BERKELEY, CA (UroToday.com) - This interesting article investigates the incidence and characteristics of renal cell carcinoma (RCC) in patients with PTEN hamartoma tumor syndrome (PHTS) and is relevant to urologists and other physicians who manage patients with kidney cancer.
The authors report 9 cases of RCC among 219 patients (4.1%) prospectively identified to have pathogenic germline PTEN mutations, representing a >31-fold increased risk compared to the general population. On central pathologic review, most tumors were either papillary (n = 6) or chromophobe (n = 2) histology; both are thought to be derived from the distal nephron, in contrast to the much more common clear cell subtype which appears to be derived from the proximal convoluted tubules. Although 4 patients had the potentially aggressive high grade, type II papillary variant of RCC, no patients had metastasis and there were no cases with RCC progression or cancer-related death. Average age at presentation was relatively low (45-years old), similar to other genetic RCC syndromes; one case was bilateral while all others were unifocal. Complete loss of PTEN protein was observed by immunohistochemistry in all but one case.
There are many important clinical implications of this study – first and foremost to promote awareness of an increased risk of RCC among patients with Cowden Syndrome and other forms of PHTS. What is Cowden syndrome, and why should urologists know about it? Cowden syndrome is an autosomal dominant inherited condition due to a mutation in the PTEN tumor-suppressor gene that is associated with an increased risk of benign and malignant neoplasms, particularly breast cancer and thyroid carcinoma. Other manifestations of PHTS, the umbrella term for clinical entities driven by PTEN mutations that includes Cowden Syndrome, can include macrocephaly, GI polyposis, uterine tumors, autism spectrum/developmental delays, and various benign mucocutaneous lesions, most commonly hamartomas. Based on this study, patients with established PTEN mutations should be recognized to be at increased risk for RCC, and appropriate clinical investigation should be strongly considered for any such patients who present with hematuria or other symptoms potentially related to RCC. The authors advocate CT or MRI for this purpose, citing the reduced sensitivity of ultrasound for papillary or chromophobe RCC, and there is no question that CT and MRI provide the best sensitivity for this diagnosis. However, ultrasound would be unlikely to miss any truly significant cancers in this setting, and given that it eliminates radiographic exposure, our perspective is that it remains a viable alternative in this younger patient population, although this will require further study. More generalized screening of PHTS patients for RCC is now also advocated by the authors on a biennial basis beginning at age 40, recognizing the 34% lifetime risk of developing RCC. Increased awareness of the PHTS spectrum of disease and more frequent referral for genetic counseling for patients and families that may harbor this condition will also be of great importance moving forward.
In summary, previous studies have suggested a relationship between PTEN mutations and RCC, but this is the first study to investigate this relationship using a relatively large prospective cohort of patients with molecularly defined PHTS. As such, it provides a wealth of interesting observations of potential clinical utility, and will undoubtedly serve as a foundation for further study in this field.
Written by:
Steven C. Campbell, MD, PhD;1,* Maria Carmen Mir, MD;1 Rebecca A. Campbell, BA2 and Natalie David2 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
1 Center for Urologic Oncology, Glickman Urologic and Kidney Institute
2 Glickman Urologic and Kidney Institute
*Corresponding Author:
Center for Urologic Oncology
Glickman Urologic and Kidney Institute
Cleveland Clinic
Papillary renal cell carcinoma is associated with PTEN hamartoma tumor syndrome - Abstract
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