A new dermoscopic algorithm for the differential diagnosis of facial lentigo maligna and pigmented actinic keratosis.

The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110 LM and 75 PAK cases. Diagnostic accuracy was 86.5% (κ: 0.73, 95% CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95% CI: 75.7-89.8%), specificity was 92.0% (95% CI: 85.9-98.1%), positive predictive value was 93.8% (95% CI: 89.0-98.6%), and negative predictive value was 78.4% (95% CI: 68.4-86.5%). This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK.

Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple Melanomas and Association with MC1R Genotype: Findings from Molecular and Immunohistochemical Analysis.

Data on somatic heterogeneity and germline-somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600E detection (κ = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test.

Staging and follow-up of cutaneous melanoma patients.

Melanoma is responsible for the greatest number of deaths caused by skin malignancies. The purpose of monitoring patients diagnosed with melanoma is to allow early detection of recurrence and any subsequent primary tumors. Several dermatological and oncological societies developed their own set of guidelines for the surveillance and management of melanoma patients depending on the stage of the disease. The object of this article is to provide a comprehensive, systematic overview that summarizes and interprets previous studies, to characterize current practices regarding progression of melanoma, division into stages of development, and subsequent surveillance. We have performed a systematic review search to December 2016 using the MEDLINE database and performed a manual search of selected references. We examined the staging system and the different surveillance programs for melanoma patients. Consistent recommendations with proven evidence are available for staging melanoma patients. Conversely, recommendations are more controversial for follow-up procedures. Given the inadequate number of randomized controlled trials, consensus on the best, universally-applicable follow-up procedure has not been reached and interpretation of the roles of imaging and laboratory tests, as well as of the appropriate frequency and duration of physical examinations, vary widely. Based on a universally-accepted staging system different surveillance procedures have been developed, which may be mainly classified in two groups: low- and high-intensity strategies.

Dermoscopy in the diagnosis and management of non-melanoma skin cancers.

Over the past two decades, dermoscopy has remarkably enhanced the diagnostic accuracy of pigmented skin lesions and, more recently, of non-pigmented skin disorders, including skin cancers, inflammatory and infectious diseases. With respect to non-melanoma skin cancers (NMSC), dermoscopy is an effective diagnostic tool for the clinical assessment of basal cell carcinoma, Bowen's disease, actinic keratosis and squamous cell carcinoma. Besides its relevance for diagnostic purposes, further applications of dermoscopy in the management of NMSC have been suggested in the preoperative evaluation, in monitoring the outcome of topical, light-based or laser treatments and in the post-treatment follow-up. This article summarizes the dermoscopic diagnostic criteria of NMSC and provides a review of the published literature as well as of our own experience on the usefulness of dermoscopy in monitoring surgical and medical treatment of NMSC.

The spectrum of dermatoscopic patterns in blue nevi.

BACKGROUND: Blue nevi are congenital or acquired, dermal dendritic melanocytic proliferations that can simulate melanocytic and nonmelanocytic lesions including melanoma, cutaneous metastasis of melanoma, Spitz/Reed nevi, and basal cell carcinoma. OBJECTIVE: We sought to investigate global and local dermatoscopic patterns of blue nevi compared with melanomas and basal cell carcinomas. METHODS: We retrospectively analyzed global and local features in 95 dermatoscopic images of blue nevi and in 190 melanomas and basal cell carcinomas that were selected as control lesions on the basis of similar pigmentation. Lesion pigmentation was classified as monochromatic, dichromatic, or multichromatic. RESULTS: A global pattern characterized by homogeneous pigmentation was observed in all of 95 (100%) blue nevi. Eighty of 95 (84.2%) blue nevi presented a homogeneous pattern consisting of one color (blue, black, or brown) or two colors (blue-brown, blue-gray, or blue-black). Fifteen of 95 (15.8%) blue nevi had a multichromatic (blue, gray, black, brown, and/or red) pigmentation. In all, 47 of 95 (49.5%) blue nevi were characterized by pigmentation in the absence of pigment network or any other local dermatoscopic features. And 48 of 95 (50.5%) blue nevi showed local dermatoscopic patterns including whitish scarlike depigmentation, dots/globules, vascular pattern, streaks, and networklike pattern. LIMITATIONS: The study was retrospective and involved only Caucasian people of Italian origin. CONCLUSION: The characteristic feature of blue nevi is a homogeneous pigmentation that is blue, blue-gray, blue-brown, or blue-black. We showed that a wide spectrum of local dermatoscopic features (whitish scarlike depigmentation, dots/globules, peripheral streaks or vessels) may also be present. In such cases, clinical and dermatoscopic distinction from melanoma or nonmelanocytic lesions may be difficult or impossible, and surgical excision is necessary.

Dermoscopic features of actinic keratosis.

Actinic keratosis (AK) is a keratinocytic neoplasm that typically develops on sun-damaged skin of elderly individuals. Only a few reports so far have described the dermoscopic diagnostic features of AK, mainly focusing on facial non-pigmented AKs. A typical feature of facial non-pigmented AK is a composite pattern named "strawberry pattern", characterized by a background erythema/red pseudonetwork consisting of unfocused, large vessels located between the hair follicles, associated with prominent follicular openings surrounded by a white halo. Dermoscopic characteristics of pigmented AK on the face include multiple slate-gray to dark-brown dots and globules around the follicular ostia, annular-granular pattern and brown to gray pseudonetwork. Recognizing specific dermoscopic features of AK can be useful in guiding the clinician in the differential diagnosis of AK with melanocytic skin lesions such as LM and non-melanocytic lesions. Histopathologic examination should be performed whenever clinical and/or dermoscopic differential diagnosis is inconclusive.

Dermoscopic patterns of acral melanocytic nevi and melanomas in a white population in central Italy.

OBJECTIVE: To investigate the dermoscopic features of acral melanocytic lesions in a white population in central Italy. DESIGN: Retrospective review. SETTING: University dermatology department. PATIENTS: Six hundred fifty-one Italian subjects, ranging in age from 6 months to 78 years. MAIN OUTCOME MEASURES: We retrospectively investigated all digital dermoscopic images of acral melanocytic lesions included in our database from January 1996 to May 2005. RESULTS: We retrieved digital images of 723 benign acral melanocytic lesions in 641 patients (235 males and 406 females; mean age, 26.5 years) and of 10 acral melanomas in 10 patients (7 males and 3 females; mean age, 65 years). Individual lesions were located on the soles (n=520), fingers (n=146), and palms (n=67). Among acral nevi, the parallel furrow (42.1%) was the most common pattern, followed by the latticelike (14.9%), nontypical (13.7%), fibrillar (10.8%), homogeneous (9.3%), globular (5.4%), and reticular (2.1%) patterns. The frequency of distribution of the latticelike, nontypical, fibrillar, and homogeneous patterns significantly differed (P<.001, P=.03, P<.001, and P=.03, respectively) between anatomical sites. Also, 13 acral nevi (1.8%), mainly located on the fingers, showed a new combined pattern (transition pattern) consisting of a brownish black network associated with a parallel furrow or latticelike pattern. All 10 acral melanomas showed a multicomponent dermoscopic pattern. CONCLUSIONS: In our series of acral nevi, we observed 8 dermoscopic patterns, with varying distribution by anatomical site. Identification of a specific pattern is highly suggestive of the benign or the malignant nature of any given acral melanocytic lesion.

Imiquimod 5% cream in the treatment of Bowen's disease and invasive squamous cell carcinoma.

BACKGROUND: Imiquimod has been successfully used for treatment of various epithelial cutaneous neoplasms. OBJECTIVE: Our aim was to evaluate the efficacy and tolerability of imiquimod 5% cream for treatment of Bowen's disease and invasive squamous cell carcinoma (SCC) in patients who were unsuitable candidates for surgery. METHOD: Five Bowen's disease lesions and 7 invasive SCC lesions on 10 patients were treated with imiquimod once daily 5 times a week for a maximum of 16 weeks. RESULTS: After 8 to 12 weeks of treatment, 4 of 5 Bowen's disease lesions (80%) and 5 of 7 invasive SCCs (71.4%) showed complete clinicopathologic regression. The remaining 3 lesions showed partial regression after 16 weeks of treatment. No recurrence has been detected after a follow-up period of 24 to 38 months (mean, 31 months). LIMITATIONS: The study is an open-label clinical trial on a small number of selected patients, with lack of excision with serial step sections. CONCLUSION: Topical application of imiquimod 5% cream might represent an alternative topical treatment to surgery in selected cases of Bowen's disease and invasive SCC.

Imiquimod treatment of superficial and nodular basal cell carcinoma: 12-week open-label trial.

BACKGROUND: Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). OBJECTIVE: To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. METHODS: Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. RESULTS: Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). CONCLUSIONS: In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months.