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Corresponding author: Mark E. Puhaindran, MBBS, Department of Hand & Reconstructive Microsurgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
Pigmented nail lesions are challenging problems. The differential diagnosis is broad and ranges from common self-limiting conditions, such as subungual hematoma and infection, to potentially fatal conditions, such as subungual melanoma. Clinical assessment and adjuncts, such as dermoscopy and imaging, are usually insufficient to establish a diagnosis, and a nail bed biopsy is often required. However, this is not an innocuous procedure and may result in permanent nail deformity. In addition, subjecting every patient with nail pigmentation to a biopsy will result in an unacceptably high rate of negative test results. Furthermore, histopathologic diagnosis of subungual melanoma remains challenging for several reasons. Once the diagnosis of subungual melanoma is established, the definitive treatment is controversial because the existing guidelines have largely been adapted from those for cutaneous melanoma. This review presents an approach to the diagnosis and management of pigmented subungual lesions and subungual melanoma, in particular, on the basis of the latest available evidence.
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Disclosures for this Article
Editors
Dawn M. LaPorte, MD, has no relevant conflicts of interest to disclose.
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All authors of this journal-based CME activity have no relevant conflicts of interest to disclose. In the printed or PDF version of this article, author affiliations can be found at the bottom of the first page.
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Dawn M. LaPorte, MD, has no relevant conflicts of interest to disclose. The editorial and education staff involved with this journal-based CME activity has no relevant conflicts of interest to disclose.
Learning Objectives
Upon completion of this CME activity, the learner will understand:
•
The differential diagnosis of pigmented nail lesions.
•
The clinical assessment and diagnosis of pigmented nail lesions.
•
Surgical treatment recommendations for subungual melanoma.
Deadline: Each examination purchased in 2022 must be completed by January 31, 2023, to be eligible for CME. A certificate will be issued upon completion of the activity. Estimated time to complete each JHS CME activity is up to one hour.
Pigmented nail lesions (PNLs) are occasionally encountered by hand surgeons in their practices. The most common pattern of pigmentation is longitudinal melanonychia (LM), characterized by a distinct pigmented band that extends from the eponychium to the distal edge of the nail (Fig. 1). Longitudinal melanonychia is usually caused by benign conditions, such as subungual hematoma and pigmented onychomycosis. However, subungual melanoma (SUM) is a dreaded differential diagnosis because of its aggressive nature and propensity to present at an advanced stage.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Histopathology is the gold standard for diagnosis. However, nail bed biopsy is not without considerable morbidity. The purpose of this article is to review the clinical approach to PNLs, discuss cost-effective strategies to establish a diagnosis, and provide an overview of the latest evidence-based guidelines for treating SUM.
Figure 1An isolated, dark brown pigmented band of a single digit. There is no periungual extension (Hutchinson sign), and the nail has a normal curvature and overlying cuticle. The most common cause is isolated melanin deposition. The ABCDEF criteria and dermoscopy are useful clinical tools to sieve lesions that may be suggestive of SUM.
Pigmentation may result from increased melanin production, melanocyte hyperplasia, or nonmelanocytic pigments. A melanotic macule is a benign, flat, pigmented lesion less than 1 cm in diameter. It is the most common cause of LM.
Histologically, increased melanin deposition in the basal layer without accompanying melanocytic hyperplasia and numerous contributory conditions exist. True melanocytic hyperplasia is present in melanocytic nevus, lentigo, and SUM. The most common causes of LM in children are melanocytic nevus and lentigo, and SUM is rare.
Subungual melanomas comprise approximately 0.7% to 3.5% of all melanomas and, in contrast to cutaneous melanoma in general, are more common in individuals of pigmented races, such as Asians and African Americans.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Up to 35% of patients at the American Joint Committee on Cancer (AJCC) stage III or higher and approximately 25% of patients undergoing sentinel lymph node biopsy have a positive lymph node.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
The AJCC uses the TNM staging system, where T refers to the size and extent of the tumor, N describes the status of the draining lymph nodes, and M refers to the presence of distant metastases. The current melanoma staging criteria are described in the Eighth Edition Cancer Staging Manual, and there is no separate staging system for SUM.
The reasons for this delay are multifactorial. They include the absence of a structured clinical approach to PNLs, varied presentation of SUM, a high incidence of amelanotic melanoma (ranging from 15% to 65%), and the absence of nail changes during the radial growth phase.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Finally, SUMs are treated by several different clinical specialties because of the varied referral patterns, making it difficult for a single group of specialists to acquire expertise in such a rare entity.
Clinicians must adopt a simple but thorough approach to PNLs because a delayed SUM diagnosis may be fatal.
Assessment of PNLs
A comprehensive history must be obtained, including the age of onset, evolution of pigmentation, occupational and environmental exposures, comorbid illnesses, medication use, smoking, trauma, and detailed family history. Physical examination should focus on the width, pattern, and homogeneity of nail pigmentation; the boundaries of the lesion; presence of nail deformity; extension of pigmentation into the periungual tissue; and involvement of multiple digits. The draining epitrochlear and axillary lymph nodes must be examined for presence of adenopathy. It is also important to examine all toenails. Levit et al
described the “ABCDEF” criteria to diagnose SUM (Table 2). These features are certainly not pathognomonic; however, these easy-to-remember criteria ensure that clinicians are less likely to miss suggestive lesions.
Table 2Clinical Features of SUM
The ABCDEF criteria for SUM
A
Age (50–70 years), African American, Native American, Asian
B
Nail band: black / brown color, breadth (≥3 mm), blurred borders
C
Change in size, nail morphology or pigment heterogeneity or absence of change with presumed appropriate treatment
D
Digit (thumb > index finger; single digit > multiple digits) Dominant hand
Clinical features that indicate a benign condition include young age at onset, multiple digit involvement, homogenous narrow bands with clearly defined boundaries, and an indolent course. Certain other characteristics may aid diagnosis. In onychomycosis, the nail is dystrophic and brittle, and there is subungual keratosis. Pigmentation is present at other mucocutaneous sites in Peutz-Jeghers syndrome and Laugier-Hunziker syndrome. The presence of endocrine and inflammatory conditions may suggest a benign cause of nail pigmentation. Nonmelanocytic pigmentation tends to distribute along the entire nail plate until the eponychium concavity in contrast to endogenous (melanin) pigments, which follow the convexity of the lunula.
Subungual hematoma is usually accompanied by a distinct traumatic episode. The area of pigmentation tends to be irregular and progresses distally with nail growth. There may be associated nail deformity or leukonychia.
In contrast to benign conditions, the features suggestive of SUM include adult onset, single-digit involvement; rapid change in size and appearance; and broad, irregular, and heterogeneously pigmented bands with periungual extension (Hutchinson sign) (Fig. 2). More apparent features, such as pain, contact bleeding, and an exophytic or ulcerative mass, indicate locally advanced disease. Nail plate splitting and a triangle-shaped pigmented band are additional characteristics of SUM not included in the ABCDEF system.
Figure 2A SUM of the thumb. The black pigmentation is variegated and involves the entire nail. There is ulceration evident through the radial nail plate. B The nail plate was removed during biopsy, revealing an exophytic, fungating mass that involves almost the entire nail matrix.
Dermoscopy is useful in diagnosing LM because it provides further clinical data points. A dermoscope is a tool commonly used by dermatologists to examine nail lesions using a surface microscope. Immersing the nail in an oil or gel medium improves visualization.
A brown background suggests pigmentation because of melanocyte proliferation. Irregular brown or black lines differing in thickness, color, spacing, and a loss of parallelism on a brown background suggest SUM.
Figure 3A Nail melanocytic nevus. Dermoscopy shows a brown band with regular longitudinal brown lines (yellow arrows). B Ethnic nail pigmentation is present in multiple digits. Dermoscopy shows a grayish band with regular vertical lines (blue arrows). C Subungual hemorrhage. This has progressively migrated distally from the proximal nail fold over 2 months. Dermoscopy shows reddish black pigmentation with well-rounded globules (black arrows) on the proximal margin and streaks over the distal margin (orange arrows). D Subungual melanoma. Inset shows black pigmentation involving >50% of the big toenail. Dermoscopy shows irregular broad and narrow bands and loss of parallelism. Red arrows show pigmentation broader at the proximal end compared with distally.
Conversely, a brown background with regular lines is suggestive of melanocytic nevi. Micro-Hutchinson sign is a rare sign characterized by pigmentation of the eponychium or cuticle that is otherwise not seen on gross inspection but, if present, is highly suggestive of melanoma. A grayish background with thin, uniform, regularly spaced, and parallel lines suggest epithelial melanocyte activation without melanocyte hyperplasia. These can result from drug- or radiation-induced LM, ethnic-type nail pigmentation, or ungual lentigo. Subungual hematoma is characterized by well-rounded globules of reddish or reddish black or purple spots on the proximal border and more filamentous or streaky pigmentation lines on the distal border. Serial review is important to ensure progressive movement of the hematoma distally as it may mask the appearance of a SUM with hemorrhage.
Limitations of clinical assessment
Several investigators did not find important differences in the ABCDEF criteria and dermoscopic findings between patients with biopsy-proven benign LM and SUM.
Interpreting dermoscopic features in children is even more challenging because some features noted in SUM may also be seen in nail matrix nevi in children.
Plain radiographs of the finger may indicate periosteal involvement, and ultrasonography may demonstrate a hypoechoic solid mass with increased vascularity in SUM. High-resolution magnetic resonance imaging may demonstrate the depth of the lesion, contrast enhancement, and variable signal intensity on the basis of melanin content. Melanotic tumors are hyperintense on T1-weighted sequences, and amelanotic tumors appear intermediate to hyperintense on T2-weighted images. However, a normal x-ray or magnetic resonance image does not rule out melanoma. Clinical diagnosis alone is inadequate, and histologic assessment is sometimes necessary. However, subjecting every patient with melanonychia to a nail bed biopsy will result in an unacceptable rate of negative biopsy results and complications, such as pain, sensitivity, and nail deformity. There are also specific histopathologic challenges associated with interpreting nail bed biopsy specimens.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
A nail bed biopsy is indicated in any clinically suspicious lesion or when the diagnosis is in doubt. We use a simple and practical clinical algorithm for PNLs based on recommendations by Piraccini et al
(Fig. 4). This algorithm is cost-effective because it emphasizes the importance of age, risk factors, clinical features, and dermoscopy to reduce unnecessary biopsies. Prospective validation of this algorithm is necessary but difficult because of the relative infrequency of SUM. We recommend serial review when the history is corroborative, the pigment is exogenous, multiple nails are involved, and in children. Equivocal lesions (eg, single nail involvement, no obvious history) should be observed closely, and a short period of appropriate treatment based on a presumptive diagnosis (eg, fungal infection) may be instituted. Failure to resolve or features of progression are absolute indications for biopsy. We encourage patients to monitor their nail lesions and recommend serial photographs to document changes.
Figure 4Diagnostic approach to and clinical workflow for PNLs.
A sample of tissue incorporating the entire thickness of the nail bed, including the origin of pigmentation, must be obtained in SUM because this allows accurate estimation of the thickness of the lesion. Biopsy of the germinal matrix should be avoided, if possible, because it is responsible for the formation of the dorsal nail plate, and any scarring will lead to visible deformity. Nail clippings may be sent for analysis if fungal infection is suspected.
Nail bed biopsy may be effectively performed as an office procedure using a digital block and a finger tourniquet. After achieving adequate exposure (Fig. 5), a size 11 blade is used to remove a 2–3-mm longitudinal core of tissue from the pigmented area. The wedge of tissue must include the interface of the PNL with the normal nail matrix and extend down to the bone. In this way, both the radial and vertical growths of a melanoma may be accurately assessed.
Figure 5A Left: during nail bed biopsy, a tourniquet is used to create a bloodless field; however, the digit should not be exsanguinated. The nail plate is atraumatically separated from the nail bed using an elevator, 2 oblique incisions are made on either side of the eponychium, and a skin flap is reflected to reveal the germinal matrix. It is important to visualize the entire nail bed because SUM may arise from the concealed germinal matrix. B Center: the pigmented segment should be sampled using a longitudinal, full-thickness incision. C Right: the adjacent matrix is then approximated accurately using 5-0 or 6-0 absorbable sutures, and a fenestrated nail plate is reapplied to allow egress of the hematoma and protect the sensitive matrix.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
This has been traditionally estimated using 2 histopathologic indices—Breslow thickness and Clark level. The Breslow thickness is a quantitative measure of the depth of the tumor from the skin surface to its deepest point. The Clark level is a descriptive term that indicates the anatomical layer of skin (epidermis, dermis, and subcutaneous fat) that is involved by the tumor. The relative importance of these indices to melanoma staging continues to evolve with advances in the understanding of tumor biology.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
The Scottish Melanoma Group reported a more advanced presentation, with a mean Breslow thickness of 4.7 mm, with 83% having Clark level IV and V involvement.
suggested that dermal invasion in the germinal matrix occurred later than in other parts of the nail unit and may justify a more conservative resection for SUM arising here. Nakamura et al
reported that the tumor-to-bone distances were 0.9 mm or more in all SUM specimens with thicknesses of ≤3 mm; however, the likelihood of bone attachment or invasion increased when tumor thickness exceeded 4 mm.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Nail bed tissue is fragile, specimens may be small and superficial, and poor tissue handling may make pathologic interpretation difficult. The peripheries of dermal-invasive SUM may show features of melanoma in situ (MIS), and a nonrepresentative sample would underestimate the extent of the disease. The nail matrix lacks a granular layer, making a precise determination of Breslow thickness difficult at times. In the subungual location, there is often poor demarcation between the papillary and reticular dermis as well as a paucity of subjacent subcutaneous adipose tissue; these histologic factors may make it difficult to precisely distinguish between Clark levels II–V.
Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Finally, a lower threshold for biopsy has created a new challenge for pathologists in having to distinguish between early lesions of MIS and the benign counterparts of melanocytic hyperplasia, lentigo, and acral nevus. Useful clues to aid the recognition of MIS lesions include a lentiginous growth pattern of single melanocytic cells predominating over nests, confluent growth or markedly increased numbers of single junctional melanocytes, prominent pagetoid scatter, increased cellular atypia, mitotic activity, and junctional intralesional lymphocytes (Fig. 6).
Figure 6Photomicrographs of A SUM in situ, featuring increased numbers of single basal and suprabasal atypical melanocytes (arrows) with focal confluent growth (double arrows), and B acral junctional nevus, featuring bland-appearing melanocytes, occurring singly as well as in nests (arrowhead). (Hematoxylin-eosin stain, magnification ×200)
Subungual melanoma may involve the entire nail complex, including the matrix and perionychium. The anatomy of the nail complex is intricate and closely related to the adjacent interphalangeal joint and terminal extensor tendon (Fig. 7).
Is the distance enough to eradicate in situ or early invasive subungual melanoma by wide local excision? from the point of view of matrix-to-bone distance for safe inferior surgical margin in Koreans.
reported that the mean distance between the deepest part of the normal nail matrix and the phalangeal bony surface was 0.90 mm, and the shortest distance was 0.27 mm. Their findings substantiate the conclusions of Nakamura et al,
which state that a wide local excision (WLE) may not achieve adequate clearance in thicker lesions, particularly if there are already areas of established bone invasion that were missed because of inadequate sampling. The absence of a distinct gliding plane between the nail matrix and bone makes it difficult to remove all adherent matrix from the bone completely.
Figure 7The germinal matrix (in solid blue) is recessed under the nail fold for almost three-fourth of the distance between the eponychium and the interphalangeal joint. The proximal end of the germinal matrix is only 1.2 mm distal to the insertion of the terminal extensor tendon (indicated by black stripes).
Surgery is the mainstay of treatment for SUM. However, there is a paucity of high-quality evidence in the literature, and much of the treatment guidelines for SUM have been adapted from data on cutaneous melanoma.
In addition, there has been greater emphasis on radial (peripheral) margins; however, there are limited data on deep margins.33,34 Similar to the face, there is little soft tissue redundancy in the digits, and overzealous resection can considerably impair function and appearance. There is controversy regarding the optimal resection margins and, consequently, the indications for a WLE and the optimal level of digital amputation. Although a limited resection has obvious functional and cosmetic benefits, the consequences of an inadequate resection and local recurrence are particularly serious in SUM.
Radial and vertical margins
Radial margins have been categorized as narrow (1–2 cm) and wide (3–5 cm).
There are no corresponding guidelines for SUM. In addition, the optimal deep margin is also unclear because of the proximity of the nail matrix to the bone and the absence of a distinct intervening plane. Successful local excision of SUM without removal of the phalanx was reported in 1992 by Park et al.
Since then, there have been promising reports on digit preservation, although the overall numbers of WLE are low compared with amputation, and the studies have a considerable selection bias.
The current indications for WLE are for SUM in situ. Amputation should be performed for all other invasive lesions. This concurs with the histologic studies on nail matrix-to-bone and tumor-to-bone distances in the digit.
Is the distance enough to eradicate in situ or early invasive subungual melanoma by wide local excision? from the point of view of matrix-to-bone distance for safe inferior surgical margin in Koreans.
The traditional treatment for dermal-invasive SUM was radical resection, and amputation at the metacarpophalangeal joint—or more proximal—was routinely recommended. Earlier studies have reported high local recurrence rates and poor survival with more distal amputations, such as at the proximal interphalangeal joint and middle phalanx.
However, the level of amputation was confounded by the extent of disease at presentation. In addition, many studies did not report the depth of the melanoma, and few provided patient-specific survival data. More recent studies have shown that the level of amputation does not affect survival.
Is the distance enough to eradicate in situ or early invasive subungual melanoma by wide local excision? from the point of view of matrix-to-bone distance for safe inferior surgical margin in Koreans.
The exception to this is when the disease has spread to involve the perionychial skin; in this setting, the level of amputation is dictated by the necessary cutaneous radial margins (see Table 3). We mark the proximal skin margin and either disarticulate the digit at the joint or make an osteotomy just proximal to the joint. The available volar soft tissue is reflected as a flap so that the final amputation stump is well-padded, stable, and cosmetically pleasing. This approach avoids excessively radical resections and consequently preserves function, particularly in the thumb. It is important to consider the patient’s functional requirements when discussing the exact level of amputation.
Nail complex reconstruction
Many techniques of nail complex reconstruction may be used after a WLE for SUM, including skin and nail bed grafts, reverse dermal grafts, local flaps, and microvascular nail complex transfers.
We prefer to use full-thickness skin grafts (FTSGs) harvested from the ipsilateral medial forearm because the procedure is simple, may be performed under local anesthesia, limits the surgery to the same limb, and produces an esthetically acceptable outcome (Fig. 8).
Figure 8Clinical outcome after WLE of the nail bed and reconstruction with a FTSG. There was a full graft take over the periosteum of the distal phalanx, minimal donor site morbidity, and the outcome was esthetically pleasing and retained a functional distal interphalangeal joint.
On the basis of the available evidence, we advocate amputation at the distal interphalangeal joint (interphalangeal joint for thumb) for all dermal-invasive SUMs confined to the nail complex and reserve WLE only for SUM in situ. When performing a WLE, we remove the entire nail complex, including the concealed germinal matrix and overlying eponychium, and reconstruct the defect using an FTSG from the ipsilateral medial forearm. Finally, the National Comprehensive Cancer Network guidelines recommend a sentinel lymph node biopsy in patients with SUM in AJCC Stage 1B and higher.
Pigmented nail lesions remain a challenging problem. Hand surgeons should choose to observe these lesions when there is a corroborative history and reassuring physical features. Dermoscopy and serial photography are essential aids. A biopsy is indicated when there are suspicious features. The principles of biopsy are careful tissue handling, sampling a representative area, and an accurate reapproximation of the nail matrix. Wide excision and reconstruction with an FTSG may be performed in biopsy-proven SUM in situ. Finally, amputation is indicated in all dermal-invasive SUMs, and the level of amputation should cater to the patient’s functional needs.
References
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Moncrieff M.
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Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting.
Is the distance enough to eradicate in situ or early invasive subungual melanoma by wide local excision? from the point of view of matrix-to-bone distance for safe inferior surgical margin in Koreans.
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