Advanced Imaging Techniques for Early in-Vivo Discrimination of Fibrofolliculomas in Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome (BHDS) is a rare genetic tumor syndrome characterized by cutaneous fibrofolliculoma and trichodiscomas, lung bullae with an elevated risk of spontaneous pneumothorax and renal cell cancer.

Due to rareness of the disease, clinical symptoms and cutaneous manifestations are often misjudged, resulting in delayed medical diagnosis and considerable health risks for patients and their families. Accurate discrimination of fibrofolliculomas from other non-malignant skin tumors can be crucial for early diagnosis and appropriate management of BHDS. In addition, they may clinically overlap with adnexal or follicular papules seen in other rare genodermatoses, including facial angiofibromas in tuberous sclerosis complex, trichilemmomas in Cowden syndrome/PTEN hamartoma tumor syndrome, and trichoepitheliomas in CYLD cutaneous syndrome.

In this study, skin lesions from 15 BHDS patients with genetic confirmed disease-causing variants in FLCN underwent reflectance confocal microscopy (RCM) and Line-Field Confocal Optical Coherence Tomography (LC-OCT) to systematically analyse the morphologic and microstructural features of fibrofolliculomas.

In RCM a dilated follicular unit was seen in 12/15 cases (80%), while in LC-OCT this feature was seen in 13/15 (87%). The characteristic round, onion-like shaped hyperreflective structures with a well-demarcated perifollicular halo, corresponding to the histopathological features of branching chords and strands of epithelial cells was seen in all cases (RCM and LC-OCT 100%), aiding clinicians in identifying fibrofolliculomas.

Advanced imaging techniques provide a non-invasive approach for early diagnosis of fibrofolliculomas. Therefore, RCM and especially LC-OCT may be promising tools for enhancing the diagnostic precision and sufficient clinical management of Birt-Hogg-Dubé syndrome.