A Misleading Anamnesis: Learning To Suspect

Leishmaniasis represents a complex, globally widespread opportunistic infection ranging from the visceral form, also called kala-azar, to the mucocutaneous and cutaneous disease. It is endemic in the Mediterranian Basin, Leishmania infantum being demonstrated as the main causative agent of autochthonous cases in Sicily, Italy. The long-term use of systemic antipsoriatic agents, including biotechnological drugs, may cause a higher susceptibility to opportunistic infections, so physicians maintain a high level of suspicion with treated patients. However, some skin tumours, because of the rare occurrence and/or the atypical clinical features, may mimic another kind of disease thus leading to a delay in diagnosis and treatment. An exemplary case is reported herein.


Case report
A 57-year-old Caucasian man, who was a farmer affected by psoriasis and treated with cyclosporine A periodically in the last two years, presented for the first time to our Unit with a one-year history of an asymptomatic, approximately round, well-demarcated lesion on the second finger of the left hand, reported as the possible consequence of a previous trauma or insect bite. In anamnesis, the patient revealed that indeed he had subsequently noticed a small bump, gradually increasing in size and elevating, but never experiencing pain in the affected area. Apart from psoriasis, medical history was also notable for the chronic obstructive pulmonary disease.
The lesion was initially treated with topical gentamycin/betamethasone cream for about one month, and then the patient commenced oral amoxicillin/clavulanate (2g/day) for two months. Because of the lack of any improvement, together with the further ulceration of the nodule, and having cutaneous leishmaniasis in mind as suspect diagnosis, general physician empirically prescribed rifampicin (600 mg/day for two months) and then oral itraconazole (200 mg/day for one month) with no significant changes of the clinical picture. He also proposed possible intralesional therapy with meglumine antimoniate, but the patient sought dermatological consultation.
Cutaneous examination revealed a firm, fleshcoloured, slightly erythematous eroded nodule, measuring 9 mm in diameter, located on the medial surface of the medial phalange, close to the interphalangeal joint. The skin surrounding the tumour was normal, except for xerosis with light scaling ( Fig.1  and 2). An x-ray film of the hand in two projections showed no evidence of bone abnormality. A biopsy specimen was obtained: hematoxylin-eosin staining revealed an ulcerated surface epithelium with hyperkeratosis and acanthosis and nests of nonpigmented atypical epithelioid cells at the dermoepidermal junction; also, nests and trabeculae of neoplastic cells extended down to the reticular dermis. http://www.mjms.mk/ http://www.id-press.eu/mjms/  Surgical excision of the neoplasm was requested, and the patient decided to continue the diagnostic and therapeutic procedure at another centre.

Discussion
Malignant melanoma (MM) is one of the most aggressive malignant neoplasms with a steadily increasing incidence in the last 30 years as well as mortality, despite the advances in treatment [1,2]. When localised at acral body sites, it is much more frequent in dark-skinned and Oriental populations [3].
Typically, the clinical hallmark of cutaneous MM is the presence of pigment, varying from black to blue, to the shades of brown, tan, pink and white, within lesions with irregular contours on clinical examination [4].

Figure 3: Histological view, H&E stain, original magnification x100 (detailed in the text)
On the contrary, amelanotic melanoma shows little or no pigment on visual inspection. Although the incidence of amelanotic melanoma among MM is low (2% to 8% of cases), the digits (and the subunguals) seem to be an area of predilection, a rate of about 25% of MM being amelanotic at these sites [5,6]. In dermatologic consultation, the skilled eye of the specialized observer as well as dermoscopy, if applicable, are the unique instruments to make an often difficult diagnosis [7,8], whereas radiographic studies of the part are useful to exclude bone lesions [9]. In facts, there is still no evidence that amelanotic melanomas behave more aggressively than their pigmented counterpart, but the lack of pigmentation obviously adds further difficulties to an already hard diagnosis. As in all types of MM, there is a direct relationship between increasing tumour thickness and decreasing survival time. Due to its atypical presentation, with consequent late detection, amelanotic melanoma is often diagnosed at a late stage of the disease with a worsened prognosis [4,10]. About our case, the confounding anamnesis represented an additional misleading, as the patient came from a rural area endemic for cutaneous leishmaniasis [11,12] and the clinical picture of the condition was also evocative [13].
Also, immunosuppression in patients treated for the chronic autoimmune disease could theoretically facilitate the occurring of opportunistic infections [14]. This concern has to be dramatically stressed nowadays with the growing use of biotechnological drugs [15].
In conclusion, we presented the case with the aim of underlining the importance for physicians of performing incisional biopsies in the presence of clinically featureless cutaneous lesions. In particular, although asymptomatic, clearly growing amelanotic papules and nodules, with no of diagnostic criteria at imaging (e.g., Dermoscopy or x-ray) and with ulceration, should be histologically evaluated to exclude malignant melanoma at a first stage. Local or systemic prolonged medical treatments should be avoided in the absence of immediate improvement.