Three new BHD case reports

Marous et al. (2017) present the case of a 38-year-old white man with confirmed BHD, manifesting cutaneous fibrofolliculomas and trichodiscomas on the face and upper chest, bilateral spontaneous pneumothorax and a choroidal nevus in the left eye. Later, the patient experienced photopsia and decreased visual field in the left eye. Microscopy revealed subtle iris melanocytosis in the left eye. Fundus evaluation in the left eye disclosed a choroidal melanoma arising from patchy inferotemporal sectoral choroidal melanocytosis. In addition, subtle pinpoint retinal pigment epithelium (RPE) microdetachments were noted. Fluorescein angiography confirmed hyperfluorescence of the melanoma and also highlighted multifocal pinpoint RPE defects in each eye.

One ophthalmic study previously reported two patients with BHD with RPE alterations, and another report described choroidal melanoma with no documentation of melanocytosis (Walter et al., 1997; Fontcuberta et al., 2011). The relationship of these findings with BHD remains unclear. It would be interesting to examine a cohort of BHD patients to investigate the prevalence of RPE alterations and choroidal melanocytic features.

Rato et al. (2017) describe two BHD patients with previously-undescribed FLCN mutations, and one of them with a type of adrenal gland tumour associated for the first time with BHD. The first case was a 60-year-old caucasian man with multiple asymptomatic skin lesions of the face, scalp and neck. The patient denied any respiratory signs or symptoms. His medical history was consistent with hypertension, diabetes mellitus, dyslipidemia and benign prostatic hypertrophy. Physical examination revealed multiple, dome-shaped, whitish and erythematous papules scattered over the scalp, face and upper neck. Biopsy of two papules showed features consistent with fibrofolliculoma. A genetic test revealed a new heterozygotic mutation in exon 6 of the FLCN gene (p.Lys192Argfs*31). Computed tomography (CT) scan of the thorax and abdomen showed numerous bilateral lung cysts without suspicious kidneys lesions. Patient had no history of spontaneous pneumothorax. Pulmonary function tests, thyroid ultrasonography and colonoscopy were normal.

The second case was a 39-year-old caucasian man with a history of epilepsy and asthma presenting with multiple asymptomatic skin lesions located on the face and neck. Similar dermatological findings were present in the patient’s family. Physical examination found numerous firm, whitish papules on the face and upper neck. Biopsy of two papules was performed and histopathological analysis was compatible with fibrofolliculoma. The patient was assessed for FLCN gene mutations and a new heterozygotic mutation was detected in exon 9 of the FLCN gene (c.1015C>T), responsible for the introduction of a premature stop codon at position 339 amino acid (p.Gln339*). This mutation has not been described previously but it can be considered pathogenic and so responsible for BHD in the patient. CT scan of the thorax and abdomen showed a lung cyst in the right middle lobe and a nodular formation. Laparoscopic left adrenalectomy was performed and histopathological examination revealed a malignant perivascular epithelioid cell tumour (malignant PEComa). Pulmonary function tests and thyroid ultrasonography were normal. This case represents the first malignant PEComa diagnosed in a patient with BHD. Some types of PEComa are seen at high frequency in tuberous sclerosis complex (TSC), like renal angiomyolipoma, as well as pulmonary lymphangioleiomyomatosis. A possible association between BHD and the occurrence of malignant PEComa in this patient is interesting but purely speculative.

These new cases reinforce the message that the management of Birt-Hogg-Dube patients should be multidisciplinary.

  • Rato M, Monteiro AF, Parente J, Aranha J, & Tavares E (2017). Birt-Hogg-Dubé Syndrome – report of two cases with two new mutations. Journal of dermatological case reports, 11 (1), 12-15 PMID: 28539984

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