The Impact of Germline BHD Mutation on Histological Concordance and Clinical Treatment of Patients With Bilateral Renal Masses and Known Unilateral Oncocytoma

Abstract

Introduction and Objective Managing patients presenting with oncocytoma in the setting of bilateral renal masses is a challenging scenario. Nevertheless, pathologic concordance of oncocytic neoplasm in one kidney with tumors in the contralateral kidney is not known. We aim to evaluate the influence of germline Birt-Hogg-Dubé (BHD) mutation on concordance rates to assist in management of these patients. Methods We reviewed records of the NIH patients between 1983 and 2009 having bilateral renal masses, known pathology bilaterally, and presence of oncocytoma or oncocytic neoplasm in at least one kidney. The presence of oncocytoma or oncocytic neoplasm in two renal units was considered concordant. Demographic, pathological and clinical data were collected. Results The patient population consisted of 40 patients: 23 with BHD and 17 patients without diagnosis of BHD. Patients with BHD were younger (p<0.01) but there were no other differences between two groups. However, patients with BHD had a statistically lower histologic concordance between bilateral masses when compared to patients without the diagnosis of BHD (Fisher's exact test, p<0.01). Additionally, the subgroup of patients (n=8) without BHD who had multifocal renal masses demonstrated 100% oncocytoma concordance between renal units. Conclusions In patients with bilateral renal masses BHD patients have significantly lower histologic concordance rates compared to patients without BHD. Patients with BHD should be monitored and managed differently than patients without detected genetic mutations, especially those with multifocal oncocytomas. Genetic testing for BHD should be considered in the algorithm for management of patients with bilateral renal masses and known oncocytoma.

Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion

“…The penetrance of these phenotypes is incomplete: 15–30% of BHD patients develop RCC [14] , and families have been reported in which cystic lung disease and pneumothorax occur in the absence of renal or skin manifestations [15] , [16] , [17] , [18] . Nearly all germline BHD mutations are truncating, and RCC from BHD patients exhibit loss of heterozygosity of chromosome 17p [14] , [19] , [20] , consistent with the hypothesis that BHD is a tumor suppressor gene.…”

Comparing oncologic outcomes in patients undergoing surgery for oncocytic neoplasms, conventional oncocytoma, and chromophobe renal cell carcinoma

“…We believe that these guidelines may be extended to patients with bilateral synchronous masses, no evidence of a genetic syndrome such as Birt-Hogg-Dube, or a known diagnosis of an oncocytoma or oncocytic neoplasm. In cases of bilateral renal masses and a known diagnosis of oncocytoma, pathologic concordance with the contralateral side has been reported to be as high as 94% [14].…”

A back-to-back tumor composed of papillary renal cell carcinoma and oncocytoma treated by laparoscopic partial nephrectomy: a case report

“…Collision tumors in the kidney have been described, and they mostly have included oncocytoma and chromophobe RCC. Hereditary disease such as Birt-Hogg-Dubé syndrome shows coexistence of oncocytoma and other RCCs of an origin similar to that of chromophobe RCC [ 5 ]. PRCC and oncocytoma have different cellular origins, and therefore such a hybrid tumor is very rare.…”