Skin microbiome in melanomas and melanocytic nevi

Background

High-throughput DNA sequencing has shown that the cutaneous microbiome varies due to different exogenous and endogenous factors.

Objectives

To characterize the microbiome of cutaneous melanomas and melanocytic nevi.

Material and Methods

Non-invasive swab specimens were taken from 15 cutaneous melanomas and 17 benign melanocytic nevi. Partial sequencing of the 16S ribosomal RNA gene was carried out on the 454 GS-FLX Titanium platform and the resulting sequence data was analysed by bioinformatics and statistical methods.

Results

95% of the OTUs (Operational Taxonomic Units) belonged to four phyla: Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes. The genus Propionibacterium was overall the mostcommongenus, followed by Staphylococcus and Corynebacterium. Statistical analysis showed no significant differences in the relative abundances of bacterial genera or bacterial diversity between the patient groups. Melanoma samples showed a marginally decreased cutaneous microbial diversity.

Conclusion

Our data suggests that the skin microbiome may not be a useful diagnostic tool for melanoma and melanocytic nevi.

     

Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi

Background:  Cdc7 is a serine-threonine kinase required for initiation of DNA replication that may play a role in the development and progression of melanoma.
Materials and Methods:  Tissue microarrays containing 40 melanomas, 40 Spitz tumors and 30 nevi were constructed. Staining for Cdc7 was scored semiquantitatively according to intensity and extent, and the values were converted into composite scores.
Results:  Nodular melanomas, atypical Spitz tumors and superficial spreading melanomas had the highest scores (nodular melanomas, 3.67; atypical Spitz tumors, 2.78 and superficial spreading melanomas, 2.44). Typical Spitz nevi, dysplastic nevi and ordinary nevi had the lowest scores. Cdc7 expression in melanomas differed significantly from non-Spitz nevi (p < 0.001). The difference was also significant when invasive melanomas were compared with dysplastic nevi (p < 0.005) and when invasive melanomas were compared with non-atypical Spitz nevi (p < 0.001). However, there was no significant difference between invasive melanomas and atypical Spitz tumors (p = 0.69) or between dysplastic nevi and ordinary nevi (p = 0.73).
Conclusion:  Cdc7 expression differs significantly among cutaneous melanocytic neoplasms and can be evaluated by routine immunohistochemical methods. The results suggest that differences in Cdc7 expression may account for some of the differences between malignant melanomas and benign melanocytic nevi.     

结缔组织痣的临床分型及组织病理研究进展

结缔组织痣(CTN)是一种良性皮肤错构瘤, 依据病变的主要构成组分分为胶原蛋白型、弹性蛋白型和蛋白多糖型三大类, 各类又包含多种遗传性及获得性疾病, 因此需结合遗传信息、临床表现和组织病理学特征确诊CTN及其具体亚型。本文依据国内外最新文献, 将CTN的临床分型及组织病理学进展进行详尽地整理综述, 以期进一步加强对此病的认识理解。     

Dermatopathology 101. Part 2 – Skin tumors

The present CME article highlights fundamental aspects with respect to the histopathology of the most common skin tumors (epidermal, adnexal, melanocytic, and mesenchymal), their laboratory workup, as well as the importance of supplementary immunohistochemical and molecular studies. The information provided is meant to assist experienced clinicians in choosing the correct biopsy technique and in interpreting dermatopathology reports, and to provide dermatology residents with a better understanding of dermatopathology. Similar to inflammatory dermatoses, the diagnosis of skin tumors, too, requires the close cooperation between clinicians and dermatopathologists. The diagnostic quality and the resultant therapeutic approach can be significantly improved if this collaboration is based on the same dermatological understanding.     

Expression of activated Akt in benign nevi, Spitz nevi and melanomas

BACKGROUND: Activated Akt expression (p-Akt) is reportedly increased in many melanomas as compared with benign nevi. The purpose of this study was to evaluate and compare p-Akt immunohistological staining in benign nevi, Spitz nevi and primary melanomas. METHODS: Immunostaining for phosphorylated Akt was performed in 41 melanocytic lesions previously classified as benign intradermal nevus (14 lesions), Spitz nevus (9 lesions) or melanoma (18 lesions). Lesions were graded for intensity of p-Akt staining by two independent observers (0, no staining; 1, slightly positive; 2, moderately positive; 3, highly positive). Scores were averaged, and statistical analyses were performed. RESULTS: Benign nevi showed less staining (mean score 1.18) compared with Spitz nevi (mean score 2.11) and melanomas (mean score 2.19). This difference was statistically significant between benign nevi and melanomas (p = 0.0047) and benign nevi and Spitz nevi (p = 0.0271). No statistical difference was detected in staining between Spitz nevi and melanomas (p = 0.8309). CONCLUSIONS: Activated Akt expression is increased in Spitz nevi and melanomas as compared with benign intradermal nevi, but is unlikely to prove useful in differentiating between the former.     

Melanocytic nevi, melanoma, and pregnancy

Malignant melanoma is among the malignant tumors whose incidence has risen markedly in recent decades. For many years the medical community debated the potential adverse effects of female hormones (whether of exogenous or pregnancy-related endogenous origin), on melanocytic nevi and malignant melanoma. Given that women have been delaying pregnancy until their thirties or forties and that the incidence of malignant melanoma increases in those decades, the likelihood of this tumor developing during pregnancy has increased. Recent clinical and experimental evidence has suggested that pregnancy does not affect prognosis in malignant melanoma and that it does not seem to lead to significant changes in nevi. This review examines the relationship between malignant melanoma and hormonal and reproductive factors. Evidence was located by MEDLINE search (in PubMed and Ovid) for articles in English and Spanish for the period from 1966 to March 2010; additional sources were found through the reference lists of the identified articles.     

Age- and site-specific variation in the dermoscopic patterns of congenital melanocytic nevi: an aid to accurate classification and assessment of melanocytic nevi

OBJECTIVES: To describe the dermoscopic features of congenital melanocytic nevi (CMN) and assess whether predominant dermoscopic patterns present in CMN are related to an individual's age (<12 years vs >or=12 years), sex, or lesional site (head, neck, and trunk vs extremities). DESIGN: Nonrandomized observational study. PATIENTS: A total of 77 consecutive patients, each with 1 CMN (n = 77 lesions), from an outpatient dermatology clinic. A diagnosis of CMN was established by (1) documentation of a melanocytic nevus during the first year of life or (2) by clinical examination and either clinical history or biopsy findings. MAIN OUTCOME MEASURES: Images of CMN were evaluated for specific dermoscopic structures and patterns. The distribution of patterns was assessed by age, sex, and lesional site. RESULTS: Most of the 77 lesions exhibited 1 of the following predominant dermoscopic patterns: reticular (18 lesions [23%]), globular (14 [18%]), or reticuloglobular (12 [16%]). Globular CMN were present in 5 of the 19 individuals who were younger than 12 years (26%) but in only 9 of the 58 individuals 12 years or older (16%). Reticular CMN were seen exclusively in the individuals who were 12 years or older. Congenital melanocytic nevi exhibiting no predominant pattern were more commonly present in the individuals younger than 12 years. Globular CMN were present in 11 head, neck, and trunk lesions (30%) compared with 3 extremity lesions (8%). Conversely, reticular CMN were present in 16 extremity lesions (40%) compared with 2 head, neck, and trunk lesions (5%). The predominant dermoscopic pattern did not vary based on sex. The most commonly observed dermoscopic structures were globules (in 64 lesions [83%]), hypertrichosis (in 61 [79%]), and reticular networks (in 55 [71%]). CONCLUSIONS: Our results suggest that the predominant dermoscopic patterns of CMN vary according to age and lesional site. These differences may inform future studies on the pathogenesis of CMN.     

Human telomerase RNA component expression in Spitz nevi,common melanocytic nevi,and malignant melanomas

BACKGROUND: Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi. METHODS: Ten specimens of each type of tumor were studied, using an in situ hybridization technique. RESULTS: All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units. CONCLUSIONS: hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.     

Melanocytic nevi with features of Spitz nevi and Clark's/dysplastic nevi ("Spark's" nevi)

Background: Nevi with cytologic characteristics of Spitz nevus and architectural features of Clark's/dysplastic nevus are not well recognized in the literature.
Methods: Twenty-seven nevi with characteristics of Spitz nevus and Clark's/dysplastic nevus are reviewed.
Results: The patients' mean age was 33 years, and 17/27(63%) patients were female. Lesions were most frequent on the trunk and lower extremities. Histopathologically, these nevi were composed of large, monomorphous spindled and/or epithelioid melanocytes. Spindle cells were often oriented parallel to the epidermis, with fused rete and lamellar fibroplasias. Lateral extension of the junctional component was a feature of compound lesions. An average of 10 years of clinical follow up in 12 patients revealed no recurrence or metastasis.
Conclusions: Recognition of this type of nevus is important to avoid confusion with malignant melanoma.     

Long- and short-term histological observations of congenital nevi treated with the normal-mode ruby laser.

OBJECTIVE: To evaluate histologically the long- and short-term changes associated with cosmetic improvement or failure of normal-mode ruby laser treatment of patients with congenital nevi. DESIGN: A biopsy of the laser-treated lesions of 10 patients with good or poor cosmetic results was performed at periods up to 8 years 10 months after treatment (mean, 4 years 9 months). Short-term findings were evaluated in 3 patients. SETTING: Ueda Setsuko Clinic and the Dermatology Unit of the Kyushu University, Fukuoka, Japan. PATIENTS: Of the 85 Japanese patients with relatively large congenital nevi who had been treated with the normal-mode ruby laser since 1990, 13 gave informed consent for biopsy and histological examination of the treated area. RESULTS: A long-term follow-up study of the 8 patients with good cosmetic results showed the presence of residual nevus cells 1.11 +/- 0.35 mm (mean +/- SD) (range, 0.63-2.05 mm) below the skin surface. Above these cells was a layer of connective tissue that formed a subtle microscopic scar that preserved the normal structure of the papillary dermis. Hair follicles were damaged at the base, and the hairs were attenuated. However, in the 2 patients with poor cosmetic results, nests of pigmented cells were commonly seen in the epidermis, and melanin was relatively abundant in basal keratinocytes. No malignant changes were observed in any patient. A short-term study in 3 patients showed damage to pigmented cells in the epidermis and upper dermis as observed following electrodesiccation. CONCLUSIONS: Multiple treatments with the normal-mode ruby laser produced immediate thermal damage to the superficial nests of nevus cells and a subsequent remodeling of the superficial connective tissue. When the thickness of the subtle microscopic scar reached 1 mm, it masked the underlying residual nevus cells and achieved a good cosmetic result. Follow-up for at least 8 years after laser treatment showed no evidence of malignant change in the treated areas.