An African-American medical student presented with a new dark band on her index finger for 1 year (Figure 199-1). The dark color and the lack of melanonychia in other fingers made this concerning. A biopsy of the nail matrix was performed, and the result showed a benign nevus.
Longitudinal melanonychia—a single dark band of nail pigment appearing in the matrix region and extended to the tip of the nail. This is concerning for melanoma. The widening of the band in the proximal nail shows that the melanocytic lesion in the matrix is growing. This young woman had a biopsy that showed a benign nevus. (Reproduced with permission from Richard P. Usatine, MD.)
Atypical pigmentation of the nail plate may result from many causes, such as melanin or hemosiderin within the nail plate, inflammatory changes, benign melanocytic hyperplasia, nevi, drugs, fungal infections, and endocrine disorders. It may also result from development of subungual melanoma. The challenge for the clinician is separating the malignant from the nonmalignant sources.
Longitudinal melanonychia (LM or melanonychia striata) is a pigmented band in the nail plate resulting from melanin deposition (Figures 199-1 and 199-2). This may result from activation or proliferation of nail matrix melanocytes. It may involve 1 or several digits, vary in color from light brown to black, vary in width (most range from 2 to 4 mm), and have sharp or blurred borders.
Close-up of longitudinal melanonychia in a single finger. Note that the color band is translucent with uniform color and width. (Reproduced with permission from E.J. Mayeaux, Jr., MD.)
Benign LM is more common in more darkly pigmented persons. It occurs in 77% of African Americans older than age 20 years and in almost 100% of those older than age 50 years.1,2 It also occurs in 10% to 20% of persons of Japanese descent. LM is common in Hispanic and other dark-skinned groups. LM is unusual in whites, occurring in only approximately 1% of the population.1
Melanoma is the seventh most common cause of cancer in patients in the United States. Subungual melanoma is a relatively rare tumor with reported incidences between 0.7% and 3.5% of all melanoma cases in the general population.3
Subungual melanoma arises on the hand in 45% to 60% of cases, and most of those occur in the thumb (Figures 199-5, 199-6, 199-7).4 On the foot, subungual melanoma usually occurs in the great toe.5 The median age at which subungual melanoma is usually diagnosed is in the sixth and seventh decades. It appears with equal frequency in males and females.5 Amelanotic melanoma represents 25% to 30% of nail melanomas.6
Longitudinal melanonychia in a single toe. Biopsy demonstrated changes consistent with melanocyte activation or lentigo, which is frequent in individuals with darkly pigmented skin. (Reproduced with permission from Richard P. Usatine, MD.)
Melanonychia secondary to chemotherapy for metastatic penile cancer. (Reproduced with permission from Richard P. Usatine, MD.)
Advanced acral lentiginous melanoma of the thumb with destruction of the nail plate and ulceration. Note the hyperpigmentation of the proximal nail fold (Hutchinson sign), which is strongly indicative of melanoma. (Reproduced with permission from Dr. Dubin at http://www.skinatlas.com.)
ETIOLOGY AND PATHOPHYSIOLOGY
LM originates in the nail matrix and results from increased deposition of melanin within the nail plate. Nail matrix melanocytes are usually quiescent, frequently clustered, and not confined to the basal layer, and are more numerous in the distal matrix. Melanocytes of the proximal matrix are DOPA (3,4-dihydrooxyphenylalanine)-negative and cannot be activated, whereas melanocytes of the distal matrix are DOPA-positive and can be activated.7 Distal matrix activation likely explains why most pigmented nail lesions are found in the ventral nail plate. Look at the distal edge of the nail in a cross-sectional view to see whether the pigment is dorsal or ventral (a dermatoscope may help).8
Ethnic-type melanonychia is due to benign melanocyte activation that often involves several nails and is more common in skin of color.9
Benign melanocytic hyperplasia (lentigo) is observed in 9% of the adult cases (see Figure 199-3) and 30% of the pediatric cases of single-biopsied LM.4
Nevi represent 12% of LM in adults, but almost 50% of cases in children. A brown-black coloration is observed in two-thirds of cases and periungual pigmentation (benign pseudo-Hutchinson sign) in one-third.
LM may also be caused by melanocytic activation from chronic trauma, especially in the great toes. It may occur in the fingernails of individuals who bite or traumatize the proximal nail fold and cuticle.
Inflammatory changes accompanying skin diseases located in the nail unit, such as psoriasis, lichen planus, amyloidosis, and localized scleroderma, rarely may result in LM caused by melanocytic activation.8
Drugs causing melanonychia include chemotherapy agents, antimalarials (mepacrine, amodiaquine, and chloroquine), and psoralens (see Figure 199-4). Drug-induced nail pigmentation typically causes longitudinal or transverse melanonychia and affects multiple nails.10
Endocrine disorders, such as Addison disease, Cushing syndrome, hyperthyroidism, and acromegaly, can be responsible for LM.
The diagnosis of subungual melanoma must always be considered in patients with LM (see Figures 199-5 and 199-6). Separating benign from malignant lesions is often difficult. Both arise most often in the thumb or index fingers, and both are more common in dark-skinned persons.5 A biopsy should be performed in an adult if the cause of LM is uncertain. Table 199-1 lists diagnostic clues for subungual melanomas.
Hutchinson sign is the extension of pigmentation to the skin adjacent to the nail plate involving the nail folds or the fingertip. It is an important indicator for nail melanoma (see Figures 199-5, 199-6, 199-7).11
Pseudo-Hutchinson sign is the presence of dark pigment around the proximal nail fold secondary to benign conditions such as ethnic melanosis and not melanoma (Figure 199-8). Another cause of pseudo-Hutchinson sign is a translucent cuticle below which the pigment of LM is visible. Trauma and drug-induced pigmentation can also produce a pseudo-Hutchinson sign.
TABLE 199-1Diagnostic Clues That Indicate Longitudinal Melanonychia (LM) Is Suspicious for Subungual Melanoma ||Download (.pdf) TABLE 199-1 Diagnostic Clues That Indicate Longitudinal Melanonychia (LM) Is Suspicious for Subungual Melanoma
Hutchinson sign (melanoma until proven otherwise)
In a single digit
Sixth decade of life or later
Develops abruptly in a previously normal nail plate
Suddenly darkens or widens (change in the LM morphology)
Occurs in the thumb, index finger, or great toe
History of digital trauma
Dark-skinned patient, particularly if the thumb or great toe is affected
Blurred, rather than sharp, lateral borders
Personal history of malignant melanoma
Increased risk for melanoma (e.g., familial atypical mole and melanoma [FAMM] syndrome)
Nail dystrophy, such as partial nail destruction or disappearance
Acral lentiginous melanoma of the thumb with a very positive Hutchinson sign. Note how the pigmented band on the nail is greater than 3 mm in width. (Reproduced with permission from Robert T. Gilson, MD.)
Acral lentiginous melanoma of the thumb with a very positive Hutchinson sign showing dark hyperpigmentation of the nail folds. Note how the light brown pigmented band on the nail is much greater than 3 mm in width. (Reproduced with permission from Ryan O'Quinn, MD.)
Benign longitudinal melanonychia in a black person demonstrating pseudo-Hutchinson sign (dark pigment around the proximal nail fold secondary to racial melanosis and not melanoma). (Reproduced with permission from Richard P. Usatine, MD.)
Table 199-1 lists diagnostic clues that indicate an increased risk for the presence of subungual melanoma.
There is an ABCDEF mnemonic system that applies to peri- or subungual melanoma:
In this system "A" stands for age (peak incidence being between the fifth to seventh decades) and African Americans, Asians, and Native Americans in whom subungual melanoma accounts for one third of melanoma cases.
"B" stands for "brown to black" and with "breadth" of 3 mm or more.
"C" stands for change in the nail band coloration or lack of change after adequate treatment.
"D" stands for the digit most commonly involved.
"E" stands for extension of the pigment onto the proximal and/or lateral nail fold (Hutchinson sign and micro-Hutchinson sign).
"F" stands for family or personal history of dysplastic nevus or melanoma.
The digits used for grasping (thumb, index finger, and middle finger) are the most commonly involved in LM and melanoma, but either may be found in any finger or toe.
Nail dermoscopy (onychoscopy) can greatly improve the diagnosis of nail pigmentation and help distinguish benign lesions from lesions that require biopsy or regular follow-up.12 However, dermoscopy is not a substitute for pathology in the differential diagnosis of questionable cases of longitudinal melanonychia and should not prevent or delay biopsy. When evaluating nail pigmentation in an adult, determine if the pigment is melanin, and eliminate blood as the most important differential.
Determine if the lesion is more likely benign (e.g., lentigo, nevus) or malignant. Brown-black bands with a regular pattern showing individual lines that have similar shades of color, similar thickness, are regularly spaced, and are parallel are a sign of benign proliferation. Benign melanonychia may also exhibit a homogeneous gray background coloration with thin longitudinal gray lines.12 A brown background is usually associated with melanocyte proliferation. When associated with regular parallel lines and regular spacing and with potential varying color and width, it suggests either a nevus or lentigo. There is usually homogeneity of color and width in each individual longitudinal line.8
Dermoscopic features of nail melanoma–related LM includes a brown to black background with or without longitudinal brown to black lines with irregular color, spacing, and thickness. Lines usually show loss of parallelism and may vary within single lines (Figure 199-9).12 A brown background associated with longitudinal lines that are irregular in color, width, spacing, or parallelism may be benign nevi in children but is suggestive of malignant melanoma in adults.12 Individual lines may show irregularity in color or width along their length, which is suspicious of melanoma, especially when associated with a diffuse dark background. Melanoma may also present as a dark background with barely visible lines.8
Dermoscopic view of a nail unit showing longitudinal melanonychia consistent with malignant melanoma. Note the brown background with longitudinal brown lines with irregular line color, spacing, and thickness. Micro-Hutchinson sign is present in the proximal nail fold. (Reproduced with permission from Ashfaq A. Marghoob, MD.)
Dermoscopic evaluation may reveal a micro-Hutchinson sign, which is pigmentation of the cuticle that is not visible to the naked eye. It is unusual but is very concerning for melanoma when found.8,12 It has also been described in congenital nevi in children. Dark lesions may also be visible through the cuticle, and this is referred to as pseudo-Hutchinson sign. Pigmentation in the hyponychial skin is a true Hutchinson sign and is highly suggestive of melanoma. It may be associated with a parallel ridge pattern on dermoscopy.2 Blood spots and micro-Hutchinson sign (see Figure 199-9) in the proximal nail fold may be found. In a retrospective observational study published in 2016, univariate and multivariable analyses determined that melanoma cases were significantly associated with a width of the pigmented band greater than two thirds of the nail plate, presence of gray and black colors, irregularly pigmented lines, Hutchinson and micro-Hutchinson signs, nail dystrophy, and granular pigmentation.13
Definitive diagnosis of a nail discoloration may be made with a biopsy of the nail matrix. Patients with darker skin color and multiple digits with translucent LM often need only be observed. Single dark lines in whites should always be biopsied. As with melanomas in other parts of the body, excision is becoming preferred to biopsy because there are reports of false-negative incisional biopsies.8 A 3-mm punch biopsy can be performed at the origin of the darkest part of a dark band within the nail matrix (Figure 199-10) of smaller lesions. Otherwise, a tangential matrix excision (shave biopsy of the matrix) is recommended.8 Histologic diagnosis of atypical melanocytic hyperplasia necessitates the complete removal of the lesion.
A. The proximal nail fold is reflected back to perform a nail matrix biopsy in a young man with new onset of longitudinal melanonychia. The 3-mm punch is placed over the origin of the dark band at the distal matrix. B. The 3-mm punch now contains the specimen for pathology. The longitudinal melanonychia was caused by melanocytic hyperplasia. (Reproduced with permission from Richard P. Usatine, MD.)
Pigmented lesions in the nail bed usually do not cause LM and are viewed through the nail as a grayish to brown or black spot.7
Subungual hematoma may be confused with LM, but the color grows out with the nail plate, exhibiting a proximal border that reproduces the shape of the lunula. Subungual hemorrhages have a distinct dermatoscopic pattern of globules, sometimes with distal streaks, with color ranging from red to brown to black (Figure 199-11). The dermoscopic diagnosis of subungual hematoma does not rule out a coincident nail tumor.8,12 A hole punched in the nail plate allows for the visualization of the underlying nail bed and confirmation of a subungual hematoma (see Chapter 204, Subungual Hematoma).
Some non-dermatophytic molds (particularly some Neoscytalidium and Trichophyton species) produce pigmented hyphae that cause nail pigmentation.
Dermoscopy of a subungual hemorrhage showing proximal globules and distal streaks. (Reproduced with permission from Richard P. Usatine, MD.)
No treatment is required for benign LM.
REFERRAL OR HOSPITALIZATION
Treatment of primary subungual melanomas includes amputation at the level of the interphalangeal joint for thumb lesions SORⒷ, the distal interphalangeal joint for fingers SORⒸ, and the metatarsophalangeal joint for toes.14 For melanoma in situ, it may be possible to remove the full nail apparatus and save the digit. Regional lymph node dissection can help with establishment of disease stage. Chemotherapy is recommended for nodal or visceral metastases.
The 5-year survival is approximately 74% for patients with stage I and 40% for patients with stage II disease. Prognostic variables negatively affecting survival include stage at diagnosis, deeper Clark level of invasion, African-American race, and ulceration.15
Because LM may indicate an undiagnosed melanoma of the nail unit, regular monitoring is extremely important. Have the patient report any rapid changes in pigmentation of the nail plate or nail folds, and strongly consider biopsy in these individuals.
DermNet NZ. Nail Disorders—https://www.dermnetnz.org/topics/nail-disorders/
DermNet NZ. Dermatoscopy Dermoscopy of the Nail—http://www.dermnetnz.org/cme/dermoscopy-course/dermoscopy-of-the-nail/.
Di Chiacchio ND, Farias DC, Piraccini BM, et al. Consensus on melanonychia nail plate dermoscopy. An Bras Dermatol. 2013;88(2):309-313—https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750907/.
eMedicine. Nail Surgery—http://www.emedicine.com/derm/topic818.htm.
Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentation. J Am Acad Dermatol. 2007;56(5):835-847.
Jellinek N. Nail matrix biopsy of longitudinal melanonychia: diagnostic algorithm including the matrix shave biopsy. J Am Acad Dermatol. 2007;56(5):803-810.
Usatine R. Nail procedures. In: Usatine R, Pfenninger J, Stulberg D, Small R, eds. Dermatologic and Cosmetic Procedures in Office Practice. Philadelphia, PA: Elsevier; 2012:216-228. The whole procedure depicted in Figure 199-8 is described in detail.
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