title: Papillary renal cell carcinoma is associated with PTEN hamartoma tumor syndrome.
abstract: OBJECTIVE
  To formally study the prevalence and histologic classification of renal cell carcinoma (RCC) in a series of patients with PTEN hamartoma tumor syndrome (PHTS).
  
  
  METHODS
  We evaluated prevalence of RCC within a prospectively-accrued series of 219 patients found to have pathogenic germline PTEN mutations. Clinical data including pathology reports were requested for all participants. Slides and tumor blocks were requested for central pathology re-review and immunohistochemistry (IHC) analysis.
  
  
  RESULTS
  Nine patients were identified with RCC. Based on Surveillance Epidemiology and End Results (SEER) data 0.28 RCC cases were expected for the group, giving an overall age-adjusted Standardized Incidence Ratio (SIR) of 31.7 (95% CI 15.4-58.1, P < 0.001) with a higher sex-adjusted SIR for females (46.7 vs 21.6 for males). Reported histology of each mutation positive patient's RCC was variable. However, on central pathology re-review of eight patients, six examined lesions were determined to be of papillary subhistology (pRCC), with the other two patients' tumors consistent with the initial report of chromophobe RCC (chRCC). IHC demonstrated complete loss of PTEN protein in all PTEN mutation positive patients' pRCCs and patchy positivity in one chRCC.
  
  
  CONCLUSIONS
  PHTS is a hereditary syndrome newly associated with pRCC, and PTEN IHC may be a helpful screening tool to identify pRCC patients with PHTS. Physicians caring for PHTS patients should note the >31-fold increased risk for RCC and have a low threshold for investigating possible RCC in patients with relevant complaints. Renal ultrasound is not sensitive for detecting pRCC and so PHTS patients should have alternate renal imaging (CT or MRI).
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mester
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Nichole
authors.initials: N
authors.lastname: Prescott
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D002648:Child; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D015995:Prevalence; D012737:Sex Factors
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human