Chronic Onychodystrophy Revealing Amelanotic Nail Unit Melanoma in a Moroccan Patient: A Case Report

Abstract

Introduction

Nail unit melanoma is a rare and potentially aggressive variant of acral lentiginous melanoma. Diagnosing amelanotic variants can be particularly challenging due to the absence of typical pigmentation. Here, we report a case of chronic onychodystrophy revealing amelanotic nail unit melanoma.

Case Presentation

A 48-year-old Moroccan patient presented with chronic persistent monodactylic nail dystrophy. Dermoscopy showed subungual hyperkeratosis with an atypical vascular pattern but no pigmented structures. A biopsy of the nail unit confirmed amelanotic melanoma. Staging (PET scan, lymph node ultrasound, and bone CT) excluded metastases. Surgical management led to metacarpophalangeal amputation of the thumb.

Conclusion

This case underscores the need to consider amelanotic melanoma in patients with atypical or persistent nail lesions. Early recognition and prompt treatment can significantly affect prognosis. Monodactylous involvement with nail dystrophy, including nail plate destruction, should lead to a nail biopsy for an early and accurate diagnosis.

Established Facts

• Amelanotic nail unit melanoma is a rare and diagnostically challenging variant of acral lentiginous melanoma due to the absence of melanin pigmentation.

• Histopathological examination, supported by immunohistochemistry (e.g., melan-A, S-100, HMB-45), is essential for confirming the diagnosis in nonpigmented lesions.

Novel Insights

• Chronic monodactylic onychodystrophy without melanonychia may be the only clinical sign of amelanotic nail unit melanoma, warranting early biopsy even in the absence of pigmentation.

• The subsequent local recurrence highlights the limitations of conservative surgical management in the context of deeply invasive lesions.

Introduction

Nail unit melanoma (NUM) is a variant of acral lentiginous melanoma that arises in the nail matrix, bed, or periungual skin and accounts for approximately 2% of all cutaneous melanomas [1]. Its prognosis is generally poorer than common cutaneous melanomas, mainly because of delayed detection and deeper invasion at the time of diagnosis [2]. Clinically, NUM may present with melanonychia or manifest as nail dystrophy or periungual pigmentation, thus posing considerable diagnostic challenges [3]. Amelanotic NUM, the variant lacking the usual brown-black pigmentation, is even rarer and poses additional diagnostic difficulties [4]. Because of its atypical clinical appearance, which can mimic onychodystrophies of varying etiologies, amelanotic NUM may remain undetected until advanced stages [4]. Its clinical ambiguity complicates early recognition, impacts treatment decisions, and worsens the prognosis [5]. Herein, we report the case of a Moroccan patient who presented a chronic onychodystrophy subsequently diagnosed as amelanotic NUM.

Case Presentation

A 48-year-old male (Fitzpatrick skin phototype IV) with no medical history presented with a chronic dystrophy of the left thumbnail, following a nail trauma that occurred 20 years ago. The lesion progressively worsened over the preceding several months, although the patient remained asymptomatic. On clinical examination, the affected nail exhibited onycholysis, destruction of the nail plate, subungual hyperkeratosis, xanthonychia, and periungual paronychia. Notably, there was no visible melanonychia or Hutchinson’s sign (shown in Fig. 1a). Dermoscopy identified subungual hyperkeratosis with an atypical vascular pattern, consisting of irregular peripheral vessels and central avascular areas, but no discernible pigmented structures (shown in Fig. 1b). Thumb mobility was preserved, and examination of the remaining fingernails revealed no abnormalities. No palpable regional lymphadenopathy was detected. An excisional biopsy of the nail unit was performed. Histopathologic evaluation demonstrated an acral lentiginous melanoma infiltrating the papillary dermis, with a Breslow thickness of 5 mm (shown in Fig. 2). There was no evidence of vascular or perineural invasion, or ulceration observed. The mitotic count was 2 mitoses per 2 mm². Immunohistochemistry confirmed the diagnosis of melanoma, with tumor cells staining positive for melan-A, S-100, and HMB-45. Staging investigations, including positron emission tomography scan, lymph node ultrasound, and bone computed tomography, excluded metastatic disease. The patient was classified as stage IIB (T4aN0M0) according to the 2017 AJCC staging system [6]. The patient underwent conservative surgical excision of the entire nail apparatus, followed by controlled wound healing (shown in Fig. 3). The patient was monitored every 3 months, and after 1 year of follow-up, he developed local recurrence leading to surgical revision with metacarpophalangeal amputation of the thumb (shown in Fig. 4).The sentinel lymph node biopsy was negative.

Fig. 1.

Clinical and dermoscopic features of amelanotic NUM. a Periungal paronychia with nail plate destruction, associated with nonpigmented subungual hyperkeratosis. b Subungual hyperkeratosis with irregular peripheral vessels and central avascular areas.

Fig. 2.

Histopathological features of amelanotic NUM showing a dermal proliferation of atypical melanocytes lacking melanin pigmentation. Immunohistochemistry confirmed the melanocytic origin with positive staining for melan-A and S-100.

Fig. 3.

Intraoperative and postoperative views of conservative surgical excision for amelanotic NUM. a Complete excision of the nail apparatus. b Immediate postoperative appearance. c Satisfactory healing and functional outcome at 3-month follow-up.

Fig. 4.

Clinical progression of local recurrence and subsequent surgical management. a Pigmented lesion at the site of recurrence. b Dermoscopic view showing irregular pigmentation suggestive of melanoma. c Postoperative outcome following metacarpophalangeal amputation of the thumb.

Discussion

Our patient illustrates a rare variant of NUM, highlighting significant diagnostic and therapeutic challenges. The nonhealing traumatic lesion that evolved into chronic onychodystrophy combined with the complete absence of pigmentation ultimately led to a marked delay in both diagnosis and effective treatment in our case. The clinical appearance of amelanotic NUM is misleading, often resulting in underdiagnosis and consequently delaying appropriate management. A recent systematic review revealed that amelanotic NUM is most frequently misdiagnosed as a nonhealing ulcer or traumatic injury [7]. These misinterpretations are followed by benign proliferative lesions, infectious lesions, or other malignant tumors. The foot is the most common anatomical site involved, followed by the heel and the hand [7]. Chronic onychodystrophy of the thumb without pigmentation is an atypical presentation that may be mistaken for pyogenic granuloma, Bowen’s disease, squamous cell carcinoma, lichen planus, or a nail bed infection [8–17].

Longstanding nail dystrophy confined to a single digit should not be underestimated, particularly when associated with nail splitting. This clinical sign has been identified as one of the most unfavorable prognostic indicators in NUM. Several authors have emphasized the need for a low threshold to perform a nail biopsy in cases of chronic dystrophy, even in the absence of melanonychia or pigmentation, as delayed diagnosis is strongly associated with worse outcomes [18].

Amelanotic NUM is, therefore, often difficult to recognize and may go unnoticed by both patients and clinicians. It is essential to remain aware that a benign-appearing lesion can indeed be a melanoma; any delay due to misdiagnosis can be life-threatening [19].

The definitive diagnosis of amelanotic NUM, as for any malignant tumor, relies on histopathologic examination, which should include details on the depth of tumor infiltration (Breslow thickness), the presence or absence of ulceration, and the completeness of tumor excision [20]. In our case, the Breslow thickness was 5 mm, reflecting a diagnostic delay. As is in our patient, immunohistochemistry plays a pivotal role in confirming the melanocytic origin of tumor cells, particularly when no pigmentation is present. On the other hand, dermoscopy is a noninvasive, accessible method for evaluating skin lesions, and it can play a crucial role in amelanotic NUM, although it does not provide a definitive diagnosis. Specific dermoscopic features associated with amelanotic melanoma include polymorphous vessels, multiple blue-gray dots, a blue-white veil, asymmetry, multiple colors, milky red areas, and scar-like depigmentation [18, 21]. Some studies suggest that dotted vessels combined with irregular linear vessels, in addition to scar-like depigmentation, may be especially predictive of amelanotic melanoma. Dermoscopy can also help differentiate between benign lesions, such as hemangiomas, and pyogenic granuloma [22].

High-frequency ultrasound may further aid in assessing lesion depth. A strong correlation has been reported between tumor thickness as measured by color Doppler ultrasound and the histologic Breslow depth in cutaneous melanoma, suggesting that ultrasound is a valuable supplemental tool when evaluating potential NUM. However, it has only been described in isolated cases of amelanotic NUM, and none of these studies employed standard ultrasound [23, 24].

The treatment of nail melanoma is primarily surgical and depends on the depth of invasion. Functional surgery is the preferred treatment for in situ or minimally invasive NM (Breslow thickness ≤0.5 mm). In cases of invasive nail melanoma, amputation is favored due to the close proximity between the nail bed epithelium and the underlying bone [25]. Mohs micrographic surgery has been proposed as an alternative for NUM, though it has been tested in only a few small series; further data are needed to assess its effectiveness [26].

The choice of conservative surgical excision with close follow-up every 3 months in our patient was supported by previous findings suggesting that the extent of surgical management may not significantly affect prognosis in NUM [2]. Our decision was also based on the absence of adverse histopathological features, including vascular or perineural invasion and ulceration, with a relatively low mitotic index (2 mitoses per 2 mm²).

Indeed, Dika et al. [27] reported in a retrospective study, involving 39 Caucasian patients with NUM, that the prognosis was correlated significantly with histopathologic factors such as Breslow thickness, regression, and ulceration but not with the type of surgery performed. Specifically, no significant survival advantage was observed between functional surgery and disarticulation [27]. Similarly, a comparative analysis of 62 stage I–II NUM cases found that recurrence rates were lower in patients treated with functional surgery (35.5%) than in those undergoing amputation (48.4%), with better 5-year survival outcomes (91.7% vs. 66.5%, respectively) [3, 28]. Furthermore, a large Mayo Clinic study of 124 surgically managed NUM cases over 96 years confirmed that the level of amputation did not affect survival when histologically clear margins were achieved. Function-preserving procedures, especially in the thumb, were shown to maintain oncologic safety while enhancing functional, sensory, and cosmetic outcomes [29].

Our patient was a young male manual worker, professionally active, and expressed strong reluctance toward amputation, further justifying a function-preserving surgical approach. However, the patient subsequently developed a pigmented local recurrence after 1 year of follow-up, necessitating additional amputation. The pigmented nature of the recurrence could be attributed to the activation of residual dormant melanocytes following the initial surgery [30].

Regarding systemic therapies, targeted therapy and immunotherapy have demonstrated improved overall survival and disease-free survival in patients with stage III and IV melanoma. However, their efficacy appears to be lower in acral lentiginous melanoma [31]. While NUM is considered a subtype of acral lentiginous melanoma, its distinct biological and molecular characteristics may lead to different responses to emerging therapies. Therefore, further studies are needed to assess the effectiveness of these treatments on nail melanoma [32].

In conclusion, amelanotic NUM, although rare, remains a significant diagnostic challenge owing to its subtle clinical presentation. Clinicians should maintain a high index of suspicion for chronic monodactylic nail dystrophies that fail to respond to standard therapies. Early biopsy and histopathologic evaluation are critical to facilitate timely intervention and optimize patient outcomes. This case report follows the CARE guidelines. The CARE checklist is included as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546886).

Statement of Ethics

This study was conducted according to the principles specified in the Declaration of Helsinki and the local ethical guidelines of the Ethics Committee for Biomedical Research of the Faculty of Medicine and Pharmacy, University Hassan II of Casablanca, Morocco (International Review Board 00002504). Written informed consent was obtained from the patient to participate in the study and for publication of the details of his medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Bouchra Baghad is the corresponding author and drafted the manuscript, performed literature review, and contributed to clinical follow-up. Fouzia Hali supervised the case management and critically revised the manuscript. Yousra Habibi and Fatima Anejjar participated in the clinical assessment and data collection. Bahija Lemrhari performed histopathological analysis and contributed to clinical follow-up. Bouchra Mouaouya contributed to histological diagnostic confirmation. Meriem Regragui reviewed histological slides and contributed to diagnostic confirmation. Mounia Diouri managed the surgical procedures and provided intraoperative insight. Soumiya Chiheb managed the surgical procedures, oversaw the entire project, and approved the submitted version.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.