Painless Nodule on Lip Reflects Rare Diseases

A 13-year-old female patient presented with a painless nodule on the inner side of her lower lip for two months. The nodule had gradually increased in size without significant discomfort. Notably, her mother had similar facial lesions and a history of epilepsy. Clinical examination revealed an ovoid, firm, non-tender nodule measuring 2 × 1 cm on the right mucosal side of the lower lip, adherent to surrounding tissue (Figure 1a,b). Gingival examination showed 1–2 mm pink, resilient growths on the labial aspect of the anterior maxilla and enamel pits on upper incisors (Figure 1c). Additionally, there were multiple 1–3 mm pink papules scattered across her face (Figure 1d). Skin examination identified hypopigmented macules on her neck (Figure 1e), as well as a pigmentation patch on her right flank (Figure 1f). All routine laboratory tests showed no abnormalities. The correct diagnosis is A. Tuberous sclerosis complex (TSC). Histopathological analysis of the lower lip lesion revealed squamous epithelial hyperplasia with fibrous and vascular proliferation, consistent with angiofibroma (Figure 2a,b). The patient met three major criteria (hypopigmented macules, facial angiofibromas, and a shagreen patch) and two minor criteria (enamel pits and oral fibromas) for TSC, leading to a clinical diagnosis of tuberous sclerosis complex (Table 1) (Northrup et al. 2021). Genetic testing identified a pathogenic TSC2 mutation (c.1760_1761del:p.Y587*), confirming the diagnosis (Figure 2c). TSC is a rare autosomal dominant disorder caused by mutations in TSC1 or TSC2, leading to hyperactivation of the mTOR pathway (Panwar et al. 2024). Clinical manifestations vary significantly among individuals, even within the same family. Classic dermatological findings include hypopigmented macules, facial angiofibromas, and shagreen patches (Northrup et al. 2021). Oral manifestations such as enamel pits and fibromas are frequently reported, affecting up to 50% of patients (Sparling et al. 2007). In this case, the presence of lower lip angiofibroma, enamel pits, and gingival fibromas, combined with genetic confirmation of a TSC2 mutation, established the diagnosis. Importantly, her mother's history of facial lesions and epilepsy suggests an inherited predisposition. Differential diagnoses like Fabry disease and sclerosing fibroma were considered but excluded based on the clinical and histological findings (Henske et al. 2016). Management of TSC requires a multidisciplinary approach, including dermatology, neurology, nephrology, and cardiology, to address potential systemic involvement (Araujo et al. 2013). Genetic counseling is recommended for the patient's family. Oral lesions such as fibromas generally do not require intervention unless symptomatic, while enamel pits benefit from preventive care to avoid caries. The patient was advised to undergo further evaluations in neurology, cardiology, and nephrology to identify systemic involvement. Family members were encouraged to undergo genetic screening for TSC. Regular follow-up was recommended for oral fibromas, and enamel pits were managed with preventive fluoride treatments. Tianqing Wang: conceptualization, writing – review and editing, writing – original draft. Jiajia Liu: conceptualization, writing – review and editing, writing – original draft. Xuefeng Zhang: conceptualization, writing – original draft, writing – review and editing. Xin Zeng: conceptualization, writing – original draft, writing – review and editing. Jiongke Wang: conceptualization, writing – original draft, writing – review and editing. The patient reported in this manuscript provided written informed consent for the publication of the case details. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.