyosarcoma - Adults 6. Lymphoma (rare)
V. Staging
A. Depends on depth/extent of invasionB. AJCC criteria: see image
B. Invasion of muscularis propria (T2) is an important prognostic indicator; requires more aggressive therapy (usually cystectomy)
VI. Clinical Course and Treatment – Urothelial Carcinoma
A. 60% of neoplasms are single, 70% are localized to the bladder
B. Tendency to develop new tumors after excision; recurrences may be of higher grade C. Prognosis depends on histologic grade and stage of progression
- Papilloma, papillary urothelial neoplasms of low malignant potential and low grade papillary urothelial carcinoma all have >90% 10 year survival
a. Less than 10% progress to higher grade - High grade papillary urothelial neoplasms – increased propensity to invade and metastasize a. Invasive urothelial carcinoma is almost always high grade
- Treatment
a. Transurethral resection: Low-grade, non-invasive papillary lesions
b. Topical immunotherapy: Carcinoma in situ, high-grade noninvasive lesions, lesions with limited (lamina propria) invasion
i. Agent used: Bacillus Calmette-Guerin (BCG) – attenuated form of tuberculous bacillus ii. Causes a granulomatous inflammatory response
c. Radical cystectomy: Muscularis propria (T2) invasion or higher, CIS or high-grade lesions refractory to BCG therapy
d. Chemotherapy: Advanced disease
Bladder Cancer in situ
Squamous Cell Carcinoma
Small Cell Carcinoma
Bladder Carcinoma Stages
Adenocarcinoma
Urothelial Carcinoma Invasive
Papillary Urothelial Carcinoma
Papillary Urothelial Carcinoma Bladder
