Nail apparatus melanoma : Moroccan case series and review of the literature

INTRODUCTION

Nail apparatus melanoma (NUM) is categorised into subungual, ungual and periungual types. Until recently, NUM was considered a variant of acral lentiginous melanoma, which accounts for 2–3% of all cutaneous melanomas.^[1] The rarity of nail melanoma means that most clinicians have limited experience in its diagnosis and management, contributing to delayed diagnosis due to patient neglect.

Our study aims to report on all patients diagnosed and treated for nail apparatus melanoma (NAM) over a 14-year period at our department of dermatology, which serves as a centre of expertise in nail diseases, with an emphasis on clinical and histological outcomes. The pathogenesis, clinical presentation, histological findings, treatment and prognosis of NUM are distinctive and are reviewed here.

MATERIAL AND METHODS

We retrospectively analysed the medical records, photographs and histopathological findings of patients diagnosed with NAM at the Dermatology Department of IBN ROCHD University Hospital, Casablanca, between 2009 and 2023. Data analysed included sex, age at diagnosis, reason for consultation, lesion site, initial clinical manifestations, personal or family history of previous melanoma, duration of pre-diagnosis symptoms, treatment and patient survival. Histopathological characteristics reviewed included histological subtype, Breslow thickness, ulceration, mitotic rate, regression and vertical growth phase. Disease staging was determined according to the American Joint Committee on Cancer guidelines (AJCC). This study was conducted in accordance with the principles of the Declaration of Helsinki and local ethical guidelines (Ethics Committee for Biomedical Research, Faculty of Medicine and Pharmacy, Casablanca, Morocco). As no procedures other than the standard of care and anonymised observational data analysis were performed, no additional ethics committee approval was required as per national guidelines.

RESULTS

We identified 34 patients diagnosed with NAM between 2009 and 2023. The Fitzpatrick skin phototype is a system that classifies skin based on its response to ultraviolet (UV) radiation, specifically how it reacts to sun exposure. It’s a scale of 1 to 6, with Type I being the most sensitive and Type VI being the most resistant. A female predominance was noted, with a male-to-female ratio of 0.47 (22 women, 12 men). The average age at diagnosis was 55 years (range 18–89 years). Twenty-nine patients (85.29%) lived in urban areas, while 5 (14.7%) resided in rural areas. Twelve patients (35.29%) reported previous nail trauma. The mean time to diagnosis was 30 months (range 3–120 months). One patient had a previous history of cutaneous melanoma. The most frequent reason for consultation was a pigmented nodular nail lesion (57.75%) followed by a longitudinal melanonychia (LM) (42.25%). Three cases presented as subungual tumours without pigmentation. One case mimicked a botryomycoma [Figures 1 and 2]. Nineteen cases (55.88%) were located on the fingers, and 15 (44.12%) on the toes. Among these, 13 cases (38.23%) involved the great toe, while 6 (17.64%) involved the thumb. Seven cases had associated destruction of the nail plate [Figures 2 and 3]. One case of cutaneous transit metastasis was observed, located on the thumb affected by ungual melanoma [Figure 3a].

Close

Figure 1:

Subungual melanoma mimicking a botryomycoma.

Export to PPT

Close

Figure 2:

Nodular melanoma of the right thumb destroying the nail plate in a 39-year-old man.

Export to PPT

Close

Figure 3:

(a) Advanced ungual melanoma of the thumb with cutaneous metastasis at the fingertip. (b) Dermoscopy shows irregular melanonychia with distal dystrophy of the nail plate and bleeding, in addition to a vascularised tissue mass at the fingertip.

Export to PPT

The Hutchinson sign was found in 87% of cases. Onychoscopy has been performed in our series since 2020. It was performed for 20 patients. The main onychoscopic signs found in ungual melanomas include a wide, heterogeneous pigmented band exceeding 2/3rd width of the nail unit, with multiple irregularly spaced lines [Figure 4]. This was often associated with in situ melanomas. Identification of a pigmented nodular lesion with ulceration, bleeding and onychodystrophy, was associated with a nodular invasive melanoma [Figure 3b].

Close

Figure 4:

(a) 18-year-old girl with a longitudinal melanonychia involving the 4^th right finger measuring 5 mm in diameter. There is a non-homogeneous color and positive Hutchinson sign. The longitudinal melanonychia had been evolving since the age of 4 years, with an increase in size for the last 2 years. (b) Onychoscopy shows a dark-brown longitudinal band with lines exhibiting irregular coloration, spacing and thickness. (c) Perioperative photo of a matrix biopsy for a suspected malignant melanonychia band. (d) Histology showed melanocytic proliferation in situ with atypical melanocytes and without signs of invasion. (Stain: hematoxylin and eosin; magnification: ×40)

Export to PPT

Histologically, the most frequent type was nodular melanoma [Figure 5] with a Breslow thickness >2 mm (17/34, 50%), followed by the micro-invasive melanoma (11/34, 32.35%), and melanoma in situ (6/34, 17.64%). Ulceration was found in 16 patients (47%). In our study, imaging was systematically performed in cases of invasive nail melanoma managed at a late stage. Lymph node ultrasound and computed tomography (CT) scans of the chest, abdomen, and pelvis were performed to assess nodal involvement and detect potential distant metastases. No sentinel lymph node biopsy was performed in our series. Metastatic disease was present in 16 patients (47%) of which 38% were lymph node metastases. The 5-year survival rate was 46%.

Close

Figure 5:

(a) Nodular melanoma of the left big toe in a 70-year-old patient. (b) Histological analysis biopsy shows a cluster of atypical epithelioid melanocytes. (Hematoxylin and eosin stain, original magnification ×40). (c) A diffuse immunohistochemical staining for Melan-A.

Export to PPT

Regarding treatment, amputation has been avoided since 2013 at our centre. Twenty-three patients underwent total excision of the nail unit (67.64%). Most patients underwent reconstruction with a skin graft following excision of the nail bed [Figure 6]. Advanced and metastatic cases were treated with amputation, lymph node dissection and chemotherapy [Table 1]. Immunological or biological treatments are unavailable in our hospital due to both availability issues and high costs.

Close

Figure 6:

Post-surgery graft following the excision of an ungual melanoma.

Export to PPT

DISCUSSION

Nail apparatus melanoma (NAM) is a rare form of cutaneous melanoma originating in the nail unit. Its epidemiology varies significantly across ethnic populations. In darker skin races, the proportion of nail melanoma in relation to all cutaneous melanomas exceeds 20%, while in the Asian population, it exceeds 40%.^[2] Compared to similar studies conducted in Japan, Brazil and Belgium, our series presents a similar epidemiological profile in terms of gender, lesion location. However, notable differences exist in terms of the average age at consultation and observed histological types [Table 2].^[3-5]

Our series shows a significant female predominance (64.7%), which is also observed in many previous studies.^[2-4] The exact reasons for this female predisposition remain unclear. Several factors have been proposed, including differences in nail growth and hormonal influences, which may explain the higher frequency of NAM in women. Further research is needed to understand these mechanisms better.

Although NAM is typically diagnosed between the ages of 50 and 70, our series includes three cases of melanoma in situ in young patients, which began as melanonychia bands present since childhood. These bands gradually increased in size without resolution during adolescence. Paediatric subungual melanoma is extremely rare, with only 21 cases reported in the literature. The decision to biopsy these lesions in children remains controversial, with some authors recommending an ‘observational’ approach to avoid nail dystrophy, assuming the lesions are benign.^[6] However, when LM affects a single nail, careful monitoring is essential. Baseline measurements and photographs should be taken, with regular monthly assessments by parents or caregivers. If the lesion remains stable, follow-up with serial photography and dermatologist evaluations may be extended to yearly visits. Any sign of rapid growth, darkening, or broadening beyond 50% of the nail plate, bleeding or associated pain should prompt immediate referral to a specialist for consideration of a nail unit biopsy.^[7] In line with our findings, we strongly recommend follow-up until puberty and monitoring of the biopsy if the band does not disappear.

The aetiopathogenetic factors of NAM are not fully understood. However, trauma to the nail is often cited as a contributing factor to subungual melanoma . The coincidence of trauma may be explained by trauma drawing attention to a pre-existing subclinical melanoma, or even trauma inducing mutations in melanocytes during the proliferation stage^.[7] This could be why the thumb and great toe are more frequently affected by melanoma due to their larger size and more extensive nail matrix area.^[8]

In contrast to cutaneous melanoma, nail melanoma does not appear to be associated with sun exposure. A study using a ultraviolet (UV) device revealed that UV-A rays penetrate the nail plate only 1.65%, while UV-B rays are completely blocked.^[9]

In most studies, patients are referred for melanonychia, but in our series, more than 57% of patients presented at the nodular ulcerated stage, indicating that NAM is often diagnosed at an advanced stage. Diagnostic delays are influenced by several factors, including the absence of pain in many cases, the neglect of nail disorders by our patients, and the tertiary care nature of our services, may explain our patients reaching us at a more advanced stage of the disease. NAM should be suspected in the presence of any unexplained melanonychia band. The ABCDEF (“A: Asymmetry, B: Border irregularity, C: Color variation, D: Diameter over 3 mm, F: Family or personal history of melanoma”) rule has been proposed as a diagnostic aid for identifying suspicious cases for subungual melanoma.^[10] Nail biopsy should be performed by a trained professional when the band exceeds 3 mm in width or occupies more than half of the nail plate, as these are key indicators of malignancy.

Educating doctors and patients is essential for the early identification of suspicious nail changes. However, studies show that many clinicians lack experience in diagnosing nail disorders. In a survey of dermatologists, only 54.2% of respondents felt ‘somewhat’ confident in evaluating nail melanomas, and 28% were ‘not at all confident.’^[11] Similarly, a study involving 363 patients found that only 5% were aware of the ABCDEF mnemonic for nail melanoma, highlighting the need for increased awareness among healthcare providers and the general public.

Once the histological diagnosis is confirmed, wide local excision is essential. In the past, amputation was the standard method, but since 2013, we have opted for conservative surgery as the preferred treatment, leading to better survival rates and quality of life for patients. Wide local excision has shown better survival rates for in situ melanomas and early invasive melanomas as compared to amputation.^[2] The use of wide local excision combined with reconstruction using full-thickness skin grafts has yielded good results, with excellent functional and aesthetic outcomes and no signs of recurrence 3 years post-surgery.^[12,13]

The poor prognosis of NAM in our cohort is primarily due to delayed diagnosis. The key prognostic factors for NAM include tumour thickness (Breslow index), ulceration and lymph node involvement. Thicker tumours, particularly those over 2 mm, are associated with a higher risk of metastasis, often to the lymph nodes and, in more severe cases, to the visceral organs.^[14] These aggressive histological features further contribute to the poor survival rates observed in our cohort. Moreover, the limited availability of advanced treatments, such as immunotherapy, further complicates management. The high cost and restricted access to these therapies, particularly in Morocco, make early detection and intervention even more crucial to improving patient outcomes.

Our study’s retrospective design and monocentric nature introduces potential bias, as most patients were referred to us at later stages. Future multicentre, prospective studies are needed to assess the impact of immunotherapy and refine early diagnosis methods.

CONCLUSION

Nail melanoma is associated with a poor prognosis in our cohort, with advanced stage at diagnosis contributing to low survival. Only early diagnosis can improve the management of nail apparatus melanoma, especially in our context, where advanced therapies such as biological and immunotherapy are not widely accessible. Enhanced education and awareness for both healthcare professionals and patients are essential for improving early diagnosis and treatment outcomes.