Vitaliano Silipo

Dermoscopy of Patients With Multiple Nevi Improved Management Recommendations Using a Comparative Diagnostic Approach

OBJECTIVE To assess the outcome on management recommendations of a comparative approach vs a morphologic approach in evaluating dermoscopic images of lesions from a series of patients with multiple nevi. DESIGN In a 2-step study, 6 experienced dermoscopists were asked to provide management recommendations (excision or follow-up) for a series of lesions from patients with multiple nevi based on dermoscopic images of the lesions. In the first step, participating dermoscopists evaluated individual images of lesions based only on morphologic structure (morphologic approach). In the second step, the same lesions were grouped by patient, allowing the participants to evaluate the lesions in the context of other nevi from the same patient (comparative approach). SETTING Academic referral center. PATIENTS Seventeen patients with 190 lesions (184 monitored nevi, 4 excised nevi, and 2 excised melanomas). MAIN OUTCOME MEASURE Using pooled data from each step, excision recommendation rates for the comparative approach and the morphologic approach were calculated. RESULTS Using the morphologic approach, 55.1% of overall recommendations favored excision; using the comparative approach, the rate decreased to 14.1%. The 2 melanomas included in the study were correctly judged to merit excision by all participants in step 1 and in step 2. Conclusion Among patients with multiple nevi, evaluation of equivocal lesions in the context of a patients other nevi results in a lower rate of excision recommendations compared with evaluation of individual lesions based on morphologic structure alone.

Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma

BackgroundThe pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients.MethodsThe expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample.ResultsNo correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a.ConclusionsOur data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed.

The ringlike pattern in vulvar melanosis: a new dermoscopic clue for diagnosis.

BACKGROUND Vulvar melanosis is a benign pigmented lesion that may clinically mimic melanoma. Whereas the dermoscopic features of other pigmented skin lesions have been extensively described, little is known about vulvar melanosis. OBSERVATIONS A retrospective dermoscopic study was conducted on 87 lesions with histopathologically proved melanosis. We describe and define, for the first time to our knowledge, a ringlike pattern, found in 28 of 87 melanotic lesions (32%), characterized by multiple round to oval structures, white to tan, with dark brown, well-defined regular borders. The structureless and globularlike patterns were observed in 18 of 87 lesions (21%), the parallel pattern in 15 (17%), and the cobblestonelike and reticularlike patterns in 4 (5%). A significant association was found between the distribution of multifocal lesions showing a ringlike vs a nonringlike pattern (82% vs 52%; P = .008), whereas a weak association was found between anatomical site and the different patterns (P = .55). The ringlike pattern was frequently combined with multifocality and simultaneous occurrence at the labia majora and the labia minora. CONCLUSION Dermoscopy can be useful for the clinical detection of vulvar melanosis, and the ringlike pattern may represent a new dermoscopic clue for the diagnosis of this lesion.

Giant and large basal cell carcinoma treated with topical photodynamic therapy.

Basal cell carcinoma (BCC) is the most common cancer affecting Caucasians and, due to its large size or to the poor condition of the patient, it can be difficult to treat it with conventional therapies: in these cases photodynamic therapy with methyl aminolevulinate (MAL-PDT) may represent a good option. A retrospective non-comparative follow-up study was performed to test the response of giant and large BCC to MAL-PDT. Twelve patients with 14 giant BCC (> or = 5 cm) and 5 patients with 5 large BCC (4-5 cm) were treated with MAL-PDT; they were evaluated 6 months after the end of the treatment to define the initial cure rate, and then at 12 and 36 months for the follow-up. At 6 months the initial cure rate for the 19 BCCs was 95% and at 36 months the overall long-term cure rate was 66%. The follow-up will last up to 5 years. MAL-PDT is a valid option for the treatment of giant and large BCC.

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 ofthe 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.

The role of Wnt/β-catenin signaling pathway in melanoma epithelial-to-mesenchymal-like switching: evidences from patients-derived cell lines

Deregulations or mutations of WNT/β-catenin signaling have been associated to both tumour formation and progression. However, contradictory results concerning the role of β-catenin in human melanoma address an open question on its oncogenic nature and prognostic value in this tumour. Changes in WNT signaling pathways have been linked to phenotype switching of melanoma cells between a highly proliferative/non-invasive and a slow proliferative/metastatic condition. We used a novel panel of cell lines isolated from melanoma specimens, at initial passages, to investigate phenotype differences related to the levels and activity of WNT/β-catenin signaling pathway. This in vitro cell system revealed a marked heterogeneity that comprises, in some cases, two distinct tumour-derived subpopulations of cells presenting a different activation level and cellular distribution of β-catenin. In cells derived from the same tumor, we demonstrated that the prevalence of LEF1 (high β-catenin expressing cells) or TCF4 (low β-catenin expressing cells) as β-catenin partner for DNA binding, is associated to the expression of two distinct profiles of WNT-responsive genes. Interestingly, melanoma cells expressing relative low level of β-catenin and an invasive markers signature were associated to the TNF-α-induced pro-inflammatory pathway and to the chemotherapy resistance, suggesting that the co-existence of melanoma subpopulations with distinct biological properties could influence the impact of chemo- and immunotherapy.

Dermoscopic and confocal microscopy patterns of vulvar mucosal melanotic macules.

CONFOCAL REFLECTANCE MICROSCOPY Confocal reflectance microscopic examination was performed with the handled Vivascope 3000 (Caliber Imaging and Diagnostics, Inc, Rochester, NY). A regular honeycomb pattern was detected in the superficial layers. At the level of the epithelialechorion junction, cord-like structures were visible, and these were composed of tubular structures rimmed by monomorphic roundish cells that corresponded to the parallel pattern seen during the dermoscopic evaluation (Fig 2, A [maroon square] and B). In the area of the dermoscopic ring-like pattern, dermal papillae appeared rimmed by bright, monomorphic, roundish cells, corresponding to hyperpigmented keratinocytes (Fig 2, A [blue square] and C ). A few plump, bright cells corresponding tomelanophages were seenwithin the dermal papillae (Fig 2, C ).

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.

Familial melanoma and multiple primary melanoma.

Cutaneous melanoma (CM) has the highest mortality rates among the most common skin cancers, and its incidence is rising worldwide, thus representing a significant health care burden. CM is considered the most lethal skin cancer if not detected and treated during its early stages. Susceptibility to CM is also associated with an increased presence of atypical nevi and the occurrence of multiple primary melanoma. Personal history of CM increases the risk of developing a second melanoma by 5-8%. A family history of melanoma has also been strongly associated with an increased risk of melanoma. Approximately 5-10% of melanoma cases occur in a familial context. The main genes involved are CDKN2A, CDK4 and MC1R. The recent technological advances have allowed the identification of new genes involved in melanoma susceptibility: breast cancer 1 (BRCA1), BRCA1-associated protein 1 (BAP1), and telomerase reverse transcriptase (TERT).Tests on these genes allow to identify a larger number of high-risk individuals with a potential of developing familial melanoma and primary multiple melanomas. These patients also have a high risk of developing internal organ malignancies, especially pancreatic cancer. It is essential that these individuals receive adequate management along with frequent dermatological examinations, dermoscopic evaluation, genetic counselling and instrumental examinations aimed at the early identification of other tumors associated with CM.

Daylight photodynamic therapy: experience in the treatment of actinic keratosis in San Gallicano Institute of Rome and a review of literature

BACKGROUND Actinic keratosis (AK) is a photo-induced skin lesion. It has been considered by several authors as in situ squamous cell carcinoma (SCC), that can evolve to invasive SCC (iSCC). Given the malignant potential and because its impossible predict which AK will evolve in iSCC, its necessary to treat each lesion. Multiple therapeutic approaches have been described to treat AKs. In addition to the topical drugs, photodynamic therapy (PDT) has become an established therapeutic modality for grade I and II of AKs of face and scalp. Recently the daylight photo-dynamic therapy (DL-PDT) has found extensive use in the care of the AK and in the field cancerization. METHODS 101 patients, 90 males and 11 females, mean age 71, phototype I-II, with multiple AK I and II of the face and the scalp, treated with DL-PDT were retrospectively studied. Patients were clinically evaluated for 3 months. RESULTS The efficacy was complete in 16 patients (15,8%), in 71 patients (70,3%) was much improved or improved and only in 14 (13,9%) subjects were minimal, while nobody had worsened or changed. The majority of patients (84,2%) patients were satisfied of the efficacy as well of the cosmetic results, only 15 (14,9%) were low satisfied and one patients was no satisfied. CONCLUSIONS This study confirms that the DL-PDT is a good alternative to c-PDT for the treatment of grade I and II AK of the face and scalp and in Rome, as in Southern Europe, its possible to perform the DL-PDT in almost every month of year.