Skin biopsy is an important procedure for a correct diagnosis of varying skin conditions, from inflammatory to neoplastic diseases. Nevertheless, some authors still consider this procedure a high risk in patients affected by leg ulcers (LUs) and prefer reserving it for selected cases [1].
Chronic LUs are defined as wounds that do not heal after at least 3 months of therapy and may be induced by underlying vascular alterations (venous, mixed arteriovenous, and arterious) in most cases [1]. Other possible causes of LUs include vasculitis, pressure sores, inflammatory diseases, traumatic injuries, and cutaneous neoplasms [2]. Concerning this wide range of possible conditions, histopathologic examination of a skin specimen from the LU is often the most exhaustive procedure for a correct diagnosis [1, 2]. This becomes even more important when considering the considerable burden associated with inappropriate treatments and chronic diseases in general, which weighs on hospitals' and patients' budgets.
A total of 866 consecutive patients with chronic non-healing LUs who were referred to our Wound Care Unit (WCU) from January 2008 to December 2016 were submitted to an ulcer biopsy (Table 1). Of these, 329 were male and 537 female (F:M ratio 1: 1.6), with a mean age of 72 years (range 50–97 years). We performed two 3-mm punch skin biopsies in each study patient: one from the border and the other from the centre of the lesion. Histopathologic examination revealed 59 (7%) neoplasms.
Table 1.
Summary of the total 866 chronic leg ulcerations undergoing biopsy at the Wound Care Unit of Bologna
| Number of biopsies | Percentage | Histologic diagnosis |
|---|---|---|
| 614 | 71 | Vascular ulcers (venous, arterial, and mixed) |
| 78 | 9 | Inflammatory dermatitis (psoriasis, eczema, panniculitis, bullous disease, infective dermatitis) |
| 73 | 8.5 | Vasculitis |
| 59 | 7 | Neoplasms |
| 13 | 1.5 | Viral infections |
| 13 | 1.5 | Post-traumatic and pressure sores |
| 8 | 1 | Erosive pustular dermatitis |
| 6 | 0.5 | Pyoderma gangrenosum |
| 2 | <0.5 | Radiodermatitis |
These occurred more commonly in elderlies (mean age was 83) and the most commonly diagnosed tumours were non-melanoma skin cancers (n = 49, 83%), in particular basal cell carcinomas (n = 33) (Fig. 1, 2) and squamous cell carcinomas (n = 16) (Fig. 3, 4). Other tumours were diagnosed as lymphomas, either primitively cutaneous or secondarism (n = 5), eccrine syringofibroadenomas (n = 2), fibroadenomas (n = 2), and porocarcinoma (n = 1).
Fig. 1.

Clinical presentation of a basal cell carcinoma from our series.
Fig. 2.

Histopathologic presentation of the basal cell carcinoma shown in Figure 1.
Fig. 3.

Clinical presentation of a squamous cell carcinoma from our series.
Fig. 4.

Histopathologic presentation of the squamous cell carcinoma shown in Figure 3.
Chronic LUs represent an increasing health burden, and there is consensus on performing skin biopsies for histopathologic examination of these lesions [3, 4, 5]. We suggest analyzing at least two samples from each lesion: of the edge and the bed of the LU. A 3-mm punch is a safe and effective tool for this purpose: no evidence of worsening has been described for any lesion undergoing this procedure, while interestingly some cases seem to benefit from the biopsy itself as it stimulates local healing [4]. The Food and Drug Administration recommends wound biopsy as a fundamental tool to detect neoplastic, immune-mediated, or infectious diseases [6]. Our experience confirms that neoplasms, in particular non-melanoma skin cancers, represent a consistent proportion of chronic LUs [7]. Emerging authors have focused on the role of chronic venous ulceration in triggering the development of basal cell carcinomas [5, 7, 8]. On the other hand, neoplastic lesions can become chronically ulcerated, for example in Marjolin ulcer, or also show ulceration from their appearance [9, 10]. In addition, ulceration is a negative prognostic factor in cutaneous neoplasms, which often present a high metastatic rate; therefore, biopsy appears even more important in these cases [9].
We believe that clinicians should be aware of the importance of an early and correct diagnosis of cutaneous neoplasms underlying chronic LUs. This could avoid diagnostic delay and guarantee the best therapeutic approach to each patient.
Statement of Ethics
The authors have no ethical conflicts to disclose.
Disclosure Statement
The authors have not received any funding source and have no conflict of interest to disclose.
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References
- 1.Margolis DJ, Berlin JA, Strom BL. Risk factors associated with the failure of a venous leg ulcer to heal. Arch Dermatol. 1999;135:920–926. doi: 10.1001/archderm.135.8.920. [DOI] [PubMed] [Google Scholar]
- 2.Tang JC, Vivas A, Rey A, Kirsner RS, Romanelli P. Atypical ulcers: wound biopsy results from a university wound pathology service. Ostomy Wound Man. 2012;58:20–22. 24, 26–29. [PubMed] [Google Scholar]
- 3.Reich-Schupke S, Doerler M, Wollina U, Dissemond J, Horn T, Strölin A, Erfurt-Berge C, Stücker M. Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review. J Dtsch Dermatol Ges. 2015;13:1006–1013. doi: 10.1111/ddg.12649. [DOI] [PubMed] [Google Scholar]
- 4.Panuncialman J, Hammerman S, Carson P, Falanga V. Wound edge biopsy in chronic wounds heal rapidly and do not result in delayed overall healing of the wound. Wound Repair Regen. 2010;18:21–25. doi: 10.1111/j.1524-475X.2009.00559.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Lutz ME, Davis MD, Otley CC. Infiltrating basal cell carcinoma in the setting of a venous ulcer. Int J Dermatol. 2000;39:519–520. doi: 10.1046/j.1365-4362.2000.00887.x. [DOI] [PubMed] [Google Scholar]
- 6.U.S. Department of Health and Human Services Food and Drug Administration Guidance for industry chronic cutaneous ulcer and burn wounds-developing products for treatment. 2006 Jun; http://www.fda.gov/cber/gdlns/ulcburn.htlm. [Google Scholar]
- 7.Yang D, Morrison BD, Vandongen YK, Vandongen YK, Singh A, Stacey MC. Malignancy in chronic leg ulcers. Med J Aust. 1996;164:718–720. doi: 10.5694/j.1326-5377.1996.tb122269.x. [DOI] [PubMed] [Google Scholar]
- 8.Gil T, Pistunovich Y, Kulikovsky M, Elmalah I, Krausz Y, Mettanes I, Lavi I, Har-shai Y. A prospective case-control study of non-healing wounds of the lower limbs-the value of biopsies for ulcerating carcinoma. J Eur Acad Derm Venereol. 2015;29:337–345. doi: 10.1111/jdv.12550. [DOI] [PubMed] [Google Scholar]
- 9.Khan K, Giannone AL, Mehrabi E, Khan A, Giannone RE. Marjolin's ulcer complicating a pressure sore: the clock is ticking. Am J Case Rep. 2016;17:111–114. doi: 10.12659/AJCR.896352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Pranteda G, Grimaldi M, Lombardi M, Pranteda G, Arcese A, Cortesi G, Muscianese M, Bottoni U. Basal cell carcinoma: differences according to anatomic location and clinical-pathological subtypes. G Ital Dermatol Venereol. 2014;149:423–426. [PubMed] [Google Scholar]
