Darrel L. Ellis

Melanoma, growth factors, acanthosis nigricans, the sign of Leser-Trélat, and multiple acrochordons. A possible role for alpha-transforming growth factor in cutaneous paraneoplastic syndromes

CARCINOMAS have been associated with such paraneoplastic syndromes as skin-tumor growth, ectopic hormone production, arthropathies, myopathies, neuropathies, multiple thromboses, nephrosis, cachexi...

In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy

Nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common skin cancers, presenting nearly as many cases as all other cancers combined. The current gold‐standard for clinical diagnosis of these lesions is histopathologic examination, an invasive, time‐consuming procedure. There is thus considerable interest in developing a real‐time, automated, noninvasive tool for nonmelanoma skin cancer diagnosis. In this study, we explored the capability of Raman microspectroscopy to provide differential diagnosis of BCC, SCC, inflamed scar tissue, and normal tissue in vivo.

Raman microspectroscopy for skin cancer detection in vitro

We investigate the potential of near-infrared Raman microspectroscopy to differentiate between normal and malignant skin lesions. Thirty-nine skin tissue samples consisting of normal, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma from 39 patients were investigated. Raman spectra were recorded at the surface and at 20-microm intervals below the surface for each sample, down to a depth of at least 100 microm. Data reduction algorithms based on the nonlinear maximum representation and discrimination feature (MRDF) and discriminant algorithms using sparse multinomial logistic regression (SMLR) were developed for classification of the Raman spectra relative to histopathology. The tissue Raman spectra were classified into pathological states with a maximal overall sensitivity and specificity for disease of 100%. These results indicate the potential of using Raman microspectroscopy for skin cancer detection and provide a clear rationale for future clinical studies.

Oestrogen receptor‐β expression in melanocytic lesions

Abstract:  Melanomas rarely occur before puberty, have a higher death rate for males, and tend to be more invasive during pregnancy. Prior to the discovery of a second oestrogen receptor (ERβ), studies with the initial oestrogen receptor, ERα, showed no obvious role for oestrogen in the pathophysiology of benign or malignant melanocytic lesions. To investigate the specific immunostaining patterns of ERα and ERβ, benign nevocytic nevi, dysplastic nevi with mild, moderate and severe cytological atypia, lentigo malignas and melanomas of varying depth (Clark) and thickness (Breslow) were studied. ERβ but not ERα was the predominant oestrogen receptor we found in all types of benign and malignant melanocytic lesions. The most intense ERβ immunostaining was seen in melanocytes in dysplastic nevi with severe cytological atypia and in lentigo malignas. ERβ expression levels also correlated with the malignant tumor microenvironment; i.e., melanocytes in proximity with keratinocytes>deeper dermal melanocytes in contact with stroma>minimally invasive melanomas>Clark Level III/IV or thick melanomas (Breslow). Discovery that ERβ expression varies in relation to the tumor microenvironment and increasing depth of invasion suggests its possible usefulness as a surrogate marker for neoplasia and prognosis in malignant melanoma.

Pregnancy and sex steroid hormone effects on nevi of patients with the dysplastic nevus syndrome

Female patients with the dysplastic nevus syndrome who were pregnant or taking sex steroid hormones were prospectively studied to evaluate the effectiveness of photography and close clinical follow-up in detecting nevus change or melanoma development. Seventeen patients, who served as their own controls, were studied during 22 pregnancies. Twenty-four patients who used oral contraceptives and seven who took hormone supplements were similarly studied. This clinical management method provided timely biopsy of changing nevi with a small number of biopsies required per patient. One melanoma occurred during pregnancy, but neither patients who were taking sex steroid hormones nor those in the control groups had melanomas. The rate of nevus change observed clinically was 3.9 times higher when patients with dysplastic nevus syndrome were pregnant than when they were not, whereas no differences were observed whether or not women took oral contraceptives or hormone supplements. The rate of histologically proven dysplastic nevi that changed was 2.0-fold higher when women were pregnant; 1.4-fold higher with the use of hormone supplements and 1.1-fold higher with the use of oral contraceptives. These preliminary data suggest pregnancy and hormone supplements may be temporally associated with an increased rate of dysplastic nevus change.

A clinical instrument for combined raman spectroscopy-optical coherence tomography of skin cancers.

The current standard for diagnosis of skin cancers is visual inspection followed by biopsy and histopathology. This process can be invasive, subjective, time consuming, and costly. Optical techniques, including Optical Coherence Tomography (OCT) and Raman Spectroscopy (RS), have been developed to perform non‐invasive characterization of skin lesions based on either morphological or biochemical features of disease. The objective of this work is to report a clinical instrument capable of both morphological and biochemical characterization of skin cancers with RS‐OCT.

In vitro changes in non-facial human skin following CO2 laser resurfacing: A comparison study

We evaluated the physical changes in human skin following CO2 laser cutaneous resurfacing with either the Sharplan SilkTouch® handpiece or the Coherent UltraPulse® laser.

Remission of severe epidermolysis bullosa acquisita induced by extracorporeal photochemotherapy

We report a patient with severe epidermolysis bullosa acquisita (EBA) whose disease was refractory to conventional treatments. New bullae continued to develop over greater than 50% of his body surface area despite therapy. His course was complicated by hyperglyeaemia, sepsis, hypoxia caused by pulmonary Aspergillus infection and an idiopathic cardiomyopathy. His EBA resolved after treatment with extracorporeal photochemotherapy (ECP). Hence, ECP may be effective in the treatment of severe EBA which has failed to respond to standard treatment regimens.

Increased epidermal growth factor receptors in melanocytic lesions

BACKGROUND Epidermal growth factor receptors (EGF/R) have been reported to be absent in melanomas or, in contrast, to be markers for potential malignancy in melanocytic lesions. OBJECTIVE Our purpose was to evaluate the literature discrepancies regarding the presence of EGF/R in melanocytic lesions and to determine whether EGF/R presence correlates with the potential for malignancy of melanocytic lesions. METHODS An EGF/R-specific polyclonal antibody was used to study melanomas, dysplastic nevi, congenital nevi, and nevocellular nevi. RESULTS All melanocytic cell types (nevus and melanoma cells) in the lesions studied had immunoreactive EGF/R. EGF/R immunoreactivity was also observed throughout the epidermal basal to granular cell layers overlying the melanocytic lesions, although dermal fibroblasts were negative. CONCLUSION The pattern of increased immunoreactive EGF/R in both benign and malignant nevocellular lesions suggests that although EGF/R are not a specific marker of potential malignancy in melanocytic lesions, they may mediate or coordinate growth of keratinocytes and nevus cells.

Localization of MGSA/GRO protein in cutaneous lesions

Melanoma growth stimulatory activity (MGSA/GRO), a cyto‐kine originally characterized as an autocrine growth factor for melanoma cells, is highly chemotactic for neutrophils and releases neutrophil elastase as well as other matrix‐degrading enzymes. Previous work has demonstrated the presence of MGSA/GRO in melanocytic lesions and in the epidermal keratinocytes of non‐lesional skin and psoriatic scale. Herein, MGSA/GRO localization was examined in a variety of human skin lesions exhibiting proliferative and/or differentiative disorders using immunohistochemical methods. Most lesions showed greater MGSA/GRO immunoreactivity in the more differentiated supra‐basal keratinocytes of the stratum spinosum and stratum granulosum than in the stratum basalis, where the dividing basal cells are found. Hair follicles, sebaceous glands, and sweat glands were also frequently positive for MGSA/GRO. The highest level of immunoreactive MGSA/GRO in diseased epidermis was detected in verruca vulgaris, followed by psoriasis, keratoacanthoma, and squamous cell carcinoma. Detection of MGSA/GRO in basal cell carcinoma was variable, being present in the sclerosing variant and absent in the more common nodular variant. Melanocytic lesions stained less intensely for MGSA/GRO than keratinocytic lesions, where the levels of MGSA/GRO expression correlated with the inflammatory response and degree of keratinocyte differentiation.