Core Viewpoint - The article discusses the case of a patient diagnosed with Birt-Hogg-Dubé (BHD) syndrome, highlighting the rapid recurrence of kidney cancer post-surgery and the importance of genetic testing for accurate diagnosis and management [1][2]. Group 1: BHD Syndrome Overview - BHD syndrome is an autosomal dominant genetic disorder caused by mutations in the FLCN gene, with a 50% inheritance probability from an affected parent [2]. - The estimated prevalence of BHD syndrome is approximately 1-2 per million, but actual numbers may be higher due to underdiagnosis of mild or asymptomatic cases [2]. Group 2: Clinical Manifestations - Skin manifestations include small, painless, skin-colored or light red papules on the face, often misdiagnosed as acne or age spots [3]. - Lung involvement is characterized by thin-walled cysts that can lead to spontaneous pneumothorax, commonly misdiagnosed in young, tall individuals [4]. - About one-third of BHD patients will develop kidney tumors, typically presenting bilaterally and multifocally, with an average onset age of 50 [5]. Group 3: Sarcomatoid Change - Sarcomatoid change is not a new cancer but a transformation of existing renal cancer, marked by rapid growth and increased aggressiveness [6]. - The occurrence of sarcomatoid change in the context of BHD syndrome is rare but significantly impacts clinical outcomes, leading to increased invasiveness and reduced survival [6]. Group 4: Treatment Adjustments - The initial treatment with axitinib and PD-1 inhibitors failed within six weeks, indicating a more aggressive tumor behavior [7]. - A multidisciplinary team (MDT) decided to switch to an alternative treatment regimen involving anlotinib combined with immunotherapy [8]. - After four months, the tumor size decreased from 12 cm to 5 cm, indicating a partial response to the new treatment plan [9]. Group 5: Diagnosis and Management of BHD - Early suspicion of BHD should arise in cases of early-onset or bilateral/multifocal kidney tumors, or when associated with spontaneous pneumothorax [10]. - Genetic testing for FLCN mutations can be performed through blood or saliva samples, with results available in about two weeks [11]. - Management strategies include annual MRI scans of the kidneys starting at age 20, regular chest CT scans, and monitoring skin lesions [12].