Journal of Skin Cancer最新文献

Background. Photodynamic therapy (PDT) has become a therapeutic option for basal cell carcinoma (BCC) in the last decade. Objectives. To study the results and predictors of BCC response to treatment with PDT and to evaluate fluorescence diagnosis of BCC. Methods. A descriptive, retrospective, and observational study was carried out. Patients with biopsy-confirmed BCC who were treated with methyl aminolevulinate and red light according to standard treatment protocols (2 sessions separated by 2 weeks, 630 nm, 37 J/cm(2), 8 minutes, Aktilite) were selected. Response was scored as clinically complete and incomplete and the patients were followed up every three months. Results. Data from 191 BCC in 181 patients with a mean age of 69.55 years and a mean follow-up period of 34.4 months were collected. The overall response was 74% of the BCC treated, with the best response in superficial BCC with a 95% of complete response. The regression analysis revealed that the superficial histological type was the primary factor predictive of a complete response. Conclusions. In the treatment of BCC with PDT, the most significant factor for predicting response is the histological type.

Objective. The aim of this study was correlation of skin adnexal tumors with age, sex, and location and determining its incidence in the Department of Pathology at Dr. D. Y. Patil Medical College and Hospital, Kolhapur, Maharashtra. Material and Methods. 56 cases were included in this study from Jan 2004 to June 2010 with respect to incidence of adnexal tumors, age, and sex distribution. All slides were stained with haematoxylin and eosin and then findings were corroborated with special stains like PAS and reticulin wherever required. Results. 80.36% (45/56) were benign and 19.64% (11/56) were malignant adnexal tumors. The sweat gland tumors constituted the largest group (42.86% 24/56) cases followed by the hair follicle tumors (35.71%, 20/56) of cases and sebaceous gland tumors (21.43%, 12/56) cases. Overall male : female ratio was 1.07 : 1. The commonest age group was 51-60 years and the commonest affected body part was head and neck region (64.28%, 36/56) followed by trunk (14.28%, 8/56). Clear cell hidradenoma and pilomatricoma were commonest benign tumors and sebaceous carcinoma was the only malignant tumor seen. Conclusion. The incidence of benign skin adnexal tumors was more as compared to the malignant tumors. Malignant tumors were seen in older age group, usually over 50 years of age.

KSHV is the etiologic agent for Kaposi's sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/ α -MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF- κ B activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF- κ B, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals.

DLEC1 has been suggested as a tumor suppressor gene in several cancers. DLEC1 D215N somatic mutation (COSM36702) was identified in a melanoma cell line through whole genome sequencing. However, little is known about the implication and prevalence of this mutation in primary melanomas or in melanocytic nevi. The aim of this study was to genotype DLEC1 D215N mutation in melanoma tissue and melanocytic nevi samples to confirm its occurrence and to estimate its prevalence. Primary melanomas (n = 81) paired with synchronous or asynchronous metastases (n = 21) from 81 melanoma patients and melanocytic nevi (n = 28) were screened for DLEC1 D215N mutation. We found the mutation in 3 primary melanomas and in 2 melanocytic nevi, corresponding to a relatively low prevalence (3.7% and 7.1%, resp.). The pathogenic role of DLEC1 215N mutation is unclear. However, since the mutation has not been previously described in general population, its involvement in nevogenesis and melanoma progression remains a possibility to be clarified in future studies.

Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat3 plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat3-deficient mice have revealed that Stat3 plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat3-deficient mouse models has demonstrated that Stat3 is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat3 (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat3 in skin tumor progression. Studies using similar Stat3-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat3 in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat3 is an attractive target for skin cancer prevention and treatment.

Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.

Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.

Mouse models have informed us that p63 is critical for normal epidermal development and homeostasis. The p53/p63/p73 family is expressed as multiple protein isoforms due to a combination of alternative promoter usage and C-terminal alternative splicing. These isoforms can mimic or interfere with one another, and their balance ultimately determines biological outcome in a context-dependent manner. While not frequently mutated, p63, and in particular the ΔNp63 subclass, is commonly overexpressed in human squamous cell cancers. In vitro keratinocytes and murine transgenic and transplantation models have been invaluable in elucidating the contribution of altered p63 levels to cancer development, and studies have identified the roles for ΔNp63 isoforms in keratinocyte survival and malignant progression, likely due in part to their transcriptional regulatory function. These findings can be extended to human cancers; for example, the novel recognition of NF κ B/c-Rel as a downstream effector of p63 has identified a role for NF κ B/c-Rel in human squamous cell cancers. These models will be critical in enhancing the understanding of the specific molecular mechanisms of cancer development and progression.

AP1 (jun/fos) transcription factors (c-jun, junB, junD, c-fos, FosB, Fra-1, and Fra-2) are key regulators of epidermal keratinocyte survival and differentiation and important drivers of cancer development. Understanding the role of these factors in epidermis is complicated by the fact that each protein is expressed, at different levels, in multiple cells layers in differentiating epidermis, and because AP1 transcription factors regulate competing processes (i.e., proliferation, apoptosis, and differentiation). Various in vivo genetic approaches have been used to study these proteins including targeted and conditional knockdown, overexpression, and expression of dominant-negative inactivating AP1 transcription factors in epidermis. Taken together, these studies suggest that individual AP1 transcription factors have different functions in the epidermis and in cancer development and that altering AP1 transcription factor function in the basal versus suprabasal layers differentially influences the epidermal differentiation response and disease and cancer development.

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy occurring mostly in older immunocompromized Caucasian males. A growing incidence of MCC has been reported in epidemiological studies. Treatment of MCC usually consists of surgical excision, pathological lymph node evaluation, and adjuvant radiotherapy. This paper reports the experience of a single tertiary center institution with 17 head and neck Merkel cell carcinoma patients. Median followup for the cohort was 37.5 months. After five years, recurrence-free survival, disease specific survival, and overall survival were 85%, 90%, and 83%, respectively. Our limited data support the use of adjuvant radiotherapy. We also report two cases of MCC located at the vestibule of the nose and two cases of spontaneous regression after diagnostic biopsy. About 40% of our patients were referred to our center for surgical revision and pathological lymph node evaluation. Increased awareness of MCC and an interdisciplinary approach are essential in the management of MCC.