Autumn Case Reports

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 cancer in BHD patients. 

BHD is characterised by skin bumps (fibrofolliculomas), lung cysts, collapsed lungs and kidney tumours. The kidney tumours are normally slow-growing so with regular scans they can be monitored and removed if they reach 3cm. At the BHD Foundation, we often get asked if BHD is associated with any other cancer types. This is a difficult question as 1 in 2 people will get some type of cancer in their lifetime and most of these people do not have BHD.  Therefore, how do we determine if other cancers are caused by BHD or are unrelated?  

The case reports below describe two different types of cancer in people with BHD. A case study on its own cannot prove a link between BHD and a cancer. To find a link you need lots of data. This is where the BHD syndrome international registry (BIRT) comes in. BIRT is a patient-reported database where patients can upload information about their BHD. This data will feed into research and help answer vital questions. The reason case studies are still important is they can help researchers to identify areas of potential research.  

Cancer in the adrenal gland

The first case* described a 38-year-old man with a tumour on his left adrenal gland. The adrenal glands are two small glands that sit on top of the kidneys and produce hormones. Further investigations led to a formal diagnosis of a rare type of cancer called adrenal cortical carcinoma (ACC). In other words, cancer in the outer layer of the adrenal gland. He was treated with surgery and chemotherapy.

The next step for the clinicians was to find out why he developed this cancer. ACC is a rare cancer and is linked to genetic conditions including Li-Fraumeni syndrome. Therefore, they performed genetic testing. The test revealed a mutation in the gene folliculin (FLCN). Variants in this gene cause BHD. A diagnosis of BHD was further supported by the finding of skin bumps and lung cysts.

Once the diagnosis of BHD was confirmed, the doctors speculated on whether there could be a link between adrenal gland cancers and BHD. So far 5 cases of adrenal gland cancer have been reported in BHD patients including one other case of ACC.

Follicular Dendritic Cell Sarcoma

The next case discussed a 34-year-old man with low iron and blood in his stools. He had a camera test to check the inside of his bowels and they found a mass. He had surgery to remove the mass and was then diagnosed with a rare cancer called follicular dendritic cell sarcoma (FDCS). FDCS is a cancer that develops from specialised immune cells. It normally occurs in lymph nodes but can occur anywhere in the body including the digestive tract as seen in this case.

Next, the clinicians investigated the cause of his cancer. The patient had an extensive family history of cancer which suggested there may be a genetic component.  He was tested for several cancer-causing genes and had a positive FLCN mutation. Similar to the previous case, he was then found to have skin bumps to support a diagnosis of BHD.

This is the first case of FDCS to be reported in a BHD patient. It must be noted FDCS is very rare cancer with only 32 cases of FDCS in the digestive tract reported. The authors felt that it was unclear whether BHD was the cause of the FDCS or if it was just a coincidence that the patient had the mutation.  

Key messages

These case reports describe two rare cancers in people with BHD. However, as discussed above this does not mean that they are caused by BHD. As more data accumulates in the registry we can start to build a clearer picture of whether any other cancers are associated with BHD and if any other cancer screening is needed.

These cases also highlight the need for increased awareness of BHD. Both patients had skin bumps before their cancer diagnosis. However, neither of them had been investigated for BHD. However, it is promising to see FLCN included in genetic cancer screens. By being diagnosed with BHD, even if it had nothing to do with their symptoms, both patients will receive vital monitoring of their kidneys. This means if they do develop kidney cancer in the future it will be identified and treated as early as possible.

*Please note this paper is unfortunately not freely available. Please contact us if you have any questions.