An apparently untreatable ulcer of the face

Dear Editors,

A 92 year‐old man presented with a right zygomatic ulcerated lesion that deepened just above the periosteal plane. The lesion appeared 2 months before, rapidly reaching 21·4 cm². No specialised evaluation was previously performed. A domestic cleaner with a generic alcoholic disinfectant was used.

At the first physical examination by the general surgeon, the lesion was mildly exuding, no necrosis was detected, the periosteal plane was evident, a mild fibrosis was present along the walls of the cavity and no granulation tissue was identified. The perilesional skin was apparently normal (Figure 1A). The patient record reported microcytic anaemia, arterial hypertension and atrial fibrillation.

Figure 1.

(A) The extensive ulcerated squamous cell carcinoma at patient presentation; (B) On histological examination, the tumour consists of irregular masses of epidermal cells that proliferate downward into the dermis. The invading masses are composed in varying proportions of semi‐normal squamous cells and of atypical (anaplastic) squamous cells. Note the hyperplasia and hypercromasia of the nuclei, absence of intercellular bridges, keartiniziation (horn pearls are present) of individual cells and presence of mitotic figures.

A biopsy of the skin margin was obtained, leading to the diagnosis of infiltrative squamous cell carcinoma, moderately differentiated (Figure 1B).

The patient's case was discussed by a multidisciplinary committee involving general and plastic surgeons, dermatologists and radiotherapists. A total body skin examination did not reveal any other skin lesions; regional lymphadenopathy was not detected either.

The risk/benefit ratio in the patient's demographic and clinical conditions did not indicate a surgical procedure. For the same reasons and for the discomfort in reaching the radiotherapy unit at least twice a week, radiation treatment was not considered appropriate as well. Moreover, both the patient and his relatives firmly refused to consent to invasive procedures or systemic therapies.

With a palliative target, the patient was medicated once a week by surgical debridment and covered with Promogran^R (Systagenix, Gargrave, UK), a dressing comprised of oxidised regenerated cellulose (45%) and collagen (55%).

Surprisingly, after only 3 months of regular weekly treatment, the lesion was completely healed (Figure 2A). A biopsy was performed in the middle of the regenerated skin, and the histological examination showed no evidence of a residual carcinoma (Figure 2B).

Figure 2.

(A) Complete re‐epithelisation of the ulcerated Cutaneous squamous cell carcinoma (cSCC) after a 3‐month weekly medication by surgical debridment and covered with Promogran^R; (B) On histological examination of the margins, the skin is trophic, and there is no evidence of residual carcinoma but evident sun exposure damages (actinic elastosis).

After a 6‐month follow up, the complete recovery of the ulcerative lesion was still present.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the Western population and is the second most common skin cancer after basal cell carcinoma (BCC) 1. Although less common than BCC, cSCC carries a risk of metastasis and thus accounts for the majority of the deaths attributable to non‐melanoma skin cancers 2.

Conventional surgical excision is the treatment of choice for small, primary cSCC. Locally advanced cSCC may render some patients unfit for surgery. Unresectable cancer is mainly treated by radiotherapy 3. Several host/tumour factors must be taken into account in treatment planning, including the patient's general conditions and specific comorbidities that might prevent the possibility of delivering curative doses of radiation without damaging vital structures, the locoregional volumetric extension of the disease and the presence or absence of distant metastases.

In its most advanced form, cSCC may be treated systemically. A number of systemic therapies have been used, including cytotoxic chemotherapy [cisplatin, 5‐fluorouracil (5‐FU), bleomycin and doxorubicin] 4, 13‐cis‐retinoic acid (13cRA) 5 and immunotherapy (interferon α2a) 6. Cetuximab 7 and gefitinib 8 have been found to be effective in treating advanced cSCC, and epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase, has been shown to be upregulated in a variety of cSCC 9.

In the present case, the wide extension and location of the ulcerative cSCC, the patient's age and general conditions and his family's strict opposition to invasive treatments rendered it not possible to offer the patient either a surgical intervention or a chemoradiation protocol with curative intent.

Promogran^R (Systagenix, Gargrave, UK) is made by oxidised regenerated cellulose and collagen 10, 11. It maintains a moist microenvironment in the wound, promoting granulation and epithelisation. It also balances the imbalance of the metalloproteases 12. Till now, Promogran^R (Systagenix, Gargrave, UK) is indicated in arterial and venous chronic wounds, pressure lesions, abrasions, traumatic lesions healing by secondary intention and dehisced surgical wounds. Interestingly, Tausche and Sebastian reported the benefits of Promogran^R use in enabling a successful split‐thickness skin grafting following a BCC excision 13.

To the best of our knowledge, our reported experience represents the first Promogran^R‐related tissue repair that was documented in a cSCC environment in the absence of any other therapeutic support. We cannot exclude that the reported lesion, although clinically atypical, could actually be a giant keratoacanthoma (KA), a rare variant of KA measuring at least 20 mm in diameter. A giant KA can mimic cSCC, and the histological distinction between these two entities is often difficult. It may even be impossible especially when the histological architecture of giant KA is not typical as in our extensively ulcerated lesion. KA has the ability to spontaneously regress, and cases of giant KAs resolving without any intervention have been reported 14, 15. On the contrary, there have been no reported cases of self‐resolving cSCC. If we consider the reported case as a giant KA, it is difficult to exclude that the excellent result observed was because of its natural history. In any case, it must be stressed that Promogran^R (Systagenix, Gargrave, UK) cannot be either considered or offered as a treatment for the locally advanced cSCC as well as giant KAs. In fact, the aims of treatment of cutaneous carcinomas are to completely remove or destroy the tumour while minimising functional and cosmetic impairment. In spite of the absence of cancer at the second histological examination, we believe that in the case of a true cSCC, larger and multiple biopsies as well as a confocal microscopy assessment would probably find residual tumour tissue.

Our observation shows that the constant use of an oxidised regenerated cellulose‐ and collagen‐made medication has been a useful tool in the rapid, complete and persistent ulcer resolution in the case reported, improving the patient's quality of life and functioning. Patients with unresectable ulcerative cSCC or ulcerative giant KAs not suitable for either radiotherapy or chemotherapy should only be considered for the treatment with Promogran^R (Systagenix, Gargrave, UK) dressing to achieve a palliation in an otherwise untreatable situation. Further investigations will be needed in order to explore the intriguing effects of the protease imbalance management in neoplastic tissues.

Alessandro Borghi, MD1, Sergio Gianesini, MD2, Massimo Pedriali, MD3, Antonio Stefanelli, MD4, Giovanni Mangiola, MD5, Patrizia Dalla Caneva, MD2, Giovanni Lanza, MD3, Annarosa Virgili, MD1, Paolo Zamboni, MD2
1Dipartimento di Scienze Mediche, Sezione di Dermatologia e Malattie Infettive
Università degli Studi di
Ferrara, Italy
2Vascular Disease Center
University of Ferrara
Ferrara, Italy
3Section of Anatomy, Histology and Pathological Cytology
University of Ferrara
Ferrara, Italy
4Department of Radiation Oncology
University Hospital SS. Anna
Ferrara, Italy
5Residenza Caterina Ferrara
Ferrara, Italy
alessandro.borghi@unife.it