Melanin Stacking Differences in Pigmented and Non-Pigmented Melanomas: Quantitative Differentiation between Pigmented and Non-Pigmented Melanomas Based on Light-Scattering Properties.

Cutaneous melanoma is a cancer with metastatic potential characterized by varying amounts of pigment-producing melanocytes, and it is one of the most aggressive and fatal forms of skin malignancy, with several hundreds of thousands of cases each year. Early detection and therapy can lead to decreased morbidity and decreased cost of therapy. In the clinic, this often translates to annual skin screenings, especially for high-risk patients, and generous use of the ABCDE (asymmetry, border irregularity, color, diameter, evolving) criteria. We have used a new technique termed vibrational optical coherence tomography (VOCT) to non-invasively differentiate between pigmented and non-pigmented melanomas in a pilot study. The VOCT results reported in this study indicate that both pigmented and non-pigmented melanomas have similar characteristics, including new 80, 130, and 250 Hz peaks. Pigmented melanomas have larger 80 Hz peaks and smaller 250 Hz peaks than non-pigmented cancers. The 80 and 250 Hz peaks can be used to quantitative characterize differences between different melanomas. In addition, infrared light penetration depths indicated that melanin in pigmented melanomas has higher packing densities than in non-pigmented lesions. Using machine learning techniques, the sensitivity and specificity of differentiating skin cancers from normal skin are shown to range from about 78% to over 90% in this pilot study. It is proposed that using AI on both lesion histopathology and mechanovibrational peak heights may provide even higher specificity and sensitivity for differentiating the metastatic potential of different melanocytic lesions.

"Fingerprinting" Benign and Cancerous Skin Lesions Using Vibrational Optical Coherence Tomography: Differentiation among Cancerous Lesion Types Based on the Presence of New Cells, Blood Vessels, and Fibrosis.

In this study, we use vibrational optical coherence tomography (VOCT) to examine the morphology and stiffness of benign and cancerous lesions. Lesion images and 3D plots of weighted displacement versus frequency and depth were used to compare the cellular, dermal collagen, new blood vessels, and fibrotic composition of normal skin, actinic keratoses (AK), nodular and superficial basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs), and melanomas. The results of this study suggest that benign and cancerous lesions differ based on the addition of new cells with increased resonant frequency and stiffness (80 Hz, 1.8 MPa), new blood vessel peaks (130 Hz, 4.10 MPa) that appear to be less stiff than normal blood vessels, and new fibrous tissue peaks (260 Hz, 15-17 MPa) that are present in carcinomas but not in normal skin and only partially present (80 Hz and 130 Hz only) in AKs. Results obtained by creating images based on the location of the 80 Hz, 130 Hz, and 260 Hz peaks of cancerous skin lesions suggest that the fibrous tissue appears to surround the new cells and new lesion blood vessels. The results of this study suggest that the morphology and location of the fibrous tissues in relation to the new cancer-associated cells and lesion blood vessels may provide information on the invasiveness and metastatic potential of skin cancers. The invasiveness and metastatic potential of melanomas may be a result of the cancer-associated cells laying down fibrous tissue that is used as a pathway for migration. The new cancer-associated blood vessels in the vicinity of the new cancer-associated cells may promote this migration and eventual metastasis. The ratios of peak heights 50/130 Hz and 80/130 Hz of normal cells, new lesion cells, new lesion blood vessels, and fibrotic tissue may be used as a "fingerprint" for detecting melanoma and to differentiate it from other skin cancers non-invasively using VOCT.

Characterization of the Biomechanical Properties of Skin Using Vibrational Optical Coherence Tomography: Do Changes in the Biomechanical Properties of Skin Stroma Reflect Structural Changes in the Extracellular Matrix of Cancerous Lesions?

Early detection of skin cancer is of critical importance since the five-year survival rate for early detected skin malignancies is 99% but drops to 27% for cancer that has spread to distant lymph nodes and other organs. Over 2.5 million benign skin biopsies (55% of the total) are performed each year in the US at an alarming cost of USD ~2.5 B. Therefore there is an unmet need for novel non-invasive diagnostic approaches to better differentiate between cancerous and non-cancerous lesions, especially in cases when there is a legitimate doubt that a biopsy may be required. The purpose of this study is to determine whether the differences in the extracellular matrices among normal skin, actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) can be assessed non-invasively using vibrational optical coherence tomography (VOCT). VOCT is a new diagnostic technology that uses infrared light and audible sound applied transversely to tissue to measure the resonant frequencies and elastic moduli of cells, dermal collagen, blood vessels and fibrous tissue in skin and lesion stroma without physically touching the skin. Our results indicate that the cellular, vascular and fibrotic resonant frequency peaks are altered in AK, BCC and SCC compared to those peaks observed in normal skin and can serve as physical biomarkers defining the differences between benign and cancerous skin lesions. The resonant frequency is increased from a value of 50 Hz in normal skin to a value of about 80 Hz in pre- and cancerous lesions. A new vascular peak is seen at 130 Hz in cancerous lesions that may reflect the formation of new tumor blood vessels. The peak at 260 Hz is similar to that seen in the skin of a subject with Scleroderma and skin wounds that have healed. The peak at 260 Hz appears to be associated with the deposition of large amounts of stiff fibrous collagen in the stroma surrounding cancerous lesions. Based on the results of this pilot study, VOCT can be used to non-invasively identify physical biomarkers that can help differentiate between benign and cancerous skin lesions. The appearance of new stiff cellular, fragile new vessels, and stiff fibrous material based on resonant frequency peaks and changes in the extracellular matrix can be used as a fingerprint of pre- and cancerous skin lesions.

The "Virtual Biopsy" of Cancerous Lesions in 3D: Non-Invasive Differentiation between Melanoma and Other Lesions Using Vibrational Optical Coherence Tomography.

Early detection of skin cancer is of critical importance to provide five year survival rates that approach 99%. By 2050, one out of five Americans by age 70 will develop some form of skin cancer. This will result in a projected rate of 50 million skin biopsies per year given the current rate of escalation. In addition, the ability to differentiate between pigmented lesions and melanomas has proven a diagnostic challenge. While dermoscopy and visual analysis are useful in identifying many skin lesions, additional non-invasive techniques are needed to assist in the analysis of difficult to diagnose skin tumors. To augment dermoscopy data, we have developed 3D maps based on physical biomarker characteristics of benign and cancerous lesions using vibrational optical coherence tomography (VOCT). 3D images based on quantitative physical data involving changes in cellular and fibrous tissue stiffness along with changes in vascular quality are used to map and evaluate different types of cancers. 3D tumor maps constructed using quantitative VOCT data and OCT images have been used to characterize the differences between melanoma and other lesions. These characteristics can be used to plan the excision of difficult lesions where extensive surgery may be needed to remove the entire tumor in one step. In addition, it is now possible to use dermoscopy and VOCT to non-invasively differentiate between different cancerous lesion types using measurements of the resonant frequency of new cellular and vascular peaks. Quantitative VOCT information along with dermoscopic findings can be collected and analyzed remotely using artificial intelligence to improve cancerous tissue diagnosis.

Blood exposure risk during procedural dermatology.

BACKGROUND: Dermatologists are at risk of body-fluid contamination during procedures. OBJECTIVE: We sought to determine the frequency of blood splash during procedural dermatology. METHODS: In all, 500 consecutive excisions were performed. Postoperatively, blood droplets on face shields and surgical gowns were counted. A survey regarding universal precautions during procedures was also conducted with members of the American College of Mohs Surgery (ACMS). RESULTS: Contamination from blood splashes during dermatologic procedures (Mohs micrographic surgery, excision, repair) occurred in 66.4%. Reconstruction type, anticoagulation use, wound location, and wound size correlated with a higher blood splash rate. Our survey showed that face shields and goggles are used inconsistently. LIMITATIONS: The 4 participating dermatologists do not represent all practicing dermatologists. It may be possible to generalize the survey results directed at physicians in the ACMS. CONCLUSION: Physician body-fluid contamination risk with procedural dermatology is clinically significant. Dermatologists and their assistants should wear preventive barriers during procedures to minimize the risk of viral transmission.

Causes of death in hyper-IgE syndrome.

BACKGROUND: Hyper-IgE syndrome (HIES) is characterized by recurrent pyogenic infections, eczema, increased serum IgE levels, and a variety of connective tissue and skeletal system abnormalities. Little has been published regarding the causes of death in these patients or pathologic findings. OBJECTIVE: To identify the cause of death in patients with HIES and to describe pathologic findings in fatal HIES. METHODS: We reviewed the medical records and autopsy slides of 6 patients with HIES with autopsies performed at our institution. RESULTS: All 6 patients with HIES were women and ranged in age from 24 to 40 years. All patients had a history of cystic lung disease and had pneumonia at the time of death, with Pseudomonas aeruginosa and fungal organisms predominating. Pulmonary fungal vascular invasion with fatal hemorrhage was observed in 3 patients, and metastatic fungal disease to the brain was observed in 2 patients caused by Aspergillus fumigatus and Scedosporium prolificans. Four patients had evidence of renal tubular injury, which was likely from amphotericin B toxicity; 3 patients had glomerulosclerosis; and 1 patient had 2 kidney angiomyolipomas. CONCLUSIONS: Our series highlights the important role Pseudomonas and Aspergillus species play in patients with HIES with cystic lung disease. Intensified antifungal and gram-negative bacterial prophylaxis need evaluation as possible strategies to prevent these infectious complications in patients with cystic lung disease. CLINICAL IMPLICATIONS: Fungal and Pseudomonas infection of cystic lung disease in HIES may be life threatening, and the proper management and prevention of these infections need continued investigation.

Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location.

Luciferase-transduced B16 murine melanoma cells (luc-B16) inoculated in ear skin do not form tumors but prevent tumor formation by luc-B16 cells injected into the footpad. To determine the requirements for such immunity, we followed the fate of luc-B16 cells following ear injection. Surprisingly, small numbers of viable luc-B16 cells were detected in tumor-free mouse skin for up to 60 days post-inoculation. After 1 week, the number of Foxp3(+)CD4(+)CD25(+) T cells (along with foxp3 mRNA expression) increased rapidly in the injected ear skin. Residual tumor cells in ears were reduced in mice treated with anti-CD25 mAb and in CD4-deficient mice, but increased in CD8-deficient mice. Strikingly, the loss of luc-B16 cells in the ear skin, either spontaneously or following amputation of the injected ear, resulted in significantly enhanced tumor formation by parental and luciferase-expressing B16 cells after footpad injection. These studies suggest that small numbers of tumor cells (possibly regulated by CD4(+)CD25(+) regulatory T cells expressing Foxp3) are required for effective host anti-tumor responses at alternate inoculation sites.

Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) involves the upper aerodigestive tract and can destroy the structure and function of organs involved in voice, speech, taste, smell and hearing, as well as vital structures necessary for survival. HNSCC has long been a treatment challenge because of the high rate of recurrences and of advanced disease at the time of diagnosis. Molecular identification of tissue biomarkers in diagnostic biopsy specimens may not only identify patients at risk for developing HNSCC but may also select patients that may benefit from more aggressive treatment modalities. Several biomarkers studied to date such as the proteins p53, cyclin D1, p16, Cox-2 enzyme, epidermal growth factor and vascular endothelial growth factor receptors, matrix metalloproteinases and the Fhit marker for genomic instability could be manipulated for the therapeutic benefit of these patients. This review presents the most updated information on molecular biomarkers with the greatest prognostic potential in HNSCC and discusses some factors that contribute to the controversy concerning their prognostic importance.