Advertisement

Multiple cutaneous lesions and pulmonary cysts

  • Sudharsan Venkatesan
    Correspondence
    Corresponding author at: Royal Darwin Hospital, 105 Docklands Drive, Tiwi, Northern Territory, Australia, 0810.
    Affiliations
    Department of General Medicine, Royal Darwin Hospital - 105 Docklands Drive, Tiwi, Northern Territory, Australia, 0810
    Search for articles by this author
  • Henrik Falhammar
    Affiliations
    Department of General Medicine, Royal Darwin Hospital - 105 Docklands Drive, Tiwi, Northern Territory, Australia, 0810

    Menzies School of Health Research - Building 58, Royal Darwin Hospital Campus, Rocklands Drive, Casuarina, Northern Territory, Australia 0810

    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital - Eugeniavägen 3, 171 76 Stockholm, Sweden

    Department of Molecular Medicine, Karolinska Institutet - Solnavägen 1, 171 77 Stockholm, Sweden
    Search for articles by this author

      1. Case description

      A 50-year-old woman presented with multiple cutaneous lesions that had been present for many years (Figure 1a and 1b) similar to other family members. Her past history was significant for seronegative arthritis, juvenile rheumatoid arthritis, iron deficiency anaemia, menorrhagia and cholecystectomy. She had never smoked. Family history was significant for thyroid cancer in her mother. Computed Tomography (CT) scan of her thorax demonstrated multiple intraparenchymal pulmonary cysts and subpleural bullae bilaterally (Figure 1c and 1d). A magnetic resonance imaging (MRI) abdomen was done to screen for renal tumours but did not reveal any abnormalities.

      2. What is the diagnosis?

      2.1 Diagnosis

      2.1.1 Birt-Hogg-Dube syndrome

      Genetic testing revealed a heterozygous variant FLCN mutation associated with Birt-Hogg-Dube Syndrome (BHDS). BHDS is a rare, autosomal-dominant disorder, described and genetically confirmed in around 200 families, characterized by the development of cutaneous lesions, renal tumours and pulmonary cysts [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ]. The gene responsible for BHDS is located on chromosome 17p11.2 [
      • Nickerson ML
      • Warren MB
      • Toro JR
      • et al.
      Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.
      ]. Germline mutations in this gene result in loss of function of folliculin (FLCN); which is thought to have a tumor-suppressor role [
      • Nickerson ML
      • Warren MB
      • Toro JR
      • et al.
      Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.
      ].
      Dermatological manifestations of BHDS include fibrofolliculomas, trichodiscomas, perifollicular fibromas and acrochordons [
      • Tong Y
      • Schneider JA
      • Coda AB
      • et al.
      Birt-Hogg-Dubé syndrome: a review of dermatological manifestations and other symptoms.
      ]. Clinical hallmarks are fibrofolliculomas, bilateral pulmonary cysts and repeated pneumothoraces [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ]. Pulmonary cysts manifest as rounded lesions with well-defined interface with normal lung parenchyma [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ]. Renal cancers are the most serious complication of BHDS with a 7-fold increased risk compared to the general population [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ]. Multiple other benign and malignant tumours have been associated in patients with BHDS [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ].
      Diagnosis should be suspected in young patients with the above clinical hallmarks [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ]. Management of BHDS should be with a multidisciplinary team, including a Genetics service. Management includes treatment/prevention of pneumothoraces and screening for renal tumours (with MRI or ultrasonography) [
      • Dal Sasso AA
      • Belém LC
      • Zanetti G
      • et al.
      Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
      ]. Although BHDS is a rare condition, increased awareness of the manifestations and imaging findings are crucial for management of complications and early detection of malignancies.

      Declaration of Competing interest

      All of the case authors declare no financial or other potential conflicts of interest.

      References

        • Dal Sasso AA
        • Belém LC
        • Zanetti G
        • et al.
        Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.
        Respir Med. 2015; 109: 289-296
        • Nickerson ML
        • Warren MB
        • Toro JR
        • et al.
        Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.
        Cancer Cell. 2002; 2: 157-164
        • Tong Y
        • Schneider JA
        • Coda AB
        • et al.
        Birt-Hogg-Dubé syndrome: a review of dermatological manifestations and other symptoms.
        Am J Clin Dermatol. 2018; 19: 87-101