BHD Winter Case Report

Every few months we highlight some of the recent Birt-Hogg-Dubé syndrome (BHD) case reports. A case report is a detailed account of (normally) a single person’s diagnosis and treatment journey. Case reports are published in medical journals and are an opportunity for clinicians to learn about how different conditions may present.

In this blog we look at two cases of rare cancer in people with BHD.

A rare soft tissue tumour

The first case described a 60-year-old woman with a pink nodule on her shoulder that had been growing for 12 months. She was known to have BHD and had skin bumps on her face, in keeping with fibrofolliculomas, a history of lung collapses and suspected kidney tumours.

A sample of the pink nodule was taken and examined under a microscope. The nodule was confirmed to be a cutaneous leiomyosarcoma (cLMS). cLMS is a type of rare soft tissue tumour that occurs in the skin. The woman had a surgical procedure called a wide local excision to remove the tumour.

The team took samples of the cLMS, normal skin and blood to check for folliculin (FLCN) variants. Faults (also called variants) in the FLCN gene are associated with BHD. Everyone has 2 copies of FLCN and only one copy needs to be faulty to lead to the skin bumps and lung cysts seen in BHD. However, it is thought that for kidney cancer to develop, the second copy of FLCN also needs to develop faults (known as loss of heterozygosity, LOH). When the team tested normal skin and blood samples they found a single FLCN variant. However, in the cLMS sample they found LOH as both copies of FLCN were faulty.

This is the third report of cLMS in someone with BHD. The other two cases also had faults in the FLCN gene. The researchers suggested that folliculin variants may drive the development of cLMS. However, there are also other genes that, when faulty, can cause it. They recommend that people diagnosed with cLMS should have a clinical assessment to see if they have any features of BHD.

A tumour in the parotid gland

The next case described a 68-year-old man with a mass on his face that had been growing in size for 2-3 years. At this point he was not known to have BHD. He had a CT and MRI scan which showed that he had a growth in his right parotid gland. He had surgery to remove the whole gland.

To identify what had caused the growth a sample of the gland was examined under a microscope. This showed a type of cancer called an oncocytic carcinoma. Oncocytic carcinomas are different to parotid oncocytomas, which have previously been described in BHD. Parotid oncocytomas are benign. This means that they are not cancerous and do not spread to other parts of the body. The rarer oncocytic carcinomas are malignant. This means there is a risk that they can spread to other parts of the body. Therefore, the patient had further surgery and radiotherapy to reduce the risk of this happening.

During his treatment he had a CT scan of his chest. This revealed lung cysts. He also had skin bumps in keeping with fibrofolliculomas. His team recommended genetic testing for BHD. The test confirmed that he had BHD.

This is the first case of an oncocytic carcinoma of the parotid gland in BHD. It’s a very rare cancer, however it’s important to distinguish it from parotid oncocytomas as it requires different treatment. Any parotid mass should be fully investigated.

This case also highlights the role that radiologists can play in diagnosing BHD. The incidental findings of cysts, on a CT scan, was instrumental in diagnosing him with BHD.  

What we can learn

These cases describe two rare cancers in BHD. A case report on its own cannot prove a link between BHD and a cancer. However, we can learn from them. These cases show us:

• The importance of investigating a lump/bump that is growing.
• Doctors should investigate people with cLMS for BHD.
• Incidental findings of lung cysts on scans should lead to further investigation.
• It’s important to distinguish between different causes of parotid masses as the treatment will differ.

To increase our understanding of BHD it is crucial that we get more data. Last year we launched the BHD syndrome international registry (BIRT). BIRT is a patient-reported database where people with BHD can upload information about their condition. This data will feed into research and help answer vital questions such as whether BHD is associated with any other conditions.

Take part in the registry now. You can also email us with any questions at contact@bhdsyndrome.org.