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1 Case Based Urology Learning Program Resident s Corner: UROLOGY Case Number 18 CBULP
2 Case Based Urology Learning Program Editor: Associate Editors: Manager: Case Contributors: Steven C. Campbell, MD PhD Cleveland Clinic Jonathan H. Ross, MD Rainbow Babies & Children s Hospital, UH David A. Goldfarb, MD Cleveland Clinic Howard B. Goldman, MD Cleveland Clinic Nikki Williams Cleveland Clinic Michael C. Gong, MD PhD Cleveland Clinic
3 A 51 year old man presents with gross hematuria. Office cystoscopy and cytology are both negative. CT scan demonstrates numerous solid, enhancing renal masses suspicious for RCC. There are at least 9 lesions in the right kidney and 6 in the left kidney. The largest lesion is 6.3 cm and is in the right kidney. Representative images from the CT of the abdomen/pelvis and chest are demonstrated.
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6 What are the salient findings?
7 What are the salient findings? CT of the abdomen and pelvis demonstrates bilateral multifocal disease. CT of the chest shows lung cysts bilaterally, but no evidence of metastatic disease.
8 What is the differential diagnosis and what is the most likely diagnosis?
9 What is the differential diagnosis and what is the most likely diagnosis? The presentation is highly suspicious for familial RCC, which can include: VHL Hereditary papillary RCC Familial Leiomyomatosis RCC Birt Hogg Dube syndrome (BHD) Familial Renal Oncocytomas Tuberous sclerosis The most likely diagnosis is BHD given the presence of lung cysts.
10 What else might you expect to find on physical examination in this syndrome?
11 What else might you expect to find on physical examination in this syndrome? Birt Hogg Dube syndrome is also associated with cutaneous manifestations such as fibrofollculomas of the face, neck and upper chest. The lesions typically appear in the 3 rd and 4 th decade and increase in size and number with age. Representative lesions are shown in the following image:
12
13 What further history is particularly relevant in this syndrome?
14 What further history is particularly relevant in this syndrome? Spontaneous pneumothorax is often found in BHD. Beyond this, your history should explore the family history for any history of renal tumors or other related manifestations of this or other familial RCC syndromes. For instance, you would ask about any history of brain, spine or eye tumors, renal failure, blindness, or seizures
15 What gene is mutated in BHD and what is the pattern of inheritance?
16 What gene is mutated in BHD and what is the pattern of inheritance? The mutated gene is FLCN on chromosome 17p11.2, which encodes the folliculin protein. This protein appears to function as a tumor suppressor through interaction with the mtor pathway, although the mechanistic details are still under investigation. The pattern of inheritance for BHD is autosomal dominant as it is with all familial RCC syndromes.
17 What RCC histologies are commonly observed in BHD?
18 What RCC histologies are commonly observed in BHD? Chromophobe RCC (23%) Hybrid tumors with characteristics of both Chromophobe RCC and Oncocytoma (67%) Oncocytoma (3%) In addition, BHD is somewhat unique among the familial RCC syndromes in that it can include other histologic subtypes, such as clear cell RCC. Other familial RCC syndromes are almost invariably limited to a single histology, such as clear cell in VHL, type I papillary in HPRCC, etc. The following images demonstrate characteristic histology for BHD.
19 Hybrid Tumors Burt Hogg Dube Features of Oncocytoma and Chromophobe RCC
20 Hybrid Tumors Burt Hogg Dube Chromphobe on L Oncocytoma on R
21 How is RCC managed in BHD?
22 How is RCC managed in BHD? If any tumors are greater than 3 cm a partial nephrectomy is typically performed with an effort to clear that kidney of all grossly evident tumors. Tumors less than 3 cm diameter can be observed because the risk of metastasis appears to be relatively low in this circumstance. Thermal ablation can also be considered and is particularly useful in a salvage setting, such as patients with tumors that need to be treated in a kidney that is already SP partial nephrectomy. Close surveillance for renal tumors is mandatory in BHD because of the almost universal presence of occult microscopic disease. This patient was managed with partial nephrectomy of the R kidney with removal of all grossly evident lesions. The left kidney has been managed with observation because all lesions on this side have remained < 3 cm.
23 What lifestyle changes should be recommended in patients with BHD?
24 What lifestyle changes should be recommended in patients with BHD? Smoking cessation, because tobacco use appears to be associated with an increased risk of RCC development in BHD. Avoid high ambient pressures which may precipitate pneumothorax.
25 Selected Reading Menko FH, et al.: Birt Hogg Dubé Syndrome: Diagnosis and Management. Lancet Oncology 2009;10: Linehan WM, et al: Hereditary Kidney Cancer. Cancer 2009;115(10 suppl):
26 Topic: Oncology: Renal Tumors Subtopics: Etiology and Familial RCC: Birt Hogg Dubé Syndrome
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