New Optical Device to Diagnose Basal Cell Carcinoma

Veronica Hackethal, MD

A new optical technology called multiphoton microscopy (MPM) could allow for noninvasive, painless, and rapid diagnosis of basal cell carcinomas (BCCs) in the clinic, according to a small pilot study published online April 24 in JAMA Dermatology.



The new technology could potentially reduce wait time from diagnosis to treatment.


"This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions," write first author Mihaela Balu, PhD, and colleagues from the University California, Irvine, and Saarland University, in Saarbrucken, Germany.


As the most common human cancer, BCC comprises 25% of all cancer cases and 75% of malignant skin cancers in the United States. Several kinds of optical imaging techniques have already been developed, but the risk for misdiagnosis remains a problem.


MPM takes advantage of chemical compounds in the skin, such as keratin, collagen, NADH, FAD, elastin, and melanin. When excited by a laser, these compounds emit light that can be used to create high-definition, 3-D images of the skin. In particular, NADH and FAD concentrations provide an indication of metabolic activity, which differs in normal cells compared with tumor cells.


In the study, Dr Balu and colleagues sought to evaluate how well MPM can visualize BCC tumor nests and their cellular structures. They used a recently developed clinical device called MPTflex (JenLab GmbH). Because it is portable, MPTflex allows for imaging parts of the body rather than only the extremities. Imaging areas near the eyes, nose, and ears, though, may still pose a problem.


The study took place between September 2012 and April 2014 at the University of California, Irvine, Beckman Laser Institute and Medical Clinic, in California. Dr Balu and colleagues performed MPM imaging on nine patients and looked at a total of 10 BCCs before biopsy. Then they compared MPM images to histopathologic findings.


They found that the main MPM feature associated with BCC lesions was nests of basaloid cells in the papillary and reticular dermis, with some showing palisading at the peripheral cell layer. These features are characteristic of BCC lesions and "correlated well" with histopathologic evaluation, according to the authors.


MPM also identified other features found in BCCs, including elongated tumor cells in the epidermis aligned in one direction and parallel collagen and elastin bundles surrounding the tumors.


The sensitivity and specificity of MPM still needs evaluation in a larger trial, the authors point out. Resolving the cellular structure of deeper nests also remains "challenging" and requires further study.


"Our study shows that in vivo MPM imaging can resolve the cellular structure inside the tumor nests corresponding to BCC lesions that include superficial components," the authors concluded. "This is important because the presence of nests of basaloid cells at the dermoepidermal junction and/or in the dermis is the main histopathologic criterion for BCC diagnosis. Therefore, this feature can be potentially used as a criterion for BCC diagnosis with MPM imaging."


In a linked opinion, Victor Neel, MD, PhD, of Harvard Medical School, likened the new MPM technology to an "optical biopsy."


"Compared with RCM [another optical imaging technology], MPM is like watching television in color instead of black and white," he enthused.


Technical obstacles exist, however. These include limited field of view, slow acquisition time, shallow penetration, and the need for patients to remain still to avoid motion artifacts. Additionally, imaging larger lesions would involve a tricky process of stitching together smaller images, according to Dr Neel.


Furthermore, the need for MPM in standard evaluation of BCC may not be "particularly urgent," he continued, given the simple and reliable technique of punch biopsy. On the other hand, there may be an "urgent need" for it in dermatologic surgery.


"Although Mohs micrographic surgery is an elegant, time-tested procedure to remove tumors, it still relies too heavily on the clinician's visual intuition to 'guess' at the initial presurgical margins of the tumor," Dr Neel writes.


Underestimating the presurgical margin can result in multiple excisions, whereas overestimating the margin results in unnecessary removal of too much normal skin, he added.


"Dermatologic surgeons should demand what every other surgical specialty has developed decades ago, namely, an imaging system to assess the presence of tumor and extent of in vivo tumor spread prior to surgery," he emphasized.


Dr Konig is cofounder of JenLab GmbH (Jena, Germany). Dr Neel reports no relevant financial relationships. 


JAMA Dermatol. Published online April 24, 2015. 




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