Port-wine stain (PWS), also known as nevus flammeus, is a congenital vascular malformation characterized by ectasia of capillaries and postcapillary venules. The incidence of PWS in newborns is approximately 0.3% to 0.5%.1) While it most commonly affects the face, PWS can appear anywhere on the body as blanchable pink to red patches, typically with a unilateral or segmental distribution that respects the midline. Most cases present as isolated skin anomalies, although PWS can be associated with complex malformation syndromes.2)

Various vascular lesions and cutaneous malignancies have been reported to develop within preexisting PWSs. Among these, pyogenic granuloma (PG) is an uncommon secondary lesion. In this report, we present a rare case of PG arising from a PWS on the scalp of a 27-year-old man and discuss previously reported conditions associated with PWS-based PGs. Additionally, we provide a comprehensive literature review highlighting other secondary lesions arising from PWSs.

A 27-year-old man presented with an asymptomatic reddish scalp mass that had developed abruptly over two weeks. Physical examination revealed a 2 cm pedunculated exophytic nodule with a hemorrhagic and ulcerative surface on the right parietal scalp, located within an irregular violaceous patch consistent with a PWS (Fig. 1A). The patient had no history of trauma or prior treatment for the PWS. The lesion was excised under local anesthesia, and the surgical wound was primarily closed (Fig. 1B).

Histopathological examination revealed a nodular lesion with surface ulceration (Fig. 2A). Proliferation of round vascular endothelial cells and focal slit-like vascular spaces were observed, along with a sparse lymphocytic infiltrate; however, nuclear pleomorphism and mitotic figures were absent (Fig. 2B). Immunohistochemical analysis showed positive staining for vimentin, CD31, CD34, Factor VIII, and SMA, and negative staining for Pan-CK and HHV-8 (Fig. 3). These findings confirmed the diagnosis of PG.

PWSs are low-flow capillary malformations that can cause significant psychological distress due to their disfigurement. They do not regress but rather grow in proportion with the child, often becoming thicker and darker in adulthood. The exact etiology of capillary malformations remains unknown, though several mechanisms have been proposed, including impaired neuronal regulation of blood flow,3) overexpression of vascular endothelial growth factor (VEGF) and its receptor,4) and compensatory collateral venous drainage.5) PWSs may occur as part of complex malformation syndromes such as Sturge-Weber syndrome, Klippel-Trénaunay syndrome, Parkes-Weber syndrome, and others.2) They are also associated with ocular abnormalities such as glaucoma and latent myelodysplasia. Additionally, various secondary lesions have been reported to develop within PWSs. Treatment goals include cosmetic improvement and the prevention of complications such as thickening, nodularity, and bleeding. Before the introduction of selective photothermolysis, treatment options included cryosurgery, ionizing radiation, CO2 lasers, and electrotherapy, but these had limited effectiveness and notable side effects.6) Today, pulsed dye laser therapy is the gold standard for PWS treatment.

PG, also known as lobular capillary hemangioma, is a benign acquired vascular lesion. Hartzell first described PG in 1904, although the term is misleading as it does not involve bacterial infection or true granuloma formation.7) PG typically presents as a rapidly growing, bleeding, and ulcerating papular lesion, often occurring in children and young adults. Common sites include the face, trunk, and oral cavity, although lesions can also develop in the gastrointestinal tract8) and larynx.9) Treatment options for PGs include surgical excision, electrodissection, cryotherapy, sclerotherapy, curettage, laser therapy, imiquimod cream, and microembolization.

While PGs are usually isolated lesions, they have rarely been reported to arise from preexisting PWSs. The pathogenesis of this association remains unclear, although erythrocyte stasis in PWS may contribute to the formation of vascular malformations or tumors.10) PWS-associated PGs are frequently linked to prior conditions, including: (1) previous treatments for PWS, such as laser therapy, intense pulsed light therapy, cryotherapy, and radiotherapy; (2) pregnancy; and (3) syndromes such as Von Recklinghausen’s disease, Sturge-Weber syndrome, phakomatosis pigmentovascularis, and Klippel-Trénaunay syndrome.

Although treatment strategies for PGs arising from PWSs do not differ substantially from those for isolated PGs, PGs developing within PWSs may exhibit more rapid enlargement, an increased tendency to bleed, and a potentially higher recurrence rate, owing to the dilated capillary beds and aberrant vascular architecture intrinsic to PWSs.

Other secondary lesions reported in PWSs include both vascular and neoplastic types. Vascular lesions comprise tufted angioma, cavernous hemangioma, arteriovenous malformation, and acral arteriovenous tumor. Neoplastic lesions include peripheral ameloblastoma, epulis fibromatosa, giant proliferative hemangioma, basal cell carcinoma (BCC), verrucous carcinoma, squamous cell carcinoma (SCC), spindle cell carcinoma, and melanoma in situ (Table 1).

The pathogenesis of secondary lesions within PWSs remains unclear, although their occurrence is well documented. Two potential mechanisms have been suggested. During embryogenesis, the normal vascular system arises through a combination of two processes: vasculogenesis and angiogenesis. Vasculogenesis refers to the formation of early vessels from endothelial cell precursors, whereas angiogenesis involves the development of new vessels from preexisting vasculature. Although angiogenesis and revascularization are distinct processes, they appear to share regulatory factors. An overlap in these regulatory mechanisms may account for the rare association between vascular tumors and vascular malformations.11) Recent findings have demonstrated that endothelial cells in both secondary and isolated PGs harbor the BRAF c.1799T>A (p.Val600Glu) mutation, as confirmed by mutation-specific immunohistochemical analysis. This mutation has been identified as a major driver in the pathogenesis of PG, particularly in secondary lesions.12) Cutaneous malignancies have been known to arise from PWS. Historical treatments for PWS before the advent of laser therapy—including grenz rays, topical thorium X, and other radiotherapy techniques—have been linked to the development of neoplastic lesions such as BCC and SCC.13)

Although the pathogenesis of secondary lesions in PWSs remains elusive, regular follow-up is advised for patients with PWSs who have known risk factors, such as a history of laser or light-based treatments, pregnancy, or syndromic associations (e.g., Sturge-Weber syndrome, Klippel-Trénaunay syndrome). Clinicians should maintain a high index of suspicion when patients present with sudden changes in a PWS—such as rapid enlargement, nodularity, ulceration, or bleeding—which may suggest the development of secondary lesions like PG or even cutaneous malignancies. We also recommend periodic clinical examinations, supported by dermoscopic evaluation when appropriate, to aid in early detection.