Monodactylous Longitudinal Melanonychia: A Sign of Bowen's Disease in Skin of Color

Abstract

Introduction

Monodactylous longitudinal melanonychia (LM) may represent both benign and malignant dermatologic disorders. However, squamous cell carcinoma in situ (SCCis) is not commonly considered in this setting.

Case Presentation

In this report, we present 2 cases of SCCis of the nail matrix in patients with skin of color who presented with monodactylous LM involving the lateral aspect of the nail.

Conclusion

These cases suggest that SCCis should be included in the differential diagnosis for monodactylous LM, especially when involving the lateral nail plate in darker skin.

Established Facts

• Longitudinal melanonychia (LM) describes the presence of brown to black pigment extending from the nail matrix to the distal nail plate.

• When LM is monodactylous, malignant etiologies must be considered.

Novel Insights

• Squamous cell carcinoma in situ (SCCis) should be considered in the setting of monodactylous longitudinal melanonychia.

• This finding may be particularly suggestive for SCCis when present on the lateral nail fold in persons of color.

Introduction

Longitudinal melanonychia (LM) is a relatively common nail finding that describes the appearance of a band of brown to black pigment that extends from the nail matrix to the distal nail plate. Most cases of LM represent a benign dermatologic process. However, when LM involves a single nail, malignant etiologies must be considered, most notably subungual melanoma. Squamous cell carcinoma in situ (SCCis) is not commonly considered in the setting of LM. We recently diagnosed several Black and Hispanic patients with SCCis of the nail matrix who presented with monodactylous LM involving the lateral aspect of the nail plate. Here, we present 2 of such cases. This observation suggests that LM may be a particularly useful clue toward SCCis in persons of color.

Case Report

Patient 1

A 38-year-old Hispanic woman (Fitzpatrick IV) presented with a solitary brown line on her toenail that had been present for several years. The patient denied any personal or family history of LM and/or melanoma. On physical examination, a light brown longitudinal streak on the right fifth toenail adjacent to the lateral nail fold was observed (Fig. 1). There was no onycholysis, nail dystrophy, or periungual changes. A longitudinal excisional biopsy including the nail plate, matrix, and bed was performed, revealing the diagnosis of SCCis confirmed by full-thickness immunohistochemical expression of K14, a Ki-67 nuclear labeling proliferation index of 10–15%, and positive staining for high-risk HPV by in situ hybridization (Ventana, Oro Valley, AZ, USA). The patient was treated with excision with 3 mm margins.

Fig. 1.

Dermoscopic image of the fifth toenail revealing a light brown longitudinal streak without overlying nail or periungual changes (a), Histopathology demonstrating irregularly thickened subungual epithelium with atypia, cellular and nuclear pleomorphism, dyskeratotic cells, and mitotic activity (b), Immunohistochemistry demonstrating full-thickness K14 expression and increased full-thickness Ki-67 nuclear labeling (not shown) (c), ISH demonstrating positivity for high-risk HPV (d). ISH, in situ hybridization.

Patient 2

A 51-year-old Black woman (Fitzpatrick V) presented with nail discoloration and plate changes over several years. The patient initially developed a brown band on her fingernail that continued to increase in size with overlying nail alterations causing a “tightness” to the lateral finger. On physical examination, the lateral aspect of the right third fingernail displayed inhomogeneous and irregularly shaped LM with associated nail plate thinning and splitting (Fig. 2). Disintegration of the nail plate with a ragged-free edge was noted, without onycholysis or periungual changes. After longitudinal excisional biopsy of the nail plate, matrix, and bed, the histopathology revealed a diagnosis of SCCis, with a high Ki-67 index of 20–25%, full-thickness expression of K14, and positive testing for high-risk HPV by in situ hybridization. The patient was managed with Mohs surgery with full-thickness skin graft repair.

Fig. 2.

Dermoscopic view of the third fingernail demonstrating an inhomogeneous and irregularly shaped brown band with a positive triangle sign and associated nail plate thinning and splitting (a), histopathology displaying irregularly thickened subungual epithelium with atypia, cellular and nuclear pleomorphism, dyskeratotic cells, and mitotic activity (b), immunohistochemistry demonstrating full-thickness Ki-67 labeling index expression and K14 expression (not shown) (c). d ISH demonstrating positivity for high-risk HPV. ISH, in situ hybridization.

Discussion

Bowen's disease, together with SCC, is the most common malignant tumor of the nail unit. It typically presents as a localized verrucous lesion but may also display periungual erythema, ulceration, onycholysis, or onychodystrophy. Longitudinal erythronychia is commonly associated with the diagnosis of SCCis, especially in tumors localized to the nail matrix [1]. While Bowen's disease of the nail progresses slowly, it can eventually lead to invasive SCC if left untreated.

LM in the setting of SCCis has been increasingly described over the past decade, particularly in Asia. In fact, a retrospective study of 51 patients with SCC or Bowen's disease of the nail unit found that LM was present in 12% of cases [2]. When present, it often involves the lateral edge of the nail plate. Furthermore, SCCis of the nail unit may be linked to specific HPV subtypes. Shimizu et al. [3] recently demonstrated that while HPV-16 accounts for half of nail SCCis, HPV-56 is detected in two-thirds of SCCis with LM.

This clinical observation appears to have a striking racial predilection. Of the 20 cases of Bowen's disease with LM reported in the past 2 decades, all occurred in Asian or Black patients. Furthermore, in 3 cases (including our first patient), LM was the only clinical manifestation [4, 5]. While LM has been observed in SCCis in Asia, we believe this may be an underreported finding in skin of color in the USA. While larger, prospective studies are needed to confirm an association between race and LM in the setting on SCCis, this finding may be explained by a lower threshold of darker phenotypes to undergo melanocytic activation.

Both melanocytic activation and hyperplasia have been reported to be the origin of LM in the setting of SCCis [6]. In our cases, melanocyte activation with an increase in melanin deposition in the nail plate, as observed with Fontana-Masson staining, was the cause of LM. No concurrent increase in the number of melanocytes was proven with immunohistochemistry. Several signaling pathways have been found to play a role in melanocyte activation. Systemically, melanocytes are activated mainly by the α-melanocyte-stimulating hormone, adre­nocorticotropic hormone, and UV light. These stimuli activate the melanocyte adenylate cyclase to increase intracellular cAMP levels and cAMP responsive-element-binding protein (CREB) transcription factors [7]. Such transcription factors include SOX10, PS6, PAX3, and LEF-1/TCF, each of which upregulates microphthalmia-associated transcription factor (MITF) [8]. In the setting of a keratinocyte carcinomas such as a SCCis, keratinocytes produce high amounts of keratinocyte growth factor and fibroblast growth factor, leading to an indirect activation of the melanogenic transcription factors [9]. Furthermore, the HPV infection itself can also independently activate the mTOR and Wnt pathways leading to an increase in PS6 and LEF-1/TCF [10]. Overall, skin of color patients, including Black and Asian individuals, are significantly more likely to experience post-inflammatory hyperpigmentation and melanocytic activation causing melanonychia, suggesting that these patients have lower thresholds required for melanocytic activation.

Given the prevalence of benign causes of LM among patients with skin of color, it can be difficult to determine when more serious entities warrant consideration. Monodactylous LM should be assumed to be malignant until proven otherwise. Furthermore, its presence may broaden the differential beyond melanoma in patients with darker phenotypes. The field of dermatology must expand its understanding of the unique dermatologic manifestations in skin of color. This is particularly important for malignant lesions, as they are often diagnosed at more advanced stages among racial minorities. Overall, these cases suggest that SCCis should be included in the differential diagnosis for monodactylous LM arising in skin of color, especially when involving the lateral nail plate.

Statement of Ethics

This report was published ethically and in accordance with the World Medical Association Declaration of Helsinki. Written informed consent was obtained from the patients for publication of this case report and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors did not receive any funding.

Author Contributions

Author: Natalie M. Williams, BS. Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work. Drafting the work or revising, it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Responsible for writing manuscript. Author: Aderonke O. Obayomi, MD., MPH. Substantial contributions to the editing of the manuscript. Drafting the work or revising, it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Author: Julio A. Diaz-Perez, MD. Participated in writing and technical editing of the manuscript. Substantial contributions to patient care, diagnosis, obtaining photomicrographs, conducting ISH, and interpreting histopathology. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Author: Brian Morrison, MD. Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work. Drafting the work or revising, it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Participated in writing and technical editing of manuscript.