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Purpose of Review: Over the last years, our understanding in molecular biology of melanoma has grown significantly and many genetic alterations have been identified affecting melanoma pathogenesis. This growing evidence has led to the development of targeted therapies which are showing promising clinical results. In addition to genetic alterations, an increasing number of studies have recently demonstrated the role of epigenetics in melanoma development and progression. Here, we summarize the current data on epigenetic research in melanoma., Recent Findings: MicroRNA (miRNA) expression profiling studies have identified several miRNAs implicated in melanoma cell cycle and proliferation, cell migration and invasion, as well as miRNAs involved in apoptosis and immune response. Abnormal methylation profiling has been associated with melanoma progression and to date aberrant hypermethylation in more than 70 genes has been described. Recent works have highlighted the increasing evidence of the role of histone modification as a central regulatory event in melanoma pathogenesis., Summary: Many of these epigenetic biomarkers may have potential diagnostic, prognostic and therapeutic implications. Future approach might be using a combination of genetic and epigenetic biomarkers.

Aims: The differential diagnosis between Spitz naevus and spitzoid melanoma can be extremely difficult, or even impossible. In recent years, many attempts have been made to find specific histopathological or immunohistochemical markers, although none has proved successful. Because the prognosis and treatment of each are very different, it is important to distinguish between these entities. We evaluated the ability of the fluorescence in situ hybridization (FISH) assay-designed to detect the copy number of the RREB1 (6p25), MYB (6q23) and CCND1 (11q13) genes and of centromere 6 (Cep 6)-in order to distinguish between Spitz naevus and spitzoid melanoma., Methods and Results: We evaluated 12 spitzoid melanomas and six Spitz naevi from our records. The diagnosis of both conditions was based on previously described histopathological criteria. We obtained valuable results for FISH in eight spitzoid melanomas and five Spitz naevi. Chromosomal aberrations were detected in seven of the eight spitzoid melanomas (FISH-positive) and in none of the five Spitz naevi. The FISH-negative spitzoid melanoma was the least typical in its group., Conclusions: FISH was able to distinguish between Spitz naevus and spitzoid melanoma, with a sensitivity of 87.5% and a specificity of 100%. Our findings suggest that FISH could prove a useful tool in the differential diagnosis between these entities., (© 2012 Blackwell Publishing Limited.)

The different features of spitzoid melanoma are not well characterized in the literature, and the lesion often has to be described in comparison with Spitz nevus. We evaluated the histopathological appearance of spitzoid melanoma by reviewing all spitzoid melanomas treated at our hospital and all referrals from 1998 to 2010. The final study sample comprised 18 cases, 11 from our institution and 7 referrals from other centers. We recorded clinical parameters (eg, age, sex, site, time between onset and excision, recurrence, and death) and a series of histopathological parameters (eg, size, ulceration, symmetry, Clark level, Breslow thickness, cell density, atypia, mitosis). Clinical and histopathological criteria were not available for the 7 referrals. Mean age was 35.2 years (15-56), and 8 patients were women. Mean size of the lesions was 7.27 mm (Clark III/IV and Breslow 2.51 mm), and these were found on the limbs and trunk. Cell density was high in 10 cases and atypia present in 9 (marked in 1). Mitoses were observed in 8 cases (atypical in 4, clusters in 4). Maturation was absent in 9 cases and zonation in 8. Our analysis revealed 5 previously undefined subtypes of spitzoid melanoma (genuine (7 cases), uniform (5 cases), packed (5 cases), polypoid (3 cases) and pigmented (2 cases)]. Four cases showed 2 patterns at the same time. The most useful parameters for the differential diagnosis were cell density, mitosis, zonation, infiltration pattern, and consumption of the epidermis. Assignation of a spitzoid melanoma to 1 of more of our 5 subtypes can enable a more confident diagnosis to be made.

The cutaneous epithelioid angiomatous nodule is an uncommon benign vascular proliferation that has only recently been described. Clinically, it usually presents as a solitary, fast-growing, small reddish papulous or nodular lesion on the trunk or limbs of adults. Histopathologic study reveals a proliferation of epithelioid cells and predominantly solid, well delimited, unilobular growth in the superficial dermis. Well defined vessels are often found permeating the lesion, which also shows a certain degree of inflammatory infiltration. The cells contain abundant pink cytoplasm, often with vacuoles, and vesicular nuclei with prominent nucleoli. The morphology of these cells is relatively uniform, without atypia or pleomorphism, although mitoses are not uncommon. We report 2 new cases of cutaneous epithelioid angiomatous nodules, the first in a 28-year-old pregnant woman and the second in a 27-year-old man. In both cases, the usual characteristics of this entity were present, but with the peculiarity of a high mitotic index. We discuss the differential diagnosis of cutaneous epithelioid angiomatous nodules with other vascular proliferations that exhibit epithelioid cytology.

The Brooke-Spiegler syndrome is a rare, autosomally dominant disease with a predisposition to develop different adnexal tumors. Clinically it is characterized by the presence of multiple cylindromas, trichoepitheliomas, and occasionally, spiradenomas. Although Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma were initially described as separate entities, the recently identified identical mutations in the gene of cylindromatosis suggest that they represent fenotypic variations of the same entity. In this article we present the case of a woman and her daughter, both affected by this rare genodermatosis.

Dermatofibrosarcoma protuberans (DFSP) is an infrequent tumor of intermediate malignancy, with little tendency to develop metastases but with a high rate of local recurrence. Cytogenetically, DFSP is characterized by a reciprocal translocation, t(17;22)(q22;q13), which is a conditioning factor in the fusion of the collagen type I alpha I gene (COL1A1) in chromosome 17q with the platelet-derived growth factor beta chain gene (PDGFB) in chromosome 22q. The fusion of these genes is variable, involving one of the 51 exons of the COL1A1 gene and exon 2 of the PDGFB gene. We present the case of a 37-year-old woman with a tumor on the arm whose histology showed a neoplastic infiltration of the subcutaneous cellular tissue made up of fusiform cells with an elongated nucleus in a storiform pattern and other more pleomorphic cells in a herringbone pattern, compatible with DFSP with a fibrosarcoma component. The molecular biology study with RT-PCR analysis of paraffin-embedded material and later sequencing showed a new fusion of exon 19 of the COL1A1 gene and exon 2 of PDGFB, supporting a diagnosis of DFSP. A study of the COL1A1-PDGFB fusion products is useful in cases where histology and immunohistochemistry are insufficient for the differential diagnosis of DFSP versus other sarcomas. It also justifies the use of new avenues of treatment with tyrosine kinase inhibitors.

Bowen's disease is a special form of squamous cell carcinoma in situ that usually develops in photoexposed areas of skin. The treatment of choice is surgery. Less frequently, it may appear in other locations such as the nails, glans penis, intertriginous areas and the perianal region, where conventional treatment may be complicated. We contribute a new case of perianal Bowen's disease, which responded to treatment with imiquimod with no evidence of clinical recurrence after 3 years of follow up. Imiquimod appears to be a therapeutic alternative for perianal Bowen's disease, which seems to have a particular tendency to recur in this location where surgery may also be complicated.

We describe the third case (to our knowledge) of multiple basal cell carcinoma associated with myotonic dystrophy and carry out a genetic study of the tumor comparing it with healthy skin. We consider that our results show that this association might be not a purely random phenomenon and that the particular genetic characteristics of this disorder might have a role in the pathogenesis of the tumor.

Primary small cell cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) is an uncommon, highly malignant, primary cutaneous neuroendocrine carcinoma. Clinically it is seen as a 0.5- to 5.0-cm pinkish purple papule or nodule, usually not ulcerated, on the head, neck, or, less frequently, the roots of the limbs. We present the case of a woman with an atypical clinical presentation of a Merkel cell tumor.

A 15 year-old girl presented with numerous congenital melanocytic nevi, occasionally hairy, with a segmental distribution at the left pre-auricular region. On the left side of the back of the neck there were multiple melanocytic nevi with a warty appearance, which had started to appear when she was 5 and which had remained stable from the time she was 10. These lesions had a distribution reminiscent of an epidermal nevus with a pattern similar to Blaschko's lines. On general physical examination there was a moderate degree of idiopathic scoliosis, with a left lumbar curvature. Biopsies were taken from both types of nevus which were diagnosed as congenital compound melanocytic nevus and acquired compound melanocytic nevus respectively. We consider that the segmental distribution of the melanocytic nevi of this patient supports the theory that a genetic defect determined the appearance of both these congenital and acquired lesions.

The patient, aged 50 years, with no relevant clinical history, complained of a symptomless, soft tumor of the right buttock that had been present for many years. On examination, it was found to be pediculate, oval, somewhat erythematous, firm on palpation, and with a central keratin plug. The greatest diameter of the lesion was 1.2 cm (Fig. 1). On surgical removal of the lesion, it was seen to be composed of a symmetric intradermal proliferation of cystic formations, uniformly distributed throughout and made up of flat, pluristratified epithelium with laminated keratin. There was little difference in the thickness of the walls of the cysts (Fig. 2). Some cysts were attached to a short tadpole-shaped, epithelial cord and surrounded by a scanty fibroblastic stroma. No hairmatrix-like differentiation nor basaloid structures were seen, nor were atypical cells present. There was hardly any inflammatory infiltration.

We report a case of cutaneous lymphadenoma, a tumour first described by Santa Cruz and Barr under the name of 'lymphoepithelial tumour'. Twenty-three cases have been reported to date. The commonest site is the head and neck, and it is most commonly diagnosed in the fourth and fifth decades. The usual clinical diagnosis is basal cell carcinoma. To date, no recurrences have been observed after local excision. The tumour is composed of dermal lobules with a biphasic pattern of epithelial and lymphoid cells. It has been suggested that it arises as a result of faulty interaction between lymphocytes and epithelial cells.