The diagnosis of nail pigmentation remains a significant challenge for dermatologists. Since this topic was addressed in a 2004 article1 in The Dermatologist, there have been several additional studies that offer direction to help clinicians be more confidant when presented with the challenge.2,3 At the core of the recommendations remains the question of whether or not to perform a diagnostic procedure. Certainly it is not appropriate to biopsy all nail pigmentation.4 Some key strategies will be suggested when confronted with pigmentation of the nail unit and some pearls of dermoscopy to help with the decision-making process.
The incidence of melanonychia varies according to skin pigmentation with percentages that may be a high as 77% in African Americans age 20 years and older and almost 100% in this population age 50 and older but varying with depth of skin color, 10% to 20% in Asians, and about 1% in whites. Specifically, melanonychia striata, or longitudinal melanonychia (LM), is characterized as either a dark brown or brown–black longitudinal band on a toenail or fingernail.5,6 The 4 most common variants of LM are melanocytic nevus, melanotic macule, melanocytic activation and melanoma in situ (Figures 1 - 3). Although there have been reports of melanocytic nevus and melanotic macules progressing to melanomas, a primary diagnosis of melanoma in situ is of particular clinical concern.5,6 Thus, clinicians must be especially cautious when diagnosing LM in order to rule out malignancy.
Commonly, a melanocyte-related lesion of LM may be a melanotic macule, a junctional nevus or in situ melanoma. Histologically, a melanotic macule exhibits melanin pigment within the matrix epithelium but no melanocytic proliferation. A junctional nevus shows discrete nests of melanocytes along the base of the matrix epithelium. Melanoma in situ exhibits an asymmetric proliferation of mainly singly displaced melanocytes within the matrix epithelium.7 To properly evaluate the pigmented lesion, the clinician must often perform an appropriate biopsy. In order to do this, it is critical to understand the origin of the pigment in LM.3,8,9
LM lesions have their origin in the nail matrix.5,6 Although the proximal nail matrix contains melanocytes, they are mostly dormant. The biopsy must usually be taken from the distal nail matrix, which contains most of the melanocytes with active melanin synthesis. Depending on the location of the band, biopsy of the nail matrix may be performed using a punch biopsy or a transverse elliptical or shave biopsy.10 The affected area can generally be biopsied with low risk of permanent nail dystrophy especially if taken from the distal matrix, which forms the undersurface of the nail plate. High-quality biopsy techniques are of utmost importance to permit correct orientation, embedding and sectioning of the specimen. The specimen should include both nail matrix and plate.2,9,11
When a patient presents with pigmentation, the first question should be to try to determine how long it has been present and whether they have some insight into the origin.9 Some patients will report that they know they traumatized the nail. While this does not allow the clinician to breathe a sigh of relief as blood under the nail plate can sometimes mask other problems, at least it is a starting point. The next step is to use a dermatoscope to evaluate the pigmentation. Onychoscopy can quickly give you a sense if the pigmentation is truly from trauma or true melanonychia, which is pigment in the nail plate that is caused by melanin.12 Onychoscopy has some limitations because as opposed to dermoscopy, the clinician is seeing the pigment in the nail plate, which may not be the origin of the pigment. Immersion gel has been recommended as the best medium to evaluate the nail plate with direct contact non-polarized light.13 One caveat is during nail matrix and nail bed dermoscopy after avulsion of the nail plate, polarized light may be used.14 One of the significant differences between onychoscopy and dermoscopy is that the nail plate can obstruct visualization of the nail pigment. Therefore, onychoscopy is helpful, but often deemed a bit less precise.
The following points can be considered:
• Blood is recognized by its round globules and a filamentous distal end.3,14
• Color of the band indicates whether it is caused by activation (gray bands) or proliferation (brown–black bands). Bands that are caused by activation are benign and do not necessarily require pathological evaluation.3,14
•
Brown–black bands with a regular pattern: Individual lines that have similar shades of color, with similar thickness, are regularly spaced and are parallel, are a sign of benign proliferation.3,14
• Brown–black bands with an irregular pattern: Lines that vary in color (and not only in shades of the same color), that are irregularly spaced, that have different thicknesses and that may lose their parallelism and cross each other are suggestive of malignant proliferation and should be biopsied and removed.
These criteria are not valid for children, in whom benign lesions often have an irregular pattern. The criteria are also often difficult to apply to adult patients.11,15
• The micro-Hutchinson sign (ie, pigmentation of the cuticle that is only observed through dermatoscopy and not clinically) can be visualized by dermatoscopy and is usually indicative of malignancy.16
•Melanin granular inclusions (<0.1 mm in diameter; may be more adequately seen under high magnification) in cases of melanocyte proliferation.
Dermatoscopy of the free edge of the nail plate can assess whether the origin of the nail plate pigment lies in the proximal or distal matrix. If the pigment is located on the upper portion of the free edge, then it is produced in the proximal matrix; if it is in the lower portion, its origin lies on the distal matrix (as is more commonly observed). If doubt persists, a nail clipping and Fontana-Mason staining may be used.
Patterns in Longitudinal Melanonychia
In a review of 100 cases of LM with intraoperative nail dermatoscopy, the following patterns were noted13,14:
• A gray pattern is suggestive of melanocytic activation.
• A regular brown pattern is suggestive of benign melanocytic hyperplasia, although it is also observed in some cases of melanoma.
• A regular brown pattern with globules and blotches is suggestive of melanocytic nevi.
• An irregular pattern is suggestive of melanoma.
In addition, the ABCDEF mnemonic still applies:
• A stands for the age and race of afflicted patients (African American, Native American and Asian American). Subungual melanoma (SM) has been reported in ages ranging from 20 to 90 with peak incidence in the fifth to seventh decades. Although cutaneous melanomas are rare in darker skin complexions, melanoma occurs in the acral area of these populations at a disproportionally higher rate. SM comprises 15% to 20% of all melanomas in African Americans, 33% in Native Americans and 10% to 31% in Asians.17-19
• B stands for the brown or black band most commonly seen in melanoma in-situ.20 In addition, a lesion with a breadth of 3 mm or more or a blurred variegated border increases the likelihood of melanoma.
• C points the clinician to a recent pattern of change in the nail morphology. If the lesion has become wider, “streakier” or has darkened significantly in a short period of time, this is a definite cause for concern.
• D represents the digit involved. SM more commonly involves the thumb, hallux or index finger of the dominant hand. If more than 1 digit is involved, this may decrease the suspicion of SM and point to some of the previously mentioned exogenous causes or be simply due to pigmented nail bands of ethnic origin.
• E stands for Hutchinson’s sign, the extension of pigment to involve the cuticle or proximal and lateral nail fold. Hutchinson’s sign corresponds to the radial growth phase of SM, and is therefore a very consistent indicator of SM. But, Hutchinson’s sign is not always pathonogmonic for SM. There are certain variants called pseudo-Hutchinson’s sign that occur in the absence of SM. These variants do not negate the importance of Hutchinson’s sign. However, they oblige the clinician to consider diagnostic possibilities other than SM such as ethnic nail fold hyperpigmentation.
• F urges the physician to get a complete family history paying specific attention to a history of dysplastic nevi or previous melanomas.
Di Chiacchio et al3 were able to emphasize the difficulty of harnessing the necessary diagnostic tools by illustrating that even nail experts were not able to diagnose a melanoma in situ with great accuracy using clinical criteria, the ABCDEF mnemonic or dermoscopy of the nail plate. The only evaluation that did increase diagnostic ability was intraoperative dermoscopy. Ideally, we want to be able to rule out melanoma with some confidence prior to surgical intervention.
In addition to trauma, other external sources of nail pigmentation include fungal infection (onychomycosis) caused by Aspergillus or Scopulariopsis, and bacterial infections with persistent Pseudomonas aeriginosa; these are important non-melanocytic origins of dyschromia. In cases of onychomycosis, the clinician should not overlook the possibility of melanoma and fungal comorbidity.21,22 In addition, certain drugs including minocycline, cancer chemotherapy agents and antimalarial drugs may cause nail dyschromia. However, in these situations, the pigmentation often involves more than 1 nail and a careful patient history may place melanoma lower on the list of differential diagnosis.
Even with succinct acronyms for risk factors, the burden of proof is still in the hands of the physician to decide which patients to biopsy. LM in a pediatric patient has been shown to generally be a nevus, while a melanotic macule is the most likely diagnosis if the pigment is pale, homogenous and pigmentation of the proximal nail fold (Hutchinson’s sign) is absent. Although most melanotic lesions are histologically diagnosed to be either melanotic macule or melanocytic nevus, a physician must never be overconfident in the physical examination that a confirmatory diagnosis can be made in the absence of a biopsy. In addition, some studies have shown evidence of benign LM progressing to melanoma in-situ after several years.7,16
Therefore, even when the histologic finding is benign, a patient must be educated to have regular dermatologic observation to check the pigmented lesion for growth or change in the event it is not completely removed. Particularly in cases where the most common discoloration, subungual hematoma, is suspected a clinician must prove that blood rather than melanin is responsible for the black appearance. There have also been incidences of LM demonstrating spontaneous regression or disappearance, but this is unusual and lesions should not be merely observed with the hope that they will simply go away.
While there have been reported cases of nail melanoma in pediatric patients, there is ongoing controversy as to whether those presenting with LM striata should be biopsied. SM is extremely rare in children, with most cases of LM being diagnosed as a melanocytic nevus. Of reported cases of pediatric LM, less than 6% have been proven histologically to be insitu melanomas. Thus, when deciding whether to perform a biopsy on a pediatric patient it is important to consider the likelihood of a SM or a LM that could progress to SM over time. Performing the biopsy runs the risk of causing a permanent nail dystrophy and unnecessary pain and trauma for the child. If biopsy is the chosen course, some clinicians support an excisional biopsy that removes the entire lesion thereby increasing the diagnostic yield of the specimen.12 It is important that the clinician make this decision along with the parents after thorough discussion of the risks.
Subungual Melanoma Treatment
Once the diagnosis of SM has been confirmed histologically, a thoughtful clinical course of action must be pursued. Prompt, early treatment often allows a more conservative surgery to be undertaken. Treatment modalities range from Mohs micrographic surgery to proximal interphalangeal amputation.2,23 Patients also often receive adjuvant chemotherapy either systemically or in the isolated limb. One study showed that limited excision with partial resection of the distal phalanx only and Moh’s surgery to ensure tumor-free margins yielded a more cosmetically acceptable result and had no negative effect on prognosis. For early lesions, local excision with complete removal of all nail unit structures followed by skin grafting has proven successful. Lymph node dissection is still rather controversial as no study has conclusively shown that it improves survival.24
Overall, LM can be managed appropriately by gathering a complete history from patients and considering all of its potential causes. Although SM may have a poor prognosis, clinicians should feel confident when confronted with patients with LM and use all of the diagnostic tools at their disposal. It is essential to stress the importance of the pathologist’s role in the diagnosis and careful communication with the clinician is critical when biopsies are taken. Nail biopsies should not be intimidating; a clinician must feel confident in arriving at a diagnosis of the pigmented lesion before it is too late.
Dr. Lamb is the director of the Westside Mount Sinai Dermatology Faculty Practice in New York, NY.
Dr. Scher is clinical professor of dermatology at Weill Cornell Medical College in New York, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Lamb A, BA, Scher RK, Husain S. The dilemma of nail pigmentation. The Dermatologist. 2004;12(11).
2. Ruben BS. Pigmented lesions of the nail unit. Semin Cutan Med Surg. 2015;34(2):101-108.
3. Di Chiacchio ND, Farias DC, Piraccini BM, et al. Consensus on melanonychia nail plate dermoscopy. An Bras Dermatol. 2013;88(2):309-313.
4. Ronger S, Touzet S, Ligeron C, et al. Dermoscopic examination of nail pigmentation. Arch Dermatol. 2002;138(10):1327-1333.
5. Norton L. Tumors. In: Scher RK, Daniel RC III, eds. Nails: Therapy, Diagnosis, Surgery. St. Louis, MO: W.B. Saunders Company; 1997.
6. Baran RD, Dawber R, de Berker D, Haneke E, Tosti A, eds. Baran and Dawber’s Diseases of the Nails and Their Management. Oxford, United Kingdom: Blackwell Science; 2001.
7. Lee DY. Dermatopathology: SY07-2 subungual melanocytic lesions. Pathology. 2014;46 Suppl 2:S12.
8. Koga H, Saida T, Uhara H. Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia. J Dermatol. 2011;38(1):45-52.
9. Goktay F, Gunes P, Yasar S, Guder H, Aytekin S. New observations of intraoperative dermoscopic features of the nail matrix and bed in longitudinal melanonychia. Int J Dermatol. Published online ahead of print June 20, 2015.
10. Haneke E, Baran R. Longitudinal melanonychia. Dermatol Surg. 2001;27(6):580-584.
11. 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):773-779.
12. Richert B, Theunis A, Norrenberg S, Andre J. Tangential excision of pigmented nail matrix lesions responsible for longitudinal melanonychia: evaluation of the technique on a series of 30 patients. J Am Acad Dermatol. 2013;69(1):96-104.
13. Di Chiacchio N, Hirata SH, Enokihara MY, Michalany NS, Fabbrocini G, Tosti A. Dermatologists’ accuracy in early diagnosis of melanoma of the nail matrix. Arch Dermatol. 2010;146(4):382-387.
14. Hirata SH, Yamada S, Enokihara MY, et al. Patterns of nail matrix and bed of longitudinal melanonychia by intraoperative dermatoscopy. J Am Acad Dermatol. 2011;65(2):297-303.
15. Iorizzo M, Tosti A, Di Chiacchio N, et al. Nail melanoma in children: differential diagnosis and management. Dermatol Surg. 2008;34(7):974-978.
16. Bonamonte D, Arpaia N, Cimmino A, Vestita M. In situ melanoma of the nail unit presenting as a rapid growing longitudinal melanonychia in a 9-year-old white boy. Dermatol Surg. 2014;40(10):1154-1157.
17. Finley RK, 3rd, Driscoll DL, Blumenson LE, Karakousis CP. Subungual melanoma: an eighteen-year review. Surgery. 1994;116(1):96-100.
18. Kato T, Suetake T, Sugiyama Y, Tabata N, Tagami H. Epidemiology and prognosis of subungual melanoma in 34 Japanese patients. Br J Dermatol. 1996;134(3):383-387.
19. Baran R, Kechijian P. Longitudinal melanonychia (melanonychia striata): diagnosis and management. J Am Acad Dermatol. 1989;21(6):1165-1175.
20. Kato T, Usuba Y, Takematsu H, et al. A rapidly growing pigmented nail streak resulting in diffuse melanosis of the nail. A possible sign of subungual melanoma in situ. Cancer. 1989;64(10):2191-2197.
21. Perrin C, Baran R. Longitudinal melanonychia caused by trichophyton rubrum. Histochemical and ultrastructural study of two cases. J Am Acad Dermatol. 1994;31(2 Pt 2):311-316.
22. Finch J, Arenas R, Baran R. Fungal melanonychia. J Am Acad Dermatol. 2012;66(5):830-841.
23. High WA, Quirey RA, Guillen DR, Munoz G, Taylor RS. Presentation, histopathologic findings, and clinical outcomes in 7 cases of melanoma in situ of the nail unit. Arch Dermatol. 2004;140(9):1102-1106.
24. Moerhrle M, Metzger S, Schippert W et al. “Functional” Surgery in subungal melanoma. Dermatol Surg 2003;29:366-374.
The diagnosis of nail pigmentation remains a significant challenge for dermatologists. Since this topic was addressed in a 2004 article1 in The Dermatologist, there have been several additional studies that offer direction to help clinicians be more confidant when presented with the challenge.2,3 At the core of the recommendations remains the question of whether or not to perform a diagnostic procedure. Certainly it is not appropriate to biopsy all nail pigmentation.4 Some key strategies will be suggested when confronted with pigmentation of the nail unit and some pearls of dermoscopy to help with the decision-making process.
The incidence of melanonychia varies according to skin pigmentation with percentages that may be a high as 77% in African Americans age 20 years and older and almost 100% in this population age 50 and older but varying with depth of skin color, 10% to 20% in Asians, and about 1% in whites. Specifically, melanonychia striata, or longitudinal melanonychia (LM), is characterized as either a dark brown or brown–black longitudinal band on a toenail or fingernail.5,6 The 4 most common variants of LM are melanocytic nevus, melanotic macule, melanocytic activation and melanoma in situ (Figures 1 - 3). Although there have been reports of melanocytic nevus and melanotic macules progressing to melanomas, a primary diagnosis of melanoma in situ is of particular clinical concern.5,6 Thus, clinicians must be especially cautious when diagnosing LM in order to rule out malignancy.
Commonly, a melanocyte-related lesion of LM may be a melanotic macule, a junctional nevus or in situ melanoma. Histologically, a melanotic macule exhibits melanin pigment within the matrix epithelium but no melanocytic proliferation. A junctional nevus shows discrete nests of melanocytes along the base of the matrix epithelium. Melanoma in situ exhibits an asymmetric proliferation of mainly singly displaced melanocytes within the matrix epithelium.7 To properly evaluate the pigmented lesion, the clinician must often perform an appropriate biopsy. In order to do this, it is critical to understand the origin of the pigment in LM.3,8,9
LM lesions have their origin in the nail matrix.5,6 Although the proximal nail matrix contains melanocytes, they are mostly dormant. The biopsy must usually be taken from the distal nail matrix, which contains most of the melanocytes with active melanin synthesis. Depending on the location of the band, biopsy of the nail matrix may be performed using a punch biopsy or a transverse elliptical or shave biopsy.10 The affected area can generally be biopsied with low risk of permanent nail dystrophy especially if taken from the distal matrix, which forms the undersurface of the nail plate. High-quality biopsy techniques are of utmost importance to permit correct orientation, embedding and sectioning of the specimen. The specimen should include both nail matrix and plate.2,9,11
When a patient presents with pigmentation, the first question should be to try to determine how long it has been present and whether they have some insight into the origin.9 Some patients will report that they know they traumatized the nail. While this does not allow the clinician to breathe a sigh of relief as blood under the nail plate can sometimes mask other problems, at least it is a starting point. The next step is to use a dermatoscope to evaluate the pigmentation. Onychoscopy can quickly give you a sense if the pigmentation is truly from trauma or true melanonychia, which is pigment in the nail plate that is caused by melanin.12 Onychoscopy has some limitations because as opposed to dermoscopy, the clinician is seeing the pigment in the nail plate, which may not be the origin of the pigment. Immersion gel has been recommended as the best medium to evaluate the nail plate with direct contact non-polarized light.13 One caveat is during nail matrix and nail bed dermoscopy after avulsion of the nail plate, polarized light may be used.14 One of the significant differences between onychoscopy and dermoscopy is that the nail plate can obstruct visualization of the nail pigment. Therefore, onychoscopy is helpful, but often deemed a bit less precise.
The following points can be considered:
• Blood is recognized by its round globules and a filamentous distal end.3,14
• Color of the band indicates whether it is caused by activation (gray bands) or proliferation (brown–black bands). Bands that are caused by activation are benign and do not necessarily require pathological evaluation.3,14
•
Brown–black bands with a regular pattern: Individual lines that have similar shades of color, with similar thickness, are regularly spaced and are parallel, are a sign of benign proliferation.3,14
• Brown–black bands with an irregular pattern: Lines that vary in color (and not only in shades of the same color), that are irregularly spaced, that have different thicknesses and that may lose their parallelism and cross each other are suggestive of malignant proliferation and should be biopsied and removed.
These criteria are not valid for children, in whom benign lesions often have an irregular pattern. The criteria are also often difficult to apply to adult patients.11,15
• The micro-Hutchinson sign (ie, pigmentation of the cuticle that is only observed through dermatoscopy and not clinically) can be visualized by dermatoscopy and is usually indicative of malignancy.16
•Melanin granular inclusions (<0.1 mm in diameter; may be more adequately seen under high magnification) in cases of melanocyte proliferation.
Dermatoscopy of the free edge of the nail plate can assess whether the origin of the nail plate pigment lies in the proximal or distal matrix. If the pigment is located on the upper portion of the free edge, then it is produced in the proximal matrix; if it is in the lower portion, its origin lies on the distal matrix (as is more commonly observed). If doubt persists, a nail clipping and Fontana-Mason staining may be used.
Patterns in Longitudinal Melanonychia
In a review of 100 cases of LM with intraoperative nail dermatoscopy, the following patterns were noted13,14:
• A gray pattern is suggestive of melanocytic activation.
• A regular brown pattern is suggestive of benign melanocytic hyperplasia, although it is also observed in some cases of melanoma.
• A regular brown pattern with globules and blotches is suggestive of melanocytic nevi.
• An irregular pattern is suggestive of melanoma.
In addition, the ABCDEF mnemonic still applies:
• A stands for the age and race of afflicted patients (African American, Native American and Asian American). Subungual melanoma (SM) has been reported in ages ranging from 20 to 90 with peak incidence in the fifth to seventh decades. Although cutaneous melanomas are rare in darker skin complexions, melanoma occurs in the acral area of these populations at a disproportionally higher rate. SM comprises 15% to 20% of all melanomas in African Americans, 33% in Native Americans and 10% to 31% in Asians.17-19
• B stands for the brown or black band most commonly seen in melanoma in-situ.20 In addition, a lesion with a breadth of 3 mm or more or a blurred variegated border increases the likelihood of melanoma.
• C points the clinician to a recent pattern of change in the nail morphology. If the lesion has become wider, “streakier” or has darkened significantly in a short period of time, this is a definite cause for concern.
• D represents the digit involved. SM more commonly involves the thumb, hallux or index finger of the dominant hand. If more than 1 digit is involved, this may decrease the suspicion of SM and point to some of the previously mentioned exogenous causes or be simply due to pigmented nail bands of ethnic origin.
• E stands for Hutchinson’s sign, the extension of pigment to involve the cuticle or proximal and lateral nail fold. Hutchinson’s sign corresponds to the radial growth phase of SM, and is therefore a very consistent indicator of SM. But, Hutchinson’s sign is not always pathonogmonic for SM. There are certain variants called pseudo-Hutchinson’s sign that occur in the absence of SM. These variants do not negate the importance of Hutchinson’s sign. However, they oblige the clinician to consider diagnostic possibilities other than SM such as ethnic nail fold hyperpigmentation.
• F urges the physician to get a complete family history paying specific attention to a history of dysplastic nevi or previous melanomas.
Di Chiacchio et al3 were able to emphasize the difficulty of harnessing the necessary diagnostic tools by illustrating that even nail experts were not able to diagnose a melanoma in situ with great accuracy using clinical criteria, the ABCDEF mnemonic or dermoscopy of the nail plate. The only evaluation that did increase diagnostic ability was intraoperative dermoscopy. Ideally, we want to be able to rule out melanoma with some confidence prior to surgical intervention.
In addition to trauma, other external sources of nail pigmentation include fungal infection (onychomycosis) caused by Aspergillus or Scopulariopsis, and bacterial infections with persistent Pseudomonas aeriginosa; these are important non-melanocytic origins of dyschromia. In cases of onychomycosis, the clinician should not overlook the possibility of melanoma and fungal comorbidity.21,22 In addition, certain drugs including minocycline, cancer chemotherapy agents and antimalarial drugs may cause nail dyschromia. However, in these situations, the pigmentation often involves more than 1 nail and a careful patient history may place melanoma lower on the list of differential diagnosis.
Even with succinct acronyms for risk factors, the burden of proof is still in the hands of the physician to decide which patients to biopsy. LM in a pediatric patient has been shown to generally be a nevus, while a melanotic macule is the most likely diagnosis if the pigment is pale, homogenous and pigmentation of the proximal nail fold (Hutchinson’s sign) is absent. Although most melanotic lesions are histologically diagnosed to be either melanotic macule or melanocytic nevus, a physician must never be overconfident in the physical examination that a confirmatory diagnosis can be made in the absence of a biopsy. In addition, some studies have shown evidence of benign LM progressing to melanoma in-situ after several years.7,16
Therefore, even when the histologic finding is benign, a patient must be educated to have regular dermatologic observation to check the pigmented lesion for growth or change in the event it is not completely removed. Particularly in cases where the most common discoloration, subungual hematoma, is suspected a clinician must prove that blood rather than melanin is responsible for the black appearance. There have also been incidences of LM demonstrating spontaneous regression or disappearance, but this is unusual and lesions should not be merely observed with the hope that they will simply go away.
While there have been reported cases of nail melanoma in pediatric patients, there is ongoing controversy as to whether those presenting with LM striata should be biopsied. SM is extremely rare in children, with most cases of LM being diagnosed as a melanocytic nevus. Of reported cases of pediatric LM, less than 6% have been proven histologically to be insitu melanomas. Thus, when deciding whether to perform a biopsy on a pediatric patient it is important to consider the likelihood of a SM or a LM that could progress to SM over time. Performing the biopsy runs the risk of causing a permanent nail dystrophy and unnecessary pain and trauma for the child. If biopsy is the chosen course, some clinicians support an excisional biopsy that removes the entire lesion thereby increasing the diagnostic yield of the specimen.12 It is important that the clinician make this decision along with the parents after thorough discussion of the risks.
Subungual Melanoma Treatment
Once the diagnosis of SM has been confirmed histologically, a thoughtful clinical course of action must be pursued. Prompt, early treatment often allows a more conservative surgery to be undertaken. Treatment modalities range from Mohs micrographic surgery to proximal interphalangeal amputation.2,23 Patients also often receive adjuvant chemotherapy either systemically or in the isolated limb. One study showed that limited excision with partial resection of the distal phalanx only and Moh’s surgery to ensure tumor-free margins yielded a more cosmetically acceptable result and had no negative effect on prognosis. For early lesions, local excision with complete removal of all nail unit structures followed by skin grafting has proven successful. Lymph node dissection is still rather controversial as no study has conclusively shown that it improves survival.24
Overall, LM can be managed appropriately by gathering a complete history from patients and considering all of its potential causes. Although SM may have a poor prognosis, clinicians should feel confident when confronted with patients with LM and use all of the diagnostic tools at their disposal. It is essential to stress the importance of the pathologist’s role in the diagnosis and careful communication with the clinician is critical when biopsies are taken. Nail biopsies should not be intimidating; a clinician must feel confident in arriving at a diagnosis of the pigmented lesion before it is too late.
Dr. Lamb is the director of the Westside Mount Sinai Dermatology Faculty Practice in New York, NY.
Dr. Scher is clinical professor of dermatology at Weill Cornell Medical College in New York, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Lamb A, BA, Scher RK, Husain S. The dilemma of nail pigmentation. The Dermatologist. 2004;12(11).
2. Ruben BS. Pigmented lesions of the nail unit. Semin Cutan Med Surg. 2015;34(2):101-108.
3. Di Chiacchio ND, Farias DC, Piraccini BM, et al. Consensus on melanonychia nail plate dermoscopy. An Bras Dermatol. 2013;88(2):309-313.
4. Ronger S, Touzet S, Ligeron C, et al. Dermoscopic examination of nail pigmentation. Arch Dermatol. 2002;138(10):1327-1333.
5. Norton L. Tumors. In: Scher RK, Daniel RC III, eds. Nails: Therapy, Diagnosis, Surgery. St. Louis, MO: W.B. Saunders Company; 1997.
6. Baran RD, Dawber R, de Berker D, Haneke E, Tosti A, eds. Baran and Dawber’s Diseases of the Nails and Their Management. Oxford, United Kingdom: Blackwell Science; 2001.
7. Lee DY. Dermatopathology: SY07-2 subungual melanocytic lesions. Pathology. 2014;46 Suppl 2:S12.
8. Koga H, Saida T, Uhara H. Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia. J Dermatol. 2011;38(1):45-52.
9. Goktay F, Gunes P, Yasar S, Guder H, Aytekin S. New observations of intraoperative dermoscopic features of the nail matrix and bed in longitudinal melanonychia. Int J Dermatol. Published online ahead of print June 20, 2015.
10. Haneke E, Baran R. Longitudinal melanonychia. Dermatol Surg. 2001;27(6):580-584.
11. 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):773-779.
12. Richert B, Theunis A, Norrenberg S, Andre J. Tangential excision of pigmented nail matrix lesions responsible for longitudinal melanonychia: evaluation of the technique on a series of 30 patients. J Am Acad Dermatol. 2013;69(1):96-104.
13. Di Chiacchio N, Hirata SH, Enokihara MY, Michalany NS, Fabbrocini G, Tosti A. Dermatologists’ accuracy in early diagnosis of melanoma of the nail matrix. Arch Dermatol. 2010;146(4):382-387.
14. Hirata SH, Yamada S, Enokihara MY, et al. Patterns of nail matrix and bed of longitudinal melanonychia by intraoperative dermatoscopy. J Am Acad Dermatol. 2011;65(2):297-303.
15. Iorizzo M, Tosti A, Di Chiacchio N, et al. Nail melanoma in children: differential diagnosis and management. Dermatol Surg. 2008;34(7):974-978.
16. Bonamonte D, Arpaia N, Cimmino A, Vestita M. In situ melanoma of the nail unit presenting as a rapid growing longitudinal melanonychia in a 9-year-old white boy. Dermatol Surg. 2014;40(10):1154-1157.
17. Finley RK, 3rd, Driscoll DL, Blumenson LE, Karakousis CP. Subungual melanoma: an eighteen-year review. Surgery. 1994;116(1):96-100.
18. Kato T, Suetake T, Sugiyama Y, Tabata N, Tagami H. Epidemiology and prognosis of subungual melanoma in 34 Japanese patients. Br J Dermatol. 1996;134(3):383-387.
19. Baran R, Kechijian P. Longitudinal melanonychia (melanonychia striata): diagnosis and management. J Am Acad Dermatol. 1989;21(6):1165-1175.
20. Kato T, Usuba Y, Takematsu H, et al. A rapidly growing pigmented nail streak resulting in diffuse melanosis of the nail. A possible sign of subungual melanoma in situ. Cancer. 1989;64(10):2191-2197.
21. Perrin C, Baran R. Longitudinal melanonychia caused by trichophyton rubrum. Histochemical and ultrastructural study of two cases. J Am Acad Dermatol. 1994;31(2 Pt 2):311-316.
22. Finch J, Arenas R, Baran R. Fungal melanonychia. J Am Acad Dermatol. 2012;66(5):830-841.
23. High WA, Quirey RA, Guillen DR, Munoz G, Taylor RS. Presentation, histopathologic findings, and clinical outcomes in 7 cases of melanoma in situ of the nail unit. Arch Dermatol. 2004;140(9):1102-1106.
24. Moerhrle M, Metzger S, Schippert W et al. “Functional” Surgery in subungal melanoma. Dermatol Surg 2003;29:366-374.
The diagnosis of nail pigmentation remains a significant challenge for dermatologists. Since this topic was addressed in a 2004 article1 in The Dermatologist, there have been several additional studies that offer direction to help clinicians be more confidant when presented with the challenge.2,3 At the core of the recommendations remains the question of whether or not to perform a diagnostic procedure. Certainly it is not appropriate to biopsy all nail pigmentation.4 Some key strategies will be suggested when confronted with pigmentation of the nail unit and some pearls of dermoscopy to help with the decision-making process.
The incidence of melanonychia varies according to skin pigmentation with percentages that may be a high as 77% in African Americans age 20 years and older and almost 100% in this population age 50 and older but varying with depth of skin color, 10% to 20% in Asians, and about 1% in whites. Specifically, melanonychia striata, or longitudinal melanonychia (LM), is characterized as either a dark brown or brown–black longitudinal band on a toenail or fingernail.5,6 The 4 most common variants of LM are melanocytic nevus, melanotic macule, melanocytic activation and melanoma in situ (Figures 1 - 3). Although there have been reports of melanocytic nevus and melanotic macules progressing to melanomas, a primary diagnosis of melanoma in situ is of particular clinical concern.5,6 Thus, clinicians must be especially cautious when diagnosing LM in order to rule out malignancy.
Commonly, a melanocyte-related lesion of LM may be a melanotic macule, a junctional nevus or in situ melanoma. Histologically, a melanotic macule exhibits melanin pigment within the matrix epithelium but no melanocytic proliferation. A junctional nevus shows discrete nests of melanocytes along the base of the matrix epithelium. Melanoma in situ exhibits an asymmetric proliferation of mainly singly displaced melanocytes within the matrix epithelium.7 To properly evaluate the pigmented lesion, the clinician must often perform an appropriate biopsy. In order to do this, it is critical to understand the origin of the pigment in LM.3,8,9
LM lesions have their origin in the nail matrix.5,6 Although the proximal nail matrix contains melanocytes, they are mostly dormant. The biopsy must usually be taken from the distal nail matrix, which contains most of the melanocytes with active melanin synthesis. Depending on the location of the band, biopsy of the nail matrix may be performed using a punch biopsy or a transverse elliptical or shave biopsy.10 The affected area can generally be biopsied with low risk of permanent nail dystrophy especially if taken from the distal matrix, which forms the undersurface of the nail plate. High-quality biopsy techniques are of utmost importance to permit correct orientation, embedding and sectioning of the specimen. The specimen should include both nail matrix and plate.2,9,11
When a patient presents with pigmentation, the first question should be to try to determine how long it has been present and whether they have some insight into the origin.9 Some patients will report that they know they traumatized the nail. While this does not allow the clinician to breathe a sigh of relief as blood under the nail plate can sometimes mask other problems, at least it is a starting point. The next step is to use a dermatoscope to evaluate the pigmentation. Onychoscopy can quickly give you a sense if the pigmentation is truly from trauma or true melanonychia, which is pigment in the nail plate that is caused by melanin.12 Onychoscopy has some limitations because as opposed to dermoscopy, the clinician is seeing the pigment in the nail plate, which may not be the origin of the pigment. Immersion gel has been recommended as the best medium to evaluate the nail plate with direct contact non-polarized light.13 One caveat is during nail matrix and nail bed dermoscopy after avulsion of the nail plate, polarized light may be used.14 One of the significant differences between onychoscopy and dermoscopy is that the nail plate can obstruct visualization of the nail pigment. Therefore, onychoscopy is helpful, but often deemed a bit less precise.
The following points can be considered:
• Blood is recognized by its round globules and a filamentous distal end.3,14
• Color of the band indicates whether it is caused by activation (gray bands) or proliferation (brown–black bands). Bands that are caused by activation are benign and do not necessarily require pathological evaluation.3,14
•
Brown–black bands with a regular pattern: Individual lines that have similar shades of color, with similar thickness, are regularly spaced and are parallel, are a sign of benign proliferation.3,14
• Brown–black bands with an irregular pattern: Lines that vary in color (and not only in shades of the same color), that are irregularly spaced, that have different thicknesses and that may lose their parallelism and cross each other are suggestive of malignant proliferation and should be biopsied and removed.
These criteria are not valid for children, in whom benign lesions often have an irregular pattern. The criteria are also often difficult to apply to adult patients.11,15
• The micro-Hutchinson sign (ie, pigmentation of the cuticle that is only observed through dermatoscopy and not clinically) can be visualized by dermatoscopy and is usually indicative of malignancy.16
•Melanin granular inclusions (<0.1 mm in diameter; may be more adequately seen under high magnification) in cases of melanocyte proliferation.
Dermatoscopy of the free edge of the nail plate can assess whether the origin of the nail plate pigment lies in the proximal or distal matrix. If the pigment is located on the upper portion of the free edge, then it is produced in the proximal matrix; if it is in the lower portion, its origin lies on the distal matrix (as is more commonly observed). If doubt persists, a nail clipping and Fontana-Mason staining may be used.
Patterns in Longitudinal Melanonychia
In a review of 100 cases of LM with intraoperative nail dermatoscopy, the following patterns were noted13,14:
• A gray pattern is suggestive of melanocytic activation.
• A regular brown pattern is suggestive of benign melanocytic hyperplasia, although it is also observed in some cases of melanoma.
• A regular brown pattern with globules and blotches is suggestive of melanocytic nevi.
• An irregular pattern is suggestive of melanoma.
In addition, the ABCDEF mnemonic still applies:
• A stands for the age and race of afflicted patients (African American, Native American and Asian American). Subungual melanoma (SM) has been reported in ages ranging from 20 to 90 with peak incidence in the fifth to seventh decades. Although cutaneous melanomas are rare in darker skin complexions, melanoma occurs in the acral area of these populations at a disproportionally higher rate. SM comprises 15% to 20% of all melanomas in African Americans, 33% in Native Americans and 10% to 31% in Asians.17-19
• B stands for the brown or black band most commonly seen in melanoma in-situ.20 In addition, a lesion with a breadth of 3 mm or more or a blurred variegated border increases the likelihood of melanoma.
• C points the clinician to a recent pattern of change in the nail morphology. If the lesion has become wider, “streakier” or has darkened significantly in a short period of time, this is a definite cause for concern.
• D represents the digit involved. SM more commonly involves the thumb, hallux or index finger of the dominant hand. If more than 1 digit is involved, this may decrease the suspicion of SM and point to some of the previously mentioned exogenous causes or be simply due to pigmented nail bands of ethnic origin.
• E stands for Hutchinson’s sign, the extension of pigment to involve the cuticle or proximal and lateral nail fold. Hutchinson’s sign corresponds to the radial growth phase of SM, and is therefore a very consistent indicator of SM. But, Hutchinson’s sign is not always pathonogmonic for SM. There are certain variants called pseudo-Hutchinson’s sign that occur in the absence of SM. These variants do not negate the importance of Hutchinson’s sign. However, they oblige the clinician to consider diagnostic possibilities other than SM such as ethnic nail fold hyperpigmentation.
• F urges the physician to get a complete family history paying specific attention to a history of dysplastic nevi or previous melanomas.
Di Chiacchio et al3 were able to emphasize the difficulty of harnessing the necessary diagnostic tools by illustrating that even nail experts were not able to diagnose a melanoma in situ with great accuracy using clinical criteria, the ABCDEF mnemonic or dermoscopy of the nail plate. The only evaluation that did increase diagnostic ability was intraoperative dermoscopy. Ideally, we want to be able to rule out melanoma with some confidence prior to surgical intervention.
In addition to trauma, other external sources of nail pigmentation include fungal infection (onychomycosis) caused by Aspergillus or Scopulariopsis, and bacterial infections with persistent Pseudomonas aeriginosa; these are important non-melanocytic origins of dyschromia. In cases of onychomycosis, the clinician should not overlook the possibility of melanoma and fungal comorbidity.21,22 In addition, certain drugs including minocycline, cancer chemotherapy agents and antimalarial drugs may cause nail dyschromia. However, in these situations, the pigmentation often involves more than 1 nail and a careful patient history may place melanoma lower on the list of differential diagnosis.
Even with succinct acronyms for risk factors, the burden of proof is still in the hands of the physician to decide which patients to biopsy. LM in a pediatric patient has been shown to generally be a nevus, while a melanotic macule is the most likely diagnosis if the pigment is pale, homogenous and pigmentation of the proximal nail fold (Hutchinson’s sign) is absent. Although most melanotic lesions are histologically diagnosed to be either melanotic macule or melanocytic nevus, a physician must never be overconfident in the physical examination that a confirmatory diagnosis can be made in the absence of a biopsy. In addition, some studies have shown evidence of benign LM progressing to melanoma in-situ after several years.7,16
Therefore, even when the histologic finding is benign, a patient must be educated to have regular dermatologic observation to check the pigmented lesion for growth or change in the event it is not completely removed. Particularly in cases where the most common discoloration, subungual hematoma, is suspected a clinician must prove that blood rather than melanin is responsible for the black appearance. There have also been incidences of LM demonstrating spontaneous regression or disappearance, but this is unusual and lesions should not be merely observed with the hope that they will simply go away.
While there have been reported cases of nail melanoma in pediatric patients, there is ongoing controversy as to whether those presenting with LM striata should be biopsied. SM is extremely rare in children, with most cases of LM being diagnosed as a melanocytic nevus. Of reported cases of pediatric LM, less than 6% have been proven histologically to be insitu melanomas. Thus, when deciding whether to perform a biopsy on a pediatric patient it is important to consider the likelihood of a SM or a LM that could progress to SM over time. Performing the biopsy runs the risk of causing a permanent nail dystrophy and unnecessary pain and trauma for the child. If biopsy is the chosen course, some clinicians support an excisional biopsy that removes the entire lesion thereby increasing the diagnostic yield of the specimen.12 It is important that the clinician make this decision along with the parents after thorough discussion of the risks.
Subungual Melanoma Treatment
Once the diagnosis of SM has been confirmed histologically, a thoughtful clinical course of action must be pursued. Prompt, early treatment often allows a more conservative surgery to be undertaken. Treatment modalities range from Mohs micrographic surgery to proximal interphalangeal amputation.2,23 Patients also often receive adjuvant chemotherapy either systemically or in the isolated limb. One study showed that limited excision with partial resection of the distal phalanx only and Moh’s surgery to ensure tumor-free margins yielded a more cosmetically acceptable result and had no negative effect on prognosis. For early lesions, local excision with complete removal of all nail unit structures followed by skin grafting has proven successful. Lymph node dissection is still rather controversial as no study has conclusively shown that it improves survival.24
Overall, LM can be managed appropriately by gathering a complete history from patients and considering all of its potential causes. Although SM may have a poor prognosis, clinicians should feel confident when confronted with patients with LM and use all of the diagnostic tools at their disposal. It is essential to stress the importance of the pathologist’s role in the diagnosis and careful communication with the clinician is critical when biopsies are taken. Nail biopsies should not be intimidating; a clinician must feel confident in arriving at a diagnosis of the pigmented lesion before it is too late.
Dr. Lamb is the director of the Westside Mount Sinai Dermatology Faculty Practice in New York, NY.
Dr. Scher is clinical professor of dermatology at Weill Cornell Medical College in New York, NY.
Disclosure: The authors report no relevant financial relationships.
References
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2. Ruben BS. Pigmented lesions of the nail unit. Semin Cutan Med Surg. 2015;34(2):101-108.
3. Di Chiacchio ND, Farias DC, Piraccini BM, et al. Consensus on melanonychia nail plate dermoscopy. An Bras Dermatol. 2013;88(2):309-313.
4. Ronger S, Touzet S, Ligeron C, et al. Dermoscopic examination of nail pigmentation. Arch Dermatol. 2002;138(10):1327-1333.
5. Norton L. Tumors. In: Scher RK, Daniel RC III, eds. Nails: Therapy, Diagnosis, Surgery. St. Louis, MO: W.B. Saunders Company; 1997.
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8. Koga H, Saida T, Uhara H. Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia. J Dermatol. 2011;38(1):45-52.
9. Goktay F, Gunes P, Yasar S, Guder H, Aytekin S. New observations of intraoperative dermoscopic features of the nail matrix and bed in longitudinal melanonychia. Int J Dermatol. Published online ahead of print June 20, 2015.
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11. 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):773-779.
12. Richert B, Theunis A, Norrenberg S, Andre J. Tangential excision of pigmented nail matrix lesions responsible for longitudinal melanonychia: evaluation of the technique on a series of 30 patients. J Am Acad Dermatol. 2013;69(1):96-104.
13. Di Chiacchio N, Hirata SH, Enokihara MY, Michalany NS, Fabbrocini G, Tosti A. Dermatologists’ accuracy in early diagnosis of melanoma of the nail matrix. Arch Dermatol. 2010;146(4):382-387.
14. Hirata SH, Yamada S, Enokihara MY, et al. Patterns of nail matrix and bed of longitudinal melanonychia by intraoperative dermatoscopy. J Am Acad Dermatol. 2011;65(2):297-303.
15. Iorizzo M, Tosti A, Di Chiacchio N, et al. Nail melanoma in children: differential diagnosis and management. Dermatol Surg. 2008;34(7):974-978.
16. Bonamonte D, Arpaia N, Cimmino A, Vestita M. In situ melanoma of the nail unit presenting as a rapid growing longitudinal melanonychia in a 9-year-old white boy. Dermatol Surg. 2014;40(10):1154-1157.
17. Finley RK, 3rd, Driscoll DL, Blumenson LE, Karakousis CP. Subungual melanoma: an eighteen-year review. Surgery. 1994;116(1):96-100.
18. Kato T, Suetake T, Sugiyama Y, Tabata N, Tagami H. Epidemiology and prognosis of subungual melanoma in 34 Japanese patients. Br J Dermatol. 1996;134(3):383-387.
19. Baran R, Kechijian P. Longitudinal melanonychia (melanonychia striata): diagnosis and management. J Am Acad Dermatol. 1989;21(6):1165-1175.
20. Kato T, Usuba Y, Takematsu H, et al. A rapidly growing pigmented nail streak resulting in diffuse melanosis of the nail. A possible sign of subungual melanoma in situ. Cancer. 1989;64(10):2191-2197.
21. Perrin C, Baran R. Longitudinal melanonychia caused by trichophyton rubrum. Histochemical and ultrastructural study of two cases. J Am Acad Dermatol. 1994;31(2 Pt 2):311-316.
22. Finch J, Arenas R, Baran R. Fungal melanonychia. J Am Acad Dermatol. 2012;66(5):830-841.
23. High WA, Quirey RA, Guillen DR, Munoz G, Taylor RS. Presentation, histopathologic findings, and clinical outcomes in 7 cases of melanoma in situ of the nail unit. Arch Dermatol. 2004;140(9):1102-1106.
24. Moerhrle M, Metzger S, Schippert W et al. “Functional” Surgery in subungal melanoma. Dermatol Surg 2003;29:366-374.
