Presenting a guide to effective management of pigmented nail lesions due to melanocytic processes, this author offers several case studies, reviews key clinical pointers for diagnosing longitudinal melanonychia and advocates the benefits of the nail matrix shave biopsy in detecting subungual melanoma.
Pigmented nail lesions represent a diagnostic challenge to podiatric clinicians, dermatologists and, in fact, all clinicians called upon to evaluate them. While mostly not a cause for concern, these lesions require a high index of suspicion to diagnose a potential or frankly malignant melanocytic process in as timely a manner as possible.
It is important to differentiate whether we are talking about pigmentation of nail plates due to melanocytic processes or discoloration of nail plates (for which there are a myriad of causes). These are two different things. Many journal articles and texts use the terms interchangeably. For the purposes of this article, I will differentiate nail plate discoloration from pigmentation due to melanocytic processes but will concentrate mostly on the latter.
There are many causes of nail plate discoloration (sometimes referred to as chromonychia or dyschromia). These include systemic diseases, dermatologic conditions (including infectious processes), inherited or congenital diseases, systemic or topical drugs, external chemical exposures, and occupational causes.1 In actuality, the breadth of causes and varied clinical presentations far exceeds the scope and intent of this article. Therefore, I will highlight only a few of these here.
It is also important to differentiate the origin of the clinical change in color. By origin, we may be referring to a specific substance, such as serum in yellow nail syndrome, hemoglobin in carbon monoxide poisoning (cherry red lunula) and melanin in adrenal insufficiency (longitudinal brown lines or diffuse brown).1 Additionally, the anatomic site of the nail unit may be different in different diseases. Specifically, discoloration can arise from or mainly involve the nail plate itself, the nail bed, the lunula (clinically visible part of the matrix) or the vascular bed underneath the nail apparatus.
In some instances, multiple sites may be involved. In other cases, the discoloring agent and anatomic site(s) are not clear or unknown. For example, with vitamin B12 deficiency, the causal agent and the anatomic site for the bluish-black discoloration are unknown.1 The brown-yellow appearance of nails in psoriasis is due to a blood glycoprotein in the nail plate.2 Reddish discoloration of the lunula may be visible in patients with heart failure, hepatic disease, rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease and carbon monoxide poisoning as previously mentioned.1,3,4
The list of causes or diseases associated with white discoloration of nails (leukonychia) is extensive and spans across systemic, inherited and infectious diseases as well as occupational causes.
Finally, nail discoloration can be congenital or acquired, transient or long-term. I encourage all readers to look at the literature, which is plentiful in this area, and avail themselves of the many useful compilations of this knowledge for easy reference, especially for the most common presentations of nail discoloration.
Key Insights On Nail Pigmentation Due To Melanocytic Processes
Melanocytic processes that originate in the nail matrix will impart a color change to the nail plate, varying from tan to brown to black in varying degrees. These changes usually take the shape of a longitudinal band or streak ranging from very narrow to involving the entire nail plate. We commonly refer to this as longitudinal melanonychia and sometimes as melanonychia striata longitudinalis. Some literature has referred to it as longitudinal pigmented bands.5 In some cases, there are multiple bands in the same nail, which also may vary in intensity of color and width. Additionally, presentations of longitudinal melanonychia can occur in multiple nails in the same patient (see photo above at the right).
Factors affecting the degree of pigmentation include the nail thickness and, most importantly, the location of the melanocytic lesion in the matrix. Lesions in the distal lunula will impart pigment in the ventral nail plate and proximal matrix lesions will impart pigment in the dorsal nail plate. Therefore, distal matrix lesions resulting in ventral plate pigmentation may appear faint clinically in comparison to the same process occurring in the proximal matrix (see the photo at the left).
A Closer Look At The Physiology
In addition to the location of the causative lesion, it is very important to understand the physiology of melanocytes in different locations. Melanocyte density in the nail unit definitely varies and will impact the clinical presentation of lesions.3 The quantity of melanocytes in nail units is much less than in normal skin.6 In the proximal nail matrix, melanocytes are mostly located in the lower second to fourth cell layers as opposed to the distal matrix, where they are more superficial in the first and second cell layers.6 Many proximal matrix melanocytes do not produce melanin but approximately 50 percent of distal matrix melanocytes do produce melanin. Melanocytes in the nail bed (distal to the lunula) are the least numerous and do not synthesize melanin, which explains why nail bed melanomas are often amelanotic and present a more difficult challenge for timely diagnosis.6,7
As recent literature confirms that acral melanoma, defined as melanoma involving the palms, soles and nail units, has a worse long-term prognosis than melanoma anywhere else on the skin, the challenge for podiatric clinicians becomes more complicated.8 Therefore, it is imperative that clinicians maintain a high index of suspicion to make a diagnosis as early as possible.
Pertinent Clinical Criteria For Diagnosing Longitudinal Melanonychia
Melanoma of the nail unit is relatively rare with an incidence of about 1 to 3.5 percent of melanoma in white-skinned individuals.5,9 It occurs equally in dark skinned and fair skinned individuals. Melanoma of the nail unit is the most common type of melanoma in deeply pigmented individuals and for this patient population, clinicians mostly diagnose this between the ages of 40 and 70.9 Further complicating this issue is the fact that in darker skinned individuals, longitudinal melanonychia is commonly visible in one or multiple nails. This is often referred to as ethnic or racial pigmentation, and is mostly benign. In addition, the clinical presentation of pigmented streaks arising from benign versus malignant lesions is not as easy to differentiate as melanoma elsewhere on the skin, for which the well-known ABCDE criteria is reliable for the most part.10
Baran and Dawber suggest the following clinical hints in attempting to distinguish between benign longitudinal melanonychia and longitudinal melanonychia derived from nail unit melanoma.5,11
There should be a heightened index of suspicion for melanoma when longitudinal melanonychia:
• begins in a single digit of a person during the sixth decade of life or later;
• develops suddenly in a previously normal nail plate;
• has changes including darkening or widening;
• occurs in either the thumb, index finger or hallux;
• occurs attendant to a history of digital trauma;
• occurs as a single band in the digit of a dark skinned individual, especially if it is in the thumb or hallux;
• appears with blurred as opposed to sharp lateral borders;
• occurs in a patient with a prior history of melanoma;
• occurs in a patient who has an increased risk for developing melanoma, such as a patient with a family history of melanoma or dysplastic nevus syndrome;
• is visible with nail dystrophy, destruction or partial nail plate absence.
Levit and colleagues, after reviewing the world literature on subungual melanoma, developed a set of criteria for the clinical detection of subungual melanoma in an attempt to enable clinicians and the public to identify longitudinal melanonychia that one should consider for biopsy.12 The result was the following ABCDEF of subungual melanoma.
A: Age. The range is 20 to 90 years with the peak in the fifth to seventh decade. Subungual melanoma is more common in African-American, Native American and Asian races.
B: Band. Pigment is brown-black. Breadth is greater than or equal to 3 mm. Border is irregular or blurred.
C: Change. There is a rapid increase in the size or growth rate of the band. Lack of change means a failure of nail dystrophy to improve with treatment.
D: Digit involved. The thumb is the most common, followed by the hallux and then the index finger. Occurrence in a single digit is more worrisome than multiple digits. Dominant hand involvement is more common than in the non-dominant hand.
E: Extension. Check for extension of the pigment onto the proximal or lateral nail fold (Hutchinson’s sign) or the free edge of the nail plate.
F: Family or personal history. Examine for previous melanoma or dysplastic nevus syndrome.
Sawada and colleagues proposed a classification of longitudinal melanonychia based on clinical and dermoscopic criteria.13 They graded pigmented bands as Types I, II or III, mostly based on depth of color of the band, background color, and the presence of pigment on periungual skin. The study goals were not only to identify suspicious bands at the in-situ stage but to also determine adequate follow-up of lesions they considered clinically and dermoscopically benign (Type I). Since these lesions did not have a biopsy, it represented a weakness in the study. In spite of that, lesions thought to be suspicious and receiving biopsy (Type III) showed a 100 percent incidence of in-situ melanoma. The researchers performed dermoscopic follow-up of all types for change.13 Over an average of five years, none of the Type I lesions showed any change and about 10 percent of the Type II lesions (five lesions) did show changes and had biopsies. Two of those lesions were melanoma in situ.
The authors conclude that dermoscopy of nail lesions can be very useful and recommended three-month follow-up for Type II lesions to look for changes.13 The ultimate point is to diagnose these lesions at the point they are still in situ and therefore theoretically curable if one removes them at that point.
Certainly, it is clear that these lesions represent a challenge for diagnosis. A recent study concluded that the overall accuracy of dermatologists in the diagnosis of nail matrix in-situ melanoma using dermoscopy and clinical criteria is low, confirming that biopsy is still the gold standard for diagnosis of these lesions.14
Since nail matrix biopsy has a risk of nail plate deformity or alteration in growth, many clinicians are hesitant to perform the procedure. At the Council for Nail Disorders Annual Scientific Meeting for the last few years, longitudinal melanonychia has been the subject of much discussion. Universally, dermatology nail experts from all parts of the world emphasize the difficulty of clinical evaluation of these lesions and the need for biopsy confirmation with even the slightest degree of clinical suspicion.
Emphasizing The Value Of The Nail Matrix Shave Biopsy In Detecting Subungual Melanoma
The nail matrix shave biopsy technique provides reliable specimens for diagnosis and minimal to no nail plate disturbance. In my opinion, the ease of this procedure coupled with its potential to be lifesaving should encourage all clinicians who evaluate these lesions to perform a biopsy at the slightest question on firm clinical grounds. When clinical findings are even questionable, the clinician should err on the side of caution and perform the biopsy or arrange to have it performed.
The tangential biopsy of the nail matrix involves direct visualization of the origin of pigment in the matrix and affords the ability to sample the upper layers of the epidermis, leaving the thickness of the matrix behind. This affords the advantage of not being a full thickness biopsy like a punch biopsy or a longitudinal elliptical excision. Since most longitudinal melanonychia is benign, the tangential biopsy is reliable and affords the best chance at minimizing nail deformity.
For the procedure, clinicians may utilize local anesthesia with a digital block. Hemostasis is very important so one must use a tourniquet. After anesthesia and prep, the surgeon may reflect the nail plate directly over the matrix, leaving the distal plate intact and using the reflected proximal nail as a biologic dressing after the procedure is over. Dermatologists commonly do this on fingernails. Alternately, one may remove the entire plate and use it as a dressing at the end.
Many dermatopathologists, however, prefer to send the reflected or removed nail for histologic analysis as sometimes the major diagnostic portion of the lesion pulls off with the plate. They caution that leaving it on the biopsy site may result in diagnostic error or even contribute to recurrence of the longitudinal band.15 I remove the entire plate as atraumatically as possible (since toenails are often thickened and sectioning is more difficult than in softer fingernails) and always include it with the matrix specimen fixed in formalin.
The photo at the left shows the matrix after reflection of the proximal nail plate. Note the excellent hemostatsis and clear visualization of the brown macule (red arrow) that gave rise to the longitudinal melanonychia (black arrow).
The photo at the right reveals how the surgeon scored the matrix brown macule in rectangular fashion and excised it tangentially. If the lesion is ultimately benign and completely removed, this effectively will clear the pigmented band. If biopsy reveals melanoma in situ, this procedure alone may be definitive. If the lesion is invasive melanoma, further surgery would be required anyway, thus illustrating the advantage of this technique.
In regard to the blade position for tangential excision of the matrix lesion, reflect the proximal fold off the matrix (red arrow). Reflect the nail plate laterally and hold it with forceps (blue arrow). Mark both the pigmented band and the matrix lesion for clarity. One does this because sometimes when removing the nail plate, the matrix lesion may hardly be visible. By marking the band and continuing in a straight line along the matrix, the location of the lesion is more certain. I always extend the band over the proximal fold before surgery begins for the same reason. Finally, one can use a 15 blade to section the matrix lesion. The specimen can be so thin as to actually see the steel blade beneath the tissue.16,17
Case Studies In Pigmented Nail Lesions
The first image in the left photo shows a pigmented band involving the lateral most aspect of the fourth toenail on the right foot. The patient had other pigmented bands and had reassurance that this one was most likely benign, and I decided to follow her clinically. Photographs are essential when doing this. Clinicians should also measure the width of the lesion.
In a six-month follow-up photo (see the second image in the left photo), one can clearly see that at the proximal most visible aspect of the band, there is some light brown extension of pigment extending medially that was not evident in the first evaluation. This is a clear indication for a biopsy. For medial and laterally based lesions, I prefer a cold steel type excision of the plate and some of the fold as it clears the lesion and guarantees that tissue needed for diagnosis will be included in the specimen.
In a six-month follow-up photo on the right, there was no appreciable change in the lesion. I decided to continue observation.
The next case highlights the approach to a Caucasian patient, who suddenly developed a new pigmented band. I consider this an indication for a biopsy.
The middle image in the left photo shows the immediate post-op view of a tangential shave of the same patient. I submitted the nail plate as I discussed previously. Note the skin marking on the proximal nail fold. The lesion was benign. One year after the biopsy, except for a small linear irregularity, the cosmetic result is very acceptable and certainly worth the peace of mind of the final diagnosis.
The subject of longitudinal melanonychia presents a vexing problem for all clinicians, mostly due to the fact that they are overwhelmingly benign but potentially fatal if they are caused by subungual melanoma. Since early diagnosis is critical, the clinician must be decisive on the question of biopsy on firm clinical grounds and be more likely to perform a biopsy when even a small doubt exists. I have presented criteria and clues for a heightened index of suspicion. The tangential shave biopsy is an excellent choice of procedure for these lesions, both for early subtle diagnosis and better cosmetic results. It is my hope that readers will become much more familiar with this entity and, more importantly, confident and decisive in its management.
Dr. Markinson is the Chief of Podiatric Medicine and Surgery in the Leni and Peter W. May Department of Orthopedic Surgery at Mount Sinai School of Medicine in New York City.
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9. Available at www.dermnetnz.org/hair-nails-sweat/melanoma-nailunit.html .
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15. Beth Ruben, MD, personal communication.
16. Di Chiacchio N, Loureiro WR, Michalany NS, Kezam Gabriel FV. Tangential biopsy thickness versus lesion depth in longitudinal melanonychia: a pilot study. Dermatol Res Pract. 2012; 353864.
17. Bertrand Richert, MD, personal communication.