Natalia Jaimes

Array-CGH Reveals Recurrent Genomic Changes in Merkel Cell Carcinoma Including Amplification of L-Myc

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P=0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26% of tumors, a deletion of 13q14-21 was recurrent in 26% of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39% of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 4/4 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

Desmoplastic melanoma: A review

Desmoplastic melanoma (DM) is a variant of spindle cell melanoma typically found on chronically sun-damaged skin of older individuals. Early diagnosis can be challenging because it is often amelanotic and has a predominantly dermal component. DM can be difficult to diagnose not only clinically but also histologically, and can be mistaken for a variety of benign and malignant nonmelanocytic spindle cell tumors when viewed on prepared histopathology slides. Pathologists have observed that DMs can manifest significant variation with respect to the extent of intratumoral cellularity, fibrosis, and/or perineural invasion. Furthermore, some tumors present with a pure desmoplastic invasive component (>90%) while other tumors display mixed features of DM and nondesmoplastic melanoma. This has led to the separation of DM into 2 histologic subtypes, pure and mixed. With a focus on the distinction between pure and mixed DM, this review will detail what is currently known about the diagnostic features of DM, discuss risk and prognostic factors, and examine the current literature on disease progression and management.

Validity and Reliability of Dermoscopic Criteria Used to Differentiate Nevi From Melanoma: A Web-Based International Dermoscopy Society Study

IMPORTANCE The comparative diagnostic performance of dermoscopic algorithms and their individual criteria are not well studied. OBJECTIVES To analyze the discriminatory power and reliability of dermoscopic criteria used in melanoma detection and compare the diagnostic accuracy of existing algorithms. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective, observational study of 477 lesions (119 melanomas [24.9%] and 358 nevi [75.1%]), which were divided into 12 image sets that consisted of 39 or 40 images per set. A link on the International Dermoscopy Society website from January 1, 2011, through December 31, 2011, directed participants to the study website. Data analysis was performed from June 1, 2013, through May 31, 2015. Participants included physicians, residents, and medical students, and there were no specialty-type or experience-level restrictions. Participants were randomly assigned to evaluate 1 of the 12 image sets. MAIN OUTCOMES AND MEASURES Associations with melanoma and intraclass correlation coefficients (ICCs) were evaluated for the presence of dermoscopic criteria. Diagnostic accuracy measures were estimated for the following algorithms: the ABCD rule, the Menzies method, the 7-point checklist, the 3-point checklist, chaos and clues, and CASH (color, architecture, symmetry, and homogeneity). RESULTS A total of 240 participants registered, and 103 (42.9%) evaluated all images. The 110 participants (45.8%) who evaluated fewer than 20 lesions were excluded, resulting in data from 130 participants (54.2%), 121 (93.1%) of whom were regular dermoscopy users. Criteria associated with melanoma included marked architectural disorder (odds ratio [OR], 6.6; 95% CI, 5.6-7.8), pattern asymmetry (OR, 4.9; 95% CI, 4.1-5.8), nonorganized pattern (OR, 3.3; 95% CI, 2.9-3.7), border score of 6 (OR, 3.3; 95% CI, 2.5-4.3), and contour asymmetry (OR, 3.2; 95% CI, 2.7-3.7) (P < .001 for all). Most dermoscopic criteria had poor to fair interobserver agreement. Criteria that reached moderate levels of agreement included comma vessels (ICC, 0.44; 95% CI, 0.40-0.49), absence of vessels (ICC, 0.46; 95% CI, 0.42-0.51), dark brown color (ICC, 0.40; 95% CI, 0.35-0.44), and architectural disorder (ICC, 0.43; 95% CI, 0.39-0.48). The Menzies method had the highest sensitivity for melanoma diagnosis (95.1%) but the lowest specificity (24.8%) compared with any other method (P < .001). The ABCD rule had the highest specificity (59.4%). All methods had similar areas under the receiver operating characteristic curves. CONCLUSIONS AND RELEVANCE Important dermoscopic criteria for melanoma recognition were revalidated by participants with varied experience. Six algorithms tested had similar but modest levels of diagnostic accuracy, and the interobserver agreement of most individual criteria was poor.

Clinical and dermoscopic characteristics of amelanotic melanomas that are not of the nodular subtype.

Background  Amelanotic melanomas remain challenging to diagnose.

Dermoscopy: An Aid to the Detection of Amelanotic Cutaneous Melanoma Metastases

BACKGROUND The recognition of amelanotic cutaneous melanoma metastases (ACMM) remains a diagnostic challenge. OBJECTIVES To describe and analyze the clinical and dermoscopic characteristics of ACMM. PATIENTS AND METHODS Cases of ACMM were retrospectively selected from the image databases of three dermatology centers. The clinical and dermoscopic images were combined into one database for analysis. RESULTS Forty‐seven ACMM were observed in 18 patients. All lesions were erythematous, symmetric, dome‐shaped papules or nodules appearing an average of 17 months after the diagnosis of the primary melanoma. ACMM presented as clinical outliers or as nonspecific papules found by palpation of the skin. The predominant dermoscopic feature was the presence of vascular structures, including serpentine (45%), glomerular (30%), irregular hairpin (23%) and corkscres‐like vessels (19%). A few lesions also revealed crystalline (or shiny white lines) when viewed using polarized dermoscopy. CONCLUSION ACMM should be considered in the differential diagnosis of new or persistent skin‐colored or pink papules in patients with a previous history of invasive melanoma, especially if the lesions reveal atypical vessels under dermoscopy. The presence of crystalline structures may be another clue for the detection of some ACMM.

Clinico-morphological features of BRAF inhibition–induced proliferative skin lesions in cancer patients

The use of BRAF inhibitors may lead to the development of cutaneous toxicities such as rashes, photosensitivity, alopecia, palmoplantar erythrodysesthesia, and proliferative skin lesions, including keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs). The latter are noteworthy for their potential to exhibit malignant features, and they may necessitate invasive treatment. Their prompt identification is of primary importance for directing supportive care efforts and maintaining dose intensity while minimizing the morbidity associated with supportive care interventions. Because such lesions are less familiar to oncologists, this study was designed to characterize their clinico‐morphological features, which have not been hitherto described.

Clinical and Dermoscopic Characteristics of Desmoplastic Melanomas

OBJECTIVE To describe and analyze the clinical and dermoscopic characteristics of desmoplastic melanoma (DM) as a function of pathologic subtype and phenotypic traits. DESIGN Retrospective case series. SETTING Eight high-risk dermatology clinics. PATIENTS Patients with DM confirmed by histopathologic analysis whose records included a high-quality dermoscopic image. MAIN OUTCOME MEASURES Clinical, dermoscopic, and histopathologic features of DM. RESULTS A total of 37 DM cases were identified. The majority of patients had fair skin, few nevi, and no history of melanoma. Lentigo maligna was the most frequent subtype of melanoma associated with DM. The most frequent clinical presentation of DM was a palpable and/or indurated lesion located on sun-exposed skin. Forty-three percent of cases were classified as pure DM, and 57% as mixed DM. Pure DM lesions were thicker than mixed DM lesions (4.10 vs 2.83 mm) (P = .22) and were less likely to have an associated epidermal non-DM component (63% vs 100%) (P = .004). Dermoscopically, DMs had at least 1 melanoma-specific structure, the most frequent being atypical vascular structures. Peppering was more frequently seen in pure DM (44% in pure DM vs 24% in mixed DM) (P = .29). In contrast, crystalline structures, polymorphous vessels, and vascular blush were more commonly seen in mixed DM. CONCLUSIONS Though DM can be difficult to diagnose based on clinical morphologic characteristics alone, dermoscopy has proved to be a useful aid during the evaluation of clinically equivocal lesions or those lesions with a benign appearance. The most common dermoscopic clues observed in DMs included atypical vascular structures, peppering, and occasionally other melanoma-specific structures.

White globules correlate with balloon cell nevi nests

inflammatory and noninflammatory lesions than did 5% BPO/CL. Weighted absolute reductions in inflammatory lesion count were 14.81 with 5% BPO/CL, 25.37 with 2.5% BPO/CL, 11.60 with BPO, 11.03 with CL, 5.89 with placebo; weighted absolute reductions in noninflammatory lesion count were 16.83 with 5% BPO/CL, 20.83 with 2.5% BPO/CL, 15.07 with BPO, 12.50 with CL, and 7.61 with placebo (Fig 2). Limitations exist in meta-analyses and include trial heterogeneity, publication bias, and deficits in the reporting of individual primary studies. We conclude that 2.5% BPO/CL is comparable to other topical products containing 5% BPO/CL in reducing lesion counts and may have an advantage over them in treating noninflammatory lesions. This may be due to the formulation itself or may be due to better adherence to the regimen because of decreased irritation. Further, both combination formulations perform statistically better than the single agents alone in treating inflammatory lesions over 10-12 weeks.

The Morphologic Universe of Melanoma

Differentiating dysplastic nevi from melanoma remains one of the main objectives of dermoscopy. Melanomas tend not to manifest any of the benign patterns described for nevi and instead usually display chaotic dermoscopic morphologies. Melanomas located on the face, chronically sun-damaged skin, volar surfaces, nails, and mucosal surfaces have additional features that can assist in their identification. However, some melanomas lack any defined dermoscopic structures. These so-called featureless melanomas can be identified via digital surveillance. This article reviews the melanoma-specific structures as a function of anatomic location (ie, melanomas on nonglabrous skin, face, volar surfaces, mucosae, and nails).

Spitz Nevi: A Bridge Between Dermoscopic Morphology and Histopathology

Few benign melanocytic lesions encountered in clinical practice elicit the level of controversy as that generated by lesions within the spectrum of Spitz nevi. Unlike melanoma, the dermoscopic structures found in Spitz nevi tend to be distributed in a symmetric and organized manner. This review highlights the melanoma-specific structures and patterns commonly seen in Spitz nevi. Knowledge of the dermoscopic structures and patterns encountered in Spitz nevi (particularly the classic symmetric starburst pattern), together with understanding of their growth dynamics, can inform the decision whether to biopsy or monitor.