Warty Dyskeratoma

Etiology

The exact etiology of this condition is unknown. Ultraviolet radiation, autoimmunity, viral factors, chemical carcinogens, and smoking have been proposed to play a role in its etiology.[5] In the case of lesions on the oral cavity, oral mucosal trauma (eg, due to biting, ill-fitting denture, or sharp tooth) or tobacco use (smoking or chewing) have been suggested as possible risk factors.[6] For lesions presenting on or near the genital area, human papillomavirus was thought to have a potential role. However, in one of the studies, polymerase chain reaction analysis in 13 lesions of warty dyskeratoma did not reveal any evidence of human papillomavirus DNA.[1] Multiple eruptive lesions of warty dyskeratoma have been described in the case of end-stage renal disease.[7]

Epidemiology

Warty dyskeratomas are typically found in males and middle-aged or older adults aged 40 to 60.[6] No racial predisposition has been identified. 

Pathophysiology

The exact origin of warty dyskeratoma is still unclear. However, this condition is usually described as a follicular adnexal neoplasm, which is supported by the histologic resemblance of the follicular infundibulum and the location usually associated with a pilosebaceous unit (see Image. Warty Dyskeratoma Pathology Architecture).[8] Immunohistochemical analysis of warty dyskeratoma lesions shows cytokeratin (CK) 7 and CK17 expression on the basal layers and CK 1 and 10 on the suprabasal layers. This cytokeratin expression pattern further supports the view that warty dyskeratoma is an adnexal tumor with follicular differentiation.[9] 

Reports of warty dyskeratoma in oral mucosa and subungual areas have been documented; interestingly, both these areas lack hair follicles.[10][11] Mucosal warty dyskeratoma may be associated with ectopic sebaceous glands.[6] Few authors have argued that the cases reported as "oral warty dyskeratoma" are a form of focal acantholytic dyskeratosis, different from the warty dyskeratomas seen on the skin surface.[12]

Some authors believe that the term "follicular dyskeratoma" better describes the lesion as compared to the original name of warty dyskeratoma, as it takes into account the possible follicular derivation and also considers the fact that most of the lesions are not verrucous clinically and a pathogenetic association with human papillomavirus has not been proven yet.[1] The absence of SERCA2 staining by immunohistochemistry, the protein product of ATP2A2, was reported, which suggests that warty dyskeratoma may represent an acquired genetic mutation of ATP2A2.

Histopathology

The lesion has been typically described as originating from a pilosebaceous unit. The distinctive histopathology helps differentiate this lesion from a wide range of similar pathologies. The most common findings include focal acantholysis and dyskeratosis.[1]

Currently, 3 primary architectural patterns have been described. The most common of these patterns is cup-shaped epidermal invagination; the other 2 forms are cystic and nodular. Few cases have shown variable combinations of the 3 patterns.[1] The lesions showing nodular patterns are usually smaller in size; therefore, they have been proposed to represent earlier stages of the lesion. Studies have suggested that the cup-shaped invaginations and cystic forms represent well-developed lesions.[1] The lining of the typical cup-shaped invagination resembles that of the follicular infundibulum.[1] In more than half of the cases, focal continuity to follicular infundibulum is found, while other cases may show the presence of small infundibular cystic structures.

Other histopathological findings include keratotic debris, grains, corps ronds (meaning "round bodies"), and villi formation with suprabasal acantholytic cells and hyalinized or fibrous stroma with intrastromal clefts (see Image. Warty Dyskeratoma Pathology Corps Ronds and Grains).[13] Foci with relatively larger epithelial cells showing abundant eosinophilic cytoplasm and a small dark nucleus may be seen, probably representing an early stage of dyskeratosis. Lymphohistiocytic perivascular infiltration may be noted.

The histopathology of subungual dyskeratoma shows a crater-like area in the nail matrix and nail bed, with intense papillomatosis at the crater's base and deep epithelial digitations in the lining. Areas of acantholysis, dyskeratotic cells, and irregular clefts are seen at the center of the tumor. Numerous multinucleated giant cells in the nail bed have also been reported.[14]

History and Physical

Clinical Features

The lesions are mostly limited to the head and neck area, with few reports of mucosal lesions. Other skin sites reported to be involved are the trunk, extremities, nails, hard palate, and genitalia. Intra-oral lesions are usually found on keratinized mucosa, eg, maxillary and mandibular alveolar ridges and the hard palate. Most of the lesions are found within sun-exposed areas.[15]

The warty dyskeratoma is a skin-colored to grey-pink umbilicated papulonodular lesion with a hyperkeratotic plug in the center and a rolled smooth edge. The size ranges from a few millimeters to a few centimeters. The lesion is usually solitary and asymptomatic.[6] Some patients may complain of pruritis, mild pain, or tenderness. Some authors postulated that itching may be due to eosinophils in histopathology.[16] Lesions on the scalp may have focal alopecia.[17][18]

Multiple lesions of warty dyskeratoma are rare. Several cases of multiple warty dyskeratomas were reported among patients with renal dysfunction.[7][19] Mucosal lesions typically present as white firm papules or nodules with a verrucous surface or central umbilication.[6][20] Warty dyskeratomas, even on the vulvar mucosa, have also been reported.[21] Few cases of subungual dyskeratoma have been reported. These cases present clinically as longitudinal or roundish erythronychia and are sometimes associated with pain.[11]

Evaluation

The clinical diagnosis of warty dyskeratoma may be difficult. Dermoscopy can help in some cases by differentiating the condition from other cutaneous lesions with a similar presentation. The typical dermoscopy features of a warty dyskeratoma consist of central hyperkeratosis with a peripheral collarette of scale.[22][23]

The first reported dermoscopic findings of warty dyskeratoma described a coarse cobblestone pattern. This corresponds with the hyperkeratotic plugs histopathologically.[24] Various descriptive terms such as "milky red doughnut-shaped" areas with "jellyfish-like" or "iris-like" appearance have been used.[25] Central scale crust with polymorphic vessels and pink-white structureless areas may be seen.[26]

Treatment / Management

The definitive treatment of warty dyskeratoma is surgical excision. Curettage or electrodesiccation have also been used. Tazarotene acid gel, laser therapy, and other treatments, eg, 3% 5-floxuridine, 0.1% tretinoin cream, and calamine lotion, have been tried with varying results.[19][27] No risk of malignant transformation or recurrence of warty dyskeratoma is known.(B3)

Differential Diagnosis

The lesion of warty dyskeratoma can be confused with various common cutaneous conditions, both clinically and histopathologically (see Table. Differential Diagnoses Warty Dyskeratoma).

Keratoacanthoma has a similar clinical morphology, with a cup-shaped papulonodule having central depression. However, keratoacanthoma lacks acantholysis or dyskeratosis in histology.[28] Additionally, squamous cell carcinoma can be clinically confused with warty dyskeratoma because of its verruciform appearance and chronic ulceration. However, sarty dyskeratoma does not show any atypia or mitotic activity in a biopsy.

Grover disease, or transient acantholytic dermatosis, is typically a benign, pruritic condition affecting multiple small erythematous papules on the chest or back of middle-aged men. Less commonly, women may also be affected. Histopathologically, focal acantholysis, dyskeratosis, and occasional spongiosis are seen. The primary histological feature of Grover disease is the presence of small foci of acantholysis with dyskeratosis, intraepidermal clefting, and sometimes vesicle formation.

Darier disease, or keratosis follicularis, is an autosomal dominantly inherited condition caused by a mutation in the gene ATP2A2 with multiple greasy, keratotic papules located on the seborrheic areas of the face, upper chest/back, and extremities with guttate leucoderma and cobblestone appearance of the hard palate. Characteristic warty papules on the dorsal hands, similar to acrokeratosis verruciformis, and nail changes (eg, V-shaped nicks and red and white longitudinal bands on the nails) are often present. Histopathologic findings include multiple areas of suprabasal acantholysis with dyskeratosis, corps ronds, and columns of parakeratosis (grains). Acantholytic actinic keratosis may present with acantholysis and dyskeratosis but differs in demonstrating atypical keratinocyte proliferation with cytologic atypia and mitoses.

Warty dyskeratoma is an unusual cause of erythronychia. Glomus tumors of nailbed can have a similar presentation, with erythronychia and pain. Magnetic resonance angiography will help to rule out this vascular tumor. Other uncommon causes of erythronychia, eg, onychopapilloma or melanoma, require histopathological evaluation of the tumor tissue.[29]

Focal acantholytic dyskeratosis was first coined by Ackerman in 1972 in an attempt to describe a distinctive histologic pattern with parakeratotic hyperkeratosis, acantholytic dyskeratosis (at all levels of the epidermis), and focal suprabasal clefts. He classified the lesions by size, number (single or multiple), and duration (persistent and transient), leading to the following 6 distinct classes:

1. Incidental
2. Multiple lesions (Darier disease)
3. Nodular with follicular involvement (warty dyskeratoma)
4. Papular
5. Systematized
6. Transient (Grover disease) [4] 

This finding has been an incidental finding in several skin lesions, including compound and junctional nevi, scars, seborrheic keratosis, basal cell carcinoma, and squamous cell carcinoma.[5]

 Table. Differential Diagnoses Warty Dyskeratoma

Prognosis

Warty dyskeratoma is a benign condition and has no known risk of malignancy or metastasis.

Complications

Incomplete removal, scarring, or surgical site infection risks are present following the excision of a warty dyskeratoma. Warty dyskeratoma has no risk of systemic involvement.