Verruciform Xanthoma- Causes, Clinical Features, Histologic Features, Diagnosis, and Treatment

What Is Xanthoma?

Xanthoma is a skin condition where fat buildup is formed underneath the skin. It can appear anywhere on the body, but mostly they form on the joints (of knees and elbows), feet, buttocks, hands, etc. Clinically they appear as flat or raised papules or bumps underneath the skin that are usually painless. The size of some xanthomas is very small, whereas some others may grow up to 7.5 cm (three inches) in diameter. It is often a sign of a medical condition that causes a rise in blood lipid contents. Following are some of the medical conditions that predispose xanthoma. It includes;

• Diabetes.

• High blood cholesterol level.

• Hypothyroidism (a condition where not enough thyroid hormone is produced by the thyroid gland).

• Hereditary disorders like familial hypercholesterolemia (a genetic condition that causes high LDL (low-density lipoprotein) cholesterol levels in the body).

• Pancreatitis (inflammation of the pancreas).

It can be treated by treating the underlying condition that causes increased blood lipids, and surgery is the other option.

What Is Verruciform Xanthoma?

Verruciform xanthoma is an uncommon benign, mucocutaneous, asymptomatic lesion with an unknown etiology. It was first described by Shafer in 1971. It chiefly occurs on the oral mucosa exhibiting a papillary or cauliflower-growth-like appearance. The extraoral verruciform xanthoma is highly uncommon and is reported on the vulva, penis, scrotum, and extremities. It is referred to by other names like “verrucous xanthoma” and “inflammatory papillary hyperplasia with foam cell response.” They are not associated with increased serum lipids as seen in xanthoma, but it occurs due to degeneration or damage of cells in the overlying epidermis.

What Causes Verruciform Xanthoma?

The exact etiology of verruciform xanthoma is highly unknown. However, certain studies hypothesized that the following etiopathogenesis leads to the development of verruciform xanthoma.

Ide et al. have suggested that possible agents like periodontal pathogens, mechanical stimuli, wet microenvironment, tobacco, alcohol, drugs, and allergens may predispose verruciform xanthoma. More other studies have hypothesized many etiopathogeneses resulting in the development of verruciform xanthoma.

Who Is More Likely to Get Affected by Verruciform Xanthoma?

Verruciform xanthoma occurs most commonly in middle-aged persons (ages between 40 to 60 years), and they rarely exceed in children. Verruciform xanthoma in children can occur in context with CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects). It is slightly seen more in men as compared to women.

The racial predisposition of verruciform xanthoma is reported more in Japanese men. The scrotal cases of verruciform xanthoma are seen as more common in middle-aged Japanese men.

What Are the Clinical Features of Verruciform Xanthoma?

Verruciform xanthoma occurs mostly in the oral mucosa, and less commonly, it affects the extraoral regions like the vulva, penis, scrotum, etc. The clinical features of verruciform xanthoma include,

• Oral lesions of verruciform xanthoma appear as well-circumscribed solitary lesions that may be either mucosa colored or slightly reddish. It may be pale or hyperkeratotic with a rough or pebbly surface. The lesions may also appear in the form of a polyp with a pedunculated (mushroom-like) base.

• Oral lesions most commonly occur in the alveolar ridge and gingiva. Followed by this buccal mucosa, the hard palate, floor of the mouth, and lips are other common sites.

• It is usually asymptomatic, with the size varying from 2 mm to 1.5 cm in diameter.

• Oral verruciform xanthoma may be associated with the following conditions:

1. Lichen planus (an inflammatory skin condition affecting the skin, mucous membranes, hair, and nails).

2. Pemphigus vulgaris (an autoimmune disorder characterized by blisters and erosions in the skin and mucous membranes).

3. Oral bulla (fluid-filled lesion).

4. Carcinoma in situ (group of abnormal cells that do not spread from the location where they formed initially).

5. Oral squamous cell carcinoma (most common oral cancer).

The oral and scrotal lesions of verruciform xanthoma do not have any association with any predisposing disorders. But the lesions occurring on the feet are mostly associated with lymphedema (obstruction of lymph nodes). Diseases like CHILD syndrome and epidermal nevi are associated with skin lesions that are multiple or that occur outside the perineum.

What Are the Histologic Features of Verruciform Xanthoma?

The histologic features of verruciform xanthoma are very important as the diagnosis is mostly made with the help of determining the histopathological features. The histological features of verruciform xanthoma include:

• It appears as verruciform, papillary, cauliflower-like growth showing a lichenoid pattern (an inflammatory pattern that is histologically characterized by basal cell keratinocyte damage in the epidermis).

• The lesion exhibits papillary, acanthotic surface epithelium covered by a thick layer of parakeratin. On staining with hematoxylin and eosin stains (H and E stain), these keratin layers exhibit a distinct orange color.

• Clefts between the epithelial projections are seen filled with parakeratin (an abnormal, pyknotic form of keratin). Elongated rete peg formations with uniform depth are seen.

• The most striking histologic feature of verruciform xanthoma is the presence of large foam cells in the connective tissue papilla between epithelial rete pegs. These foam cells are nothing but lipid-containing macrophages.

Some of the other histologic features observed in verruciform xanthoma include:

1. Chronic inflammatory cells infiltrate.

2. Presence of Langerhans cells and fibroblast.

How Is Verruciform Xanthoma Diagnosed?

Patients who are suffering from verruciform xanthoma often present with a history of a tender, asymptomatic lesion on the oral mucosa or skin. The various diagnostic measures used to diagnose verruciform xanthoma include;

1. Histologic Examination: The clinical features of verruciform xanthoma do not give a definitive diagnosis. The diagnosis is mostly made at histologic examination. An excisional biopsy is suggested by the doctor to determine the underlying histologic features. The characteristic feature that distinguishes verruciform xanthoma is the presence of fat-laden macrophages with foamy cytoplasm confined to the connective tissue of papillae.

2. Dermoscopic Findings: The dermoscopic findings reveal the presence of surface papilla comprising linear or hairpin-shaped vessels which are surrounded by a white marginal rim. Vessels in dermal papillae and papillated acanthotic epidermis are dilated. The vessels disappear, and lipid-laden foaming cells become visible under compression. These distinct features from dermoscopic findings are useful in diagnosing verruciform xanthoma.

3. Laboratory Diagnosis: Tests determining cholesterol triglyceride levels, phospholipid levels, free fatty acid levels, lipoprotein serum fraction, and glucose determinations are also useful to a certain extent in diagnosing verruciform xanthoma.

What Are the Differential Diagnoses of Verruciform Xanthoma?

The differential diagnoses of verruciform xanthoma include;

• Condyloma acuminatum (genital warts).

• Condyloma latum.

• Verrucous carcinoma.

• Molluscum contagiosum.

• Seborrheic keratosis.

• Verruca vulgaris.

• Verrucous hyperplasia.

• Xanthoma.

• Papillomas.

The differential diagnosis of verruciform xanthoma lesions in the penis is “erythroplasia of Queyrat (Bowen disease of glans penis).”

How Is Verruciform Xanthoma Treated?

Surgical treatment is the best approach used by doctors to treat verruciform xanthoma. Doctors plan a local surgical excision of verruciform xanthoma, which is often curable. Recurrence after surgical excision is rare. Various other treatment options like cryotherapy, electro section, laser treatment, and radiation therapy are not considered in treating verruciform xanthoma.

Verruciform xanthoma associated with any other underlying disease like CHILD syndrome should be managed properly. Consulting a dermatologist will be much helpful in knowing more about the condition and how to manage it.

Conclusion:

Verruciform xanthoma is an uncommon benign skin condition that occurs chiefly in the oral mucosa. Extraoral lesions of verruciform xanthoma are less common, affecting the vulva, penis, scrotum, etc. It is usually asymptomatic. Clinically it appears as a solitary lesion exhibiting papillary or cauliflower-like growth with varying sizes. Histologic features are the most important in distinguishing verruciform xanthoma. The hallmark of diagnosis in verruciform xanthoma is the presence of lipid-laden macrophages with foamy cytoplasm in the connective tissue papillae. It is best treated by surgical excision, and there are no further complications.