Introduction

Vascular anomalies are defects in vascular development that lead to abnormally formed blood vessels.¹ These lesions can be categorised into vascular tumours and vascular malformations.

Vascular tumours are caused by increased endothelial cell proliferation and angiogenesis. They are subclassified into benign types (e.g., pyogenic granuloma (PG), hemangiomas, and tufted angioma (TA)), locally aggressive or borderline types (e.g., kaposiform hemangioendothelioma (KHE), and Kaposi sarcoma (KS)) and malignant types (e.g., as angiosarcoma and epithelioid hemangioendothelioma). These tumours do not always appear at birth and may regress before or during puberty.^2,3 

Conversely, vascular malformations are structural defects without excessive endothelial cell proliferation. They are classified according to the type of blood vessels involved: venous, arterial, capillary, lymphatic, or combined malformations, where multiple types of malformations coexist within a single lesion.² They mostly appear at birth or soon after birth and may expand throughout life and never regress on their own.^1,3

Benign vascular tumours, like PG, hemangiomas, and KS, are frequently misdiagnosed as vascular malformations, leading to the wrong treatment approaches.⁴ This article aims to distinguish the differences between these entities and emphasise the importance of accurate diagnosis for optimal patient care.

Pyogenic granuloma

PG, also known as lobular capillary hemangioma, is a benign vascular tumour which affects skin or mucous membranes. Historically, PG was seen as an excessive granulomatous reaction to an infectious factor, hence the name “pyogenic granuloma” now this term is recognised as a misnomer.⁵

PG is a frequent lesion that may develop at any age. The lesion develops in three stages, and it usually appears as a solitary, red, pedunculated papule. In rare cases, it may present as a protruding plaque. In addition, multiple grouped or disseminated lesions have occasionally been observed.^5,6

Aetiology and pathogenesis

Various factors are implicated in the pathogenesis of PG, such as local trauma, irritation, and systemic conditions, however the aetiology is still unclear.⁷ The mechanism underlying pathogenesis is based on the imbalance of factors that promote angiogenesis and factors that inhibit it, causing a rapid proliferation of capillaries.⁵ 

Several studies have reported PG as a “reactive” or “reparative” process, where a certain stimulus induces the excessive proliferation of connective tissue.⁸ Other triggers can be infections and pre-existing vascular malformations.⁵ Additionally, PG can be an adverse cutaneous effect of some medications, such as oral contraceptives and BRAF inhibitors⁶. Hormonal changes in puberty and especially in pregnancy may also contribute to the development of PG.⁸

Clinical features

PG starts to manifest as a small and red papule that tends to grow rapidly over weeks to months, and then eventually stabilises in size. The colour can change from red to reddish-brown or purple. Small lesions have a diameter of a few millimetres, while larger lesions can reach several centimetres,⁵ and become lobulated, developing into mushroom-like and pediculated tumours. 

PG tends to bleed abundantly, which is the main reason patients go to the doctor.⁶ It can occur on cutaneous or mucosal sites, but cutaneous lesions are more frequently seen. Among the mucosal sites, the most common one for PG is the oral cavity, while they are rarely found in the gastrointestinal tract.⁵

In the oral cavity, it frequently affects the gingiva, but it may also appear on the lips, tongue, and buccal mucosa.⁸ Intraoral PG is particularly frequent during pregnancy,⁶ and it is called granuloma gravidarum. Head and neck regions, as well as trunk and extremities, are also commonly affected areas.⁵

Histopathology

Histologically, PG shows capillaries and venules grouped in lobules, each with a central feeding vessel and developing in a highly vascular granulation tissue. These lobules sit in fibrous tissue with some immune cells. This mild inflammation looks like normal granulation tissue. The surface skin may be thin, ulcerated, or show a scaly rim.⁵

Treatment

The main treatment for PG is surgical excision. Alternative options include laser, cryotherapy, or medical therapy with topical or oral medicines. Medical treatments require careful monitoring for possible side effects, especially in children and elderly patients.⁶

Hemangiomas

Hemangioma is the most common benign vascular tumour in infancy, which arises from endothelial cell proliferation.⁹ The most frequently affected sites are the head and neck region, followed by chest and trunk, and upper and lower extremities.³ They can develop anywhere blood vessels are present, also in deeper tissues, including the larynx, muscles, liver, and brain. 

While they often appear in young children, hemangiomas can also develop later in life. Congenital hemangiomas are present at birth, whereas infantile hemangiomas typically develop in the first weeks of life.¹⁰

Aetiology, classification and clinical features

The aetiology seems to be linked to the function of glucose transporter isoform 1 (GLUT 1) and placental vascular antigens. This leads to an imbalance in growth factors, causing a cycle of initial blood vessel growth (proliferation) followed by regression (involution). At first, there are high levels of proteins that promote blood vessel growth, and later, other proteins become more active and cause the involution.¹⁰ Hemangiomas can be classified into infantile and congenital hemangiomas.

Infantile hemangiomas

Infantile hemangiomas are the most common type, representing 90% of cases. They rapidly grow in the first few months after birth, but they tend to regress on their own in early childhood.³ They can appear at different depths in the skin. If they form near the skin’s surface, they appear bright red and are commonly referred to as "strawberry hemangiomas". Deeper ones, called "cavernous hemangiomas", are under the skin, and they appear bluish or flesh-toned.¹¹ 

Congenital hemangiomas

Congenital hemangiomas are very rare, and look clinically similar to infantile hemangiomas, but they are biologically different.³ They usually appear bluish-red with unclear edges. These hemangiomas are fully formed at birth and do not grow afterwards. There are three types:¹²

• Rapidly involuting congenital hemangioma (RICH)
• Non-involuting congenital hemangiomas (NICH)
• Partially involuting congenital hemangiomas (PICH)

Histopathology

Histologically, hemangiomas are classified as:¹⁰

• Capillary hemangiomas: Consist of small, closely packed vessels resembling capillaries, often found in the skin and subcutaneous tissues
• Cavernous hemangiomas: Feature large, dilated vascular spaces or cavities, typically located in deeper structures

Treatment

Most infantile hemangiomas do not require treatment as they regress spontaneously. However, intervention is necessary when they cause life-threatening complications such as ulceration. Administration of oral propranolol is the first-choice treatment. Alternatives are the administration of atenolol or steroids.¹³

Surgical excision and pulsed dye laser (PDL) are also suggested treatments for infantile hemangiomas, though PDL is more established for superficial lesions like telangiectasia and may be controversial for deep lesions.⁹

Regarding congenital hemangiomas, these are treated based on size, location, and complications. If they tend to regress, they only need to be monitored. Surgical excision, PDL, or sclerotherapy can help, but medications are not as effective as they are for infantile hemangiomas.¹³

Kaposi sarcoma

KS is a low-grade vascular tumour, which means that it grows and spreads more slowly than high-grade tumours. KS lesions mostly occur in the skin and mucosa, but they may affect all organs. KS is associated with human herpesvirus 8 (HHV8) infection.

There are four epidemiological-clinical forms:¹⁴

1. Classic KS
2. African (endemic) KS
3. Acquired Immune Deficiency Syndrome (AIDS)-associated (epidemic) KS
4. Iatrogenic KS

KS is the most frequent malignancy among patients with AIDS or with immunosuppression induced by drugs or transplants.¹⁴

Aetiology and pathogenesis

HHV8 is found in all forms of KS. This virus affects the normal cell functions, but it is not enough to cause the disease, as it needs specific proteins or cytokines.¹⁵ Early KS lesions originate from circulating mononuclear blood cells and endothelial precursor cells. Infection with HHV8 interferes with the blood endothelial cells, leading them to resemble lymphatic endothelial cells.

KS usually develops when the individual presents with immune system dysfunction and inflammation. Like other herpesviruses, HHV8 remains latent within host cells and develops multiple strategies to evade immune system response.¹⁴

Clinical features 

The most common form of KS, cutaneous KS, is characterised by pink-purple, rounded, well-defined maculopapules that are painless and non-itchy. These lesions can vary in size and may eventually develop into purplish nodules or plaques. Common affected areas include the face, upper trunk and lower extremities.

The mucosal form of KS is also frequent, and it appears on the conjunctival, oropharyngeal and genital mucosa. Around 60% of individuals with AIDS-related KS develop oral cavity lesions, which are linked to a poorer prognosis. In addition, lymph nodes and visceral spread may be reported.¹⁶

Histopathology

KS develops in three stages:¹⁵

1. Patch: Proliferation of spindle cells forming irregular and complex vascular channels with extravasated red blood cells and immune cells, such as macrophages and lymphocytes
2. Plaque: Changes become deeper and more noticeable and extend into the subcutis
3. Nodular: Tumoral cells vary more in size and shape, and grow faster. The slit-like spaces that resemble abnormal blood vessels become more pronounced

Treatment

Treatment for KS depends on the type, but systemic therapies are similar.¹⁷ Chemotherapy remains the key treatment for endemic and systemic forms.¹⁵ HIV-related KS requires antiretroviral therapy (ART). Approved treatments include liposomal doxorubicin, paclitaxel, and pomalidomide. Recurrence is very common because therapies cannot eliminate the virus, since it remains latent.¹⁷ Combination of ART with chemotherapy is recommended in severe KS cases.¹⁵

Key differences

PG, hemangiomas, and KS are all vascular lesions, but they differ significantly in their nature, causes, treatment and clinical behaviour. 

Table 1. Key differences between pyogenic granuloma, hemangioma and Kaposi sarcoma.

Diagnostic challenges

Lesions like PG, hemangiomas, and KS can mimic each other. Therefore, accurate differential diagnosis is crucial to ensure appropriate management.⁶ Clinical features, imaging (e.g., MRI), and immunohistochemical markers may help differentiate benign from malignant forms, ensuring an accurate management.^4,8 Recent advances in immunohistochemistry have clarified the aetiology of these lesions and improved diagnostic accuracy and management strategies.

Summary

Vascular anomalies encompass a broad range of conditions, notably including pyogenic granuloma (PG), hemangiomas, and Kaposi sarcoma (KS). These lesions differ significantly in their biological behaviour, ranging from benign to malignant, and are associated with varying causes such as trauma, congenital factors, and viral infections like HHV8. Despite their differences, these lesions can appear clinically similar, often leading to misdiagnosis and inappropriate treatment.

Accurate diagnosis is therefore essential and relies on careful assessment of clinical presentation, histopathological findings, and supportive imaging techniques such as MRI. Treatment approaches also vary: PG often requires excision; hemangiomas may be managed conservatively or with propranolol; while KS necessitates systemic therapy. Correct classification ensures optimal care and avoids unnecessary complications.