Renal Neoplasia Occurring in Patients With PTEN Hamartoma Tumor Syndrome: Clinicopathologic Study of 12 Renal Cell Carcinomas From 9 Patients and Association With Intrarenal "Lipomas".
Diana KozmanChia-Sui KaoJane K NguyenSteven C SmithElizabeth L KehrMaria TretiakovaChristopher G PrzybycinSean R WilliamsonPedram ArganiCharis EngSteven C CampbellJesse K McKenneyReza AlaghehbandanPublished in: The American journal of surgical pathology (2023)
The aim of this study was to assess the histopathologic spectrum of renal tumors in patients with PTEN hamartoma tumor syndrome (PHTS), with a specific focus on potential features predictive of the underlying syndrome. A multi-institutional study was conducted to obtain clinical and pathologic data on renal tumors arising in patients with PHTS, either diagnosed by germline mutational analysis or clinical criteria for Cowden syndrome. Histologic sections of the renal tumors were re-reviewed for classification. Twelve renal epithelial tumors from 9 patients were identified (4 males and 5 females, with a mean age of 41.8 y), 7 of whom carried germline PTEN mutations. All 12 renal epithelial tumors were renal cell carcinomas (RCCs): 5 were chromophobe RCCs, 4 papillary RCCs, and 3 RCC not otherwise specified. Pathologic stage distribution was: 7 (59%) pT1a, 2 (17%) pT1b, 1 (8%) pT2a, 1 (8%) pT2b, and 1 (8%) pT3a. World Health Organization/International Society of Urological Pathology (WHO/ISUP) histologic grade was applicable in 7 (54%) nonchromophobe tumors: 4 (57%) G2, 2 (29%) G3, and 1 (14%) G4. An unexpected histologic finding was the presence of 2 patients with incidental microscopic collections of intrarenal adipocytes that had no features of angiomyolipoma (and were negative with 2 sensitive PEComa markers: cathepsin-K and GPNMB); both were classified as lipoma/"lipomatous hamartomas." The average follow-up interval was 67.8 months (13 to 172 mo): 5 patients had no evidence of disease, 2 were lost to follow-up, 1 died of other (non-PHTS) causes (ie, prostate cancer), and 1 was alive with metastatic RCC to the lung (RCC not otherwise specified with rhabdoid differentiation). All tumors showed loss of nuclear PTEN staining by immunohistochemistry. Fumarate hydratase was retained and 2SC was negative in all papillary RCCs. CK7 was moderate-strong/diffuse positive in 4 of 5 chromophobe RCCs and in 3 of 4 papillary RCCs. Renal epithelial tumors associated with PHTS represent a heterogeneous group of RCCs, but classic chromophobe and papillary RCC are most common. The majority have a favorable clinical behavior as would be predicted by subtype. In contrast to other hereditary renal neoplasia syndromes, morphologic features of the RCCs do not allow identification of PHTS-associated neoplasia with any degree of specificity in the absence of clinical setting and/or prior history, but the presence of microscopic "lipomas" within the kidney may provide a clue in rare cases. Therefore, clinical suspicion and genetic counseling with germline testing remain necessary for identifying PHTS-associated RCC.
Keyphrases
- renal cell carcinoma
- prostate cancer
- end stage renal disease
- high grade
- ejection fraction
- newly diagnosed
- squamous cell carcinoma
- chronic kidney disease
- gene expression
- prognostic factors
- magnetic resonance
- adipose tissue
- small cell lung cancer
- case report
- insulin resistance
- magnetic resonance imaging
- mesenchymal stem cells
- radical prostatectomy
- stem cells
- cell therapy
- low grade
- neoadjuvant chemotherapy
- patient reported outcomes
- dna methylation
- dna repair
- human immunodeficiency virus
- risk assessment
- pi k akt
- hepatitis c virus
- hiv testing
- high intensity
- locally advanced
- human health
- clear cell
- hiv infected
- smoking cessation
- protein kinase
- climate change