Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

An Evolving Approach to the Detection of Melanoma and Other Skin Cancers Using In Vivo Reflectance Confocal Microscopy

An Evolving Approach to the Detection of Melanoma and Other Skin Cancers Using In Vivo... To make a definitive diagnosis of skin cancer, dermatologists have been required to obtain skin biopsy specimens of suspicious lesions and to examine tissue pathologic abnormalities ex vivo under light microscopy. In the past decades, high diagnostic sensitivity, which is associated with a low biopsy threshold,1 has been increasingly emphasized in skin cancer screening to combat melanoma deaths and to counter the rising incidence and morbidity of nonmelanoma skin cancer. Distinguishing malignant from benign lesions, however, has always been associated with biopsies of innocuous mimickers of skin cancer, such as nevi and seborrheic keratoses. A 2012 international 10-year multicenter study,2 for example, estimated that 28.4 nevi are biopsied for every melanoma detected. These procedures have been accepted and rationalized as a “cost of doing business”—that is, our accepted set point on a receiver operating characteristic curve that aims to maximize sensitivity for melanoma diagnosis at the expense of specificity. Today this central paradigm in skin cancer diagnosis may be standing at a fundamental crossroads in the United States; in 2016, the Current Procedural Terminology (CPT) manual, which is created by an editorial panel appointed by the American Medical Association, introduced codes for the use of noninvasive cellular assessment of skin lesions via reflectance confocal microscopy (RCM).3 This landmark achievement now permits clinicians to submit a procedural bill for potential reimbursement to an insurance carrier after the acquisition and/or interpretation of RCM images. Why is this noteworthy? To date, the use of RCM in dermatology has been studied best in skin cancer diagnosis. An increasing number of publications have shown that, in capable hands, RCM holds the potential to dramatically increase the accuracy of skin cancer diagnosis,4 thereby improving the positive predictive value of lesions selected for a biopsy to rule out skin cancer.5,6 These findings have significant potential not only to alter the workflow of dermatology but also to improve the quality of dermatological care that patients receive. For example, patients and physicians may wish to maximize specificity at the expense of time or cost, such as when a suspicious lesion is located on a cosmetically sensitive area like the face. In addition, as nonsurgical therapies of basal cell carcinoma (BCC) are increasingly used, an “optical biopsy” via RCM may eliminate the need for pretreatment surgical diagnostic biopsies.7,8 Thus far, RCM examinations have been primarily limited to academic centers with robust financial resources and dedicated research programs in noninvasive skin imaging. The cost of RCM devices, whether it be the traditional wide-probe VivaScope model 1500 or the newer, handheld VivaScope model 3000 (Caliber ID), has prohibited many dermatologists from using RCM in their practice. The possibility to now recoup the investment cost of purchasing a device may diminish one of the barriers to widespread US adoption of RCM.9 As more dermatologists contemplate incorporating RCM into their busy practice or referring patients to centers that perform RCM, many new practical questions arise, such as: What setup and training are required for RCM imaging in clinic? Which cases could benefit the most from RCM imaging? What are the most robust diagnostic criteria, and do they differ by patient phenotype and genotype? What are the limitations and pitfalls of the technique? In this issue of JAMA Dermatology, Borsari et al10 and Grazziotin et al11 take a step forward in addressing parts of these unanswered questions by pointing out (1) some of the indications and limitations of RCM imaging and (2) the associations between RCM melanoma types and patient characteristics, respectively. The 3-year prospective study by Borsari et al10 comes from a specialized medical center that is adept and experienced in the integration of RCM in skin cancer diagnosis. The authors10 refer lesions with atypical clinical or dermoscopic findings that do not meet clear-cut criteria for malignancy for secondary screening with RCM. Indeed, if RCM would be applied to lesions selected to undergo biopsy with a high pretest probability of malignancy, it is unlikely to be a cost- or time-effective procedure. If used on lesions selected to undergo biopsy with a low to moderate pretest probability of malignancy, however, RCM is likely to prevent unnecessary biopsies and reduce health care expenditures. After imaging 1279 suspicious lesions with RCM, Borsari et al10 determined that only about half of the lesions needed to be excised, with the other half referred for 1-year clinical and dermoscopic monitoring to estimate potential RCM false-negative findings. This approach builds on previous work,6 which suggested that RCM may be particularly useful as a sequential screening test of lesions suspicious for skin cancer by preventing unnecessary biopsies with minimal loss in sensitivity. In the present study, the authors10 report skin cancer diagnostic sensitivity and specificity to be 95.3% and 83.9%, respectively. In post hoc analysis, the authors10 found that RCM yielded the best diagnostic performance for lesions located on sun-damaged skin, particularly on the head and neck areas, and for lesions showing regression structures on dermoscopy. Indeed, in our experience, RCM can be helpful in discriminating an early melanoma on sun-damaged skin from a solar lentigo or flat seborrheic keratosis (Figure). Interestingly, the prevalence of melanoma among “equivocal” lesions selected for RCM by Borsari et al10 was nearly 20%, which is relatively high2; this suggests that the findings in this practice setting, a tertiary care referral center, are unlikely to be generalizable to most private dermatology practices. Figure. View LargeDownload Melanoma In Situ A, A 2-cm brown patch with specks of dark brown pigmentation is seen on the shoulder (arrowhead). B, Dermoscopy shows a reticular pattern with focal dots and area with light brown angulated lines. The lesion is suspicious for melanoma on sun-damaged skin. The clinician considered a partial biopsy to secure the diagnosis before proceeding to a large definitive excision. In such a case, reflectance confocal microscopy (RCM) can simulate an “optical partial biopsy” and differentiate with confidence melanoma on sun-damaged skin from solar lentigo. C, An RCM optical section (0.5 × 0.5 mm2) at the level of the dermal epidermal junction shows irregular junctional thickening with dendritic cells (asterisk) and a large, atypical nucleated dendritic cell (arrowhead). The RCM findings are diagnostic for melanoma and rule out the possibility of solar lentigo. Hence, the lesion was excised in toto with 5-mm margins. The final histopathological diagnosis was melanoma in situ, lentigo maligna type. Borsari et al10 also show that RCM was highly effective in confirming a suspicion of BCC; these results are in line with a 2015 meta-analysis of 6 studies that reported summary sensitivity and specificity estimates of RCM for diagnosis of BCC to be 97% and 93%, respectively.12 The increased confidence and high specificity in the diagnosis of BCC provided by RCM could obviate the need for initial biopsy and histopathological examination, allowing clinicians to proceed directly to definitive treatment. In our personal experiences, RCM is indeed very useful for arriving at the specific diagnosis of BCC. It is worth mentioning that the improvement in specificity associated with the application of a sequential screening test, as seen in this study,10 will often lead to some loss in sensitivity and potential delay in diagnosis. This occurs not only because of the inherent limitation of the test itself, but also because it introduces the potential for patient dropout and noncompliance with the follow-up visit. Borsari et al10 reported that 14 melanomas (5.8% out of a study total of 243) were assessed as not warranting biopsy at baseline RCM examination. These melanomas were finally excised because clinical considerations took precedence over the RCM findings (eg, changing lesions in elderly individuals), because of patients' insistence that the lesion be removed, or due to atypical change at subsequent visits. An important lesson to be taken from their experience is that results of RCM testing should be reconciled with the overall clinical judgment.13 They10 also reported that 21 of 689 participants (3%) who were recommended to undergo biopsy of lesions with suspicious RCM findings did not return for the procedure. Notably, the authors10 did not report the suspected diagnosis of these 21 participants, nor did they include data on patient adherence for RCM-negative lesions to 1-year clinical and dermoscopic follow-up; hence, skin cancer sensitivity reported by the authors10 may be overestimated. Although Borsari et al10 did not aim to describe the features of “missed” melanomas, a few cautionary words are provided for novice RCM users. Our experience and literature reports suggest approaching the following lesions with caution when using RCM: (1) nodular lesions, because the depth of penetration of RCM light is limited to the superficial dermis; in these cases RCM diagnosis of skin cancer is informative, but a negative finding may not be entirely reassuring (akin to a shave biopsy of a nodular lesion); (2) lesions with marked ulceration or hyperkeratosis, which may detract from RCM imaging quality; and (3) lesions without consistent agreement between clinical, dermoscopic, and RCM findings. Some readers may justifiably note that RCM cannot have a favorable impact on sensitivity if its use is limited to a sequential screening test. In real life, however, the decision processes that lead to biopsy vs monitoring of equivocal lesions are complex and variably influenced by the anatomical location of the lesion, the physician’s experience, threshold for biopsy, biases, confidence, and “gut” feelings, and the patient’s individual level of concern and risk tolerability, to name but a few contributing factors. As RCM becomes more readily accessible, faster and easier to use, the threshold for performing an “optical noninvasive biopsy” with RCM may prove be markedly lower than that for performing a surgical biopsy. Also in this issue of JAMA Dermatology, Grazziotin et al11 investigate the associations between epidemiologic, genetic, and clinical features with RCM melanoma phenotype in a cohort of Spanish patients at high risk for melanoma. The authors were able to identify notable associations between (a) dendritic cell melanoma type and older age, lentigo maligna histologic subtype, solar lentigines, and greater cumulative ultraviolet radiation exposure, and (b) round cell melanoma type and younger age and skin phototype I. Small sample size precluded a multivariate analysis of these associations, and absent from this study are the inter-observer and intra-observer agreement for classification of melanomas into these proposed RCM patterns. However, these findings confirm the prior observation of Pellacani et al14 that distinct subsets of melanoma can be identified by their predominant RCM-cellular morphology. Future studies might also benefit from integrating genetics data from the melanomas to support these RCM-based morphologic classifications. Nonetheless, the study by Grazziotin et al11 shows the potential for RCM to refine our ability to study melanoma-genesis via noninvasive imaging of skin lesions. The future of noninvasive imaging and diagnosis in dermatological practice is bright. Today with access to dermoscopy, RCM, and optical coherence tomography, we are able to “see” the skin at the bedside in ways that our predecessors could hardly imagine. For the use of RCM in skin cancer diagnosis, early strides have been made, but more work remains. Randomized clinical trials with longer follow-up periods are needed to best estimate the impact of RCM on diagnostic accuracy, costs, and potential for overdiagnosis and misdiagnosis. Back to top Article Information Corresponding Author: Alon Scope, MD, Department of Dermatology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Hashomer 5262000, Israel (scopea1@gmail.com). Published Online: August 31, 2016. doi:10.1001/jamadermatol.2016.1966. Conflict of Interest Disclosures: None reported. Funding/Support: This work was supported by the European Commission Marie Curie FP7 Reintegration Grant to Dr Scope (PIRG07-GA-2010-268359). Role of the Funder/Sponsor: The funding source had no role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. References 1. Goldsmith SM. Cost analysis suggests overemphasis on biopsy rate for melanoma diagnosis. J Am Acad Dermatol. 2013;68(3):517-519.PubMedGoogle ScholarCrossref 2. Argenziano G, Cerroni L, Zalaudek I, et al. Accuracy in melanoma detection: a 10-year multicenter survey. J Am Acad Dermatol. 2012;67(1):54-59.PubMedGoogle ScholarCrossref 3. Derm Coding Consult. Winter 2015 PDF. https://www.aad.org/members/publications/derm-coding-consult. Accessed May 1, 2016. 4. Stevenson AD, Mickan S, Mallett S, Ayya M. Systematic review of diagnostic accuracy of reflectance confocal microscopy for melanoma diagnosis in patients with clinically equivocal skin lesions. Dermatol Pract Concept. 2013;3(4):19-27.PubMedGoogle ScholarCrossref 5. Alarcon I, Carrera C, Palou J, Alos L, Malvehy J, Puig S. Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions. Br J Dermatol. 2014;170(4):802-808.PubMedGoogle ScholarCrossref 6. Pellacani G, Pepe P, Casari A, Longo C. Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: a longitudinal prospective study. Br J Dermatol. 2014;171(5):1044-1051.PubMedGoogle ScholarCrossref 7. Chen CS, Sierra H, Cordova M, Rajadhyaksha M. Confocal microscopy-guided laser ablation for superficial and early nodular basal cell carcinoma: a promising surgical alternative for superficial skin cancers. JAMA Dermatol. 2014;150(9):994-998.PubMedGoogle ScholarCrossref 8. Hibler BP, Sierra H, Cordova M, et al. Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof of principle pilot study [published online January 13, 2016]. Br J Dermatol. doi:10.1111/bjd.14414.PubMedGoogle Scholar 9. Lieblich LM. Confocal laser scanning reflectance microscopy and the Ricky Nelson phenomenon. Arch Dermatol. 2005;141(10):1318-1319.PubMedGoogle ScholarCrossref 10. Borsari S, Pampena R, Lallas A, et al. Clinical indications for use of reflectance confocal microscopy for skin cancer diagnosis [published online August 31, 2016]. JAMA Dermatol. doi:10.1001/jamadermatol.2016.1188.Google Scholar 11. Grazziotin TC, Alarcon I, Bonamigo RR, et al. Association between confocal morphologic classification and clinical phenotypes of multiple primary and familial melanomas [published online August 31, 2016]. JAMA Dermatol. doi:10.1001/jamadermatol.2016.1189.Google Scholar 12. Kadouch DJ, Schram ME, Leeflang MM, Limpens J, Spuls PI, de Rie MA. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy. J Eur Acad Dermatol Venereol. 2015;29(10):1890-1897.PubMedGoogle ScholarCrossref 13. Marghoob AA, Scope A. The complexity of diagnosing melanoma. J Invest Dermatol. 2009;129(1):11-13.PubMedGoogle ScholarCrossref 14. Pellacani G, De Pace B, Reggiani C, et al. Distinct melanoma types based on reflectance confocal microscopy. Exp Dermatol. 2014;23(6):414-418.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Dermatology American Medical Association

An Evolving Approach to the Detection of Melanoma and Other Skin Cancers Using In Vivo Reflectance Confocal Microscopy

JAMA Dermatology , Volume 152 (10) – Oct 1, 2016

Loading next page...
 
/lp/american-medical-association/an-evolving-approach-to-the-detection-of-melanoma-and-other-skin-fXoHBxKp7t

References (13)

Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
2168-6068
eISSN
2168-6084
DOI
10.1001/jamadermatol.2016.1966
pmid
27580064
Publisher site
See Article on Publisher Site

Abstract

To make a definitive diagnosis of skin cancer, dermatologists have been required to obtain skin biopsy specimens of suspicious lesions and to examine tissue pathologic abnormalities ex vivo under light microscopy. In the past decades, high diagnostic sensitivity, which is associated with a low biopsy threshold,1 has been increasingly emphasized in skin cancer screening to combat melanoma deaths and to counter the rising incidence and morbidity of nonmelanoma skin cancer. Distinguishing malignant from benign lesions, however, has always been associated with biopsies of innocuous mimickers of skin cancer, such as nevi and seborrheic keratoses. A 2012 international 10-year multicenter study,2 for example, estimated that 28.4 nevi are biopsied for every melanoma detected. These procedures have been accepted and rationalized as a “cost of doing business”—that is, our accepted set point on a receiver operating characteristic curve that aims to maximize sensitivity for melanoma diagnosis at the expense of specificity. Today this central paradigm in skin cancer diagnosis may be standing at a fundamental crossroads in the United States; in 2016, the Current Procedural Terminology (CPT) manual, which is created by an editorial panel appointed by the American Medical Association, introduced codes for the use of noninvasive cellular assessment of skin lesions via reflectance confocal microscopy (RCM).3 This landmark achievement now permits clinicians to submit a procedural bill for potential reimbursement to an insurance carrier after the acquisition and/or interpretation of RCM images. Why is this noteworthy? To date, the use of RCM in dermatology has been studied best in skin cancer diagnosis. An increasing number of publications have shown that, in capable hands, RCM holds the potential to dramatically increase the accuracy of skin cancer diagnosis,4 thereby improving the positive predictive value of lesions selected for a biopsy to rule out skin cancer.5,6 These findings have significant potential not only to alter the workflow of dermatology but also to improve the quality of dermatological care that patients receive. For example, patients and physicians may wish to maximize specificity at the expense of time or cost, such as when a suspicious lesion is located on a cosmetically sensitive area like the face. In addition, as nonsurgical therapies of basal cell carcinoma (BCC) are increasingly used, an “optical biopsy” via RCM may eliminate the need for pretreatment surgical diagnostic biopsies.7,8 Thus far, RCM examinations have been primarily limited to academic centers with robust financial resources and dedicated research programs in noninvasive skin imaging. The cost of RCM devices, whether it be the traditional wide-probe VivaScope model 1500 or the newer, handheld VivaScope model 3000 (Caliber ID), has prohibited many dermatologists from using RCM in their practice. The possibility to now recoup the investment cost of purchasing a device may diminish one of the barriers to widespread US adoption of RCM.9 As more dermatologists contemplate incorporating RCM into their busy practice or referring patients to centers that perform RCM, many new practical questions arise, such as: What setup and training are required for RCM imaging in clinic? Which cases could benefit the most from RCM imaging? What are the most robust diagnostic criteria, and do they differ by patient phenotype and genotype? What are the limitations and pitfalls of the technique? In this issue of JAMA Dermatology, Borsari et al10 and Grazziotin et al11 take a step forward in addressing parts of these unanswered questions by pointing out (1) some of the indications and limitations of RCM imaging and (2) the associations between RCM melanoma types and patient characteristics, respectively. The 3-year prospective study by Borsari et al10 comes from a specialized medical center that is adept and experienced in the integration of RCM in skin cancer diagnosis. The authors10 refer lesions with atypical clinical or dermoscopic findings that do not meet clear-cut criteria for malignancy for secondary screening with RCM. Indeed, if RCM would be applied to lesions selected to undergo biopsy with a high pretest probability of malignancy, it is unlikely to be a cost- or time-effective procedure. If used on lesions selected to undergo biopsy with a low to moderate pretest probability of malignancy, however, RCM is likely to prevent unnecessary biopsies and reduce health care expenditures. After imaging 1279 suspicious lesions with RCM, Borsari et al10 determined that only about half of the lesions needed to be excised, with the other half referred for 1-year clinical and dermoscopic monitoring to estimate potential RCM false-negative findings. This approach builds on previous work,6 which suggested that RCM may be particularly useful as a sequential screening test of lesions suspicious for skin cancer by preventing unnecessary biopsies with minimal loss in sensitivity. In the present study, the authors10 report skin cancer diagnostic sensitivity and specificity to be 95.3% and 83.9%, respectively. In post hoc analysis, the authors10 found that RCM yielded the best diagnostic performance for lesions located on sun-damaged skin, particularly on the head and neck areas, and for lesions showing regression structures on dermoscopy. Indeed, in our experience, RCM can be helpful in discriminating an early melanoma on sun-damaged skin from a solar lentigo or flat seborrheic keratosis (Figure). Interestingly, the prevalence of melanoma among “equivocal” lesions selected for RCM by Borsari et al10 was nearly 20%, which is relatively high2; this suggests that the findings in this practice setting, a tertiary care referral center, are unlikely to be generalizable to most private dermatology practices. Figure. View LargeDownload Melanoma In Situ A, A 2-cm brown patch with specks of dark brown pigmentation is seen on the shoulder (arrowhead). B, Dermoscopy shows a reticular pattern with focal dots and area with light brown angulated lines. The lesion is suspicious for melanoma on sun-damaged skin. The clinician considered a partial biopsy to secure the diagnosis before proceeding to a large definitive excision. In such a case, reflectance confocal microscopy (RCM) can simulate an “optical partial biopsy” and differentiate with confidence melanoma on sun-damaged skin from solar lentigo. C, An RCM optical section (0.5 × 0.5 mm2) at the level of the dermal epidermal junction shows irregular junctional thickening with dendritic cells (asterisk) and a large, atypical nucleated dendritic cell (arrowhead). The RCM findings are diagnostic for melanoma and rule out the possibility of solar lentigo. Hence, the lesion was excised in toto with 5-mm margins. The final histopathological diagnosis was melanoma in situ, lentigo maligna type. Borsari et al10 also show that RCM was highly effective in confirming a suspicion of BCC; these results are in line with a 2015 meta-analysis of 6 studies that reported summary sensitivity and specificity estimates of RCM for diagnosis of BCC to be 97% and 93%, respectively.12 The increased confidence and high specificity in the diagnosis of BCC provided by RCM could obviate the need for initial biopsy and histopathological examination, allowing clinicians to proceed directly to definitive treatment. In our personal experiences, RCM is indeed very useful for arriving at the specific diagnosis of BCC. It is worth mentioning that the improvement in specificity associated with the application of a sequential screening test, as seen in this study,10 will often lead to some loss in sensitivity and potential delay in diagnosis. This occurs not only because of the inherent limitation of the test itself, but also because it introduces the potential for patient dropout and noncompliance with the follow-up visit. Borsari et al10 reported that 14 melanomas (5.8% out of a study total of 243) were assessed as not warranting biopsy at baseline RCM examination. These melanomas were finally excised because clinical considerations took precedence over the RCM findings (eg, changing lesions in elderly individuals), because of patients' insistence that the lesion be removed, or due to atypical change at subsequent visits. An important lesson to be taken from their experience is that results of RCM testing should be reconciled with the overall clinical judgment.13 They10 also reported that 21 of 689 participants (3%) who were recommended to undergo biopsy of lesions with suspicious RCM findings did not return for the procedure. Notably, the authors10 did not report the suspected diagnosis of these 21 participants, nor did they include data on patient adherence for RCM-negative lesions to 1-year clinical and dermoscopic follow-up; hence, skin cancer sensitivity reported by the authors10 may be overestimated. Although Borsari et al10 did not aim to describe the features of “missed” melanomas, a few cautionary words are provided for novice RCM users. Our experience and literature reports suggest approaching the following lesions with caution when using RCM: (1) nodular lesions, because the depth of penetration of RCM light is limited to the superficial dermis; in these cases RCM diagnosis of skin cancer is informative, but a negative finding may not be entirely reassuring (akin to a shave biopsy of a nodular lesion); (2) lesions with marked ulceration or hyperkeratosis, which may detract from RCM imaging quality; and (3) lesions without consistent agreement between clinical, dermoscopic, and RCM findings. Some readers may justifiably note that RCM cannot have a favorable impact on sensitivity if its use is limited to a sequential screening test. In real life, however, the decision processes that lead to biopsy vs monitoring of equivocal lesions are complex and variably influenced by the anatomical location of the lesion, the physician’s experience, threshold for biopsy, biases, confidence, and “gut” feelings, and the patient’s individual level of concern and risk tolerability, to name but a few contributing factors. As RCM becomes more readily accessible, faster and easier to use, the threshold for performing an “optical noninvasive biopsy” with RCM may prove be markedly lower than that for performing a surgical biopsy. Also in this issue of JAMA Dermatology, Grazziotin et al11 investigate the associations between epidemiologic, genetic, and clinical features with RCM melanoma phenotype in a cohort of Spanish patients at high risk for melanoma. The authors were able to identify notable associations between (a) dendritic cell melanoma type and older age, lentigo maligna histologic subtype, solar lentigines, and greater cumulative ultraviolet radiation exposure, and (b) round cell melanoma type and younger age and skin phototype I. Small sample size precluded a multivariate analysis of these associations, and absent from this study are the inter-observer and intra-observer agreement for classification of melanomas into these proposed RCM patterns. However, these findings confirm the prior observation of Pellacani et al14 that distinct subsets of melanoma can be identified by their predominant RCM-cellular morphology. Future studies might also benefit from integrating genetics data from the melanomas to support these RCM-based morphologic classifications. Nonetheless, the study by Grazziotin et al11 shows the potential for RCM to refine our ability to study melanoma-genesis via noninvasive imaging of skin lesions. The future of noninvasive imaging and diagnosis in dermatological practice is bright. Today with access to dermoscopy, RCM, and optical coherence tomography, we are able to “see” the skin at the bedside in ways that our predecessors could hardly imagine. For the use of RCM in skin cancer diagnosis, early strides have been made, but more work remains. Randomized clinical trials with longer follow-up periods are needed to best estimate the impact of RCM on diagnostic accuracy, costs, and potential for overdiagnosis and misdiagnosis. Back to top Article Information Corresponding Author: Alon Scope, MD, Department of Dermatology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Hashomer 5262000, Israel (scopea1@gmail.com). Published Online: August 31, 2016. doi:10.1001/jamadermatol.2016.1966. Conflict of Interest Disclosures: None reported. Funding/Support: This work was supported by the European Commission Marie Curie FP7 Reintegration Grant to Dr Scope (PIRG07-GA-2010-268359). Role of the Funder/Sponsor: The funding source had no role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. References 1. Goldsmith SM. Cost analysis suggests overemphasis on biopsy rate for melanoma diagnosis. J Am Acad Dermatol. 2013;68(3):517-519.PubMedGoogle ScholarCrossref 2. Argenziano G, Cerroni L, Zalaudek I, et al. Accuracy in melanoma detection: a 10-year multicenter survey. J Am Acad Dermatol. 2012;67(1):54-59.PubMedGoogle ScholarCrossref 3. Derm Coding Consult. Winter 2015 PDF. https://www.aad.org/members/publications/derm-coding-consult. Accessed May 1, 2016. 4. Stevenson AD, Mickan S, Mallett S, Ayya M. Systematic review of diagnostic accuracy of reflectance confocal microscopy for melanoma diagnosis in patients with clinically equivocal skin lesions. Dermatol Pract Concept. 2013;3(4):19-27.PubMedGoogle ScholarCrossref 5. Alarcon I, Carrera C, Palou J, Alos L, Malvehy J, Puig S. Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions. Br J Dermatol. 2014;170(4):802-808.PubMedGoogle ScholarCrossref 6. Pellacani G, Pepe P, Casari A, Longo C. Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: a longitudinal prospective study. Br J Dermatol. 2014;171(5):1044-1051.PubMedGoogle ScholarCrossref 7. Chen CS, Sierra H, Cordova M, Rajadhyaksha M. Confocal microscopy-guided laser ablation for superficial and early nodular basal cell carcinoma: a promising surgical alternative for superficial skin cancers. JAMA Dermatol. 2014;150(9):994-998.PubMedGoogle ScholarCrossref 8. Hibler BP, Sierra H, Cordova M, et al. Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof of principle pilot study [published online January 13, 2016]. Br J Dermatol. doi:10.1111/bjd.14414.PubMedGoogle Scholar 9. Lieblich LM. Confocal laser scanning reflectance microscopy and the Ricky Nelson phenomenon. Arch Dermatol. 2005;141(10):1318-1319.PubMedGoogle ScholarCrossref 10. Borsari S, Pampena R, Lallas A, et al. Clinical indications for use of reflectance confocal microscopy for skin cancer diagnosis [published online August 31, 2016]. JAMA Dermatol. doi:10.1001/jamadermatol.2016.1188.Google Scholar 11. Grazziotin TC, Alarcon I, Bonamigo RR, et al. Association between confocal morphologic classification and clinical phenotypes of multiple primary and familial melanomas [published online August 31, 2016]. JAMA Dermatol. doi:10.1001/jamadermatol.2016.1189.Google Scholar 12. Kadouch DJ, Schram ME, Leeflang MM, Limpens J, Spuls PI, de Rie MA. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy. J Eur Acad Dermatol Venereol. 2015;29(10):1890-1897.PubMedGoogle ScholarCrossref 13. Marghoob AA, Scope A. The complexity of diagnosing melanoma. J Invest Dermatol. 2009;129(1):11-13.PubMedGoogle ScholarCrossref 14. Pellacani G, De Pace B, Reggiani C, et al. Distinct melanoma types based on reflectance confocal microscopy. Exp Dermatol. 2014;23(6):414-418.PubMedGoogle ScholarCrossref

Journal

JAMA DermatologyAmerican Medical Association

Published: Oct 1, 2016

There are no references for this article.