Although nail unit tumors are relatively rare, having an appropriate index of suspicion is critical to ensuring prompt diagnosis and treatment. Accordingly, this author offers practical pearls on detecting various types of benign and malignant tumors, including periungual fibromas, pyogenic granuloma and melanoma, in the nail unit.
A tumor of the nail unit is linked histopathologically to anatomical structures and can present in the nail bed, nail matrix or in or around the nail plate. Although most of these tumors are rare, it is important for the podiatric physician to be familiar with and recognize these entities due to the sheer volume of nail pathology we see on a daily basis in practice.
Before discussing the potential tumors of the nail unit, it is important to review basic nail anatomy. The nail plate, which functions to protect the underlying distal phalanx and continually renews itself during a person’s life, is comprised mainly of keratin and water.
The nail matrix has a role in creating the nail plate via “matrical keratinization,” which occurs via a distally oriented axis, unlike the non-nail epidermis.1 This keratinization occurs in the presence of an epithelium that is lacking the granular layer (aka the stratum granulosum). There are distal and proximal portions of the nail matrix that create the ventral and dorsal nail plate respectively. Interestingly, the granular layer develops in the presence of nail disease such as onychomycosis and psoriasis.2
Melanocytes are also located within the nail matrix. The melanocytes in Caucasians do not typically have matured melanosomes in comparison to the melanocytes in African-Americans and Asians.3 Normally, the nail matrix melanocytes are in a quiescent state but they can become activated and produce melanin, which transfers to surrounding keratinocytes. This resulting pigmentation produces a hyperpigmented linear streak that is visible clinically.
The nail plate is only two to five layers thick and gets thicker as it moves distally. The nail bed lacks a granular layer and contains sparse to no melanocytes. The nail plate is tightly attached to the nail bed and has encapsulated neurovascular structures called glomus bodies that regulate blood supply in cold weather.
Essential Insights On Longitudinal Melanonychia And Erythronychia
Before delving into the list of possible benign and malignant tumors, it is important to look at two patterns that can occur in the nail unit. Both can represent benign entities and, in some cases, malignant entities. These can affect one digit (localized) or multiple (polydactylous), and both toenails and fingernails can be involved in some cases.
Longitudinal melanonychia is visible as a brown/black streak in the nail starting proximally and running distally. This is very common in darker skin types as a natural variation but may also be associated with systemic etiologies, medications, infectious causes and local causes.1 In most patients, this is a result of matrix melanocyte activation or melanocyte hyperplasia.1 Melanocyte activation is the most common benign cause of this pigmentation. However, the pigmentation may be a lentigo, which has a different source than melanocyte activation. A benign junctional nevus within the nail matrix may cause a slight increase in matrix melanocytes whereas melanocyte activation characterizes melanocyte overactivity in their suprabasal location.
Longitudinal erythronychia, which involves the presence of a red streak within the nail, may be as something as common as a collection of splinter hemorrhages or as sinister as a melanoma. If one digit is involved, the limited differential diagnoses are: wart, onychopapilloma, glomus tumor, melanoma in situ or basal cell.4 Besides the pink-red streak, the nail plate may have a distal “V” chip in it, splitting or onycholysis present.4 Dermoscopy makes it easier to see these attributes. If multiple nails have longitudinal erythronychia, then a systemic issue such as lichen planus, Darier’s disease or, in rare cases, amyloidosis and hemiplegia may be the cause.4 A biopsy technique such as the longitudinal biopsy, which samples both the distal matrix and nail bed, is preferred. A longitudinal biopsy involves partial avulsion of the nail plate at the area of the streak and a fusiform incisional biopsy of the tissue beginning at the distal matrix and involving the nail bed.
Nail Pigmentation In A Child: Is It Melanoma Or Lentigo?
Nail melanoma presenting as longitudinal melanonychia in a child is extremely rare. The most frequent cause of this pigmentation in a child is nevi with nests. Just as plantar nevi can mimic acral melanoma, nail nevi can mimic nail melanoma.1 Nail matrix nevi are typically junctional nevi. In children, the nests of melanocytes can be large and irregular with the melanocytes and their nuclei looking atypical.1 The presence of the nests suggest nevi are present.
Several authors over the years have concluded that a pigmented streak in a child’s nail or a total hyperpigmentation of the pediatric toenail return as lentigo, atypical melanocytic hyperplasia or melanocytic activation, and not as subungual melanoma.5
Longitudinal melanonychia in children may arouse suspicion due to the bands of pigmentation, large band width and Hutchinson-like signs. Even histologically, longitudinal melanonychia, which authors had interpreted in the literature as possible melanoma, actually had atypical melanocytic hyperplasia when one applied recent diagnostic criteria.5 For these children, one should ensure regular follow-up and close attention to clinical photographs and dermoscopy exam findings. Due to the long-term sequelae that may result from the procedure, it is best to reserve biopsy of a pediatric nail melanonychia for pigmentation that is changing or evolving.
What You Should Know About Benign Nail Unit Tumors
Periungual fibromas. Fibromas are generally slow growing, painless tumors of the nail unit that can develop in any subepidermal structure. True fibromas are smooth and have a pea-like appearance. If occurring near the nail matrix, periungual fibromas will generally cause nail dystrophy. Depending on the location of the tumor, the nail dystrophy may manifest as nail thinning or as a depression in nail plate.
Acquired periungual fibrokeratomas are histologically separate from true fibromas but also may cause nail plate dystrophy. These benign nodules have a hyperkeratotic tip, emerge from the proximal aspect of the nail unit and researchers believe they are the result of trauma.6 In addition to their flattened, flesh-colored appearance on the superficial aspect of the nail plate, periungual fibrokeratomas may also have a filamentous, rounded appearance, which has caused some practitioners to call them “garlic clove” fibromas. The frequency of these fibrokeratomas is unknown. Since there is no reporting system for these lesions, a review of the literature yields numerous case presentations. Acquired periungual fibrokeratomas occur in both sexes and researchers have reported the condition in people ranging from age 12 to 70.7 In younger children, it may represent a supernumerary digit.
Differential diagnoses of the periungual fibroma include a cutaneous horn, Koenen’s tumors and periungual warts. A cutaneous horn is a projection above the skin, which may have a benign lesion or a malignant entity at its base.8 Authors have described cutaneous horns as forming over hyperproliferative lesions such as warts, seborrheic keratoses and actinic keratoses. Squamous cell carcinoma is the most common malignancy clinicians find at the base of these lesions. An excisional biopsy of the lesion is diagnostic and can be curative.
Hereditary digital fibrokeratomas (Koenen’s tumors) occur in 50 percent of tuberous sclerosis cases. These lesions develop on both toenails and fingernails.9 Individual lesions are flesh colored with a smooth surface and a hyperkeratotic tip, which makes them difficult to distinguish from an acquired fibrokeratoma. They appear in patients around the age of 12 and increase in number and size as time progresses. Koenen’s tumors typically arise from the nail fold and may destroy or thin the nail plate over time as the lesions multiply and enlarge. Debridement of nails can be challenging in the presence of multiple lesions on the nail. Simple excision at the base of the lesion assists in management of these lesions.
Periungual warts or verrucae are a result of human papillomavirus (HPV) infection of the epithelium. These benign, hyperproliferative lesions typically have a hyperkeratotic covering and are flesh-colored. Periungual verrucae can cause damage to the nail unit depending on its location.10 They can present on both toenails and fingernails. The condition often stems from nail biting and may recur after treatment. Management of these lesions can range from topical therapy (cryotherapy, salicylic acid) to surgical excision.
Pyogenic granuloma. Pyogenic granulomas usually arise in or around the nail unit and are typically caused by trauma (friction from activity, ingrown nail, retronychia and aggressive pedicuring).11 They are vascular tumors affecting the periungual tissue and nail bed.
If pyogenic granulomas are present on multiple toes and fingers, one should suspect the use of a medication like a systemic retinoid or antiretroviral therapy, or a systemic issue such as psoriasis. If pyogenic granuloma is caused by trauma or an ingrown nail, address that accordingly. One can use topical steroids and antibiotics to treat the condition locally but if a medication is a suspected source, a change in dosage may be indicated. If that is not possible, local therapy is warranted. I have also used in-office hyfrecation of the lesions when possible. If a suspected pyogenic granuloma has not decreased or receeded by standard methods, and is grossly present upon the patient’s next visit, consider a biopsy to rule out amelanotic melanoma.
Glomus tumor. Characterized by pinpoint pain exacerbated by the cold, glomus tumors are more common on the fingers than the toes. Occurring more frequently in women in their 40s, a glomus tumor can present as a small red or bluish spot visible through the nail plate, or as a longitudinal erythronychia. A simple test of identifying a glomus tumor is Love’s pin test.11 This involves probing with a blunt instrument to determine the area of most pinpoint tenderness. Another method is to apply an ice cube to the nail and determine if the pain worsens. Both are highly sensitive tests to determine the presence of a glomus. Magnetic resonance imaging (MRI) can also determine the extent and borders of the lesion. Surgical excision involving nail plate avulsion is the standard method of treating this entity.
Is The Nail Unit Tumor Malignant?
Melanoma. Subungual melanoma may clinically present as a wide pigmented band (greater than 3 mm), the presence of Hutchinson’s sign distally or proximally, variation in pigmentation or multiple bands, and disruption of the nail plate itself. The ABCs of nail melanoma are listed in the table “A Closer Look At The ABCs Of Nail Melanoma” at right. Following nail unit biopsy (which can be a matrix shave, a longitudinal excision or a punch biopsy), the pathologist has the difficult assessment regarding level of invasion, which is not the same as listing it for the epidermis. Both Clark’s level and Breslow’s depth are modified due to the thinness of the tissue of the nail unit. As I stated earlier, there is a lack of a granular layer in the nail matrix and nail bed, so already the layers of the epidermis in this area are thinner. Breslow’s depth is not quite applicable to the nail unit and more research will determine how to stage invasion for nail melanoma.1
Squamous cell carcinoma. Squamous cell carcinoma is the most frequent malignant tumor of the nail unit.11 Bowen’s disease is squamous cell carcinoma in situ at the level of the epidermis. Men develop nail squamous cell carcinoma more than women and more often in the fingernails. However, the photo above shows squamous cell carcinoma in the nail bed of the hallux in a woman. She presented with a nail bed that would “bleed” every time she ran on a treadmill. Biopsy of the lesion revealed squamous cell carcinoma and she chose to have a Mohs surgeon perform the resulting excision in order to maintain the function and cosmesis of the toe.
Those who do develop squamous cell carcinoma of the nail unit often have a history of genital HPV infection or have a partner with that history.11 Clinically, the nail may present with a benign-looking change such as a periungual wart or fibroma. Subungual placement is most frequent and debridement will reveal excessive hyperkeratosis or an ulceration. When it comes to squamous cell carcinoma of the nail unit, pain is not common for the patient. A biopsy that encompasses the affected nail bed is paramount.
Keys To Securing The Best Specimen For Biopsy
Many physicians do not routinely perform nail biopsies on a daily basis. Nail surgeons have a number of biopsy techniques to choose from but many prefer one or two procedures on a consistent basis. Artifacts from certain procedures may create impediments for histopathologic interpretation.
Before performing a shave matrix biopsy, it is imperative to perform a surgical removal of the nail plate in order to visualize a pigmented streak or other nail bed pathology. One can replace the removed nail plate with a temporary dressing. However, avulsion of any kind results in loss of nail epithelium, which may be stuck to the nail plate. Another issue with obtaining a nail unit biopsy is crushing of the specimen with forceps. This can lead to artifacts in the specimen processing.
Often, the surgeon does not provide orientation of the margins of the biopsy specimen and the pathologist will not know which is lateral, distal, etc. Lack of designation of the tissue type submitted also can lead to misinterpretation, especially with a potential nail melanoma.
How can a surgeon provide the best specimen for the dermatopathologist to interpret? First, identify the tissue submitted, specifically the nail plate, bed, matrix, etc. Second, one can submit the nail specimen in a cassette in formalin with this nail diagram (www.cta-lab.com/nail_resources.html) to show orientation of the specimen. Also, if you choose to perform a biopsy of the nail unit, avoid using forceps to prevent crushing the artifact and gently use fine-tipped scissors instead.4 If the nail plate had avulsion and then replacement with a biologic dressing for the nail unit, note that on the pathology lab form.
Even with their rare appearance, nail unit tumors are a clinical entity that podiatric physicians have a potential of seeing due to the sheer volume of nails we treat on a daily basis. With study and practice, the physician can not only become adept at recognizing these tumors but also gain expertise in choosing the correct biopsy technique and specimen collection to get the optimal histopathologic diagnosis.
Dr. Vlahovic is a Clinical Associate Professor and J. Stanley and Pearl Landau Fellow at the Temple University School of Podiatric Medicine in Philadelphia.
1. Perrin C. Tumors of the nail unit. A review. part I: acquired localized longitudinal melanonychia and erythronychia. Am J Dermatopathol. 2013;35(6):621–636.
2. Krönauer C, Gfesser M, Ring J, Abeck D. Transonychial water loss in healthy and diseased nails. Acta Derm Venereol. 2001;81(3):175-7.
3. Perrin C, Michiels JF, Pisani A, Ortonne JP. Anatomic distribution of melanocytes in normal nail unit: an immunohistochemical investigation. Am J Dermatopathol. 1997;19(5):462-7.
4. Jellinek N. Longitudinal erythronychia: Suggestions for evaluation and management. J Am Acad Dermatol. 2011; 64(1):167.
5. Cooper C, Arva NC, Lee C, et al. A clinical, histopathologic, and outcome study of melanonychia striata in childhood. J Am Acad Dermatol. 2015;72(5):773-9.
6. Bart RS, Andrade R, Kopf AW, Leider M. Acquired digital fibrokeratomas. Arch Dermatol. 1968;97(2):120-9.
7. Baykal C, Buyukbabani N, Yazganoglu KD, Saglik E. Acquired digital fibrokeratoma. Cutis. 2007;79(2):129-32.
8. Solivan GA, Smith KJ, James WD. Cutaneous horn of the penis: its association with squamous cell carcinoma and HPV-16 infection. J Am Acad Dermatol. 1990;23(5 Pt 2):969-72.
9. Devi B, Dash M, Behera B, Puhan MR. Multiple koenen tumors: An uncommon presentation. Indian J Dermatol. 2011;56(6):773-5.
10. Patidar S. Combination Treatment of Periungual Warts. J Cutan Aesthet Surg. 2008; 1(1):23–24
11. Richert, B et al. Nail tumors. Clin Dermatol. 2013; 31(5):602-617.