Onychomatricoma

An onychomatricoma is a subungual tumor of the fingers and toes, described in 1992.[1]

The terminology describing onychomatricomas has slowly been adjusted over time. In 1992, the original description termed this tumor an onychomatrixoma, based on the description of a filamentous, tufted tumor in the matrix. Subsequently, the term onychomatricoma was introduced into the English literature in 1995.[2] The term onychomatricoma is most descriptive and breaks down as onycho (nail) matric (matrix) oma (tumor).

Currently, histologic criteria have been used to establish subclassifications of onychomatricomas as 1 of 3 types. The clinical relevance of these subclassifications has not yet been well established, but they are described in Histologic Findings.

The etiology of onychomatricomas is not yet known. Patients do not usually report any history of trauma.

One literature review has noted that onychomycosis may be found more commonly in association with toe onychomatricomas; almost half the reported cases have had a fungal association. However, the significance of onychomycosis in these patients is not yet well established and may or may not play a role in the pathophysiology of onychomatricomas.

Another theory espoused is that onychomatricomas are fibroproliferative in origin and are epithelial and connective-tissue hamartomas simulating the nail matrix. This theory is further supported by an electron microscopy study that associated onychomatricoma to a nail matrix origin.[3] On immunohistochemistry, onychomatricomas express the same pattern of cytokeratins and integrins as seen in normal nail matrix. Keratin expression patterns have also suggested differentiation toward the nail bed and the nail isthmus.[4]

One report has noted an onychomatricoma arising from the ventral part of the proximal nail fold, thus taking on a pterygium aspect.[5] A dorsal pterygium bridging the proximal nail fold may also be noted. In such cases, tumor is also produced by the ventral surface of the proximal nail fold (as opposed to most cases, in which only the matrix produces tumor). This odd variant produces 2 layers of plate sandwiched together, which makes diagnosis more difficult.[6]

Onychomatricomas were originally believed to be benign nail lesions. However, the literature suggests that malignant potential cannot be completely excluded.

In ultrastructure studies, E-cadherin and beta-catenin have been noted at the cell membrane in the epithelial invaginations, while P-cadherin is restricted to basal cells. In contrast to other matrical tumors, nuclear beta-catenin was not present, suggesting that onychomatricoma may lack the transcriptional activating role of beta-catenin noted in follicular and odontogenic matrical tumors.[7]

Genome studies have suggested chromosome 11 plays a role in this tumor.[8]

Frequency

The frequency of onychomatricomas in the United States has not been determined. One epidemiological study reported no more than 80 known cases in the literature.[9]  The frequency of onychomatricomas internationally has not been determined.

Race

In the English literature, one case occurred in a Black patient,[10] while all other reports have been in White persons.[11]

Sex

The most current literature suggests the male-to-female ratio for onychomatricomas is approximately 1:1.

Age

The mean age of presentation is 47.9 years, as of the last tabulation.[9] One report now exists of a presentation in a child.[12]

Few long-term studies are available on onychomatricomas. In one case, surgical removal yielded no recurrence at 2-year follow-up. Similar results were also noted in a 2-year follow-up. Nail regrowth occurs without incident.

A continuum with potentially malignant onychomatricoma may exist. Awareness of the possibility is prudent.[11]

The clinical history may be nonspecific because this is usually a painless growth. Patients may report a change in nail color or nail thickening. Prior history of onychomycosis may be important; however, this is not yet well established.

Other important information to inquire about in the history is previous trauma to the region and a family or personal history of cancer.

Occurrence is predominantly (63%) on the fingers.[10] The percentage of lesions on the first, second, third, and fifth fingers is 37%, 15%, 37%, and 11%, respectively.[9] Multiple-digit occurrences in a single patient has been reported.

The following clinical tetrad has been reported: (1) xanthonychia, (2) longitudinal ridging, (3) splinter hemorrhage, and (4) notable overcurvature. Erythema and swelling of the proximal nail fold, tenderness with nail compression, and longitudinal melanonychia have also been seen.[10] Clinical presentation can be nonspecific and include pterygium.[6] See the image below.

Courtesy of Dr. Militello.

The ventral nail may have woodwormlike holes. See the image below.

Note the woodworm-like features. Courtesy of Dr. Militello.

Nail avulsion exposes the filiform tumor arising from the matrix. Upon surgical removal or nail avulsion, the tumor has been described to have the macroscopic appearance of an "anemone."[12] This is due to the nail matrix having developed multiple filamentlike digitations that extend up and ultimately insert and protrude into the bottom of the proximal nail. As a result, the bottom of the proximal nail has multiple small holes that are visible and correspond to the matrix projections.

Diagnosis of an onychomatricoma is primarily based on histological analysis of the tumor. Bacterial and fungal cultures should be requested to exclude infections, as damage to the nail caused by onychomatricomas increases patient susceptibility to bacterial and fungal invasion.[22]

Less invasive techniques such as dermoscopy, MRI, ultrasound, and confocal microscopy have been reported as a potential adjuvants to diagnosis.

The most common dermoscopic features include longitudinal white lines, proximal and distal splinter hemorrhages, and holes in the distal margin.[9, 23]

MRI images are typical. The sagittal images highlight the tumor core in the matrix area and the invagination of the lesion into the funnel-shaped nail plate. The center has a low signal with a peripheral rim signal identical to that of normal epidermis. The distal filamentous extensions present a higher signal on T2-weighted images owing to the mucoid stroma with a high water content. Axial slices accurately show the holes in the substance of the nail plate filled with the filamentous extensions.

Ultrasonography can also help with the diagnosis.[24, 25] Results in a few cases have shown a hypoechoic and hypovascular growth in the matrix. Interesting findings include hyperechoic linear dots inside their hypoechoic structure, with projections into the matrix reaching into the interplate space. To date, no bone erosions or remodeling of the distal phalanx have been reported.

Recent research supports the use of reflectance confocal microscopy to assist in rapid and noninvasive diagnosis of onychomatricoma. The presence of longitudinal dark areas and bright-gray lines forming channel-like structures can help to identify onychomytricomas prior to surgical excision.[26]

Ordering a radiograph to exclude bony involvement by this or another condition in the differential diagnosis list is prudent.

Complete surgical excision is the recommended therapeutic approach for onychomatricomas. Surgical excision generally involves nail plate avulsion with complete excision of the tumor back to the origin at the nail matrix.[9] Mohs micrographic surgery allows for clearance of the tumor with minimal removal of the unaffected nail matrix and conserved nail regeneration potential when the cosmetic and functional impact of complete excision are a concern.[27]

In 2002, Perrin et al[28] described the histology of onychomatricomas, establishing criteria involving 3 prerequisites, as follows:

• Fibroepithelial tumor with two anatomic zones based on proximal and distal location: The proximal zone, beneath the proximal nail folds, starts at the root of the nail and extends to the cuticle. This zone corresponds to the tumor base and is composed of deep epithelial invaginations and fibrillary stroma. The distal zone corresponds to the lunula and is characterized by multiple tumor digitations or projections lined with matrix epithelium and cavities filled with serous fluid.

• Matrical tumor in two layers: The 2 layers are (1) a superficial cellular layer with fibrillary collagen and (2) a deep, less-cellular layer filled with dense collagen bundles.

• Thick nail plate formed by a thick keratogenous zone: The nail is perforated by cavities filled with serous fluid.

Alternate histoclinical presentations and considerations

Usually, an onychomatricoma forms from the proximal nail matrix without involving other sites, such as the ventral proximal nail fold. However, reports describe formation in other sites that produce a resultant unusual presentation. These sites include the following:

• The ventral part of the proximal nail fold without matrix involvement: This tumor produces pressure on the matrix and results in a nail depression.

• The matrix, but also covering the ventral nail fold to include the angle at which it meets the dorsal epidermis: Clinically, this appears like the pterygium of lichen planus but without the histologic joining of the matrix granular metaplasia.

• Clinical mimic of nail Bowen disease, with a yellow thick nail: This is due to the pressure of the onychomatricoma on the distal differentiated matrix. The histological subungual tissue reveals minute digitations, but not the classic digitations that give the anemone look.

Because nail plates are not always available as part of the biopsy specimen (or in case reports on onychomatricomas), the diagnostic criteria have been refined based on immunohistochemistry findings. Specific staining criteria include antibody AE13 staining in a V-shaped expression pattern in the epithelium ridges of an onychomatricoma.

Nail clippings may show glove-finger epithelial projections of the nail matrix epithelium extending into the nail plate. This has recently been shown to form a pattern that could potentially assist with diagnosis via analysis of the nail clippings alone.[29] In using nail clippings, this report found multiple small holes in a frontal view of the nail clippings after hematoxylin and eosin staining. The cavities stained positively for cytokeratin and were found to have lining derived from epithelium.

Histologically, a continuum exists for fibroepithelial neoplasms of the nail in their epithelial-stromal ratio, stromal cellularity, and stromal atypia. These details have been proposed to be the basis for a more descriptive naming system for onychomatricomas, based on cellular proliferation ratios and atypia. The terms espoused are as follows:

• Unguioblastoma: This is a tumor with a predominant epithelial component. The epithelium-to-stromal proliferation is at a ratio of 3:2.

• Unguioblastic fibroma: This is a tumor with a predominant and more characteristic cellular stroma. The stromal cells have parallel spindle-to-fusiform nuclei. The epithelium-to-stromal ratio is reportedly less than 2:3.

• Atypical unguioblastic fibroma: This is a tumor in which the cellular stroma shows nuclear pleomorphism and atypia with an increase in mitotic activity. Also present may be areas of focal necrosis. Here, the stromal region displays the parallel spindle formation noted in the unguioblastic fibroma, but with much more cellularity. No ratios are reported for this class.

Once surgical excision is performed, basic wound care measures should be instituted.

Complete surgical removal of the tumor is the goal of therapy. Surgical excision generally involves nail plate avulsion with complete excision of the tumor back to the origin at the nail matrix.[9] Mohs micrographic surgery allows for clearance of the tumor with minimal removal of the unaffected nail matrix and conserved nail regeneration potential when the cosmetic and functional impact of complete excision are a concern.[27]

No drug studies have been performed on onychomatricomas. Surgical excision is believed to be the best therapeutic approach