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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".

Publication ,  Journal Article
Kozman, D; Kao, C-S; Nguyen, JK; Smith, SC; Kehr, EL; Tretiakova, M; Przybycin, CG; Williamson, SR; Argani, P; Eng, C; Campbell, SC ...
Published in: Am J Surg Pathol
September 1, 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.

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Published In

Am J Surg Pathol

DOI

EISSN

1532-0979

Publication Date

September 1, 2023

Volume

47

Issue

9

Start / End Page

1001 / 1010

Location

United States

Related Subject Headings

  • Pathology
  • PTEN Phosphohydrolase
  • Neoplastic Syndromes, Hereditary
  • Membrane Glycoproteins
  • Male
  • Lipoma
  • Kidney Neoplasms
  • Humans
  • Hamartoma Syndrome, Multiple
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kozman, D., Kao, C.-S., Nguyen, J. K., Smith, S. C., Kehr, E. L., Tretiakova, M., … Alaghehbandan, R. (2023). 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". Am J Surg Pathol, 47(9), 1001–1010. https://doi.org/10.1097/PAS.0000000000002079
Kozman, Diana, Chia-Sui Kao, Jane K. Nguyen, Steven C. Smith, Elizabeth L. Kehr, Maria Tretiakova, Christopher G. Przybycin, et al. “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".Am J Surg Pathol 47, no. 9 (September 1, 2023): 1001–10. https://doi.org/10.1097/PAS.0000000000002079.
Kozman, Diana, et al. “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".Am J Surg Pathol, vol. 47, no. 9, Sept. 2023, pp. 1001–10. Pubmed, doi:10.1097/PAS.0000000000002079.
Kozman D, Kao C-S, Nguyen JK, Smith SC, Kehr EL, Tretiakova M, Przybycin CG, Williamson SR, Argani P, Eng C, Campbell SC, McKenney JK, Alaghehbandan R. 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". Am J Surg Pathol. 2023 Sep 1;47(9):1001–1010.

Published In

Am J Surg Pathol

DOI

EISSN

1532-0979

Publication Date

September 1, 2023

Volume

47

Issue

9

Start / End Page

1001 / 1010

Location

United States

Related Subject Headings

  • Pathology
  • PTEN Phosphohydrolase
  • Neoplastic Syndromes, Hereditary
  • Membrane Glycoproteins
  • Male
  • Lipoma
  • Kidney Neoplasms
  • Humans
  • Hamartoma Syndrome, Multiple
  • Female