Renal tumor pathology Flashcards
Renal tumors
Malignant
- renal cell carcinoma
- urothelial carcinoma
- nephroblastoma (Wilms) = kids
Benign
- adenoma
- oncocytoma
- angiomyolipoma
- simple cyst
Renal cell carcinoma
- 85% of all renal malignancies
- originates from renal tubules
Several subtypes
- clear cell - 75%
- papillary - 15%
- chromophobe - <5%
- others are very rare
Epidemiology of renal cell carcinoma
- Older – 6th decade and up
- M>F 3:1
Associated with:
- Smoking (cigarettes, cigars, pipes)
- Obesity
- Hypertension
- Unopposed estrogen therapy
- Exposure to:
- –Asbestos
- –Petroleum products
- –Heavy metals
- Chronic renal failure and Acquired cystic kidney disease
- Von Hippel-Lindau syndrome
Renal cell carcinoma - symptoms
Classic triad (rare)
- costovertebral angle tenderness
- hematuria
- flank mass
Constitutional symptoms if large
- often identified incidentally on CT scan
Paraneoplastic syndromes
- hypercalcemia (PTH like hormone)
- polycythemia (increased EPO)
- hypertension (increased renin)
- cushings (ACTH)
- eosinophilia, leukemoid reactions
Von Hippel Lindau Syndrome
Features:
- Renal cell carcinomas, usually bilateral and multiple
- retinal angiomatosis
- cerebellar hemangioblastoma
- multiple angiomas, adenomas, and cysts throughout the body.
- Caused by mutation in VHL tumor suppressor gene on 3p25-26
Clear cell renal cell carcinoma - gross and microscopic
75% of renal cell carcinomas
Gross
- variable size
- solitary, unilateral, well demarcated, lobular mass
- bright yellow/gray/white = lipid + glycogen in cells - very specific for clear cell
- commonly large areas of necrosis –> abundant hemorrhage
- yellow tumor with lots of hemorrhage = clear cell
Microscopic
- polygonal cells with abundant clear to eosinophilic granular cytoplasm, no papillae (cells are not always clear)
- delicate branching vasculature - interconnected or sinusoidal pattern
- growth patterns –> alveolar (nests), trabecular (cord like), tubular, and cystic
- usually well differentiated; occasionally marked nuclear atypia with bizarre nuclei and giant cells
Clear cell RCC - genetics
Mutations/loss of VHL gene locus (3p25) in both sporadic and familial cases
VHL gene encodes a protein that functions in degradation of other proteins. An important target is Hypoxia inducible factor-1 (HIF-1). When VHL is mutated HIF-1 levels remain high and this protein increases the transcription and production of pro-angiogenic proteins such as VEGF and TGF-β1. Insulin-like growth factor
another target of VHL gene is upregulated.
Papillary RCC - gross and microscopic
Gross
- > 0.5 cm, mean size 8 cm, up to 23 cm
- well circumscribed, mostly encapsulated, eccentrically located in the cortex
- necrosis, hemorrhage is common
- frequently multifocal and bilateral
Microscopic
- single layer of cuboidal or low columnar cells with eosinophilic (pink) cytoplasm arranged on fibrovascular stalks forming papillary structures
- lipid-laden macrophages (foam cells) in stalks are characteristic
- psammoma bodies are comon
Papillary RCC - genetics
Sporadic –> trisomy 7, 16, 17 and loss of Y chromosome in males
Hereditary –> germ line mutation in c-met gene (7q31); also seen in sporadic
Chromophobe RCC - gross and microscopic
- genetics
Gross
- well circumscribed, slightly lobulated
- 2-22 cm (mean 8 cm)
- pale yellow/tan or brown
Microscopic
- cells arranged in solid sheets, broad trabeculae or rarely tubules
- cells with prominent cell membranes (PLANT CELL LIKE)
- pale to pink granular cytoplasm
- halo around the nucleus
(dont have to know)
Genetics - multiple chromosome losses and extreme hypodiploidy
Sarcomatoid RCC
Poorly differentiated spindle cell component arises in one of the other types
- much worse prognosis
RCC - prognosis
- May remain silent until large size
- Average 5-year survival: 70% (45% if metastases at diagnosis).
- Hematogenous metastasis (lung, bone, liver, adrenals) present at diagnosis in 25%.
- Sarcomatoid usually metastatic, survival <1 yr
- Clear cell slightly worse than papillary or chromophobe
- Better prognosis if small and incidental
- Stage of disease is most important prognostic factor
RCC - treatment
- nephrectomy
- partial nephrectomy
- –> usually done for tumors less than/equal to 4 cm on imaging; need to retain renal function
- ablation (cryotherapy)
- treatment for mets = resection/chemo
Urothelial carcinoma
- 5-10% of the renal tumors
- Arises from the urothelium of the renal pelvis
- Symptoms: hematuria, hydronephrosis
- Increased incidence in patients with analgesic nephropathy
- May occasionally be multiple (pelvis, ureter, bladder)
- Histologically identical to bladder
- Five year survival rate is 50- 70% for low stage; 10% for high stage lesions
Nephroblastoma - Wilms Tumor
Most common primary renal tumor of childhood (by far).
- 4th most common pediatric malignancy in US.
Clinical presentation:
- Usually 2 to 5 years of age (under 15 years).
- Palpable mass, hematuria, intestinal obstruction, hypertension.
Gross
- Solitary, spherical, sharply demarcated, pale tan to gray.
- Focal hemorrhage, necrosis and cyst formation.
- Often extends beyond the renal capsule.
- 5-10% are bilateral
Microscopic –> Attempts to recapitulate nephrogenesis
- Triphasic morphology in most tumors:
- Blastema (most undifferentiated): sheets of small blue cells
- Epithelial: abortive tubules and glomeruli formation
- Stroma (connective tissue): fibrous, skeletal or smooth muscle, fat, cartilage, bone.
- Percentage of each component variable
