| Abstract|| |
Subungual tumors are rare in general. Of all tumors, subungual squamous cell carcinoma (SSCC) is the most frequent one. Protean clinical presentations and the lack of awareness of the disease are responsible for an incorrect or delayed diagnosis and subsequent delayed treatment. We have reported here four patients with SSCC who were previously wrongly diagnosed with a benign process and treated unsuccessfully for years. We would like to highlight the need of a biopsy in chronic or recurrent nail lesions that fail to respond to a previous conservative treatment in order to rule out SSCC.
Keywords: Human papillomavirus, nail, neoplasms, squamous cell carcinoma, viral wart
|How to cite this article:|
Batalla A, Feal C, Rosón E, Posada C. Subungual squamous cell carcinoma: A case series. Indian J Dermatol 2014;59:352-4
What was known?
Squamous cell carcinoma is the most frequent of malignant subungual tumors. Nevertheless, it is commonly misdiagnosed, which leads to a poor prognosis and more aggressive treatments.
| Introduction|| |
Subungual squamous cell carcinoma (SSCC) is a rare entity with an extremely varied clinical presentation. The lack of awareness among physicians, its indolent natural history, and the higher prevalence of other benign conditions on the ungual apparatus are responsible for delay in its diagnosis. We have reported here four cases of SSCC with a previous mistaken diagnosis of a benign process unsuccessfully treated for years.
| Case Report|| |
Epidemiological, clinical, and histological patient data are shown in [Table 1]. [Figure 1] shows the different clinical presentation of cases herein reported. The first patient presented with involvement of two digits. Radiological studies did not reveal alterations, except for an incidental osteochondroma in the fourth patient . Histological examination revealed SSCC in all cases, but immunostaining for human papillomavirus (HPV) was only positive in the first patient, who presented with deeper tissue involvement [Figure 2]. All surgical procedures resulted in free-margin tumoral excisions, without recurrences or nodal involvement during follow-up between 5 and 30 months.
|Figure 1:a) Keratotic and verrucous lesion below the nail plate mimicking a viral wart (case 1), (b) Crusted subungual lesion (case 2), (c) Erythematous and eroded lesion covered by crusts and keratotic material (case 3), (d) Prominent onycholysis and fleshy nodular lesion (case 4)|
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|Figure 2: (a) Positive immunostaining for HPV in case 1 (arrows)HPV immunostaining, ×200), (b) Moderately differentiated subungual squamous cell carcinoma in the second patient. Keratinocytes with higher nuclear/cytoplasmic ratio, but still keratinizing (asterisks). Presence of mitotic figures (arrows). (H and E, ×100), (c and d) Well-differentiated squamous cell carcinoma in third and fourth patients. Lobular aggregations of slightly atypical keratinocytes and incipient horn pearl formation (arrows)(H and E, ×100)|
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| Discussion|| |
Tumors located in subungual tissues include squamous cell carcinoma (SCC), Bowen's disease, melanoma, basal cell carcinoma, and keratoacanthoma among others. These malignant subungual tumors are uncommon, of these SSCC is the most frequent. , Usually, SSCC affects a single digit, the thumb and the great toe being the most frequently involved. ,, Multiple fingers involvement has also been described.  The incidence is higher in men between the fifth and seventh decades of life. ,,,
The proposed aetiologies of the disease include chronic infection, chemical or physical microtrauma, genetic disorders such as congenital ectodermal dysplasia, radiation, tar, arsenic or exposure to minerals, sun exposure, immunosuppression, and previous HPV infection. ,, HPV involvement has gained importance, as HPV DNA was recovered from 60% to 90% of cases of SSCC and >60% were related to HPV 16. Genital-digital transmission has been suggested as a plausible pathogenetic factor in SSCC, as HPV 16 is the most frequent serotype found in genital warts.  However, there are probably other factors implicated in malignancy, as viral warts in hands are very common and the development of SSCC remains rare. In the cases herein reported, all potential causative factors of SSCC were excluded with the clinical history data and the physical examination. None of the patients presented or had history of genital warts.
The clinical features may be variable and include chronic pain and swelling, onycholysis, or nail plate dyschromia. The most frequent presentation consists of wart-like appearance involving the nail bed and periungual areas in association with nail dystrophy. Other findings raising suspicion of SSCC include nodularity, bleeding, and ulceration. , The differential diagnoses are many. Viral warts, onychomycosis, or chronic paronychia remain the most commonly mistaken entities. ,
Besides, the tumor masked by the nail plate, lack of awareness, and overlying secondary infections lead to misdiagnosis for an average of 4-40 years. , Therefore, exploratory nail plate removal and subsequent biopsy are advised in all patients with chronic nail conditions that fail to respond to conventional treatment. In patients with recurrent nail infections or chronic ulcerations, tissue culture is also needed. Imaging studies may be done to assess possible bone involvement. ,,,
As a result of delayed diagnosis, most patients with SSCC present with invasive disease, with bony involvement ranging from 16% to 66%. ,, SSCC is considered a low-grade malignancy and less aggressive than SCC arising elsewhere.  Lymph node involvement is reported in <2% of patients. Tendency to metastasize is low but it has been reported in a few cases. ,,, The tendency to recurrence is higher on the nail unit than in other anatomic areas. This fact can probably be due to residual HPV in surrounding areas or, more frequently, due to incomplete tumor removal.  Therefore, long term follow-up is recommended in SSCC patients. ,,
There is no standardized treatment for SSCC. The therapy of choice depends on the extent of the tumor. Lesions without bone involvement can be microscopically excised. Wide local excision and simple excision have also been proven effective, the former being preferred because of the lower recurrence rate. Amputation of the distal phalanx is usually the recommended treatment for patients with bone infiltration. Radiation therapy has also been reported to be effective. ,,
In conclusion, a high index of suspicion for SSCC is required. Therefore, an early biopsy in chronic persistent or recurrent nail lesions, and subsequent early SSCC diagnosis may prevent more aggressive treatments and assures a favourable prognosis.
| Acknowledgement|| |
We are indebted to ML Carpintero, JJ Álvarez, and C Álvarez for their collaboration with this manuscript.
| References|| |
|1.||Meesiri S. Subungual squamous cell carcinoma masquerading as chronic common infection. J Med Assoc Thai 2010;93:248-51. |
|2.||Kelly KJ, Kalani AD, Storrs S, Montenegro G, Fan C, Lee MH, et al. Subungual squamous cell carcinoma of the toe: Working toward a standardized therapeutic approach. J Surg Educ 2008;65:297-301. |
|3.||Bui-Mansfield LT, Pulcini JP, Rose S. Subungual squamous cell carcinoma of the finger. AJR Am J Roentgenol 2005;185:174-5. |
|4.||Porembski MA, Rayan GM. Subungual carcinomas in multiple digits. J Hand Surg Eur Vol 2007;32:547-9. |
|5.||Patel PP, Hoppe IC, Bell WR, Lambert WC, Fleegler EJ. Perils of diagnosis and detection of subungual squamous cell carcinoma. Ann Dermatol 2011;23 Suppl 3:S285-7. |
|6.||Dalle S, Depape L, Phan A, Balme B, Ronger-Savle S, Thomas L. Squamous cell carcinoma of the nail apparatus: Clinicopathological study of 35 cases. Br J Dermatol 2007;156:871-4. |
|7.||Nasca MR, Innocenzi D, Micali G. Subungual squamous cell carcinoma of the toe: Report on three cases. Dermatol Surg 2004;30(2 Pt 2):345-8. |
|8.||Moy RL, Eliezri YD, Nuovo GJ, Zitelli JA, Bennett RG, Silverstein S. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas. JAMA 1989;261:2669-73. |
|9.||Ruiz Santiago H, Morales-Burgos A. Cryosurgery as adjuvant to Mohs micrographic surgery in the management of subungual squamous cell carcinoma. Dermatol Surg 2011;37:256-8. |
|10.||Huang KC, Hsu RW, Lee KF, Li YY. Late inguinal metastasis of a well-differentiated subungual squamous cell carcinoma after radical toe amputation. Dermatol Surg 2005;31(7 Pt 1):784-6. |
What is new?
1. Human papillomavirus infection probably has an important role in the development of subungual squamous cell carcinoma.
2. Subungual squamous cell carcinoma has a high recurrence rate. Therefore, long term follow-up is indicated.
[Figure 1], [Figure 2]