Sonographic Features of Onychopapilloma: A Single Center Retrospective Observational Study

(1) Background: Onychopapilloma is a benign tumor of the nail bed and distal matrix. which usually manifests as monodactylous longitudinal eryhtronychia associated with subungual hyperkeratosis. The impossibility to rule out a malignant neoplasm is an indication for surgical excision and histological examination. Our aim is to report and describe the ultrasonographic features of onychopapilloma. (2) Methods: we conducted a retrospective analysis of patients with a histological diagnosis of onychopapilloma who underwent ultrasonographic examination in our Dermatology Unit from January 2019 to December 2021. (3) Results: Six patients were enrolled. Erythronychia, melanonychia, and splinter hemorrhages were the main dermoscopical findings. Ultrasonography detected nail bed dishomogeneity in three patients (50%) and a distal hyperechoic mass (5 patients, 83.3%). Color Doppler imaging did not show vascular flow in any of the cases. (4) Conclusions: the detection of a subungual distal non-vascularized hyperechoic mass by US, together with classical onychopapilloma clinical features, supports the diagnosis, especially in those patients who were unable to perform excisional biopsy.


Introduction
Onychopapilloma is a benign tumor of the nail bed and the distal matrix that was first described by Baran and Perrin in 1995 [1]. It typically presents as a pink longitudinal band in the nail plate, called longitudinal erythronichia. Distal onycholysis with or without a V-shaped chipping at the free edge of the nail plate, subungual hyperkeratosis, and splinter hemorrhages are other frequent dermoscopical features. Rarely, it can present as melanonychia, leukonychia, or chromonychia.
Since its recent description, only 316 cases of onychopapilloma have been reported in 25 manuscripts so far. The clinical, dermoscopic, and histopathological features of previously described onychopapillomas are shown in Table 1. This tumor generally occurs in patients in their fifth or sixth decade of life, with some exceptions. However, data on gender prevalence are conflicting. After reviewing the available data extracted from reports in the literature, we identified 113 cases of onychopapilloma in male patients and 183 cases in female patients. In 311 out of 316 cases, the patients received surgery. The histopathological features included papillomatosis, acanthosis, hyperkeratosis, and matrix metaplasia of the nail bed . No ultrasound (US) reports have been published to this date.

Materials and Methods
We retrospectively reviewed ultrasonographic images of onychopapillomas performed at the Dermatology Unit of Fondazione IRCCS Ca' Granda from 1 January 2019 to 31 December 2021. The US platform implemented was a Hitachi Arietta V850 with a multifrequency linear array transductor (15.0-18.0 MHz). Transverse and sagittal ultrasonographic images were obtained.
The study was conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national), with the Helsinki Declaration of 1975, as revised in 2000, and with the Taipei Declaration. All patients provided written informed consent for study participation and publication of photographic material. Because of the retrospective nature of the study, only a notification to the Ethics Committee was requested.

Results
The epidemiological, clinical, and US findings are summarized in Table 2. Six patients were included in the study, of whom two were males (33.3%) with a medium age of 55.5 (age ranging 23-75). Erythronychia, melanonychia, and splinter hemorrhages were the main clinical findings at onychoscopy (Figure 1). Ultrasonography detected two main features: nail bed dishomogeneity found in three patients (50%) and a distal hyperechoic mass corresponding to the hyperkeratotic spur (five patients, 83.3%) ( Figure 2). Color Doppler imaging confirmed the absence of vascular flow in all cases.

Results
The epidemiological, clinical, and US findings are summarized in Ta tients were included in the study, of whom two were males (33.3%) with a of 55.5 (age ranging 23-75). Erythronychia, melanonychia, and splinter hemo the main clinical findings at onychoscopy (Figure 1). Ultrasonography detec features: nail bed dishomogeneity found in three patients (50%) and a dista mass corresponding to the hyperkeratotic spur (five patients, 83.3%) ( Fig  Doppler imaging confirmed the absence of vascular flow in all cases.

Discussion
Onychopapilloma is a benign nail tumor. The most frequent clinical features are longitudinal erythronychia and subungual hyperkeratosis.  Although onychopapilloma is reported as the most common cause of localized longitudinal erythronychia [26], benign tumors, such as the glomus tumor, and malignant neoplasms, such as amelanotic melanoma, Bowen disease, and squamous cell carcinoma, must be considered in the differential diagnosis of monodactylous longitudinal erythronychia in association with a subungual mass. Surgical excision is usually required in all of these cases. [27,28] Clinical and dermoscopic studies could not distinguish between malignancies and histologically confirmed onychopapilloma. [11] On the other hand, melanonychia was reported as a rare presentation of onychopapilloma. Differential diagnosis of longitudinal melanonychia includes the activation of nail matrix melanocytes, benign entities (lentigo or nevus), and malignant entities (melanoma)

Discussion
Onychopapilloma is a benign nail tumor. The most frequent clinical features are longitudinal erythronychia and subungual hyperkeratosis . Although onychopapilloma is reported as the most common cause of localized longitudinal erythronychia [26], benign tumors, such as the glomus tumor, and malignant neoplasms, such as amelanotic melanoma, Bowen disease, and squamous cell carcinoma, must be considered in the differential diagnosis of monodactylous longitudinal erythronychia in association with a subungual mass. Surgical excision is usually required in all of these cases [27,28]. Clinical and dermoscopic studies could not distinguish between malignancies and histologically confirmed onychopapilloma [11].
On the other hand, melanonychia was reported as a rare presentation of onychopapilloma. Differential diagnosis of longitudinal melanonychia includes the activation of nail matrix melanocytes, benign entities (lentigo or nevus), and malignant entities (melanoma) [29]. Interestingly, Starace et al. recently described six cases of pigmented onychopapilloma and reported that onychoscopy could not rule out melanocytic lesions; therefore, histological examination was necessary [21].
However, surgical excision is not without risks to the patient. Delvaux et al. reported their experience with 68 patients with onychopapilloma. Of these, 42% had mild to moderate sequelae (distal fissuring, cicatricial longitudinal erythronychia, punctiform hemorrhages, or onycholysis); while recurrence was observed in 20% of the cases. Four patients were kept on clinical follow-up and did not show any signs of progression [15].
US is a valuable tool to aid clinicians in the differential diagnosis of subungual masses [29]. We first reported the US features of six cases of onychopapilloma. In five cases, the presence of a distal subungual hyperechoic mass was identified. No vascular signal was detected by Doppler analysis in any of the examined cases. Moreover, nail bed dishomogeneity was observed in three patients. In our opinion, the nail bed dishomogeneity may represent the US equivalent of the nail bed epithelium acanthosis and matrix metaplasia ( Figure 3). The described hyperechoic aspect may histologically correspond to hyperkeratosis. Indeed, compact keratinocytes proliferation US appearance has been described as hyperechoic; for example, in psoriatic scaly plaques [30]. De Berker et al. described how the enhanced transparency of the thinned nail plate and the compression exerted at the margins by the normal nail can act together to generate the reddish band of longitudinal erythronychia [31].
J. Clin. Med. 2023, 12, x FOR PEER REVIEW 6 of 8 hemorrhages, or onycholysis); while recurrence was observed in 20% of the cases. Four patients were kept on clinical follow-up and did not show any signs of progression. [15] US is a valuable tool to aid clinicians in the differential diagnosis of subungual masses [29]. We first reported the US features of six cases of onychopapilloma. In five cases, the presence of a distal subungual hyperechoic mass was identified. No vascular signal was detected by Doppler analysis in any of the examined cases. Moreover, nail bed dishomogeneity was observed in three patients. In our opinion, the nail bed dishomogeneity may represent the US equivalent of the nail bed epithelium acanthosis and matrix metaplasia ( Figure 3). The described hyperechoic aspect may histologically correspond to hyperkeratosis. Indeed, compact keratinocytes proliferation US appearance has been described as hyperechoic; for example, in psoriatic scaly plaques.  Imaging may be helpful in characterizing a subungual lesion [32]: the US appearance of glomus tumors, squamous cell carcinoma, and melanoma usually corresponds to a hypoechoic mass, in contrast to that observed in onychopapilloma [33][34][35][36]. Glomus tumors are described as well-defined and hypervascularized lesions, usually surrounded by a Imaging may be helpful in characterizing a subungual lesion [32]: the US appearance of glomus tumors, squamous cell carcinoma, and melanoma usually corresponds to a hypoechoic mass, in contrast to that observed in onychopapilloma [33][34][35][36]. Glomus tumors are described as well-defined and hypervascularized lesions, usually surrounded by a capsule. Squamous cell carcinomas may present an anechoic avascular central zone, corresponding to an area of central necrosis [33]. Moreover, squamous cell carcinomas are characterized by a low-flow vascular signal at Color Doppler that is mostly found at the periphery of the lesion and extends toward the center. Nail unit melanoma is described as an ill-defined hypoechoic mass with intralesional vascularization, which may be difficult to detect in thin lesions. Bony erosions of the distal phalanx may be associated with all three tumors [34][35][36].
Surgical excision is recommended for subungual masses that present as painful lesions, typically glomus tumors, or if history and clinical or dermoscopic features are not sufficient to rule out t malignancy [11]. Onychopapillomas may also require surgical treatment due to associated issues such as difficulty picking up small objects (48.2%), pain (40.7%), and distal nail fragility (38.9%) [15]. Clinical follow-up may be indicated in most cases of asymptomatic onychopapilloma. US may be a useful tool to support the diagnosis of onychopapilloma in cases with classical clinical presentation such as longitudinal erythronychia and subungual hyperkeratotic mass. US detection of a subungual distal non-vascularized hyperechoic mass, together with classical clinical features, should represent an indication for clinical and sonographic follow-up, especially in patients unable to perform an excisional biopsy.
However, this case series is too limited and other literary data are scarce; therefore, further studies are needed to determine whether US features may be predictors of malignant versus benign diagnosis. Moreover, the sensitivity of ultrasound is too low to exclude malignancies in a precocious state.

Conclusions
US is a non-invasive diagnostic tool that can aid dermatologists in the differentiation of nail tumors presenting with monodactylous longitudinal erythronychia. We are the first to have reported the US features of onychopapilloma, including nail bed dishomogeneity and a distal hyperechoic mass without vascular flow. US may be a useful tool to support the diagnosis of onychopapilloma for the patients who are unable to perform excisional biopsies.