- Email: [email protected]
Sensitivity of handheld reflectance confocal microscopy for the diagnosis of basal cell carcinoma: A series of 344 histologically proven lesions
J AM ACAD DERMATOL VOLUME 73, NUMBER 2
80.5% and 64.1%, respectively.2 The confocalist in our study is, in fact, the same trained confocalist in this previous study that had a reported specificity of 64.1%. This suggests that our confocalist’s diagnostic capabilities, as indicated by increased specificity, improved overtime with further experience with using RCM. Also, based on the histopathology results of the 119 lesions, our calculated benign-to-malignant ratio was 2.13:1 (81 benign lesions biopsied, 38 malignant lesions). Studies on the use of dermoscopy in practice report a reduction in the benignto-malignant ratio of excised melanocytic lesions from 18:1 to 4:1 with it’s use.3 This suggests that RCM may dramatically reduce the biopsy rate of benign lesions beyond clinical and dermoscopic examination. Ultimately, these results should encourage more dermatologists to pursue training in RCM and integrate its use in daily clinical practice. Danielle Giambrone, BS,a Mahin Alamgir, MD,b Aisha Masud, BS,c Tara Bronsnick, MD,a and Babar Rao, MDa,b Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ,a Maimonides Medical Center, Brooklyn, NY,b and Cornell University, Ithaca, NYc Funding sources: None. Conflict of interests: Dr Rao is a consultant for CaliberID. Ms Giambrone, Dr Bronsnick, Ms Masud, and Dr Alamgir have no conflicts to declare. IRB status: Rutgers, reapproved on Nov 7, 2014, entitled ‘‘Confocal Microscopy of Suspicious Lesions.’’ New York and New Jersey, Quorum IRB, re-approved Dec 14, 2014 entitled ‘‘In Vivo Confocal Microscopy of Suspicious Lesions.’’ Correspondence to: Danielle Giambrone, BS, 1 World’s Fair Drive, Suite 2400, Somerset, NJ 08873-1344 E-mail: [email protected] REFERENCES 1. Ahlgrimm-Siess V, Hofmann-Wellenhof R, Cao T. Reflectance confocal microscopy in the daily practice. Semin Cutan Med Surg. 2009;28:180-189. 2. Rao BK, Mateus R, Wassef C, et al. In vivo confocal microscopy in clinical practice: comparison of bedside diagnostic accuracy of a trained physician and distant diagnosis of an expert reader. J Am Acad Dermatol. 2013;69:295-300. 3. Terushkin V, Warycha M, Levy M, et al. Analysis of the benign to malignant ratio of lesions biopsied by a general dermatologist before and after adoption of dermoscopy. Arch Dermatol. 2010; 146:343-344. http://dx.doi.org/10.1016/j.jaad.2015.03.052
Letters 319
Sensitivity of handheld reflectance confocal microscopy for the diagnosis of basal cell carcinoma: A series of 344 histologically proven lesions To the Editor: Most studies about the sensitivity of reflectance confocal microscopy (RCM) for the diagnosis of the basal cell carcinoma (BCC) are based on the retrospective analysis of the RCM images acquired by the traditional wide-probe (TWP)-RCM. We evaluated the sensitivity of handheld (HH)-RCM for the diagnosis of BCC in clinical practice. All histologically confirmed BCCs excised at the University Hospital of Saint-Etienne, France, that underwent a HH-RCM (VivaScope 3000; MAVIG GmbH, M€ unchen, Germany) examination between 2011 and 2014 were included. RCM examination was dedicated to cases from which a biopsy specimen was obtained because they were equivocal at dermoscopy. BCCs of the eyelid margin were excluded.1 HH-RCM diagnosis was retrospectively searched in the patient’s clinical records. The diagnosis of BCC was established in the presence of tumor islands of tightly packed cells with or without peripheral palisading of elongated cells, or if $2 of the following criteria were present: dark silhouette with peripheral thickened collagen bundles, dark peritumoral clefts, linear or convoluted dilated blood vessels, and polarized elongated cells in the epidermis (streaming).2-4 All examinations were carried out by 3 dermatologists experienced with dermoscopy and who began reading RCM images in 2010. Our study revealed excellent sensitivity of HH-RCM for the diagnosis of BCC in a series of 344 lesions (Table I). Interestingly, the sensitivity of 87.5% reported in 2011 suggests that BCC is easy to recognize with RCM even for dermatologists with little experience. A learning curve was noticed from 2011 to 2013/2014. Most misdiagnosed BCCs were not completely negative for BCC at RCM, but had equivocal images where it was difficult to affirm with certainty the presence of tumor islands and dark silhouettes. No statistically significant difference in the sensitivity for different histologic subtypes and body sites was found for 2013 and 2014 (Table II; chi-squared test; P [.05). The sensitivity in the last 2 years was similar to previous study data reported in the literature,2-5 ranging from 93% to 100%. However, these studies cannot be directly compared with ours because all but 1 of these studies5 were based on retrospective analysis of RCM images and not on the diagnoses performed at the patient’s bedside. Moreover, they evaluated smaller series (39,5 45,4 52,2 and 833
J AM ACAD DERMATOL
320 Letters
AUGUST 2015
Table I. Reflectance confocal microscopy sensitivity for basal cell carcinoma Year Number of BCCs
2011
Diagnosed by histopathology Examined under RCM Correctely diagnosed by RCM Incorrectly diagnosed by RCM, n (%) Uncertain diagnosis of BCC No elements of BCC RCM sensitivity (%)
2012
2013
2014
Total
280 88 77
196 84 76
281 76 72
232 96 90
989 344 315
7 (8) 4 (4.5) 87.5
4 (4.8) 4 (4.8) 90.5
4 (5.3) 0 94.7
5 (5.2) 1 (1) 93.8
20 (5.8) 9 (2.6) 91.6*
BCC, Basal cell carcinoma; RCM, reflectance confocal microscopy. *Mean RCM sensitivity.
Table II. Reflectance confocal microscopy sensitivity for basal cell carcinoma stratified by histologic subtype and localization
BCC features
No. of BCCs, n (%)
Histologic subtype Nodular 76 Infiltrative 40 Superficial 56 Location Trunk 39 Face 119 Neck 4 Inferior limb 4 Upper limb 3 Scalp 2 Vulva 1
RCM sensitivity (%)
Confidence interval
(44.2) (23.2) (32.6)
94.7 90.0 96.4
89.6-99.7 80.7-99.3 [91.6
(22.7) (69.2) (2.3) (2.3) (1.7) (1.2) (0.6)
97.4 93.3 100.0 100.0 100.0 100.0 0.0
[92.5 88.8-97.8 — — — — —
Labeille, MD,a Alexander Witkowski, MD,c Fre deric Cambazard, PhD,a and Jean-Luc Perrot, MDa Departments of Dermatologya and Pharmacology,b University Hospital of Saint-Etienne, SaintEtienne, France, and the Department of Dermatology,c University Hospital of Modena and Reggio Emilia, Modena, Italy Supported by a medical educational grant from F. Hoffmann-La Roche Conflicts of interest: None declared. Correspondence to: Elisa Cinotti, MD, H^opital Nord, 42055 Saint Etienne Cedex 2, France E-mail: [email protected]
BCC, Basal cell carcinoma; RCM, reflectance confocal microscopy.
BCCs, respectively) and used different diagnostic criteria and different criteria threshold for BCC. HH-RCM was found to have a slightly lower sensitivity than TWP-RCM.4 This could be related to the fact that HH-RCM acquires smaller images (1 mm in diameter vs 8 mm in diameter) and is more often used on the face, where hair follicles and dermal collagen architecture are more prominent and can mask tumor islands. In our experience, to help differentiate a hair follicle from a BCC tumor island we can move to the surface of the skin during RCM examination and check for the presence of a follicle orifice in its correspondence. Despite the drawback of the slightly reduced BCC detection rate, HH-RCM is handy, and its image acquisition is faster than TWP-RCM, making it more suitable for the clinical practice. Elisa Cinotti, MD,a Cecile Jaffelin, MD,a Victoria Charriere, MD,b Pierre Bajard, MD,b Bruno
REFERENCES 1. Cinotti E, Perrot JL, Campolmi N, et al. The role of in vivo confocal microscopy in the diagnosis of eyelid margin tumors: 47 cases. J Am Acad Dermatol. 2014;71:912-918.e2. 2. Guitera P, Menzies SW, Longo C, et al. In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases. J Invest Dermatol. 2012;132:2386-2394. 3. Nori S, Rius-Dıaz F, Cuevas J, et al. Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study. J Am Acad Dermatol. 2004;51:923-930. 4. Castro RP, Stephens A, Fraga-Braghiroli NA, et al. Accuracy of in vivo confocal microscopy for diagnosis of basal cell carcinoma: a comparative study between handheld and wide-probe confocal imaging. J Eur Acad Dermatol Venereol. October 22, 2014. http://dx.doi.org/10.1111/jdv.12780 [Epub ahead of print]. 5. 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;171:1044-1051. http://dx.doi.org/10.1016/j.jaad.2015.04.048
80.5% and 64.1%, respectively.2 The confocalist in our study is, in fact, the same trained confocalist in this previous study that had a reported specificity of 64.1%. This suggests that our confocalist’s diagnostic capabilities, as indicated by increased specificity, improved overtime with further experience with using RCM. Also, based on the histopathology results of the 119 lesions, our calculated benign-to-malignant ratio was 2.13:1 (81 benign lesions biopsied, 38 malignant lesions). Studies on the use of dermoscopy in practice report a reduction in the benignto-malignant ratio of excised melanocytic lesions from 18:1 to 4:1 with it’s use.3 This suggests that RCM may dramatically reduce the biopsy rate of benign lesions beyond clinical and dermoscopic examination. Ultimately, these results should encourage more dermatologists to pursue training in RCM and integrate its use in daily clinical practice. Danielle Giambrone, BS,a Mahin Alamgir, MD,b Aisha Masud, BS,c Tara Bronsnick, MD,a and Babar Rao, MDa,b Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ,a Maimonides Medical Center, Brooklyn, NY,b and Cornell University, Ithaca, NYc Funding sources: None. Conflict of interests: Dr Rao is a consultant for CaliberID. Ms Giambrone, Dr Bronsnick, Ms Masud, and Dr Alamgir have no conflicts to declare. IRB status: Rutgers, reapproved on Nov 7, 2014, entitled ‘‘Confocal Microscopy of Suspicious Lesions.’’ New York and New Jersey, Quorum IRB, re-approved Dec 14, 2014 entitled ‘‘In Vivo Confocal Microscopy of Suspicious Lesions.’’ Correspondence to: Danielle Giambrone, BS, 1 World’s Fair Drive, Suite 2400, Somerset, NJ 08873-1344 E-mail: [email protected] REFERENCES 1. Ahlgrimm-Siess V, Hofmann-Wellenhof R, Cao T. Reflectance confocal microscopy in the daily practice. Semin Cutan Med Surg. 2009;28:180-189. 2. Rao BK, Mateus R, Wassef C, et al. In vivo confocal microscopy in clinical practice: comparison of bedside diagnostic accuracy of a trained physician and distant diagnosis of an expert reader. J Am Acad Dermatol. 2013;69:295-300. 3. Terushkin V, Warycha M, Levy M, et al. Analysis of the benign to malignant ratio of lesions biopsied by a general dermatologist before and after adoption of dermoscopy. Arch Dermatol. 2010; 146:343-344. http://dx.doi.org/10.1016/j.jaad.2015.03.052
Letters 319
Sensitivity of handheld reflectance confocal microscopy for the diagnosis of basal cell carcinoma: A series of 344 histologically proven lesions To the Editor: Most studies about the sensitivity of reflectance confocal microscopy (RCM) for the diagnosis of the basal cell carcinoma (BCC) are based on the retrospective analysis of the RCM images acquired by the traditional wide-probe (TWP)-RCM. We evaluated the sensitivity of handheld (HH)-RCM for the diagnosis of BCC in clinical practice. All histologically confirmed BCCs excised at the University Hospital of Saint-Etienne, France, that underwent a HH-RCM (VivaScope 3000; MAVIG GmbH, M€ unchen, Germany) examination between 2011 and 2014 were included. RCM examination was dedicated to cases from which a biopsy specimen was obtained because they were equivocal at dermoscopy. BCCs of the eyelid margin were excluded.1 HH-RCM diagnosis was retrospectively searched in the patient’s clinical records. The diagnosis of BCC was established in the presence of tumor islands of tightly packed cells with or without peripheral palisading of elongated cells, or if $2 of the following criteria were present: dark silhouette with peripheral thickened collagen bundles, dark peritumoral clefts, linear or convoluted dilated blood vessels, and polarized elongated cells in the epidermis (streaming).2-4 All examinations were carried out by 3 dermatologists experienced with dermoscopy and who began reading RCM images in 2010. Our study revealed excellent sensitivity of HH-RCM for the diagnosis of BCC in a series of 344 lesions (Table I). Interestingly, the sensitivity of 87.5% reported in 2011 suggests that BCC is easy to recognize with RCM even for dermatologists with little experience. A learning curve was noticed from 2011 to 2013/2014. Most misdiagnosed BCCs were not completely negative for BCC at RCM, but had equivocal images where it was difficult to affirm with certainty the presence of tumor islands and dark silhouettes. No statistically significant difference in the sensitivity for different histologic subtypes and body sites was found for 2013 and 2014 (Table II; chi-squared test; P [.05). The sensitivity in the last 2 years was similar to previous study data reported in the literature,2-5 ranging from 93% to 100%. However, these studies cannot be directly compared with ours because all but 1 of these studies5 were based on retrospective analysis of RCM images and not on the diagnoses performed at the patient’s bedside. Moreover, they evaluated smaller series (39,5 45,4 52,2 and 833
J AM ACAD DERMATOL
320 Letters
AUGUST 2015
Table I. Reflectance confocal microscopy sensitivity for basal cell carcinoma Year Number of BCCs
2011
Diagnosed by histopathology Examined under RCM Correctely diagnosed by RCM Incorrectly diagnosed by RCM, n (%) Uncertain diagnosis of BCC No elements of BCC RCM sensitivity (%)
2012
2013
2014
Total
280 88 77
196 84 76
281 76 72
232 96 90
989 344 315
7 (8) 4 (4.5) 87.5
4 (4.8) 4 (4.8) 90.5
4 (5.3) 0 94.7
5 (5.2) 1 (1) 93.8
20 (5.8) 9 (2.6) 91.6*
BCC, Basal cell carcinoma; RCM, reflectance confocal microscopy. *Mean RCM sensitivity.
Table II. Reflectance confocal microscopy sensitivity for basal cell carcinoma stratified by histologic subtype and localization
BCC features
No. of BCCs, n (%)
Histologic subtype Nodular 76 Infiltrative 40 Superficial 56 Location Trunk 39 Face 119 Neck 4 Inferior limb 4 Upper limb 3 Scalp 2 Vulva 1
RCM sensitivity (%)
Confidence interval
(44.2) (23.2) (32.6)
94.7 90.0 96.4
89.6-99.7 80.7-99.3 [91.6
(22.7) (69.2) (2.3) (2.3) (1.7) (1.2) (0.6)
97.4 93.3 100.0 100.0 100.0 100.0 0.0
[92.5 88.8-97.8 — — — — —
Labeille, MD,a Alexander Witkowski, MD,c Fre deric Cambazard, PhD,a and Jean-Luc Perrot, MDa Departments of Dermatologya and Pharmacology,b University Hospital of Saint-Etienne, SaintEtienne, France, and the Department of Dermatology,c University Hospital of Modena and Reggio Emilia, Modena, Italy Supported by a medical educational grant from F. Hoffmann-La Roche Conflicts of interest: None declared. Correspondence to: Elisa Cinotti, MD, H^opital Nord, 42055 Saint Etienne Cedex 2, France E-mail: [email protected]
BCC, Basal cell carcinoma; RCM, reflectance confocal microscopy.
BCCs, respectively) and used different diagnostic criteria and different criteria threshold for BCC. HH-RCM was found to have a slightly lower sensitivity than TWP-RCM.4 This could be related to the fact that HH-RCM acquires smaller images (1 mm in diameter vs 8 mm in diameter) and is more often used on the face, where hair follicles and dermal collagen architecture are more prominent and can mask tumor islands. In our experience, to help differentiate a hair follicle from a BCC tumor island we can move to the surface of the skin during RCM examination and check for the presence of a follicle orifice in its correspondence. Despite the drawback of the slightly reduced BCC detection rate, HH-RCM is handy, and its image acquisition is faster than TWP-RCM, making it more suitable for the clinical practice. Elisa Cinotti, MD,a Cecile Jaffelin, MD,a Victoria Charriere, MD,b Pierre Bajard, MD,b Bruno
REFERENCES 1. Cinotti E, Perrot JL, Campolmi N, et al. The role of in vivo confocal microscopy in the diagnosis of eyelid margin tumors: 47 cases. J Am Acad Dermatol. 2014;71:912-918.e2. 2. Guitera P, Menzies SW, Longo C, et al. In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases. J Invest Dermatol. 2012;132:2386-2394. 3. Nori S, Rius-Dıaz F, Cuevas J, et al. Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study. J Am Acad Dermatol. 2004;51:923-930. 4. Castro RP, Stephens A, Fraga-Braghiroli NA, et al. Accuracy of in vivo confocal microscopy for diagnosis of basal cell carcinoma: a comparative study between handheld and wide-probe confocal imaging. J Eur Acad Dermatol Venereol. October 22, 2014. http://dx.doi.org/10.1111/jdv.12780 [Epub ahead of print]. 5. 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;171:1044-1051. http://dx.doi.org/10.1016/j.jaad.2015.04.048