Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

OBJECTIVE: Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an uncommon melanocytic tumor characterized by an intrinsic aggressiveness, with specific histological and clinicopathological features. Acral melanoma involves the palms, soles and sub-ungueal sites. PATIENTS AND METHODS: A total of 244 patients with acral melanoma were included in our analysis. The current study was performed in three different medical centers: Sapienza University of Rome, San Gallicano Institute of Rome and University of Magna Graecia (Italy). The Kaplan-Meier product was used to estimate survival curves for disease-free survival and overall survival. The log-rank test was used to evaluate differences between the survival curves. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Spearman's test and subsequently data were analyzed performing Cox proportional-hazard regression. RESULTS: In both univariate and multivariate analyses Breslow thickness (p < 0.0001) and ulceration (p = 0.003) remained the main predictors. General BRAF mutation was detected in 13.8% of cases. We found that median Breslow value and the percentage of recurrences were similar in hand-acral melanoma and foot-acral melanoma, as well as there were no differences in both short and long-term. CONCLUSIONS: The absence of differences in survival between hand-acral melanoma and foot-acral melanoma shows that the aggressiveness of the disease is related to distinct mutational rate, as well as to anatomical site-specific features, rather than to the visibility of the primary lesion.

Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal-dominant disorder characterized by the association of sebaceous tumors or keratoacanthomas with an early onset visceral cancer in the spectrum of Lynch syndrome. OBSERVATIONS: A total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of six patients with MTS were analysed. Two main clinico-dermoscopic features were observed: (1) clinically pink to white papules/nodules with a central crater, dermoscopically characterized by radially arranged, elongated crown vessels surrounding opaque structureless yellow areas at times covered by blood crusts (n = 13) and (2), clinically pink to yellow papules/nodules without a central crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like globules and branching arborizing vessels (n = 7). Confocal microscopy was available in three sebaceous adenomas and revealed a good histopathologic correlation; sebaceous lobules were composed by clusters of ovoid cells with dark nuclei and bright, highly refractile glistening cytoplasm. They were delimited by a rim of epithelial cells, corresponding to basaloid cells. CONCLUSIONS: A better characterization of clinical, dermoscopic and confocal microscopy features of sebaceous tumors may improve their recognition and consequently, aid to rise the suspect for MTS.

Typical and atypical dermoscopic presentations of dermatofibroma.

BACKGROUND: Dermatofibroma is a common skin neoplasm that is usually easy to recognize, but in some cases its differentiation from melanoma and other tumours may be difficult. OBJECTIVE: To describe the dermoscopic features of dermatofibromas, with special emphasis on the characteristics of atypical patterns, and to calculate pattern frequency according to the patients age and gender, anatomical site and histopathological subtype. METHODS: Two groups of patients were consecutively seen, one with dermatofibromas that were surgically excised because of clinically and/or dermoscopically equivocal aspects or following patient request, and another with non-equivocal dermatofibromas. Each lesion was scored for previously reported global dermoscopic patterns and for additional features. RESULTS: A typical pattern was observed in 92 of 130 (70.8%) lesions, whereas an atypical pattern, that we named the 'non Dermatofibroma (DF)-like' pattern, was seen in 38 of 130 (29.2%). Atypical dermatofibromas showed features reminiscent of different conditions, such as melanoma in 21(16.2%) cases, vascular tumour in six (4.6%), basal cell carcinoma in five (3.8%), collision tumour in three (2.3%) and psoriasis in three (2.3%). A significant association was found between the 'melanoma-like' pattern/'vascular tumour-like' pattern and males, whereas a trend was observed between the above-mentioned patterns and hemosiderotic/aneurysmal DFs. 'Peripheral pigment network and central white scar-like patch' pattern was found associated with females and classic histopathological variant of DF. CONCLUSION: Dermatofibromas may display different morphological faces. The typical dermoscopic patterns allow a confident diagnosis, whereas a full surgical excision is always recommended in all doubtful cases.

Seven-point checklist of dermoscopy revisited.

BACKGROUND: Most dermoscopic algorithms to diagnose melanoma were established more than 10 years ago and have been tested primarily on clear-cut melanomas and excised melanocytic naevi. OBJECTIVES: To assess the diagnostic performance of pattern analysis and seven-point checklist on lesions that reflect the current clinical setting, compared with a revised seven-point checklist with a lower threshold for excision. METHODS: Eight experienced dermatologists viewed dermoscopic images of 100 excised melanomas, 100 excised naevi and 100 monitored naevi. Each lesion was evaluated by pattern analysis and scored as naevus, melanoma or lesion to be excised. Images were then evaluated using the seven-point criteria, with both standard and revised thresholds for excision. RESULTS: Pooled data using the pattern analysis algorithm showed that 82% of melanomas and 87·5% of monitored naevi were correctly scored as lesion to be excised and benign naevus, respectively. Using the standard and revised thresholds for the seven-point checklist, excision was recommended for 77·9% and 87·8% of the lesions in the melanoma set, respectively. The standard threshold produced 'no excision' recommendations for 85·6% of the monitored naevi, compared with 74·5% using the revised threshold. Pattern analysis, standard seven-point and revised seven-point algorithms resulted in recommendations of 'excision' for 63·6%, 60·3% and 72·0% of the excised naevi, respectively. CONCLUSIONS: The diagnostic approach to naevi and melanoma should be adapted to the current clinical setting, in which patients may present with early-stage melanomas and multiple atypical naevi. To increase sensitivity, a revised seven-point checklist with a lower threshold for excision should be used.

Cost-effectiveness analysis of topical treatments for actinic keratosis in the perspective of the Italian health care system.

Actinic keratosis (AK) is the most common cutaneous malignant neoplasm and its prevalence continues to increase. According to the most recent findings, AK is currently considered the initial stage, in situ, of squamous cell carcinoma. Field-directed therapies for AKs are the preferred treatment since they have the advantage to clear the clinically visible lesions and also subclinical lesions within the cancerous field. We assessed the cost-effectiveness of topical treatments for AKs including 3% diclofenac in 2.5% hyaluronic acid (HA) gel, imiquimod 5% cream and photodynamic therapy with methyl aminolevulinate (MAL-PDT) in the perspective of the Italian Health Care System (SSN). We used a decision tree analytical approach and efficacy data were drawn from published clinical trials. Cost was evaluated from the SSN perspective during a time horizon of 3 months. A responder was defined as a patient with all lesions clinically cleared and showing an excellent cosmetic result. Based on the applied model, the cost per complete responder was calculated. Diclofenac 3% in HA was less expensive (Euro 256) than MAL-PDT (Euro 320) and imiquimod (Euro 342). Effectiveness was similar and better for diclofenac 3% in HA and MAL-PDT (0.813%) in comparison to 0.734% of imiquimod, respectively. The one-way and probabilistic sensitivity analyses confirmed the results of base case scenario. Based on this cost-effectiveness model, diclofenac 3% in HA can be considered the treatment of choice for AK lesions and surrounding field under a pharmacoeconomic point of view.

Novel and recurrent p14 mutations in Italian familial melanoma.

CDKN2A and CDK4 are the only known high-penetrant genes conferring proneness to cutaneous melanoma. The CDKN2A locus consists of four exons and encodes several alternate transcripts, two of which are p16(INK4a) and p14(ARF), and originate from different open reading frames. Exon 1alpha is specific for p16(INK4a), while exon 1beta characterizes p14(ARF). Most CDKN2A mutations are located in exons 1alpha and 2, while exon 1beta variations have been identified in rare melanoma-prone pedigrees. In a previous study, we investigated 155 Italian melanoma cases, including 94 familial melanomas (FAMs) and 61 sporadic multiple primary melanomas (MPMs), for p16(INK4a)/CDK4 germline alterations and identified 15 p16(INK4a) and 1 CDK4 point mutations. In the present work, we extended our search to p14(ARF) mutations and CDKN2A deletions in the remaining samples. We identified the recurrent g.193+1G> A mutation in two FAM cases, while an additional pedigree displayed the previously undescribed variant g.161G> A. Multiplex ligation-dependent probe amplification (MLPA) screening for copy variations resulted negative in all cases. In Italy, the overall frequency of p14(ARF) mutations is 3.2% in FAM and 0% in sporadic MPM. Re-evaluation of our patients' cohort emphasizes that the chance of identifying CDKN2A/CDK4 mutations in FAM is mainly influenced by the number of affected family members and the presence of one or more MPM cases. Accordingly, mutation rate rises to 61% in selected cases. Further studies are expected in order to investigate CDKN2A rarer mutations, including atypical deletions and inherited epimutations.

Fatty acid synthase expression in melanoma.

BACKGROUND: Fatty acid synthase (FAS), the key enzyme responsible for the synthesis of fatty acids, is weakly expressed in some normal human tissues. Recently, FAS has been demonstrated to be overexpressed in many non-neoplastic highly proliferative lesions and in aggressive carcinomas with poor outcome, including colon, breast and ovary carcinomas. METHODS: In order to evaluate the prognostic significance of FAS in human melanoma, we analysed by means of immunohistochemistry, using a monoclonal anti-FAS antibody, 77 primary melanomas and 30 nodal and cutaneous metastasis. Thirty nevi (15 dermal and 15 junctional nevi) were used as controls. All patients were followed-up for 5 years. RESULTS: Thirty-four melanomas expressed strong FAS immunostaining; the remaining 43 cases showed weak expression or were negative. All cutaneous and nodal metastasis were strongly positive. All patients with metastases deceased during the follow up period. Control specimens expressed weak staining. None of these patients developed recurrence. Statistical analysis revealed significant association of FAS expression with Breslow thickness (p = 0.012). The intensity of FAS immunostaining was also predictive of prognosis (p = 0.049). CONCLUSIONS: FAS is a reliable prognostic marker in human melanomas. FAS predictive strength is increased when associated with Breslow thickness. The observation of FAS in human melanomas may stratify patients for stricter follow-ups and suggest different therapeutic approaches.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): case report with nodal and diffuse muco-cutaneous involvement.

Sinus histiocytosis with massive lymphadenopathy (SHML) (Rosai-Dorfman disease) is a rare self-limited histiocytic disorder of unknown origin, usually present with cervical lymphadenopathy, fever, elevated ESR and haematologic abnormalities. Extranodal lesions may occur as initial manifestations of the disease. In most cases skin lesions are associated with nodal or extranodal localization. A 54-year-old male is reported who, for a period of ten months, presented numerous slowly enlarging, rounded papular lesions on the face, neck, trunk as well as severe cervical lymphadenopathy without general and haematological disturbances. Thereafter a fungating mass developed in the nasal cavity. Histological, histochemical and immunohistochemical tests of skin, mucosal and lymph-node lesions were consistent with a diagnosis of SHML. The immunohistochemical characterization of the cytophagocytic S-100+ macrophages revealed that they were highly positive for the adhesion molecules Vitronectin receptor av/b3, which is used by tissue macrophages for removal of effete cells through phagocytosis.

Neurofibromatosis type 1 associated with systemic vasculopathy.

Systemic vasculopathy in patients with neurofibromatosis type 1 is rare. We describe a case of unusual cerebral and renal involvement in a young, 29-year-old patient, who died of a cerebral ischemic attack one year after our observation.

Ossifying fasciitis of the nose.

A case of ossifying fasciitis in a 22-year-old woman is described. The lesion, which appeared suddenly, was located on the tip of the nose. Histologically the lesion contained spindle-shaped myofibroblastic cells, trabeculae of woven bone rimmed by plump osteoblasts within a myxoid stroma.