Hidden Beneath the Nail Plate: A Case Report of Subungual Squamous Cell Carcinoma Mimicking Benign Nail Dystrophy

Abstract

Introduction

Subungual squamous cell carcinoma (SCC) is a rare malignancy often misdiagnosed due to its clinical resemblance to benign nail conditions.

Case Presentation

A 26-year-old male neurosurgeon presented with a 4-year history of isolated nail changes, including longitudinal erythronychia and distal splitting of the left fourth fingernail. Despite the absence of pain or mass, his occupational exposure to ionizing radiation and active tobacco use raised suspicion. Dermoscopy was inconclusive, and imaging ruled out bone involvement. Histopathological evaluation of the excised nail unit confirmed SCC in situ. The patient underwent complete nail unit excision with periosteal dissection, followed by flap reconstruction. At 4-month follow-up, he showed no signs of recurrence.

Conclusion

This case underscores the need for early biopsy in persistent nail alterations, even among young patients, particularly when risk factors such as radiation exposure exist. Prompt histologic diagnosis allowed for timely, function-preserving surgical intervention.

Established Facts

• Subungual squamous cell carcinoma is a rare nail unit malignancy often misdiagnosed as benign nail disorders.

• Chronic trauma, HPV infection, ionizing radiation, and tobacco use are recognized risk factors.

Novel Insights

• This case describes subungual squamous cell carcinoma in a 26-year-old neurosurgeon, much younger than the typical age group.

• Occupational radiation exposure combined with tobacco use may have contributed to early onset, highlighting the need for early biopsy in persistent nail changes.

Introduction

Subungual squamous cell carcinoma (SCC) is an uncommon malignancy of the nail unit that often escapes early recognition due to its subtle onset and clinical similarity to benign conditions [1]. Common presenting features include longitudinal erythronychia, distal onychoschizia (nail splitting), subungual hyperkeratosis, onycholysis, and nail plate splitting or discoloration [2]. These findings frequently overlap with those of onychomycosis, verruca vulgaris, glomus tumor, onychopapilloma, subungual melanoma, and lichen planus [2–4]. Subungual SCC is most often diagnosed in older adults, with large series reporting a mean age of 60–63 years and a male predominance, while the estimated prevalence in the nail unit ranges between 0.0012% and 0.028% [3, 5, 6]. Although uncommon, cases in young adults have also been reported, including patients aged 19, 29, and 35 years, and one Mohs surgery series included individuals as young as 26 [6, 7]. Reported risk factors include high-risk HPV infection, chronic trauma, ionizing radiation, and tobacco use [3, 4, 8]; though retrospective series note that the etiology often remains undefined and the true incidence of occupational radiation-related SCC is unknown. Early diagnosis is essential to prevent deep tissue invasion and permanent functional loss [8]. As our case illustrates, persistent nail alterations may reflect an underlying malignancy even in young adults, emphasizing the need for timely histopathologic evaluation in atypical presentations.

Case Report

A 26-year-old male neurosurgeon presented with a 4-year history of isolated nail changes involving the left fourth digit, characterized by progressive longitudinal erythronychia and a V-shaped distal nail plate split over the past year. He denied any history of trauma, pain, bleeding, purulent discharge, or cold intolerance. The patient had no relevant family history of malignancy or genetic disorders. There were no psychosocial stressors or comorbid psychiatric conditions reported. Physical examination revealed a well-demarcated 2-mm wide longitudinal erythematous band extending from the proximal nail fold to the hyponychium, accompanied by distal onychoschizia (shown in Fig. 1). No abnormalities were detected in the other fingernails or toenails. The patient had a history of occupational radiation exposure and reported active tobacco use, both of which are known risk factors for subungual SCC. He had worked in a neurosurgical operating room where he was regularly exposed to ionizing radiation through Gamma Knife procedures. The patient reported occupational exposure to ionizing radiation for an average of 12 months, approximately 5 days per week and 4 h per day during neurosurgical procedures. Although individual dosimetry records were not available, this regular exposure was considered a potential contributory factor. The absence of quantitative data represents a limitation of this report. Dermoscopy revealed a solitary splinter hemorrhage without vascular patterns, keratin debris, or subungual mass, and no representative dermoscopic image could be documented. Radiographic and PET-MRI imaging ruled out underlying bone invasion or metabolic activity. Plain radiographs showed preserved cortical and trabecular bone structure without evidence of osteolysis or periosteal reaction (shown in Fig. 2). Differential diagnoses included onychopapilloma, glomus tumor, verruca vulgaris, subungual melanoma, and in situ SCC. Given the chronicity of symptoms, occupational risk profile, and high clinical suspicion for malignancy, immediate total nail unit excision was performed (shown in Fig. 3). This approach was preferred over limited punch or longitudinal biopsy to avoid sampling error and provide both diagnostic and therapeutic benefit in a single procedure. The decision was made after careful discussion with the patient regarding available options. Histopathologic examination demonstrated irregular epithelial hyperplasia with marked keratinocyte atypia, parakeratosis, and focal basement membrane disruption, accompanied by atypical mitotic figures and a mild inflammatory infiltrate, consistent with well-differentiated subungual SCC (shown in Fig. 4a, b). p16 immunostaining and HPV PCR were not performed, which represents a limitation given the established association between HPV and nail unit SCC. No pharmacologic intervention was required. The surgical excision extended down to the periosteum and was completed in a single session under local anesthesia. Complete nail unit excision down to the periosteum was performed by the department of plastic and reconstructive surgery, followed by reconstruction using a thenar flap. Although Mohs micrographic surgery is recommended in selected cases due to its tissue-sparing properties and lower recurrence rates, this modality was not available in our center. Because the lesion was confined to the nail unit without bone invasion, conventional excision followed by reconstruction with a thenar flap was performed, achieving both complete removal and functional preservation. No adverse or unanticipated events occurred during the perioperative or postoperative period. The patient reported no postoperative complications and demonstrated full adherence to postoperative wound care instructions, with excellent tolerability. At 4 months of follow-up, the patient remained disease-free with preserved digit function (shown in Fig. 5). Given the early-stage, in situ diagnosis without bone invasion, the prognosis was considered excellent following complete excision. Postoperatively, the patient entered a surveillance program consisting of clinical examination and regional lymph-node assessment every 6 months for 5 years, with annual radiographs of the involved digit. The clinical progression of the patient’s subungual SCC is summarized chronologically in Figure 6. The patient first noticed nail changes 4 years before diagnosis, which gradually progressed to splitting and dystrophy. One year prior to referral, a V-shaped distal onychoschizia developed. He sought medical evaluation at that stage, leading to dermatology referral, imaging studies, and subsequent total nail unit excision. Such a prolonged interval between onset and diagnosis is consistent with reported delays in nail SCC, often exceeding several years because of its nonspecific clinical presentation.

Fig. 1.

Longitudinal erythronychia and V-shaped distal nail plate split on the left fourth digit.

Fig. 2.

Anteroposterior and lateral hand radiographs showing no evidence of bone involvement.

Fig. 3.

Gross view of nail unit during excision, limited to nail bed without bony extension.

Fig. 4.

a Epithelial hyperplasia with focal basement membrane disruption (H&E, ×100). b Atypical mitotic figures highlighted by black arrows (H&E, ×400).

Fig. 5.

Four-month postoperative view showing intact flap and preserved nail contour without recurrence.

Fig. 6.

Timeline of clinical progression.

Written informed consent was obtained from the patient for publication of this case report and accompanying images. The CARE Checklist has been completed by the authors and is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000548466).

Discussion

Subungual SCC most commonly affects individuals in their fifth to seventh decades, making its occurrence in a 26-year-old male particularly unusual [1–3]. In one of the most extensive retrospective reviews, all patients diagnosed with nail unit SCC were over the age of 40, and none reported an occupational exposure to radiation [3]. The current case is unique not only due to the patient’s age but also the presence of two well-established risk factors – tobacco use and repeated exposure to ionizing radiation through Gamma Knife procedures in the neurosurgical operating room setting – which may have contributed to early oncogenic transformation. Although longitudinal erythronychia is recognized as a potential clinical indicator of underlying malignancy, the co-existence of a V-shaped distal cleft and the absence of pain or a visible subungual mass can divert clinical suspicion toward benign entities [3, 4]. This reinforces the need for biopsy even in seemingly indolent presentations, particularly when changes persist beyond 6 months without response to empiric treatment [1–3]. Dermoscopic evaluation, in our case, failed to reveal a mass, highlighting its limited sensitivity in non-pigmented and flat subungual lesions. Histopathologic confirmation remains the gold standard for diagnosing subungual SCC as imaging and dermoscopy often fail to detect early-stage lesions lacking mass formation or pigmentation [2–4]. In the present case, a biopsy revealed focal basement membrane disruption and atypical mitotic figures, consistent with carcinoma in situ – a pattern observed in similar early-detected cases in the literature [1–4]. This reinforces the utility of early tissue sampling in cases with persistent erythronychia or unexplained nail plate alteration [4, 8]. While non-invasive methods provide adjunctive information, histologic evaluation should not be delayed when clinical suspicion persists [1, 2].

The differential diagnosis of nail unit tumors is often challenging because their clinical manifestations overlap with benign and malignant conditions. Reported mimickers include onychopapilloma, glomus tumor, verruca vulgaris, subungual melanoma, and lichen planus, frequently leading to delayed diagnosis [6, 9]. In our patient, onychopapilloma was unlikely in the absence of a longitudinal keratotic band; glomus tumor was excluded due to the lack of paroxysmal pain or cold sensitivity; verruca vulgaris was ruled out by the absence of papillomatous hyperkeratosis; and subungual melanoma was excluded because no pigmentation or melanonychia was present. Histopathology demonstrated stromal invasion, thereby ruling out SCC in situ. These considerations justified proceeding with immediate complete nail unit excision, a strategy consistent with previous reports emphasizing the need for early and definitive intervention to avoid prolonged diagnostic delay and minimize the risk of progression [6, 7].

Recent literature has expanded understanding of risk factors and diagnostic approaches in nail unit SCC. High-risk HPV infection is strongly implicated in pathogenesis, with p16 overexpression frequently observed in periungual and subungual tumors [10]. Chronic trauma, UV exposure from nail lamps, and occupational chemical contact have also been documented as contributory factors [11, 12]. In addition to histopathology, which remains the diagnostic gold standard, several non-invasive or minimally invasive tools have been explored. Intraoperative dermoscopy can help in defining tumor margins, while reflectance confocal microscopy and ex vivo fluorescence confocal microscopy have shown promise for real-time microscopic assessment of nail tumors, allowing earlier diagnosis and intraoperative margin evaluation [13, 14]. Photodynamic diagnosis has also been investigated as an adjunctive technique [15]. With respect to management, Mohs micrographic surgery continues to demonstrate superior local control compared to conventional excision, with recurrence rates as low as 3.5% in large series, although its availability remains limited [6]. These insights highlight the need for early biopsy of persistent nail dystrophy, integration of novel diagnostic modalities where available, and close attention to high-risk groups such as healthcare workers.

The choice of surgical approach – complete nail unit excision down to the periosteum – was guided by the absence of bone invasion and the goal of preserving function and cosmesis [3, 8]. Although Mohs micrographic surgery is considered the gold standard for many nail unit malignancies, especially in cosmetically sensitive locations, a conventional excision with histologically clear margins may suffice in selected early-stage cases [1, 8]. Reconstruction with a thenar flap provided excellent coverage and maintained dexterity, as evidenced by the uneventful follow-up. The patient expressed relief at receiving a definitive diagnosis after years of uncertainty and was satisfied with both the cosmetic and functional outcomes following surgical treatment. Beyond oncologic outcomes, the psychosocial and occupational impact of nail unit SCC should be considered, particularly in younger patients. Published case reports note that delayed diagnosis often causes prolonged anxiety and functional impairment, while surgical treatment may affect fine motor skills essential for professional activities [7, 12]. In our patient, the confirmation of malignancy after years of unexplained nail changes brought both relief and anxiety. He expressed concern about hand function and potential implications for his neurosurgical career, although functional recovery after reconstructive surgery was reassuring. This case underscores the importance of addressing psychological wellbeing and occupational needs alongside oncologic control, a dimension increasingly emphasized in recent literature on nail SCC [7, 12].

This case highlights the importance of considering subungual SCC in the differential diagnosis of persistent nail abnormalities, even in young patients without overt clinical signs, particularly when cumulative risk factors such as radiation exposure are present. A major strength of this case is the early detection and complete excision in a high-risk but young individual. A limitation is the lack of molecular analysis to confirm HPV involvement, which may have further clarified etiology. Early histologic assessment remains essential for timely diagnosis and function-preserving treatment.

Statement of Ethics

The authors confirm that this case report was conducted in compliance with institutional ethical standards. Ethical approval is not required for this case report in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors declare that they have no conflicts of interest to disclose.

Funding Sources

The authors did not receive any funding for this work.

Author Contributions

G.I.K., S.Ç.G., S.Ç., Ö.G., and S.P.K. contributed equally to the drafting, revision, and final approval of this letter. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work.

Funding Statement

The authors did not receive any funding for this work.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.