Dermoscopy of nail pigmentations

INTRODUCTION — Nail pigmentation is most commonly caused by deposits of melanin or hemosiderin within the nail plate. It is rarely due to deposits of other pigments of endogenous or exogenous origin. Melanin deposits result from activation or proliferation of nail matrix melanocytes and in most cases present as a longitudinal pigmented band called longitudinal melanonychia or melanonychia striata [1].

Nail dermoscopy (onychoscopy) can greatly improve the differential diagnosis of nail pigmentation and helps clinicians with at least minimal training in dermoscopy to distinguish benign lesions, which do not require additional examinations, from lesions that require excision for pathologic evaluation or regular follow-up [2,3]. However, dermoscopy should not be considered a substitute for pathology in the differential diagnosis of doubtful cases of longitudinal melanonychia [4].

This topic will discuss the causes of nail pigmentation and the dermoscopic evaluation of benign and malignant pigmented nail lesions. Nail disorders, longitudinal melanonychia, and an overview of dermoscopy are discussed separately.

●(See "Overview of nail disorders".)

●(See "Longitudinal melanonychia".)

●(See "Overview of dermoscopy".)

ANATOMY OF THE NAIL AND DISTRIBUTION OF NAIL MELANOCYTES — The nail apparatus includes the nail matrix, the nail bed, the nail folds, and the hyponychium (figure 1). The nail matrix is localized very close to the bone, under the proximal nail fold and in the lunula area. It consists of a proximal part that produces the dorsal nail plate and a distal part that produces the ventral nail plate.

The nail plate strictly adheres to the nail bed, whose rete ridges are longitudinally oriented. Nail matrix melanocytes are quiescent, not confined to the basal layer, and frequently clustered. They are more numerous in the distal than in the proximal matrix [5].

Melanocytes of the proximal matrix are DOPA-negative and cannot be activated, whereas melanocytes of the distal matrix are DOPA-positive and can be activated [6]. This explains why most pigmented nail lesions originate in the distal matrix and are localized in the ventral nail plate. The nail bed only contains DOPA-negative dormant melanocytes, which cannot be activated.

CAUSES OF NAIL PIGMENTATION

Nail pigmentation due to melanin deposition — Melanonychia can be caused by activation or proliferation of nail matrix melanocytes. Some fungi can produce melanin and also cause melanonychia.

Melanonychia due to melanocyte activation often involves several nails and is more common in individuals with darkly pigmented skin. Common causes of melanocyte activation include traumas, inflammatory nail disorders, drugs, and nonmelanocytic tumors [1,3].

Melanonychia due to melanocyte proliferation includes nail matrix nevi, lentigo, and melanoma. (See "Overview of nail disorders", section on 'Longitudinal melanonychia'.)

Nail pigmentation due to blood deposition — Blood extravasation is common in toenails as a consequence of acute or chronic repetitive trauma. It can cause a dark nail pigmentation that may be clinically difficult to distinguish from melanic pigmentation.

EXAMINATION OF NAIL AND PERIUNGUAL TISSUES

Types of dermatoscopes — Dermoscopy of the nail plate and periungual tissues can be performed using both polarized and nonpolarized dermatoscopes. Areas to be examined include the nail plate, the nail plate free edge, the hyponychium, and the nail folds (figure 1). Dermoscopy can also be utilized intraoperatively to assess the morphology and margins of the lesion and to optimize excision.

Nonpolarized contact dermoscopy of the nail plate requires the use of ultrasound gel as interface medium, as it allows better contact with the convex nail surface. For nonpolarized contact dermoscopy of the free edge, gel or alcohol can be used as interface medium; alcohol is used for evaluation of the proximal and lateral nail folds and hyponychium.

Intraoperative dermoscopic examination of the nail matrix is usually performed with polarized, noncontact instruments.

Limitations of nail dermoscopy

●The main limitation of dermoscopy in the evaluation of nail pigmentation due to melanin deposition is that the lesions that are examined with dermoscopy correspond to the melanin deposition in the nail plate, and not to the site of melanin production.

●The diagnostic accuracy of nail dermoscopy may be poorer than naked-eye examination when performed by clinicians with limited experience in the interpretation of nail dermoscopy. Dermoscopy requires at least a minimal amount of training to provide advantage over the clinical examination.

●Dermoscopy alone cannot establish the diagnosis of malignancy; histopathologic examination remains the gold standard for the diagnosis of malignant lesions of the nail apparatus.

DERMOSCOPIC PATTERNS OF NAIL PLATE PIGMENTATION

Background color — When examining longitudinal melanonychia of the nail plate with a dermatoscope, the most important feature to evaluate first is the color of the band background:

●Bands with gray background are in most cases due to melanocyte activation and usually do not require further studies. The gray background may be homogeneous or appear as thin, regular, longitudinal lines (picture 16B). In case of melanocyte activation caused by trauma, blood spots or splinter hemorrhages can also be seen (picture 1).

●Bands with brown/black background are associated with melanocyte proliferation [7-10]. Although dermoscopy can help distinguish between benign and malignant lesions, excision for pathologic evaluation is necessary for the definitive diagnosis of suspicious lesions [11].

Arrangement of lines within brown/black bands — In lesions with a brown/black background that suggests melanocyte proliferation, it is important to look at the shape and distribution of the lines within the band:

●Longitudinal lines with regular thickness, spacing, coloration, and parallelism suggest a benign lesion (nevus or lentigo) (picture 2A). Margins of benign lesions are also sharp.

●Longitudinal lines of irregular thickness, spacing, parallelism, and color have been associated with nail melanoma (picture 3) [7-10,12].

However, establishing if lines are regular or irregular is often difficult and somewhat subjective [13]. In addition, this criterion is not suitable in children, as nevi in children almost always present as lines of different color and thickness [14].

Homogeneous black pigmentation — In the author's experience, it is not uncommon to see nail melanoma presenting with a brown or black, homogeneous band with no visible lines but areas of pigment variation (picture 4).

Dots and globules — Dots and globules corresponding to clumps of atypical melanocytes within the nail plate have been associated with melanoma in adults [15]. However, dots and globules are not uncommon in benign nevi in childhood (picture 5), where they may represent a dermoscopic sign of regression of melanonychia [16]. It is in fact not uncommon for nevi in children to fade with time [17].

Blood spots — Blood spots from subungual hemorrhage appear as well-circumscribed dots or blotches with a red to red-black pigmentation. Blood spots are not uncommon in advanced melanoma, due to tumor bleeding [12].

DERMOSCOPY OF NAIL PLATE FREE EDGE — Examination of the distal edge of the nail plate is important to establish the localization of the pigment within the nail plate. In most cases of melanonychia, the pigment is in the lower (ventral) part of the nail plate because most bands originate from the distal matrix (picture 6) [18].

Distal edge dermoscopy is not useful when the nails are very thin, as in small children, or when the pigment is very light or dark (picture 7) [14].

DERMOSCOPY OF PROXIMAL NAIL FOLD — The periungual spread of pigment is called the Hutchinson sign (picture 8) [19]. It can involve the proximal and lateral nail folds and also the hyponychial skin, and is considered a clue to the diagnosis of subungual melanoma. However, a pseudo-Hutchinson sign has been reported in a variety of benign lesions, including nevi, longitudinal melanonychia occurring in individuals with darkly pigmented skin, and drug-induced nail pigmentation. (See "Overview of nail disorders", section on 'Longitudinal melanonychia'.)

The micro-Hutchinson sign is a pigmentation of the cuticle that is not visible to the naked eye but can be seen on dermoscopy [19]. It has been reported as a quite specific but uncommon dermoscopic feature of early melanoma of the nail apparatus [7,12,15]. However, the micro-Hutchinson sign has also been described in congenital nevi in children (picture 9) and, in the author's experience, is also commonly seen in benign lesions in individuals with darkly pigmented skin (picture 10) [20].

Moreover, very dark lesions may be visible through the cuticle that is transparent (pseudo-Hutchinson sign) (picture 11) [19].

DERMOSCOPY OF THE HYPONYCHIUM — The presence of pigmentation in the hyponychial skin is a true Hutchinson sign and is highly characteristic of nail melanoma [21]. On dermoscopy, the distribution of the pigmentation shows the same parallel ridge pattern described for acral melanoma (picture 12). (See "Dermoscopy of pigmented lesions of the palms and soles", section on 'Parallel ridge pattern'.)

In contrast, pigmentation of the hyponychium occasionally observed in benign lesions, particularly in nevi, has a different pattern consisting of a brushy linear structure across the skin marks (picture 13) [22].

INTRAOPERATIVE DERMOSCOPY OF THE NAIL MATRIX — Intraoperative dermoscopy allows the direct visualization of the nail matrix. Four nail matrix dermatoscopic patterns have been described in longitudinal melanonychia [23]:

●Fine, regular, grayish lines are characteristic of melanocyte activation (95 percent sensitive, 100 percent specific).

●Regular, longitudinal, brown lines are characteristic of benign melanocyte hyperplasia (100 percent sensitive, 95 percent specific) (picture 14).

●Regular, longitudinal, brown lines with globules or blotches of regular size are characteristic of nevi (100 percent sensitive, 100 percent specific).

●Longitudinal lines with irregular color and thickness (with or without globules or blotches) are characteristic of melanoma (87 percent sensitive, 100 percent specific) (picture 15).

Intraoperative dermoscopy may increase accuracy in the diagnosis of early melanoma [24].

DIFFERENTIAL DIAGNOSIS OF NAIL PIGMENTATIONS

Approach — The clinical differential diagnosis of melanonychia is challenging. Dermoscopy can differentiate nonmelanic (eg, subungual hematomas, infections) from melanic pigmentations due to melanocyte activation or proliferation. The color of the band indicates whether it results from melanocytic activation (gray band) or proliferation (brown/black band) [2]. An algorithmic approach to the differential diagnosis and management of melanonychia is provided in the figure (algorithm 1).

Although dermoscopy can help distinguish between benign and malignant nail lesions, excision for pathologic evaluation is necessary for the definitive diagnosis of suspicious lesions [11,25]. Excision is preferred to biopsy, as it is important for the pathologist to evaluate the whole lesion. There are reports in the literature of misdiagnosis of nail melanoma due to false negative incisional biopsies [1]. For lesions measuring 3 mm or less, a punch excision is indicated. Otherwise, a tangential matrix excision (shave biopsy of the matrix) is recommended [1,14]. (See "Nail biopsy: Indications and techniques", section on 'Nail matrix biopsy'.)

Benign lesions

Longitudinal melanonychia in individuals with darkly pigmented skin — Longitudinal melanonychia is common in individuals with darkly pigmented skin and typically affects multiple nails (picture 16A) [26]. In individuals of African descent, melanonychia occurs in up to 77 percent of young adults and almost 100 percent over 50 years [26]. In Japanese populations, it affects 10 to 20 percent of adults. On dermoscopy, this type of physiologic melanonychia presents as a gray homogeneous band with or without thin regular lines (picture 16B) [1].

Traumatic melanonychia — Traumatic or frictional melanonychia may occur in the fingernails of individuals who bite or traumatize the proximal nail fold and cuticle [27]. It is also common in the fourth and fifth toenails, which are exposed to chronic friction from shoes. Dermoscopy shows a gray homogeneous pale brown or gray band; dots due to blood extravasation and splinter hemorrhages are common (picture 1).

Drug-induced melanonychia — Drugs causing melanonychia include chemotherapy agents, antimalarials, and psoralens [28]. Drug-induced nail pigmentation typically affects several nails and may present as longitudinal or transverse melanonychia. Dermoscopy shows gray homogeneous bands with or without thin regular lines (picture 17).

Postinflammatory melanonychia — Melanonychia can develop in nails affected by inflammatory skin conditions such as psoriasis, lichen planus, or Hallopeau acrodermatitis. A single nail can be affected. On dermoscopy, the band has a gray background.

Fungal melanonychia — Some nondermatophytic molds (particularly Neoscytalidium dimidiatum) and Trichophyton rubrum (var nigricans) produce pigmented hyphae that cause nail pigmentation [29]. In most cases, dermoscopy shows multicolored pigmentation with presence of yellow dots and spikes (picture 18). White or yellow streaks and reverse, triangular patterns are distinctive features of fungal melanonychia [30].

Nevi — Nail matrix melanocytic nevi are most commonly seen in children and may be congenital or acquired. Nevi represent approximately 12 percent of longitudinal melanonychia in adults and 48 percent in children.

Bands of longitudinal melanonychia due to nail matrix nevi can vary in size, from a few millimeters to the whole nail width, as well as in color, from light brown to black. Periungual pigmentation is common in congenital nevi. In children, lesions may enlarge very rapidly and may become more intensely pigmented or show a fading of the pigmentation [17,31-34].

Dermoscopic features of nevi are different in adults and in children [35]. In adults, it is typical to observe a brown background color with longitudinal brown to black regular parallel lines (picture 2A). In children, the lines are usually very irregular, present variations in color and thickness, and often show loss of parallelism (picture 2B). Black dots, corresponding to melanin granules <1 mm in size are also frequently seen in the nail plate (picture 5) [14].

Lentigo — Lentigo is histologically characterized by an increased number of melanocytes arranged as single cells within the epithelium of the nail matrix. The number of melanocytes in lentigo ranges from 5 to 31 (with a median of 14) per millimeter of basal membrane length [36].

Dermoscopy of longitudinal melanonychia due to nail matrix lentigo shows a brown background with lines that are often irregular (picture 19). Differentiating lentigo from melanoma in situ is often difficult, even by histopathology.

Onychopapilloma — Onychopapilloma is a rare benign nail tumor that typically presents with longitudinal erythronychia. (See "Overview of nail disorders", section on 'Longitudinal erythronychia'.)

In patients with darkly pigmented skin, it may present with longitudinal melanonychia [37]. Dermoscopy shows a homogeneous brown or gray band in the nail plate with splinter hemorrhages and a characteristic gray keratotic mass at the free distal edge (picture 20) [38].

Hematoma — Subungual hematoma is a collection of blood in the space between the nail bed or matrix and the nail plate. It can be the consequence of an acute injury or of repetitive minor trauma. It appears as a well-circumscribed dot or blotch with a red-purple-black pigmentation that moves distally with nail growth.

Dermoscopy shows an area of homogeneous purple/black pigmentation with round globules at the periphery and a "filamentous" distal end; a peripheral fading of the pigmentation is common (picture 21) [39].

Malignant lesions

Melanoma — Nail melanoma presents as longitudinal melanonychia in up to 70 percent of cases [1]. Nail melanoma is rare in White people (1 to 2 percent of melanomas) but more frequent in people from East Asia (10 to 20 percent of melanomas) and in Black people (25 percent of melanomas) [1]. The thumb and the big toe are most frequently affected. A pigmentation of the periungual skin (Hutchinson sign), indicating a radial growth phase of the tumor, is highly suggestive of nail melanoma, but may be absent in early or in situ lesions.

Dermoscopic features of longitudinal melanonychia that suggest melanoma include a brown background involving most of the nail plate with longitudinal brown to black lines with irregular color, spacing, and thickness (picture 3) [25]. Lines also show parallelism disruption [12]. Blood spots are also commonly seen.

Sometimes melanoma presents with a very dark background that does not allow visualization of longitudinal lines (picture 4). However, the presence of pigment variation suggests the diagnosis [14].

The presence of the micro-Hutchinson sign in the proximal nail fold has been reported as a feature of early melanoma in individuals with lightly pigmented skin [12]. In the author's experience, this is not uncommon in benign lesions of patients of African descent (picture 10).

When the Hutchinson sign involves the hyponychium, dermoscopy reveals the parallel ridge pattern (picture 12) [21]. (See "Dermoscopy of pigmented lesions of the palms and soles", section on 'Parallel ridge pattern'.)

Amelanotic melanoma represents 25 to 30 percent of nail melanomas [1]. It usually arises from the nail bed, where melanocytes are dormant, and presents as a subungual nodule that may ulcerate. Nail plate changes are also common. Dermoscopy shows linear irregular vessels and milky red areas as in amelanotic melanoma of the skin (picture 22) [12]. (See "Dermoscopic evaluation of skin lesions".)

Bowen disease/squamous cell carcinoma — Longitudinal melanonychia can be associated with Bowen disease or squamous cell carcinoma [40]. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Cutaneous squamous cell carcinoma in situ (Bowen's disease)' and "Overview of nail disorders", section on 'Squamous cell carcinoma'.)

On dermoscopy, the pigmented band has a gray background. Diagnostic features include white scale, red dotted vessels, and absence of normal dermatoglyphs [41].

MELANONYCHIA IN CHILDREN — Melanonychia in children is a difficult problem, as the clinical and dermoscopic features of the lesion are often alarming and there are no specific guidelines for management. In children, most cases of melanonychia are due to nail matrix nevi, whereas nail melanoma is exceedingly rare [31-33,42,43].

On dermoscopy, nail matrix nevi in children often display features that are considered clues to diagnosis of melanoma in adults, such as a brown/black band with irregular lines of different color and thickness (picture 23). Thus, dermoscopic criteria that warrant an excision such as that used in adults cannot be used in children [14]. A close clinical follow-up may be a reasonable management approach for children with melanonychia [3].

SUMMARY AND RECOMMENDATIONS

●Dermoscopic examination of nails – Dermoscopic examination of nails improves the differential diagnosis of nail pigmentation and helps clinicians trained in dermoscopy to distinguish benign lesions, which do not require additional examinations, from lesions that require excision for pathologic evaluation or regular follow-up. However, dermoscopy should not be considered a substitute for histopathologic examination in cases of nail pigmentations suspicious for malignancy. (See 'Introduction' above.)

●Dermoscopic features of longitudinal melanonychia – Longitudinal lines with regular thickness, spacing, coloration, and parallelism suggest a benign lesion (nevus or lentigo) (picture 2A). Longitudinal lines of irregular thickness, spacing, parallelism, and color have been associated with nail melanoma (picture 3). However, in the author's experience, it is not uncommon to see nail melanoma presenting with a brown or black, homogeneous band with no visible lines but areas of pigment variation (picture 4). (See 'Dermoscopic patterns of nail plate pigmentation' above.)

●Differential diagnosis of nail pigmentations – Nail pigmentations can be caused by a variety of benign and malignant lesions, including physiologic melanonychia occurring in individuals with darkly pigmented skin (picture 16A-B), nail matrix lentigines and nevi (picture 2A-B), and nail melanoma. An algorithmic approach to the dermoscopic differential diagnosis and management of melanonychia is provided in the figure (algorithm 1). (See 'Differential diagnosis of nail pigmentations' above.)