Differential diagnosis of this condition includes the Birt-Hogg-Dubé syndrome and tuberous sclerosis. As the skin lesions are typically painful, it is also often necessary to exclude other painful tumors of the skin (including blue rubber bleb nevus, leiomyoma, eccrine spiradenoma, neuroma, dermatofibroma, angiolipoma, neurilemmoma, endometrioma, glomus tumor and granular cell tumor; the mnemonic "BLEND-AN-EGG" may be helpful). Other skin lesions that may need to be considered include cylindroma, lipoma, poroma and trichoepithelioma; these tend to be painless and have other useful distinguishing features.

Nevi are typically diagnosed clinically with the naked eye or using dermatoscopy. More advanced imaging tests are available for distinguishing melanocytic nevi from melanoma, including computerized dermoscopy and image analysis. The management of nevi depends on the type of nevus and the degree of diagnostic uncertainty. Some nevi are known to be benign, and may simply be monitored over time. Others may warrant more thorough examination and biopsy for histopathological examination (looking at a sample of skin under a microscope to detect unique cellular features). For example, a clinician may want to determine whether a pigmented nevus is a type of melanocytic nevus, dysplastic nevus, or melanoma as some of these skin lesions pose a risk for malignancy. The ABCDE criteria (asymmetry, border irregularity, color variegation, diameter > 6 mm, and evolution) are often used to distinguish nevi from melanomas in adults, while modified criteria (amelanosis, bleeding or bumps, uniform color, small diameter or de novo, and evolution) can be used when evaluating suspicious lesions in children. In addition to histopathological examination, some lesions may also warrant additional tests to aid in diagnosis, including special stains, immunohistochemistry, and electron microscopy. Typically; the nevi which exist since childhood are harmless

Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogenous white areas.

Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of illuminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.

The skin lesions may be difficult to diagnose clinically but a punch biopsy will usually reveal a Grenz zone separating the tumour from the overlying skin. Histological examination shows dense dermal nodules composed of elongated cells with abundant eosinophilic cytoplasm arranged in fascicles (spindle cells). The nuclei are uniform, blunt-ended and cigar-shaped with only occasional mitoses. Special stains that may be of use in the diagnosis include Masson's trichrome, Van Gieson's stain and phosphotungstic acid–haematoxylin.

The renal cell carcinomas have prominent eosinophilic nucleoli surrounded by a clear halo.

The management of a nevus depends on the specific diagnosis, however, the options for treatment generally include the following modalities:

Verruciform xanthoma is uncommon, with a female:male ratio of 1:1.1

The annual malignant transformation rate of leukoplakia rarely exceeds 1%, i.e. the vast majority of oral leukoplakia lesions will remain benign. A number of clinical and histopathologic features are associated with varying degrees of increased risk of malignant transformation, although other sources argue that there are no universally accepted and validated factors which can reliably predict malignant change. It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink or remain stable.

- Presence and degree of dysplasia (mild, moderate or severe/carcinoma in situ). Dysplasia is the most important predictor of malignant change, and about 10% of leukoplakia lesions show dysplasia when biopsied.

- Leukoplakia located on the floor of the mouth, the posterior and lateral tongue, and the retromolar areas (the region behind the wisdom teeth) have higher risk, whereas white patches in areas such as the top surface of the tongue and the hard palate do not have significant risk. Although these "high risk" sites are recognized, statistically, leukoplakia is more common on the buccal mucosa, alveolar mucosa, and the lower labial mucosa. Leukoplakia of the floor of the mouth and tongue accounts for over 90% of leukoplakias showing dysplasia or carcinoma on biopsy. This is thought to be due to pooling of saliva in the lower part of the mouth, exposing these areas to more carcinogens held in suspension.

- Red lesions (erythroplasia) and mixed red and white lesions (erythroleukoplakia/"speckled leukoplakia") have a higher risk of malignant change than homogenous leukoplakia.

- Verrucous or nodular areas have a higher risk.

- Although smoking increases risk of malignant transformation, smoking also causes many white patches with no dysplasia. This means that statistically, white patches in non smokers have a higher risk.

- Older people with white patches are at higher risk.

- Larger white patches are more likely to undergo malignant transformation than smaller lesions.

- White patches which have been present for a long period of time have higher risk.

- Persons with a positive family history of cancer in the mouth.

- Candida infection in the presence of dysplasia has a small increased risk.

- A change in the appearance of the white patch, apart from a change in the color, has a higher risk. Changes in the lesion such as becoming fixed to underlying tissues, ulceration, cervical lymphadenopathy (enlargement of lymph nodes in the neck), and bone destruction may herald the appearance of malignancy.

- White patches present in combination with other conditions that carry a higher risk (e.g. oral submucous fibrosis), are more likely to turn malignant.

- Although overall, oral cancer is more common in males, females with white patches are at higher risk than men.

Visual diagnosis is made by the "stuck on" appearance, horny pearls or cysts embedded in the structure. Darkly pigmented lesions can be challenging to distinguish from nodular melanomas. Furthermore, thin seborrheic keratoses on facial skin can be very difficult to differentiate from lentigo maligna even with dermatoscopy. Clinically, epidermal nevi are similar to seborrheic keratoses in appearance. Epidermal nevi are usually present at or near birth. Condylomas and warts can clinically resemble seborrheic keratoses, and dermatoscopy can be helpful. On the penis and genital skin, condylomas and seborrheic keratoses can be difficult to differentiate, even on biopsy.

To date, the gold standard in the diagnosis of seborrheic keratosis is represented by the histolopathologic analysis of a skin biopsy.

Differential diagnosis includes seborrheic keratosis, verruca simplex, condyloma acuminatum, granular cell myoblastoma, vulvar intraepithelial neoplasia, bowenoid papulosis, erythroplasia of Queyrat, and verrucous carcinoma

Due to the rarity of different types of vascular conditions, angiokeratomas may be misdiagnosed. A biopsy of the lesion can produce a more accurate diagnosis.

Verrucous perforating collagenoma is a very rare skin disorder which presents with papules with a transepidermal elimination of collagen.

Outpatient treatments such as interventional radiology, lasers, and physical therapy are employed to reduce the severity of the vascular lesions. However, in some cases lasers have caused a reaction in the tissue causing it to expand and become exposed to infection. Excision and grafting may be necessary to remove the lesion. Recovery time on such an operation ranges from 3 to 12 weeks depending on location of the graft, healing time and the possibility of complications.

Epithelioma cuniculatum (also known as Carcinoma cuniculatum, and Ackerman tumor) is a skin lesion, a type of verrucous carcinoma that may occur on the sole of the foot.

No treatment of seborrheic keratoses is necessary, except for aesthetic reasons. Since a slightly increased risk of localized infection caused by picking at the lesion has been described, if a lesion becomes itchy or irritated by clothing or jewelry, a surgical excision is generally recommended.

Small lesions can be treated with light electrocautery. Larger lesions can be treated with electrodesiccation and curettage, shave excision, or cryosurgery. When correctly performed, removal of seborrheic keratoses will not cause much visible scarring except in persons with dark skin tones.

Oral florid papillomatosis is a condition characterized by a white mass resembling a cauliflower covering the tongue and extending onto other portions of the mucous membranes. This is a type of verrucous carcinoma.

Morbidity and mortality range from both extremes as the significance correlate with the underlying systemic disease.

There seems to be beneficial responses to clindamycin therapy as the lesions regress. This leads to the hypothesis that microorganisms may be playing a role in the initial stages of Kyrle disease.

A family with Kyrle disease were examined which their skin lesions were benign. However, when three of the young adult members were closely examined, they had posterior subcapsular cataracts and two of those three developed multiple tiny yellow-brown anterior stromal corneal opacities. In order to determine if there is any correlation between Kyrle disease and the ocular observations, more cases of Kyrle disease are to be analyzed.

All in all, since Kyrle disease is relatively rare, more cases need to be studied and analyzed in order to understand the underlying pathogenesis and to improve the management of the disease.

Reported treatments include topical agents, dermabrasion, cryotherapy, laser therapy, and surgical excision. These therapies have a high failure rate because of incomplete relief of symptoms, scarring, or recurrence .

Though similar in appearance, ILVEN will not respond to therapies known to affect psoriasis. ILVEN can be very difficult to live with but can be treated. The most effective method is full-thickness excision of the lesion. CO2 Laser Surgery can resurface the skin to give a flat, smoother and more normal appearance, but does not remove the lesion.

Porokeratosis is a specific disorder of keratinization that is characterized histologically by the presence of a cornoid lamella, a thin column of closely stacked, parakeratotic cells extending through the stratum corneum with a thin or absent granular layer.

-The plaques are characterized histologically by hyperkeratosis which is a thickening of the outer layer of skin. Hyperkeratosis is often associated with an abnormal amount of keratin production. Also characteristic is moderate acanthosis a thickening of the stratum spinosum with elongation of rete ridges.

- Characteristic histologic feature is regular alternation of slightly raised parakeratotic areas without a granular layer (hypogranulosis) and slightly depressed orthokeratotic areas with prominent granular layer (hypergranulosis). Orthokeratotic hyperkeratosis is characterised by hyperkeratosis with non-nucleated cells. Parakeratotic hyperkeratosis is characterised by hyperkeratosis with nucleated cells.

- The orthokeratotic area shows a basket-weave-pattern.

- The dermis shows scattering of chronic inflammatory infiltrate (Munro's microabscess) sometimes giving a spongiform appearance.

This is very similar to linear psoriasis, but it has been noted that the diseases are distinct entities by immunohistochemical analyses.

Reactive perforating collagenosis is a rare, familial, nonpuritic skin disorder characterized by papules that grow in a diameter of 4 to 6mm and develop a central area of umbilication to which keratinous material is lodged. The cause of reactive perforating collagenosis is unknown.

Papillomatosis cutis carcinoides (also known as "Gottron's carcinoid papillomatosis" and "Papillomatosis cutis carcinoides of Gottron–Eisenlohr") is a cutaneous condition characterized by verrucous skin lesions, and is due to an HPV infection of the skin.

This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer." Chewing betel nuts is an additional risk factor commonly seen in Taiwan.

Diagnosis is mainly clinical, based on the history and clinical appearance. The differential diagnosis includes other oral white lesions such as Leukoplakia, squamous cell carcinoma, oral candidiasis, lichen planus, white sponge nevus and contact stomatitis. In contrast to pseudomembraneous candidiasis, this white patch cannot be wiped off. Tissue biopsy is sometimes carried out to rule out other lesions, although biopsy is not routinely carried out for this condition.

Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis. They are associated with human papillomavirus, the causative agent of genital warts. The lesions have a typical dysplastic histology and are generally considered benign, although a small percentage will develop malignant characteristics.

It is considered as a pre-malignant condition. Other terms used to describe the condition are: Erythroplasia of Queyrat, Squamous cell carcinoma in situ and Bowen’s disease. The term "Bowenoid papulosis" was coined in 1977 by Kopf and Bart and is named after dermatologist John Templeton Bowen.

The term “intraepithelial neoplasia” defines a premalignant intraepithelial change.

On the vulva it is termed VIN (vulvar or vulval intraepithelial neoplasia); on the penis, PIN (penile intraepithelial neoplasia); and on or around the anus, AIN (anal intraepithelial neoplasia). The terminology has been very confusing and it is now recommended that the terms Bowen’s disease, erythroplasia of Queyrat, and bowenoid papulosis should not be used for lesions in the anogenital area. However, dermatologists still recognize a distinct clinical variant, bowenoid papulosis, characterized by discrete papules in a younger age group and a tendency for spontaneous regression. Additionally, some authorities believe that erythroplasia of Queyrat and Bowen’s disease remain useful terms in men.