An unusual case of nasal chromoblastomycosis degenerating into squamous cell carcinoma from a nonendemic region

Chromoblas tomycos i s (CBM) i s a s low ly progressive granulomatous mycosis of the skin and subcutaneous tissue caused by inoculation of dematiaceous fungi mainly on the lower limbs. This infection occurs in tropical and subtropical regions, but there have been several case reports from temperate regions. If not diagnosed and treated at an early stage, it may rarely undergo malignant transformation into squamous cell carcinoma (SCC), which is its most serious complication [1]. Herein, we report an unusual case of CBM from Tunisia, a nonendemic area, occurring in a distant site from the original lesion and degenerating into SCC. CASE REPORT


INTRODUCTION
C h r o m o b l a s t o m y c o s i s ( C B M ) i s a s l o w l y progressive granulomatous mycosis of the skin and subcutaneous tissue caused by inoculation of dematiaceous fungi mainly on the lower limbs. This infection occurs in tropical and subtropical regions, but there have been several case reports from temperate regions. If not diagnosed and treated at an early stage, it may rarely undergo malignant transformation into squamous cell carcinoma (SCC), which is its most serious complication [1]. Herein, we report an unusual case of CBM from Tunisia, a nonendemic area, occurring in a distant site from the original lesion and degenerating into SCC.

CASE REPORT
In 2006, a sixty-year-old healthy male from north Tunisia presented himself to our dermatology department with an infiltrated 6 × 5 cm erythematous plaque on the right thigh. A histopathological examination revealed the presence of fungal elements. A mycologic examination confirmed the diagnosis of CBM, but the species was not identified. On interrogation, the patient reported no travels to tropical areas, but worked as a masseur in a Turkish bath in conditions of high humidity and heat. The patient also remembered having been injured in this site two years ago at work. The patient was treated with terbinafine at a dose of 500 mg/day. There was a significant decrease in the size of the lesion, but he was lost to follow-up after three months. Several years later, he developed a fleshy reddish mass coming from the right nasal cavity with mucopurulent discharge. Over the last three months, it had rapidly extended and involved the nasal dorsum. An examination revealed a bleeding 4 × 3 cm ulcer-budding nasal tumor with an irregular edge surmounted by telangiectasias (Fig. 1). Dermoscopy revealed a vascular pattern with polymorphous vessels. No cervical lymph nodes were palpable. On the right thigh, we found a 12 × 13 cm slightly elevated pruritic erythematous and verrucous plaque with atrophy and depigmentation in most places (Fig. 2). The rest of the examination was normal. There was no evidence of immunodeficiency. Clinically, the differential diagnoses of the tumor form of CBM and SCC were considered. Biopsies were taken from several sites of the nasal lesion and the plaque on the thigh. Histopathology revealed the presence of fungal elements in a granulomatous reaction and mixed inflammatory infiltrate (Figs. 3a and 3b). Other endonasal and nasal dorsum biopsy fragments showed moderately differentiated SCC (Fig. 3c). A direct microscopic examination showed fumagoid cells (Fig. 4a). Fungal cultures of the two samples on Sabouraud dextrose agar showed a growth of pigmented, velvety-dark colonies (Figs. 4b -4d). A microscopic examination of the colonies revealed cylindrical septate hyphae, and conidiophores swollen at their termination carrying ovoid conidia suggestive of the Fonsecaea pedrosoi species (Fig. 4e). From these features, the diagnosis of nasal CBM with SCC degeneration was reached. A neck-chest-abdomen CT scan was normal. We started a combined therapy consisting of terbinafine at 500 mg and itraconazole at 200 mg daily, and referred the patient to the oncosurgery department.

DISCUSSION
CBM is one of the most prevalent transcutaneous traumatic implantations in individuals living in tropical and subtropical climate areas of America, Asia, and Africa [2]. However, sporadic cases are being increasingly more often described in temperate zones, such as Western Europe and North Africa. In Maghreb countries, and particularly in Tunisia, CBM has been rarely reported: so far five cases have been published [3]. All etiological agents of CBM are black fungi with low pathogenicity thermosensitive at 40-42 o C and living as saprophytes in the soil, plants, thorns, debris, and transported wood. They have also been isolated in saunas, where the conditions of high humidity and heat create a tropical microclimate that might explain the development of fungi even in temperate areas [4]. This is probably the case in our patient, who worked as a masseur in a Turkish bath.
The typical lesions usually tend to be found in exposed and nonprotected areas of the body, especially the feet and legs. According to Minotto R et al., 27% of cases involve other areas, including the medial canthus of the eye, the ears, neck, shoulder, chest, wrists, and buttocks [5]. The nasal cavity is rarely affected by CBM and there have been only a few such cases described [6]. Our patient's first lesion occurred unusually in an unexposed location-the inner part of a thigh-which might also be explained by his professional occupation. In general, CBM is a localized infection invading body sites in the immediate area of the original lesions, but usually without metastasis to distant sites. The site of our patient's second lesion might have been explained by autoinoculation due to itching.    b c a syphilis. A positive diagnosis is usually confirmed by characteristic mycological and histopathological results. When skin biopsies or scrapings are examined under microscopy, pathognomonic muriform cells are seen. These rounded, cigar-colored, and crosschambered structures are distinctive, and are also known as Medlar bodies, sclerotic bodies, and fumagoid cells [8]. Histologically, CBM typically reveals a dermal granulomatous infiltrate with a predominance of epithelioid cells surrounding fumagoid bodies [7]. A culture allows the isolation and identification of the causal organisms in about fifteen days. Initially, colonies are deep-green, depicting a dark velvet aspect with time. Presumptive species identification may be achieved by mycological morphologic methods, but molecular techniques are suggested for definitive identification.
CBM lesions are usually recalcitrant and extremely difficult to eradicate. If not diagnosed and treated early, CBM has a chronic evolutional course with numerous complications, such as secondary bacterial infection, lymphoedema, and chronic nonhealing ulcers.
The major risk is malignant transformation mainly into SCC [1]. The risk of malignant transformation is around 1%, as illustrated in a Madagascar study in which neoplasia was reported in 14 out of 1400 cases over a period of fifty years [8]. The first reported case of malignant degeneration was described by Caplan in 1968 in a patient from Nicaragua presenting with verrucous plaque lesions on the legs, left thigh, and right hand, which evolved over a period of approx. eleven years [9]. Subsequently, around 23 cases of tumors derived from CBM were documented worldwide (Table 1) [9][10][11][12][13][14][15][16][17][18][19][20]. The sex ratio was 19/2. The average disease evolution time was 19.7 years. The main affected site was the lower limbs. Cases of CBM-derived SCC were, in the majority, cured after surgical excision.

CONCLUSION
Malignancy must be suspected in the case of any suspicious change, such as the development of ulceration, a rapid growth, or a poor response to treatment. Without a doubt, the conditions of the affected tissue, which involve inflammation and chronic reparatory processes, are significant predisposing factors. Our patient had endonasal CBM that had slowly and asymptomatically evolved and had recently degenerated.