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A Novel Marker of Kidney Neoplasia

Jorge R. Toro, MD; Gladys Glenn, MD, PhD; Paul Duray, MD; Thomas Darling, MD, PhD; Gregor Weirich, MD; Berton Zbar, MD; Marston Linehan, MD; Maria L. Turner, MD

Arch Dermatol. 1999;135:1195-1202.

Background  Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited predisposition for development of fibrofolliculomas, trichodiscomas, and acrochordons. Concurrent internal tumors, such as colonic polyps and renal carcinoma, have been described in patients with BHD.

Objective  To evaluate kindreds with familial renal tumors for cutaneous manifestations of BHD.

Design  One hundred fifty-two patients from 49 families underwent complete oral and skin examination. Skin lesions were identified by their clinical appearance, and the diagnosis was confirmed by results of histologic examination. Individuals underwent screening for familial renal neoplasms.

Setting  A tertiary referral research hospital.

Patients  Individuals with familial renal tumors and their asymptomatic at-risk relatives.

Main Outcome Measure  We determined whether any form of renal cancer is associated BHD.

Results  We identified 3 extended kindreds in whom renal neoplasms and BHD appeared to segregate together. Two kindreds had renal oncocytomas and a third had a variant of papillary renal cell carcinoma. Thirteen patients exhibited BHD. Seven individuals, including a set of identical twins, had renal neoplasms and BHD. An additional 4 patients (3 deceased and not examined) in these families had renal neoplasms but not BHD. Birt-Hogg-Dubé syndrome without renal neoplasms was present in 6 individuals. Thirteen patients with fibrofolliculomas and trichodiscomas presented clinically with multiple smooth skin-colored to grayish-white papules located on the face, auricles, neck, and upper trunk. Oral papules were present in 9 of 28 and achrochordons in 11 of 28 patients. Features of BHD not previously appreciated included deforming lipomas in 5, collagenomas in 4, and pulmonary cysts in 4 of 28 patients. Families with BHD did not display germline mutations in the von Hippel-Lindau gene or in the tyrosine kinase domain of the MET proto-oncogene.

Conclusions  Birt-Hogg-Dubé syndrome may be associated with familial renal tumors. Birt-Hogg-Dubé and renal tumors segregate together in an autosomal dominant fashion. Patients with BHD and their relatives are at risk for development of renal tumors. Therefore, patients with BHD and their relatives should undergo abdominal computed tomography and renal ultrasound screening for renal tumors.

From the Dermatology Branch (Drs Toro, Darling, and Turner), the Genetic Epidemiology Branch (Dr Glenn), the Laboratory of Pathology (Dr Duray), the Laboratory of Immunology (Drs Weirich and Zbar), and the Urologic Oncology Branch (Dr Linehan), National Cancer Institute, National Institutes of Health, Bethesda, Md.

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