What Is Subungual Melanoma (Nail Cancer)?
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A Mark under the Nail: A Bruise or Melanoma?
Nail melanoma is the form of melanoma diagnosed latest. The reason is not biological but perceptual: a dark mark under the nail first makes everyone think, “I must have hit it somewhere.” This is usually true, but when it is not, the cost is high. At diagnosis, the average tumor thickness is more than 3 millimeters; in skin melanoma, it is about 1 millimeter. This article aims to explain clearly which marks can wait and which should not.
Points we have corrected and added in this article:
- Treatment has changed. The former standard of digit amputation (removal) is being replaced for superficial, thin tumors by digit-preserving wide excision. No difference in survival has been demonstrated.
- Acral melanoma has different genetics. BRAF mutation occurs in 50% of skin melanomas, but here the rate is 10–35%; by contrast, KIT mutation is considerably more common. This invalidates the simple sequence of “immunotherapy first, then a BRAF drug.”
- Single-agent immunotherapy is less effective in nail melanoma – the response rate is around 10%. In contrast, with the ipilimumab plus nivolumab combination, the response rate in nail melanoma has risen to 61%.
- A common misconception: “Bleeding under a nail grows forward and out over time.” This is not always true: about 15% of hemorrhages do not move forward – and about 23% of melanomas also have bleeding.
- In the old text, survival rates and some frequency data have been updated.
Terminology: What Is What?
Terminology in this field is confusing; it was also mixed up in our old text. The correct terms are:
| Term | Meaning |
|---|---|
| Nail unit melanoma (NAM) | The correct umbrella term. It includes melanoma arising anywhere in the nail unit – the matrix, nail bed, nail folds or hyponychium. |
| Subungual melanoma | Literally means “under the nail plate” and is used almost synonymously with nail unit melanoma in practice. However, this is not entirely accurate: the vast majority of cases arise from the nail matrix, with fewer arising from the nail bed. This is why the biopsy should be taken from the matrix. |
| Periungual melanoma | Melanoma arising from the skin around the nail (the lateral and proximal nail folds) |
| Melanonychia | Brown-black pigmentation of the nail plate. Longitudinal melanonychia (melanonychia striata) is a band extending from the matrix to the free edge of the nail. |
The most important conceptual distinction: Melanonychia is a finding, not a diagnosis. Its causes include ethnic pigmentation, drugs, trauma, inflammation, benign lentigo and moles (nevi); melanoma is only one cause and accounts for a minority. In melanoma, however, the first finding in two-thirds of cases is longitudinal melanonychia. Not every band is melanoma, but every melanoma must be examined.
In classification, nail unit melanoma belongs to the acral lentiginous melanoma family – melanoma of hairless (glabrous) skin sites such as the palms, soles and nails. This means that it is a genetically distinct disease, differing from skin melanoma in more than location alone. For general information on melanoma, see our malignant melanoma article.
How Common Is It?
| Category | Data |
|---|---|
| Proportion of all melanomas in white populations | 0.7–3.5% |
| In people of Asian ancestry | 10–23% |
| In dark-skinned populations | 15–35% |
| Approximate incidence | Per 100,000 people per year ~0.1 |
| Most commonly affected digits | Thumb and big toe, 75–90% of cases. In hand cases, the thumb accounts for 53–58%; in foot cases, the big toe for 86%. |
| Average age at diagnosis | 50-70 years; most commonly in the 6th and 7th decades |
| Sex | No clear predominance; European registries report a slight female excess |
| Data from Turkey | In a Turkish study examining 612 melanoma patients, the proportion of acral lentiginous melanoma was 11.4% – considerably above the 2–3% in Western countries. |
We are removing a figure from our old article. The statement “It accounts for 75% of melanomas in African populations, 25% in China and 10% in Japan” is repeated in many sources but is not supported by modern registry data and also confuses acral melanoma with nail melanoma. The current data are as follows: acral melanoma accounts for 33.6%of all melanomas in Black Americans, 23.1%in people of Asian ancestry, 9.3% in Hispanic whites, and only 1% in non-Hispanic whites. In East Asian countries, this proportion reaches 54–58%.
Is Incidence Increasing? The answer is “both yes and no.” While skin melanoma is increasing markedly, acral melanoma follows a much slower curve. In Sweden, the rate from 1990-2020 remained stable. United States data showed an annual increase of 2.3–2.7% in white and Hispanic populations, while the increase in Black and Asian populations was not statistically significant. Thus, saying either “acral melanoma is stable” or “it is increasing” would be incomplete.
Symptoms and Warning Signs
The most common first finding in nail melanoma is a longitudinal brown-black band on the nail. However, about one-third of cases are unpigmented (amelanotic), and in this group the disease presents as a mass, nail deformity, bleeding or a nonhealing wound rather than pigmentation.
The ABCDEF Rule
Described for nail melanoma in 2000, this is the most widely used mnemonic:
| Letter | Meaning |
|---|---|
| A | Age – age 50-70; and ancestry: African, Asian or Indigenous American ancestry |
| B | Band – brown to black color; width 3 mm or more; irregular or blurred borders |
| C | Change – rapid widening of the band; or a nail abnormality that, despite appropriate treatment, does not change |
| D | Digit – most commonly thumb > big toe > index finger; a single digit being affected is more suspicious than multiple digits |
| E | Extension – pigment spreading onto the nail folds: Hutchinson’s sign |
| F | Family – a personal or family history of melanoma or dysplastic nevi |
A New and Stronger Tool: MATRIX Criteria (2026). The ABCDEF rule is a descriptive mnemonic; its original paper did not report sensitivity or specificity, and validation studies found it inadequate for distinguishing benign melanonychia from melanoma.
In 2026, British Journal of Dermatology published a model developed and validated in 196 patients. The MATRIX scoring model is designed to determine who should undergo biopsy among patients with longitudinal melanonychia in a single digit:
In 2026, British Journal of Dermatology published a model developed and validated in 196 patients. The MATRIX scoring model is designed to determine who should undergo biopsy among patients with longitudinal melanonychia in a single digit:
- M – Monodigital involvement
- A – Age 50 or older
- T – Thick band, over 3 mm
- R – Recent change
- I – Irregular pattern in the nail plate
- X – eXternal pigmentation or nail splitting
Dermoscopy Findings Favoring Melanoma
- Longitudinal lines with irregular colors, thicknesses and spacing, and a loss of parallelism – this is the core criterion
- A brown-black background (in benign melanocytic activation, the background is gray and the lines are thin and regular; in a nevus, the background is brown but the lines are regular)
- The band covers more than two-thirds of the nail width (a benign nevus usually covers less than one-third)
- Micro-Hutchinson’s sign – pigmentation around the nail that is invisible to the naked eye and seen only on dermoscopy
- Triangular sign – the band is wider at the base than at the tip, indicating that the lesion is growing faster than the nail
- Granular pigmentation: present in 40%of melanomas, but only 3.5% of benign lesions
Reported odds ratios also support these findings: asymmetry increases the odds of melanoma by 34-fold, Hutchinson’s sign by 18-fold, and multiple colors by 11.6-fold.
Hutchinson’s Sign and Its Mimic
True Hutchinson’s sign is pigment spreading from the matrix into tissue around the nail and is a strong finding favoring melanoma – but it is not definitively diagnostic.
False (pseudo-) Hutchinson’s sign is a benign condition producing the same appearance. The most common cause is cuticle transparency: pigment in the plate can be seen through the thin, transparent cuticle – the pigment has not actually spread into the skin; it only looks that way. Other causes include ethnic melanonychia, congenital nevi, Laugier-Hunziker syndrome, Peutz-Jeghers syndrome, drug-induced discoloration, radiotherapy, chronic trauma, subungual bleeding, fungal infection and subungual squamous cell carcinoma.
False (pseudo-) Hutchinson’s sign is a benign condition producing the same appearance. The most common cause is cuticle transparency: pigment in the plate can be seen through the thin, transparent cuticle – the pigment has not actually spread into the skin; it only looks that way. Other causes include ethnic melanonychia, congenital nevi, Laugier-Hunziker syndrome, Peutz-Jeghers syndrome, drug-induced discoloration, radiotherapy, chronic trauma, subungual bleeding, fungal infection and subungual squamous cell carcinoma.
Subungual Bleeding (Hematoma) or Melanoma?
This distinction is the most practical part of the article, because it is where most diagnostic delays occur.
Contrary to popular belief, the rule that “bleeding grows out over time” is not absolute. About 85% of subungual hemorrhages move forward and disappear as the nail grows – but 15% do not move. More importantly: about 23% of nail melanomas also have bleeding. Thus, the inference “I saw blood, so it cannot be melanoma” is wrong, and this very inference delays diagnosis.
| Favors bleeding (hematoma) | Favors melanoma | |
|---|---|---|
| Color and shape | Red-purple-black, homogeneous spots and round clusters; splinter-like projections at the edges | Pigment in fine, longitudinal lines. |
| Border | Sharply defined, with a rounded edge at the base | Indistinct, irregular border |
| Reaching the free edge | Discontinuous; does not reach the tip as a continuous line | Reaches the free edge as a continuous line |
| Over time | Color darkens, moves forward | Widens, darkens, stays in place |
| History of trauma | Usually present | Usually absent – but a quarter of patients recall trauma |
Practical timing information: fingernails grow about 3 mm per month, and toenails about 1 mm per month. Complete outgrowth of a hemorrhage in a fingernail may therefore take about 6 months, and in the big toe, 12-18 months.
When Is “Wait and See” Acceptable? Only for indeterminate lesions and under the following conditions: photographic dermoscopic follow-up, reassessment after 3-4 months and after 1 year, and during that time the mark disappears, moves forward or darkens – without any melanoma criteria.
Situations Requiring Biopsy without Waiting: the presence of any melanoma criterion, no history of trauma, a new band in an adult affecting a single digit, and the mark not moving forward.
Situations Requiring Biopsy without Waiting: the presence of any melanoma criterion, no history of trauma, a new band in an adult affecting a single digit, and the mark not moving forward.
Diagnosis: How Should a Biopsy Be Taken?
The critical point: the biopsy must be taken from the nail MATRIX. Because the pigment-producing cells are in the matrix, taking a section from the nail plate alone or sampling the nail bed is inadequate for diagnosis. A piece from the plate can at most indicate whether the color comes from melanin, blood or fungus; it cannot diagnose melanoma.
The standard approach is as follows: local anesthesia is applied to the digit, the nail plate is lifted or a window is made, the proximal nail fold is reflected with lateral incisions, and the matrix is exposed. At this stage, intraoperative dermoscopy can be used to locate the precise source of the pigment.
| Band characteristic | Preferred biopsy technique |
|---|---|
| Narrower than 3 mm, distal matrix | 3 mm punch or shave biopsy |
| Wider than 3 mm, centrally located | Tangential (shave) matrix biopsy – the Haneke technique |
| Laterally located band | Lateral longitudinal excisional biopsy |
| Wider than 6 mm | Multiple punches, transverse matrix incision or en bloc excision |
Risk of Permanent Nail Deformity: The risk is greatest when the posterior (proximal) matrix is involved, because this region produces the upper nail surface. Tangential matrix biopsy was developed precisely to reduce this risk. The concern that “a biopsy will damage my nail” can therefore largely be addressed by choosing the right technique; it is never a valid reason to delay biopsy.
Diagnostic delay is the real problem in this disease. In a series of 84 patients, the average duration of the band in patients diagnosed with melanoma was 128.9 months, compared with 38.3 months in benign lesions (p=0.017). Another series found an average diagnostic delay of 33 months.
This is reflected directly in tumor thickness: in nail melanoma, median Breslow thickness at diagnosis is 3.1-3.4 mm, and in large series the average is more than 4 mm; the ulceration rate is 58–76%. For comparison, the population median in skin melanoma is about 0.8-1 mm.
This leads to a very important conclusion: the poor prognosis of nail melanoma is not because the tumor is inherently more aggressive, but because it is detected far too late.
This is reflected directly in tumor thickness: in nail melanoma, median Breslow thickness at diagnosis is 3.1-3.4 mm, and in large series the average is more than 4 mm; the ulceration rate is 58–76%. For comparison, the population median in skin melanoma is about 0.8-1 mm.
This leads to a very important conclusion: the poor prognosis of nail melanoma is not because the tumor is inherently more aggressive, but because it is detected far too late.
Surgical Treatment: The Standard Has Changed
This is the most important update in the article. For years, the treatment of nail melanoma was taught as digit removal (amputation). Today, the situation is different, at least for superficial, thin tumors.
| Study | Findings |
|---|---|
| Nakamura et al. 50 in situ plus 12 invasive cases, wide excision down to the bone |
Local recurrence in in situ cases: 8%; in invasive cases, no local recurrence; no patient required amputation; survival during follow-up was 100% |
| Oh et al., JAAD 2023 140 patients: 107 functional surgery, 33 amputation |
Recurrence: 21.5% (functional) versus 30.3% (amputation); 5-year recurrence-free survival: 74.8% vs 57.9%. However, average tumor thickness between the groups was 0.7 mm versus 3.14 mm – in other words, there is selection bias. |
| Meta-analysis (5 studies, 109 patients) | In in situ and minimally invasive nail melanoma, amputation and conservative surgery show no difference in local recurrence (OR 1.57) |
| Systematic review Mohs 23, nail unit excision 254, amputation 34 |
Local recurrence: 8.7% / 4.7% / 2.9% – no statistically significant difference |
| Mohs surgery series, JAAD 2025, 69 patients | Local recurrence: 1.4%; patients requiring amputation to clear the margins accounted for only 7.2% – in other words, 92.8% of patients preserved their digit |
Let us be honest: the level of evidence is not high. A Cochrane systematic review in 2023 screened 3,372 records, examined 36 full texts and found not a single eligible prospective comparative study. All the evidence is retrospective. The authors concluded that digit amputation may be “more than necessary in many cases.”
The apparently better results in the functional-surgery arms of the series above also largely reflect selection bias: patients with thin tumors underwent digit-preserving surgery, while those with thick tumors underwent amputation. The defensible statement is not “digit-preserving surgery is better,” but “digit-preserving surgery has not been shown to be inferior in survival or recurrence for in situ and thin invasive nail melanoma.”
The definitive answer will come from the Japanese JCOG1602 (J-NAIL) trial: 85 patients at 21 centers, en bloc excision of the nail unit with the periosteum; the primary analysis in 2029 is planned.
The apparently better results in the functional-surgery arms of the series above also largely reflect selection bias: patients with thin tumors underwent digit-preserving surgery, while those with thick tumors underwent amputation. The defensible statement is not “digit-preserving surgery is better,” but “digit-preserving surgery has not been shown to be inferior in survival or recurrence for in situ and thin invasive nail melanoma.”
The definitive answer will come from the Japanese JCOG1602 (J-NAIL) trial: 85 patients at 21 centers, en bloc excision of the nail unit with the periosteum; the primary analysis in 2029 is planned.
When Is Amputation Still Necessary?
- Bone (distal phalanx) involvement is present
- When a clear deep surgical margin cannot be achieved
- In thick, nodular or ulcerated tumors – at a Breslow thickness of 0.8 mm or more, recurrence risk after functional surgery rises markedly
Even when needed, amputation is recommended as distally as possible (at the last joint or farther toward the tip); more proximal amputation has not been shown to improve survival.
Sentinel Lymph Node Biopsy
Indications are the same as for skin melanoma: Breslow thickness 1.0 mm or more, or 0.8 mm or more with adverse features such as ulceration. Sentinel node positivity in fingernail melanoma has been reported at 28%; additional nodes were also involved in 40% of patients with a positive result. In acral melanoma, sentinel node positivity is higher than in skin melanoma of the same thickness and retains its prognostic value.
Systemic Treatment: Acral Melanoma Is a Different Disease
Our old article summarized treatment as “immunotherapy first, then BRAF drugs.” This is correct for skin melanoma but misleading for acral and nail melanoma.
BRAF Mutation Frequency
The key difference determining eligibility for targeted therapy
Skin (cutaneous) melanoma
~50%
Acral melanoma
10–35%
By contrast, KIT mutation shows the reverse pattern: it occurs in 1–3% of melanomas overall, but in acral melanoma this rises to 10–36%. In acral melanomas, 45–58% are “triple wild-type” (no BRAF, NRAS or NF1 mutation), compared with 5–10% in skin melanoma.
| Feature | Acral melanoma | Skin melanoma |
|---|---|---|
| BRAF mutation | 10–35% | ~50% |
| KIT mutation | 10–36% | 1–3% |
| Tumor mutational burden | Median 2.1 mutations/Mb – markedly lower | Much higher |
| PD-L1 expression | 14–33% | 45–62% |
| Immune-cell content | Low CD8+ T cells, high regulatory T cells – a “cold” tumor | “Hotter” |
| Whole-genome doubling | 71% | Much lower |
A finding specific to nail melanoma: CDK4 gene amplification has been detected in 32%of subungual tumors, compared with only 9% at other acral sites. This suggests that nail melanoma may have a distinct molecular profile even within the acral melanoma family.
Immunotherapy: Single-Agent Treatment Is Inadequate; Dual Therapy Is Clearly Superior
Immunotherapy Response Rates in Acral Melanoma
Objective response rate in advanced disease
Nail melanoma – ipilimumab plus nivolumab
61%
Acral melanoma – ipilimumab plus nivolumab
40–43%
Acral melanoma – single-agent anti-PD-1
16–26%
Nail melanoma – single-agent anti-PD-1
9–10%
For comparison, the single-agent anti-PD-1 response rate in skin melanoma is about 40–43%. In the Japanese series, median overall survival with dual therapy was 43.6 months versus 20.7 months with a single agent.
The pattern here is clinically striking. Nail melanoma is among the melanomas responding most poorly to anti-PD-1 single-agent therapy, with a response rate around 10%. By contrast, it responds disproportionately well to ipilimumab plus nivolumab: in the Japanese series, the response rate in nail unit melanoma was 61% versus 10% (p<0.001). This is one of the rare examples showing that tumor location truly matters in treatment selection.
Other Options
- KIT inhibitors (imatinib, nilotinib): the pooled response rate in KIT-mutant acral melanoma is 22%, with median survival of 21.1 months. Responses occur with exon 11 and 13 mutations; exon 17 mutations and amplification alone do not respond. KIT testing is therefore meaningful in acral melanoma.
- BRAF/MEK inhibitors: effective in the minority with BRAF mutations, but compared with skin melanoma, response duration is shorter.
- New combinations: in the CAP-03 trial conducted in China with 50 acral melanoma patients (kamrelizumab plus apatinib plus temozolomid), the response rate was 64%, and median progression-free survival was 18.4 months – the most striking acral-specific signal to date, but not yet approved.
- There is no treatment approved specifically for acral melanoma anywhere in the world. All treatments are adapted from general melanoma studies.
Postoperative (Adjuvant) and Preoperative (Neoadjuvant) Treatment
Postoperative pembrolizumab or nivolumab has become standard in resected stage IIB-IV melanoma. In these studies, however, acral patients made up only 2.9–5.4%, and none was powered for the acral subgroup. Real-world data from the Netherlands found recurrence-free survival in acral melanoma patients receiving adjuvant anti-PD-1 to be 14.8 months versus 37.4 months – significantly shorter than in skin melanoma.
In macroscopic stage III disease, the trial published in 2024, NADINA trial changed practice: two preoperative cycles of ipilimumab plus nivolumab increased 12-month event-free survival, compared with immediate surgery followed by adjuvant therapy, from 57.2% to 83.7%; a major pathological response was achieved in 59% of patients, and these patients could receive only 6 weeks of treatment. This approach can also be used in nail melanoma patients with palpable lymph-node involvement – but acral patients made up only about 6% in this study too.
Prognosis and Survival
We are updating the survival figures in our old article. The “99% / 66% / 27%” values in the text belong to an earlier period of the United States cancer registry system. Current figures (SEER 21, 2015-2021, 5-year relative survival for all melanomas):
The main reason for this improvement is the spread of immunotherapy and targeted therapies over the last ten years. These figures, however, apply to all melanomas; the picture is worse in acral melanoma.
| Spread | Old figure | Current |
|---|---|---|
| Localized (no spread) | 99% | 100% |
| Regional spread | 66% | 75.7% |
| Spread to distant organs | 27% | 34.6% |
| Acral melanoma | Nonacral melanoma | |
|---|---|---|
| 5-year melanoma-specific survival | 80–81% | 91–93% |
| 10-year | 67.5% | 87.5% |
| Proportion diagnosed at stage I | 38–45% | 64–68% |
When compared at the same stage, the difference narrows markedly: 84.6% versus 88.6% at stage I; 62.1% versus 64% at stage II; and 16.2% versus 16.4% at stage IV. Much of acral melanoma’s worse outcome is therefore due to late diagnosis – not the nature of the tumor.
| Stage | 5-year melanoma-specific survival in acral melanoma |
|---|---|
| Stage 0 (in situ) | 100% |
| Stage I | 93.8% |
| Stage II | 76.2% |
| Stage III | 63.4% |
Series specific to nail melanoma report 5-year survival of about 70–77%.
A Notable Anomaly: In acral melanoma, 5-year survival in stage IIB and IIC patients was worse than in stage IIIB patients. Thus, “no lymph-node involvement” does not always mean a better prognosis. This supports considering postoperative treatment for patients with thick but node-negative acral melanoma too.
Risks and Misconceptions
The relationship with sunlight – a careful answer. Unlike skin melanoma, nail melanoma is not a sun-related cancer; it cannot be prevented by sun protection, and classic risk factors such as fair skin, freckles and sunburn do not apply.
However, a 2020 whole-genome analysis of 87 acral melanomas revealed an interesting exception: a minority of tumors, most of them subungual, had an ultraviolet-specific mutational signature. This signature was present in 6 of 7 fingernail tumors and 5 of 15 toenail tumors. Apparently, unlike the sole, the nail unit is not completely protected from sunlight.
However, a 2020 whole-genome analysis of 87 acral melanomas revealed an interesting exception: a minority of tumors, most of them subungual, had an ultraviolet-specific mutational signature. This signature was present in 6 of 7 fingernail tumors and 5 of 15 toenail tumors. Apparently, unlike the sole, the nail unit is not completely protected from sunlight.
Is Trauma a Cause? This is the question patients ask most often and misunderstand most. A systematic review and meta-analysis published in 2026 examined 97 studies. Only two case-control studies provided comparative data; in these, a history of trauma was found in 28%of acral melanoma patients and 7% of those without it (odds ratios 5.2 and 8.1).
The authors’ conclusion is clear: “It is not possible to conclude that there is a causal relationship between trauma and the development of acral melanoma.” Both studies were noted to have substantial recall bias – people tend to remember a previous impact after noticing a problem with their nail.
Regardless of this debate, the practical conclusion is the same: every nail lesion that appears after trauma and does not resolve requires early biopsy. “I hit it” is not an explanation but a deferred question.
The authors’ conclusion is clear: “It is not possible to conclude that there is a causal relationship between trauma and the development of acral melanoma.” Both studies were noted to have substantial recall bias – people tend to remember a previous impact after noticing a problem with their nail.
Regardless of this debate, the practical conclusion is the same: every nail lesion that appears after trauma and does not resolve requires early biopsy. “I hit it” is not an explanation but a deferred question.
A Well-Known Example: Bob Marley. In the summer of 1977, at age 32, he noticed pain in his right big toe after a football match. The diagnosis was acral lentiginous melanoma involving the nail and nail bed – precisely the subject of this article. He declined removal of the toe on religious grounds and underwent more limited surgery. The melanoma spread, and he died in 1981 at age 36.
There are two lessons in this story. First, its beginning follows the classic pattern of this disease: trauma followed by a neglected nail change. The second is hopeful: treatment options today are very different, and preserving the digit and controlling the disease are no longer mutually exclusive in most cases.
There are two lessons in this story. First, its beginning follows the classic pattern of this disease: trauma followed by a neglected nail change. The second is hopeful: treatment options today are very different, and preserving the digit and controlling the disease are no longer mutually exclusive in most cases.
Access to Treatment in Turkey
Access to melanoma drugs in Turkey is considerably narrower than the options recommended by international guidelines. This directly affects patients with nail melanoma.
This table has serious implications for nail melanoma: the only reimbursed adjuvant option requires a BRAF mutation – yet only 10–35% of patients with acral melanoma have a BRAF mutation. The apparently most effective combination is not covered by reimbursement. This information was compiled from secondary sources, and reimbursement conditions in Turkey change frequently; the current Health Implementation Communiqué should be checked before planning treatment.
| Treatment | Status in Turkey |
|---|---|
| Ipilimumab plus nivolumab (the most effective option in nail melanoma) | Authorized, but not reimbursed by SGK |
| Single-agent nivolumab | Reimbursed in metastatic disease after chemotherapy. Stage II adjuvant use is not authorized. |
| Pembrolizumab | Authorized, but not reimbursed for any melanoma indication |
| Single-agent ipilimumab | Reimbursed after chemotherapy in metastatic disease |
| Dabrafenib plus trametinib | Reimbursed in first-line metastatic treatment and stage III adjuvant treatment. |
| Vemurafenib plus kobimetinib | Reimbursed in first-line metastatic treatment |
| Nivolumab plus relatlimab | No record of authorization in Turkey was found |
Frequently Asked Questions
- I Have a Dark Line on My Nail. Should I See a Doctor Immediately?
- In the following situations, yes, without delay: if it has newly appeared in adulthood, affects only one digit, is wider than 3 mm, has irregular borders, is growing or darkening, spreads onto the skin around the nail, or causes nail splitting or deformity. Bands that began in childhood, affect several digits and have been unchanged for years are usually benign.
- I Hit My Nail and It Bruised. How Long Should I Wait?
- A true hemorrhage moves forward as the nail grows. In a fingernail, this may take about 6 months, and in the big toe, 12-18 months. However, 15% of hemorrhages do not move – and 23% of melanomas also have bleeding. If there is no clear history of trauma, or the mark does not move forward, it should be assessed without waiting.
- Will a Biopsy Permanently Damage My Nail?
- There is a risk, but it depends on the technique and should not be exaggerated. The risk of permanent deformity is greatest when the posterior matrix is involved; tangential matrix biopsy was developed precisely to reduce this risk. When melanoma is a possibility, nail appearance is a secondary concern.
- Will My Digit Be Amputated?
- In most cases, no. This is the issue that has changed most in recent years. For superficial (in situ) and thin tumors, digit-preserving wide excision is performed, and in series more than 90% of patients preserve their digit. Amputation is considered for bone involvement, inability to achieve clear margins, or thick, ulcerated tumors. When necessary, it is performed as far toward the tip as possible.
- Is Nail Melanoma Caused by the Sun?
- No. This is a type of melanoma unrelated to sunlight and cannot be prevented through sun protection. (Genomic studies found an ultraviolet signature in a minority of nail tumors, but it is not the main mechanism of this disease.) The way to protect oneself is early recognition – people who use nail polish are therefore also advised to inspect their bare nails from time to time.
- I Have Dark Skin. Isn’t My Melanoma Risk Low?
- For skin melanoma, yes, but not for this type. Acral melanoma can account for up to a third of all melanomas in dark-skinned populations, and survival is also worse in these groups. The belief that “melanoma doesn’t happen to us” is one of the main reasons for delay in this group.
- Why Is My Treatment Different from Someone Else’s?
- Because acral melanoma is genetically different from skin melanoma: BRAF mutations are less common, KIT mutations more common, mutational burden lower, and the tumor immunologically “colder.” The response to single-agent immunotherapy is therefore lower, while the response to dual immunotherapy is substantially better. KIT testing is also meaningful in this group.
- Can It Be Completely Cured If Detected Early?
- Yes. In nonspreading (in situ) nail melanoma, 5-year survival is 100%, and at stage I, 93.8%. The single most important factor determining the course of this disease is how early it is recognized.
Glossary
- Nail matrix
- The region beneath the nail root where the nail is produced. Most melanomas arise here.
- Melanonychia
- Brown-black pigmentation of the nail. A finding, not a diagnosis.
- Hutchinson’s sign
- Pigment spreading onto the skin around the nail. Favors melanoma but is not definitive.
- Acral melanoma
- Melanoma of hairless sites such as the palms, soles and nails.
- Amelanotic
- Unpigmented melanoma containing no pigment. About a third of nail melanomas are of this type.
- Breslow thickness
- Tumor depth in millimeters. The most important determinant of staging and prognosis.
- In situ
- Cancer confined to the uppermost skin layer, without spread.
- Sentinel lymph node
- The first node reached by lymphatic drainage from the tumor. It is removed and examined to assess spread.
- Functional surgery
- Wide excision that preserves the digit.
- Dermoscopy
- Examination of skin and nail lesions with an illuminated magnifying device.
DROZDOGAN Academy Commentary
Nail melanoma is a typical example of diseases in oncology that are “neglected because they are rare.” Below, we share our own assessment.
⚡ Why Does This Matter?
Because the real issue here is timing, not treatment. Nail melanoma is a disease with 5-year survival of 100% when detected in situ. In real life, however, the average tumor thickness at diagnosis exceeds 3 millimeters, and in series the average duration of the band reaches ten years. A disease that is almost entirely curable is therefore systematically detected late. This is a problem to be solved not by drug development but through awareness.✅ What Has Genuinely Improved in Recent Years
First and most importantly, surgery. The equation “nail melanoma = digit amputation” has been resolved. In Mohs series, 92–96% of patients preserve their digit, and local recurrence rates do not differ from amputation. This is a gain in quality of life that would have been unimaginable ten years ago, and means patients need not decide out of fear that “I must sacrifice my digit to get rid of cancer.”Second, recognition that acral melanoma is a distinct disease. Whole-genome studies have shown that these tumors develop on a different genetic background from skin melanoma: BRAF is uncommon, KIT common, mutational burden low, and the tumor “cold.” This knowledge directly affects treatment.
Third, the maturation of diagnostic tools. Published in 2026, the MATRIX criteria finally offer a measurable answer to “whom should we biopsy,” with 100% sensitivity and 80% specificity. The ABCDEF rule was a useful mnemonic, but not a validated tool.
⚠️ Points That Should Not Be Exaggerated
The level of surgical evidence is low. The Cochrane review screened 3,372 records and found not a single prospective comparative study. The apparently better results in digit-preserving surgery arms of published series also largely reflect selection bias: patients with thin tumors preserve the digit; those with thick tumors undergo amputation. The correct statement is not “conservative surgery is superior,” but “it has not been shown to be disadvantageous”. The definitive answer will come from Japan’s JCOG1602 trial in 2029.In systemic treatment, acral melanoma is still an orphan. There is no treatment approved specifically for this subtype anywhere in the world. Acral patients make up 3–6% of adjuvant and neoadjuvant studies; decisions for these patients are therefore extrapolations from studies that barely include them. Dutch real-world data showing recurrence-free survival of 14.8 versus 37.4 months in acral patients receiving adjuvant anti-PD-1 indicate that this extrapolation is not without a cost.
And errors are repeated in the literature. Figures such as “75% of melanomas in African populations are nail melanoma” are repeated in dozens of sources but are not supported by modern registry data. Similarly, the trauma-melanoma relationship rests on two case-control studies and substantial recall bias.
🩺 Our Position in Practice
1. A newly appearing band on a single digit in an adult is melanoma until proven otherwise. This may sound exaggerated, but it is defensible given the delays reported in the literature. Bands that began in childhood and affect several digits are excluded.2. “I hit it” is not an explanation. A quarter of patients recall trauma, and a causal trauma-melanoma relationship has not been established. A lesion appearing after trauma that does not resolve is an indication for biopsy.
3. The biopsy must be taken from the matrix. A nail-plate section or nail-bed sample is not diagnostic and only wastes time. This requires referral to a center with appropriate experience.
4. Amputation should not be the first option discussed. Beginning with “you may lose your digit” is unnecessary and reduces acceptance of biopsy. The correct sequence is tissue diagnosis first, then a surgical decision based on thickness.
5. KIT and BRAF testing should be requested together. In acral melanoma, the likelihood of BRAF is low and of KIT high. Testing only BRAF and saying “there is no targetable mutation” is an incomplete assessment for this group.
6. In metastatic disease, single-agent anti-PD-1 is a weak choice for nail melanoma. The response rate is around 10%, rising to 61% with dual therapy. The lack of reimbursement for this combination in Turkey represents a real, concrete inequality for this patient group and deserves discussion.
❓ Open Questions
When JCOG1602 is completed, will digit-preserving surgery also prove safe in thick tumors? Will a treatment specific to acral melanoma be developed, and will the 64% response rate of combinations such as CAP-03 be confirmed? What is the true benefit of adjuvant immunotherapy in acral patients; will a subgroup analysis answer this? Will MATRIX criteria be validated in independent cohorts? And for Turkey: will the ipilimumab-nivolumab combination be reimbursed in subgroups such as acral melanoma, in which a single agent has been shown to be inadequate ?Our Brief Verdict: Nail melanoma is one of oncology’s most frequently “missed” diagnoses, and the cost of missing it is disproportionate to how nearly preventable that cost is. The most valuable intervention in this disease is not a drug but a sentence: “How long have you noticed this mark on your nail, and did you really hit it?” Everything that follows – dermoscopy, matrix biopsy, digit-preserving surgery and molecular testing – depends on asking this question in time.
Transparency Note. (1) Reimbursement information for Turkey was compiled from a 2025 publication; the SGK Health Implementation Communiqué could not be viewed directly, and conditions change frequently. The status of nivolumab-relatlimab and enkorafenib-binimetinib in Turkey could not be verified. (2) The Turkish nail unit melanoma series (Balkan Med J 2025, experience from two tertiary centers) could not be accessed; the Turkish data in this article are based on a 2018 acral melanoma study involving 612 melanoma patients. (3) Mutation percentages specific to nail unit melanoma come from small series and conflict across sources; acral melanoma data were therefore used, with CDK4 amplification presented as the only definite nail-specific finding. (4) No numerical rate of permanent nail deformity after matrix biopsy is provided because it could not be verified from the primary source. (5) Reliable pooled data on median diagnostic delay and the percentage of misdiagnosed patients could not be found. (6) Nivolumab plus relatlimab has no published acral-subgroup data. (7) The acral subgroup analysis of CheckMate 067 could not be accessed. (8) Meta-analysis survival data specific to nail unit melanoma could not be verified from the primary source and were relayed from secondary sources.
This article is for information and does not replace personal medical advice. Any new or changing nail pigmentation must be evaluated by a dermatologist. Treatment decisions should be made by a team involving dermatology, pathology, plastic/hand surgery and medical oncology.
References
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