BHD is a rare multisystemic genetic disease, describe in 1977 with a dominant autosomal inheritance, with a reported prevalence until today of 1/200,000.
It is cause by a mutation with inactivation of the FLCN gene, which encodes a tumour suppressor protein (Folliculin).
More than 2000 FLCN mutations have been identified.
It carries an increased risk of developing benign and malignant tumours.
The predominant features of the disease are 1.Cutaneous lesions in the form of fibrofolliculomas characteristically on the face. 2.Pulmonary cysts with spontaneous secondary pneumothorax. 3.Increased risk of renal cancer (FIG1).
Other less frequently associated lesions are: Thyroid and parathyroid adenoma or carcinoma, adenomatous polyps and colon cancer, breast cancer and melanoma.
BHD syndrome is characterized by phenotypic heterogeneity, and great variability in disease severity between different members of the same family and between different families.
That makes a differential diagnosis broad and other hereditary conditions may mimic features of BHD.
That leads to a delay on a diagnosis of the entity which can result in potentially fatal prognosis.
The knowledge of radiological presentation is essential to contribute to an early diagnosis that allows therapeutic options for all the features of the disease and improves its prognosis .
We review the entity based on experience in our geographic environment in Girona, Spain, with a prevalence higher than that described in the literature, with a current record of 70 patients with the FLNC mutation.
This prevalence must be understood from the concept of Founder Mutation in the environment, which means that mutation has persisted in the region over thousands of years and has coexisted with a very endogamous relationship between its inhabitants.
RADIOLOGICAL FINDINGS: KIDNEY INVOLVEMENT The appearance of the kidney cancer is the most serious and threatening complication and has been known for less time.
It appears in 25% of patients and is frequently bilateral, multifocal and slow growing.
The average age of presentation is 50,7 years although appearances at younger age shave been described.
Histopathologically, patients with BHD are affected by oncocytosis, which corresponds to the presence of multiple microscopic oncocytic lesions that are the precursors of the renal cancer and explain the recurrences.
The associated histological types are in order of frequency: Oncocytoma-chromophobe hybrid tumour 50%, chromophobe tumour 34%, Clear cell carcinoma 9%, Oncocytoma 5%, Papillary tumour 2%, Renal cyst, angiomyolipoma.
Oncocytoma and chromophobe carcinoma have a similar origin from cell between the collecting tubules and can coexist in the form of a hybrid tumour (FIG2), however the management and prognosis can be different.
The form of radiological presentation between the different types of lesion is very similar, since they have homogeneous enhancement similar to or less than the cortex.
Some more specific features of oncocytoma such hypodensity in a simple CT scan, segmental inversion enhancement, thickening of the perirenal fascia, central scar (30%) and wheel sign.
The challenge is still to be able to differentiate a benign form malignant carcinoma.
MRI is the most appropriate tool for monitoring these lesions.
The usually appear isointense or slightly hypointense in the parenchyma on T2 even oncocytoma can be more hyperintense.
Necrosis is very uncommon.
The gadolinium study shows early enhancement equal to or less than the cortex , with progressive washout (FIG3).
Because of the lack of radiological specificity to differentiate the lesions, the following data must be taken into account: 1.Suspect BHD when patient presents multiple and bilateral renal lesions. 2.Renal lesions in BHD have a very slow growth. 3.Criterion for surgery is established when the lesion is more than 30 mm. 4.
During follow-up of patient undergoing surgery with changes in the surgical bed, DWI can be of great help to demonstrate small foci of recurrence.
It is recommended to be strict in the follow-up renal cyst that appear in patients with BHD as some will evolve to Bosniak IV (FIG4).
RADIOLOGICAL FINDINGS:LUNG INVOLVEMENT FLCN mutation to cyst formation is not yet entirely understood.
Patients present irregular thin-walled cyst or bullae of subpleural, paramediastinal or pericisural, location, with lenticular morphology and predominantly involvement below the level of carina (FIG5).
Lesions predispose to spontaneous pneumothorax which can be the first clinical presentation of BHD specially in young adults.
FOLLOW-UP OF PATIENTS AND FAMILY MEMBRES WITH FLNC MUTATION There is little consensus between different countries and follow-up strategies given the discussion on economic costs, study duration, patient commitment to follow-up, among other variables.
The most accepted strategy is: -First study at age of 20-years-old -Follow-up Renal MRI every 1 or 2 years with Gadolinium, or Ultrasound if no MRI is available. -Basal thoracic CT study There is no scientific evidence to justify follow-up with thyroid ultrasound or colonoscopy .
The questions that arise as radiologist, especially take into account that more patients are going to be detected in the next years, is whether this strategy is the most suitable: -Is the use of Gadolinium justified every two years from the age of 20 years old? -Could it be replaced by an ultrasound with echocontrast? Annual US alone even is safe and less expensive than MRI may missed tumours smaller than 3 cm -Could the initial study be done with contrast and follow-up without contrast if the patient does not present any initial renal lesion? -Would larger bullae or pneumothorax episodes imply chest monitoring?