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Concordance of reflectance confocal microscopy with histopathology in the diagnosis of lentigo maligna
3141
2359
Concordance of reflectance confocal microscopy with histopathology in the diagnosis of lentigo maligna Tyler Menge, University of Michigan Medical School, Ann Arbor, MI, United States; Brian Hibler, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Miguel Cordova, MD, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Anthony Rossi, MD, Memorial Sloan Kettering Cancer Center, New York, NY, United States Background: Lentigo maligna (LM) is a form of melanoma in situ that may progress slowly, but is associated with higher rates of local recurrence compared to other subtypes of melanoma. Diagnosis of LM can be challenging, as blind biopsies are prone to sampling error due to the heterogeneous nature of LM and its characteristic wide subclinical extension. Reflectance confocal microscopy (RCM) provides noninvasive, real-time imaging of cell structure and may be a useful adjunct in diagnosing LM and defining its borders. Few studies have compared performance of RCM to histopathology in diagnosing LM, and specific clinical or microscopic features influencing RCM interpretation are not well described. Objective: To determine the degree of concordance between RCM and conventional histopathologic analysis in the evaluation of suspected LM and to identify factors that may obscure diagnosis of LM with RCM. Methods: Under IRB approval, 16 patients were seen by the Dermatology Service at Memorial Sloan Kettering Cancer Center for evaluation of known or suspected LM. Cases included primary LM as well as recurrent and/or previously treated lesions. For each case, RCM was performed and images were assessed for LM using an accepted algorithm. A total of 59 biopsies were performed in areas of concern. RCM and histopathology interpretations were reviewed for degree of concordance. In cases of diagnostic discordance, clinical histories and images were analyzed for patterns leading to misdiagnosis with RCM. Results: RCM and histopathology interpretations were concordant in 52/59 biopsy sites (88%). There were no false negatives (sensitivity 100%) and 7 false positives (specificity 71%) using RCM. The false positives included actinic keratosis (2), dermatoheliosis (2), solar lentigo (1), dermal melanocytosis (1), and a pigmented and traumatized seborrheic keratosis (1). Of note, 5/7 false positives occurred in the same patient with multiply recurrent LM previously treated by imiquimod. Features suggestive of LM in the false positive group included the presence of numerous atypical cells at the DEJ and follicular localization of these cells.
Conservative surgery of a subungual melanoma in situ Francine Papaiordanou, MD, Prof. Rubem David Azulay Dermatology Institute, Rio de Janeiro, Brazil; Robertha De Carvalho Nakamura, MD, Prof Rubem David Azulay Dermatology Institute, Rio de Janiero, Brazil; Eckart Haneke, MD, PhD, Dermatology Practice Dermaticum, Freiburg, Germany, Department of Dermatol, Inselspital, Univ Bern, Germany; Erika Araujo Machado, MD, Prof. Rubem David Azulay Dermatology Institute, Brazil; Luiza Ferreira D’Almeida, MD, Prof Rubem David Azulay Dermatology Institute, Brazil Subungual melanoma (SUM) is a rare subtype of melanoma. It arises from the nail matrix, but may involve the other components of the nail unit. This disease is frequently misdiagnosed, which leads to a delay in proper treatment and a poor prognosis, especially due to short matrix-to-bone distance. The final diagnosis must be confirmed by an adequate histopathologic examination. Excisional biopsies are regarded as gold standard in order to avoid sampling errors. The conservative surgery for SUM is currently recognized by the international literature (when at early stages), and offers to the patient a safe, effective and curative treatment, preserving their functional ability. In this article we intent to report a case of SUM successfully treated with conservative surgery (resection of the nail unit, preserving the digit). Commercial support: None identified.
Conclusion: RCM shows excellent sensitivity for detecting LM although features of benign macules on a background of heavily sun-damaged skin can obscure diagnosis and limit its specificity. Further studies that characterize these baseline architectural changes in sun-damaged skin are needed to more reliably distinguish LM. Commercial support: None identified.
3593 Confocal characterization of primary melanoma. Noninvasive prediction of histological prognostic markers Zamira Barragan, MD, Hospital Clınic de Barcelona, Barcelona, Spain; Johanna Brito, MD, Hospital Clınic de Barcelona, Barcelona, Spain; Ll ucia Al os, MD, Hospital Clınic de Barcelona, Barcelona, Spain; Susana Puig, MD, PhD, Hospital Clınic de Barcelona, Barcelona, Spain; Josep Malvehy, MD, PhD, Hospital Clınic de Barcelona, Barcelona, Spain; Cristina Carrera, MD, PhD, Hospital Clınic de Barcelona, Barcelona, Spain Introduction: Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that provides real-time evaluation of skin with cellular resolution. Recent RCM studies on melanoma morphology let the recognition of different tumor phenotypes. Hypothesis: Melanomas can present in vivo features that translate biological and prognostic behavior, and these findings can be visible by RCM. Objective: To detect dermoscopic and confocal criteria present in primary melanomas related to histological features that play an important role as prognostic markers. Methodology: Retrospective study of clinical, dermoscopical and confocal images, in addition to further revision of histopathologic slides of primary melanomas diagnosed from February 2011 to February 2015. Only sporadic melanomas on trunk and limbs with high quality images available were included. Results: 92 primary melanomas were reviewed; 44 male and 48 female with a mean age of 60.4 years old (SD 16.2) mainly located on posterior trunk (50%). The most frequent dermoscopic pattern was multicomponent (55.4%), and the predominant confocal global pattern was the so-called dendritic pattern (44.6%). Histologic melanoma subtypes included in situ (30.4%), superficial spreading (56.6%), lentigo maligna (6.5%) and nodular (5.4%) subtypes. Dermoscopic presence of pigment network was related to both lower Breslow and mitotic rate (both P ¼ .002), in contrast to the presence of vessels was related to both higher mitotic rate and Breslow index (P ¼.001). Confocal presence of dermal nest was related to a higher mitotic rate (P ¼ .006), similarly, presence of atypical basal cells and nucleated visible cells in dermis (P ¼.03). The observation of diffuse inflammatory infiltrate in dermis was strongly associated with mean increase in Breslow thickness of 0.6 mm (P ¼ .04) and the increase of the number of the mitosis count (P ¼ .04).
3907 Effect of beta-blockers on malignant melanoma risk of recurrence and overall mortality Suzanne J. Tintle, MD, MPH, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; Margaret Schwarz, MD, MBA, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; William Conaway, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; Christopher Haley, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; Yesul Kim, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States Introduction: Early data suggest beta-blockers, presumably through their antiangiogenic effects, may influence cutaneous malignant melanoma (CMM) recurrence and even overall survival, though conflicting reports have also been published. Methods: Retrospective case-control study of patients diagnosed with CMM from the years of 1970 to 2014 at one academic medical center. 1339 patients met inclusion criteria. Patients with a diagnosis of melanoma prior to the study period, and those with evidence of lymph node, visceral and/or in-transit metastasis at the time of diagnosis were excluded. Those with a history of beta-blockers and/or phosphodiesterase-5 inhibitor use were compared to those without to evaluate for differences in melanoma recurrence and overall mortality. Results: Of 1339 patients diagnosed with CMM, 74.1% had taken a beta-blocker. There was no statistically significant difference between the incidence of recurrent CMM in patients taking a beta-blocker (16.8%; 58/346) versus those who had not (16.3%; 162/993) (P ¼ .87, Fisher’s exact test) over an average follow-up period of 3.21 years (median follow-up, 7 years). However, the average length of time to recurrence of melanoma was longer in patients taking a beta-blocker (mean 3.19 years) than in those who had never taken a beta-blocker (mean 2.94 years), though this difference was not statistically significant (P ¼ .54; two-tailed Student’s t-test). There was no difference in overall mortality in those who took a beta-blocker versus those who did not (risk ratio 0.66; P ¼ .1256, Fisher’s exact test). Limitations: Retrospective review, single institution, short length of follow-up.
Limitations: Single center retrospective study, and only trunk and limbs melanomas were included. Conclusions: Melanoma can be better characterized by dermoscopy and confocal microscopy in terms of prediction of Breslow and mitotic rate in histopathology.
Conclusion: The addition of a beta-blocker may provide a modest but measurable increase in disease-free survival following diagnosis of cutaneous malignant melanoma (CMM). The benign side effect profiles of these anti-angiogenic medications would likely allow easy adoption into a ‘‘cocktail’’ of targeted immunotherapies used in malignant melanoma. Phase II randomized clinical trials of propranolol in melanoma progression are underway.
Commercial support: None identified.
Commercial support: None identified.
MAY 2016
J AM ACAD DERMATOL
AB187
2359
Concordance of reflectance confocal microscopy with histopathology in the diagnosis of lentigo maligna Tyler Menge, University of Michigan Medical School, Ann Arbor, MI, United States; Brian Hibler, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Miguel Cordova, MD, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Anthony Rossi, MD, Memorial Sloan Kettering Cancer Center, New York, NY, United States Background: Lentigo maligna (LM) is a form of melanoma in situ that may progress slowly, but is associated with higher rates of local recurrence compared to other subtypes of melanoma. Diagnosis of LM can be challenging, as blind biopsies are prone to sampling error due to the heterogeneous nature of LM and its characteristic wide subclinical extension. Reflectance confocal microscopy (RCM) provides noninvasive, real-time imaging of cell structure and may be a useful adjunct in diagnosing LM and defining its borders. Few studies have compared performance of RCM to histopathology in diagnosing LM, and specific clinical or microscopic features influencing RCM interpretation are not well described. Objective: To determine the degree of concordance between RCM and conventional histopathologic analysis in the evaluation of suspected LM and to identify factors that may obscure diagnosis of LM with RCM. Methods: Under IRB approval, 16 patients were seen by the Dermatology Service at Memorial Sloan Kettering Cancer Center for evaluation of known or suspected LM. Cases included primary LM as well as recurrent and/or previously treated lesions. For each case, RCM was performed and images were assessed for LM using an accepted algorithm. A total of 59 biopsies were performed in areas of concern. RCM and histopathology interpretations were reviewed for degree of concordance. In cases of diagnostic discordance, clinical histories and images were analyzed for patterns leading to misdiagnosis with RCM. Results: RCM and histopathology interpretations were concordant in 52/59 biopsy sites (88%). There were no false negatives (sensitivity 100%) and 7 false positives (specificity 71%) using RCM. The false positives included actinic keratosis (2), dermatoheliosis (2), solar lentigo (1), dermal melanocytosis (1), and a pigmented and traumatized seborrheic keratosis (1). Of note, 5/7 false positives occurred in the same patient with multiply recurrent LM previously treated by imiquimod. Features suggestive of LM in the false positive group included the presence of numerous atypical cells at the DEJ and follicular localization of these cells.
Conservative surgery of a subungual melanoma in situ Francine Papaiordanou, MD, Prof. Rubem David Azulay Dermatology Institute, Rio de Janeiro, Brazil; Robertha De Carvalho Nakamura, MD, Prof Rubem David Azulay Dermatology Institute, Rio de Janiero, Brazil; Eckart Haneke, MD, PhD, Dermatology Practice Dermaticum, Freiburg, Germany, Department of Dermatol, Inselspital, Univ Bern, Germany; Erika Araujo Machado, MD, Prof. Rubem David Azulay Dermatology Institute, Brazil; Luiza Ferreira D’Almeida, MD, Prof Rubem David Azulay Dermatology Institute, Brazil Subungual melanoma (SUM) is a rare subtype of melanoma. It arises from the nail matrix, but may involve the other components of the nail unit. This disease is frequently misdiagnosed, which leads to a delay in proper treatment and a poor prognosis, especially due to short matrix-to-bone distance. The final diagnosis must be confirmed by an adequate histopathologic examination. Excisional biopsies are regarded as gold standard in order to avoid sampling errors. The conservative surgery for SUM is currently recognized by the international literature (when at early stages), and offers to the patient a safe, effective and curative treatment, preserving their functional ability. In this article we intent to report a case of SUM successfully treated with conservative surgery (resection of the nail unit, preserving the digit). Commercial support: None identified.
Conclusion: RCM shows excellent sensitivity for detecting LM although features of benign macules on a background of heavily sun-damaged skin can obscure diagnosis and limit its specificity. Further studies that characterize these baseline architectural changes in sun-damaged skin are needed to more reliably distinguish LM. Commercial support: None identified.
3593 Confocal characterization of primary melanoma. Noninvasive prediction of histological prognostic markers Zamira Barragan, MD, Hospital Clınic de Barcelona, Barcelona, Spain; Johanna Brito, MD, Hospital Clınic de Barcelona, Barcelona, Spain; Ll ucia Al os, MD, Hospital Clınic de Barcelona, Barcelona, Spain; Susana Puig, MD, PhD, Hospital Clınic de Barcelona, Barcelona, Spain; Josep Malvehy, MD, PhD, Hospital Clınic de Barcelona, Barcelona, Spain; Cristina Carrera, MD, PhD, Hospital Clınic de Barcelona, Barcelona, Spain Introduction: Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that provides real-time evaluation of skin with cellular resolution. Recent RCM studies on melanoma morphology let the recognition of different tumor phenotypes. Hypothesis: Melanomas can present in vivo features that translate biological and prognostic behavior, and these findings can be visible by RCM. Objective: To detect dermoscopic and confocal criteria present in primary melanomas related to histological features that play an important role as prognostic markers. Methodology: Retrospective study of clinical, dermoscopical and confocal images, in addition to further revision of histopathologic slides of primary melanomas diagnosed from February 2011 to February 2015. Only sporadic melanomas on trunk and limbs with high quality images available were included. Results: 92 primary melanomas were reviewed; 44 male and 48 female with a mean age of 60.4 years old (SD 16.2) mainly located on posterior trunk (50%). The most frequent dermoscopic pattern was multicomponent (55.4%), and the predominant confocal global pattern was the so-called dendritic pattern (44.6%). Histologic melanoma subtypes included in situ (30.4%), superficial spreading (56.6%), lentigo maligna (6.5%) and nodular (5.4%) subtypes. Dermoscopic presence of pigment network was related to both lower Breslow and mitotic rate (both P ¼ .002), in contrast to the presence of vessels was related to both higher mitotic rate and Breslow index (P ¼.001). Confocal presence of dermal nest was related to a higher mitotic rate (P ¼ .006), similarly, presence of atypical basal cells and nucleated visible cells in dermis (P ¼.03). The observation of diffuse inflammatory infiltrate in dermis was strongly associated with mean increase in Breslow thickness of 0.6 mm (P ¼ .04) and the increase of the number of the mitosis count (P ¼ .04).
3907 Effect of beta-blockers on malignant melanoma risk of recurrence and overall mortality Suzanne J. Tintle, MD, MPH, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; Margaret Schwarz, MD, MBA, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; William Conaway, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; Christopher Haley, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States; Yesul Kim, Penn State Hershey Medical Center, Department of Dermatology, Hershey, PA, United States Introduction: Early data suggest beta-blockers, presumably through their antiangiogenic effects, may influence cutaneous malignant melanoma (CMM) recurrence and even overall survival, though conflicting reports have also been published. Methods: Retrospective case-control study of patients diagnosed with CMM from the years of 1970 to 2014 at one academic medical center. 1339 patients met inclusion criteria. Patients with a diagnosis of melanoma prior to the study period, and those with evidence of lymph node, visceral and/or in-transit metastasis at the time of diagnosis were excluded. Those with a history of beta-blockers and/or phosphodiesterase-5 inhibitor use were compared to those without to evaluate for differences in melanoma recurrence and overall mortality. Results: Of 1339 patients diagnosed with CMM, 74.1% had taken a beta-blocker. There was no statistically significant difference between the incidence of recurrent CMM in patients taking a beta-blocker (16.8%; 58/346) versus those who had not (16.3%; 162/993) (P ¼ .87, Fisher’s exact test) over an average follow-up period of 3.21 years (median follow-up, 7 years). However, the average length of time to recurrence of melanoma was longer in patients taking a beta-blocker (mean 3.19 years) than in those who had never taken a beta-blocker (mean 2.94 years), though this difference was not statistically significant (P ¼ .54; two-tailed Student’s t-test). There was no difference in overall mortality in those who took a beta-blocker versus those who did not (risk ratio 0.66; P ¼ .1256, Fisher’s exact test). Limitations: Retrospective review, single institution, short length of follow-up.
Limitations: Single center retrospective study, and only trunk and limbs melanomas were included. Conclusions: Melanoma can be better characterized by dermoscopy and confocal microscopy in terms of prediction of Breslow and mitotic rate in histopathology.
Conclusion: The addition of a beta-blocker may provide a modest but measurable increase in disease-free survival following diagnosis of cutaneous malignant melanoma (CMM). The benign side effect profiles of these anti-angiogenic medications would likely allow easy adoption into a ‘‘cocktail’’ of targeted immunotherapies used in malignant melanoma. Phase II randomized clinical trials of propranolol in melanoma progression are underway.
Commercial support: None identified.
Commercial support: None identified.
MAY 2016
J AM ACAD DERMATOL
AB187