Hereditary / Familal Renal Cell Carcinoma
Definition
- Several clinico-pathologic syndromes exist, defined by distinct genetic abnormalities
Diagnostic Criteria
| Syndrome | Genetic Abnormality | Extra-renal | Renal Carcinoma |
|---|---|---|---|
| von Hippel Lindau | VHL |
Retinal and CNS hemangioblastomas, pancreatic and other cystadenomas, pheochromocytomas | Multiple clear cell carcinomas |
| Birt Hogg Dubé | FLEN 17p11.2 dominant |
Cutaneous fibrofolliculomas, trichodiscomas, skin tags, lung cysts & pneumothorax | Multiple hybrid chromophobe-oncocytomas |
| Hereditaary leiomyomatosis and renal cell carcinoma | FH 1q42-43 dominant |
Cutaneous and uterine leiomyomas, rare kindreds with uterine leiomyosarcoma | Aggressive papillary RCC |
| Hereditary papillary RCC | MET 7q31 dominant |
None | Multiple type 1 papillary RCC |
| Constitutional chromosome 3 translocation | Various |
None | Multiple clear cell RCC |
| Succinate dehydrogenase | SDH |
Pheochromocytomas, head & neck paragangliomas and gastric GIST | Bubbly, flocculent pale to clear cytoplasm |
- von Hippel Lindau
- Most common renal carcinoma syndrome
- Prevalence 1:35,000
- Multifocal clear cell carcinomas
- Surrounding kidney parenchyma frequently has innumerable microscopic foci of clear cells
- Renal cysts frequent
- Most common renal carcinoma syndrome
- Birt Hogg Dubé
- Various types of renal cell carcinomas may occur (Pavlovich 2002)
- Most (84%) are chromophobe or hybrid chromophobe-oncocytoma
- Very low incidence of aggressive behavior
- Hybrid tumors have also been reported in non-syndromic cases (Petersson)
- Most others are clear cell carcinomas
- Frequently high grade
- Behavior same as non-syndromic cases
- Most (84%) are chromophobe or hybrid chromophobe-oncocytoma
- Frequent microscopic foci of oncocytosis
- Clusters of cells with eosinophilic cytoplasm, sharp cell borders and large nuclei
- Not restricted to kidneys with chromophobe or hybrid tumors
- May be seen even in BHD syndrome kidneys with clear cell carcinomas
- Various types of renal cell carcinomas may occur (Pavlovich 2002)
- Hereditary leiomyomatosis and renal cell carcinoma
- Usually solitary tumors
- Papillary or tubulopapillary pattern lined by tall cells with abundant eosinophilic cytoplasm
(Merino)
- Large pleomorphic nuclei
- Large inclusion-like eosinophilic nucleoli
- Large pleomorphic nuclei
- May have focal clear cells
- In the past, some cases reported as type 2 papillary carcinoma or as collecting duct carcinoma
- Negative for mucin, ulex lectin binding, CK7, CD10
- Clinically aggressive
- Hereditary papillary renal cell carcinoma
- Very rare
- Type 1 papillary renal cell carcinomas
(Schmidt)
- Papillae lined by cuboidal cells
- Usually low cytologic grade
- Constitutional chromosome 3 translocation carcinomas
- Very rare
- Multiple clear cell carcinomas
- Succinate dehydrogenase mutation carcinomas
- Very rare
- Mean age 37 years
- Various patterns reported, including oncocytoid and papillary tumors
- SDH subtype IPOX staining can detect deficiencies but not widely used
- Keratins frequently negative
- CD117 negative
- May be focally positive for PAX8 and EMA
- Recent reports describes distinctive features (Gill 2011, 2014)
- Circumscribed but not encapsulated
- Not infiltrative but may surround occasional normal elements
- Numerous clear to pale cytoplasmic inclusions imparting a bubbly, flocculent appearance to cytoplasm
- Inclusions are actually giant mitochondria
- Frequently cystic and multifocal, bilateral
- Very good behavior unless sarcomatoid areas (high grade nuclei or coagulative tumor necrosis)
- Irregular nuclei 2x size of usual bland nuclei, prominent nucleoli, coarse chromatiin
- Circumscribed but not encapsulated
- Very rare
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Last update: 12/30/16
