We describe a computer vision-based mosaicking method for in vivovideos of reflectance confocal microscopy (RCM). RCM is a microscopic imaging technique, which enables the users to rapidly examine tissue in vivo. Providing resolution at cellular-level morphology, RCM imaging combined with mosaicking has shown to be highly sensitive and specific for non-invasively guiding skin cancer diagnosis. However, current RCM mosaicking techniques with existing microscopes have been limited to two-dimensional sequences of individual still images, acquired in a highly controlled manner, and along a specific predefined raster path, covering a limited area. The recent advent of smaller handheld microscopes is enabling acquisition of videos, acquired in a relatively uncontrolled manner and along an ad-hoc arbitrarily free-form, non-rastered path. Mosaicking of video-images (video-mosaicking) is necessary to display large areas of tissue. Our video-mosaicking methods addresses this need. The method can handle unique challenges encountered during video capture such as motion blur artifacts due to rapid motion of the microscope over the imaged area, warping in frames due to changes in contact angle and varying resolution with depth. We present test examples of video-mosaics of melanoma and non-melanoma skin cancers, to demonstrate potential clinical utility.

Extramammary Paget disease or EMPD is a rare skin cancer that presents with a red patch in the vulva or anus in women, and in the scrotum, penis and anus in men. Diagnosing EMPD is challenging because the entire area affected by the disease is not visible with the naked eye, or can be misdiagnosed with other skin conditions such as infection or inflammation. This is particularly important when monitoring treatment response, as treatments can irritate the skin and look identical (red patch) to residual EMPD.

Reflectance confocal microscopy or RCM is an imaging system which uses a light source that does not damage the skin and that allows to see cells on the superficial layers on the skin. RCM has been used to diagnose EMPD as one can see the cancer cells in the skin in real time.

Skin cancer is the most common type of cancer worldwide. In the United States, the incidence is rising, with over two million people diagnosed each year [1]. More cases of skin cancer are diagnosed each year than breast, prostate, lung, and colon cancer combined. The lifetime risk of developing skin cancer is estimated to be 20%[2]. Although nonmelanoma skin cancer is rarely fatal and associated with a very low mortality rate, melanoma can be highly fatal. Approximately 76,000 individuals will be diagnosed with invasive melanoma in 2012 [3]. Skin cancer can be easily cured with early detection and excision. Early detection is essential, especially for melanoma, which has a grim prognosis once it has metastasized. Today, detection requires a biopsy to definitively determine if a lesion is malignant or benign.

RCM is emerging as a promising and versatile tool to assist dermatologic surgeons in the diagnosis and approach of cutaneous tumors. Compared with dermoscopy, it has demonstrated increased sensitivity and specificity in the clinical diagnosis of melanocytic lesions and doubtful dermoscopies, and many other applications are being studied. Nevertheless, it is important to note that traditional histopathology remains the gold standard for the definitive diagnosis of skin lesions.

RCM still has many limitations, which have been mitigated as more research is performed, and the device has been improved. In 2007, a consensus conference was organized to standardize concepts, and in 2009 an Internet-based study invol- ving six reference centers was conducted to evaluate the repro- ducibility of those concepts and the derived terminology. 53, 54

The examination of a single lesion takes 5-15 minutes. A clinical examination and dermoscopy are essential to determine what should be assessed by RCM, for lesions with fewer altera- tions in the initial tests are more likely to present fewer charac- teristic findings using RCM.40

Another important limitation to be overcome with techni- cal improvements in the near future is the visualization of the dermis, given that the reflection of the light only allows viewing to a depth of 350 m only (i.e., papillary or superficial reticular dermis).

However, while dermoscopy has probably already reached its full diagnostic accuracy potential, we expect great advances in RCM in the next few years.1 As was the case for dermoscopy, we expect RCM become part of the dermatologists’ daily practice as an auxiliary method in the diagnosis and treatment of skin cancer.