The distinct contributions of murine T cell receptor (TCR)gammadelta+ and TCRalphabeta+ T cells to different stages of chemically induced skin cancer.

Epithelial tissues in which carcinomas develop often contain systemically derived T cell receptor (TCR)alphabeta+ cells and resident intraepithelial lymphocytes that are commonly enriched in TCRgammadelta+ cells. Recent studies have demonstrated that gammadelta cells protect the host against chemically induced cutaneous malignancy, but the role of alphabeta T cells has been enigmatic, with both protective and tumor-enhancing contributions being reported in different systems. This study aims to clarify the contributions of each T cell type to the regulation of squamous cell carcinoma induced in FVB mice by a two-stage regimen of 7,12-dimethylbenz[a]anthracene initiation followed by repetitive application of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. This protocol permits one to monitor the induction of papillomas and the progression of those papillomas to carcinomas. The results show that whereas gammadelta cells are strongly protective, the nonredundant contributions of alphabeta T cells to the host's protection against papillomas are more modest. Furthermore, at both high and low doses of carcinogens, alphabeta T cells can contribute to rather than inhibit the progression of papillomas to carcinomas. As is likely to be the case in humans, this study also shows that the contribution of T cells to tumor immunosurveillance is regulated by modifier genes.

In vivo reflectance confocal microscopy imaging of melanocytic skin lesions: consensus terminology glossary and illustrative images.

BACKGROUND: Reflectance confocal microscopy (RCM) has been used for over 10 years for in vivo skin imaging. However, to date no standard RCM terminology has been published. OBJECTIVE: To establish a glossary of terms for RCM evaluation of melanocytic lesions. METHODS: Prominent RCM researchers were presented with RCM images of melanocytic lesions. Reviewers evaluated RCM images for image quality, lesion architecture, and cellular details. Reviewers could utilize published descriptors or contribute unpublished terminology to describe lesion attributes. An online meeting was conducted to reach consensus that integrates and defines existing and new RCM descriptive terms. RESULTS: We present a glossary with descriptors of image quality, normal skin morphology, lesion architecture, and cellular details for RCM evaluation of melanocytic lesions. LIMITATIONS: Usefulness of the glossary in RCM diagnosis of melanocytic lesions needs to be assessed. CONCLUSION: Standardization of terminology is important toward implementation of RCM in the clinical setting.

The diagnostic accuracy of in vivo confocal scanning laser microscopy compared to dermoscopy of benign and malignant melanocytic lesions: a prospective study.

BACKGROUND: The diagnosis of melanoma at an early, curable stage is an important challenge for clinicians. Confocal scanning laser microscopy (CSLM) is a high-resolution, noninvasive technology that may facilitate improved diagnostic accuracy over clinical examination. The aim of this study was to evaluate the diagnostic accuracy of CSLM compared to dermoscopy in a prospective examination of benign and malignant melanocytic lesions. METHODS: 125 patients with suspicious pigmented lesions were prospectively recruited to undergo a clinical, dermoscopic and CSLM examination. A diagnosis was made preoperatively with each technique, and the lesion was then excised and diagnosed using histopathology. RESULTS: 125 patients with 125 lesions were studied comprising 88 melanocytic nevi and 37 melanomas. Dermoscopy had a sensitivity of 89.2%, a specificity of 84.1%, a positive predictive value of 70.2% and a negative predictive value of 94.9%. CSLM was found to have a sensitivity of 97.3%, a specificity of 83.0%, a positive predictive value of 70.6% and a negative predictive value of 98.6%. No melanomas were misidentified when both techniques were used together. CONCLUSIONS: CSLM had a relatively higher sensitivity than dermoscopy; however, the specificity was similar with CSLM and dermoscopy. These results suggest that dermoscopy and CSLM are complementary.

In vivo confocal scanning laser microscopy of benign lentigines: comparison to conventional histology and in vivo characteristics of lentigo maligna.

BACKGROUND: An important challenge facing clinicians is recognizing and distinguishing benign pigmented lesions from cutaneous melanoma. Lentigines are a type of benign pigmented lesion that can resemble melanoma. Physician diagnostic accuracy is less than perfect, prompting research into noninvasive technology such as reflectance mode in vivo confocal scanning laser microscopy (CSLM). OBJECTIVES: Our aims were twofold: to describe the in vivo characteristics of benign lentigines with reflectance CSLM and to compare them with histopathology; and to contrast the in vivo CSLM differences of lentigines, lentigo maligna, and lentigo maligna melanomas. METHODS: Patients with a suspect pigmented lesion were prospectively recruited to undergo CSLM before biopsy. Lentigo simplex, solar lentigo, or malignant melanoma, lentigo maligna type, were included in the study. Images were qualitatively described and compared with histopathologic findings. RESULTS: Ten patients, whose lesions included 6 lentigines and 4 lentigo malignas, were examined with CSLM. Distinct architectural and cytologic features were noted in benign lentigines compared with melanomas. The most striking finding in lentigines was observed at the dermoepidermal junction. In all cases of lentigines there was an increase in the density of dermal papillae surrounded by a bright monomorphic layer of cells. Distinct patterns were noted, as these papillae assumed irregular geometric shapes or formed papillary projections with a rim of bright, highly refractile, monomorphic, and cytologically benign-appearing cells. These findings were absent in all of the melanomas studied. Lentigines had an absence of atypical melanocytes, whereas the melanomas had bright, atypical, polymorphous cells present in a pagetoid pattern with coarse, branching dendrites observed throughout the epidermis. LIMITATIONS: This is a descriptive pilot study involving a limited number of patients. CONCLUSION: Unique CSLM characteristics of lentigines were found that have not been previously described, facilitating rapid in vivo discrimination from malignant melanoma. This descriptive study supports the further examination of CSLM features of lentigines to aid in the diagnosis of melanoma and discrimination from benign lesions.

Prognostic significance of vascularity in cutaneous melanoma: pilot study using in vivo confocal scanning laser microscopy.

BACKGROUND: Tumor vascularity may be of strong prognostic significance in cutaneous melanoma. We are the first to use a novel, noninvasive, in vivo confocal scanning laser microscope (CSLM) to evaluate vascularity in cutaneous melanoma. OBJECTIVE: Our purpose was to apply a CSLM to assess vascularity in melanoma and to evaluate the prognostic significance of these findings. METHODS: Patients with a suspicious pigmented lesion were prospectively recruited to undergo CSLM prior to skin biopsy, and those diagnosed with melanoma were included in this study. A blinded observer graded tumor vascularity from still digital CSLM images. The CSLM vascularity grading was correlated to tumor thickness and ulceration as a proxy for clinical prognosis. RESULTS: Sixty-six patients and 67 lesions underwent imaging with CSLM. Eleven patients were diagnosed with melanoma, including six in situ and five invasive melanomas. Prominent vascularity was observed in all advanced melanomas. There was an overall increase in mean tumor thickness between the absent (x = 0.315 mm) to prominent (x = 1.51 mm) categories. CONCLUSION: In this pilot study, vascularity was readily detected in cutaneous melanomas using CSLM. Prominent vascularity was observed in patients with advanced cutaneous melanomas. Our preliminary results are encouraging and indicate potential for the use of CSLM to assess vascularity in cutaneous melanoma, with potential prognostic and therapeutic implications.