Mohs Micrographic Surgery Concordance Between Mohs Surgeons and Dermatopathologists KRISTINA SEMKOVA, MD, MSC,* RAJ MALLIPEDDI, BSC (HONS), MBBS, MD, FRCP,† ALISTAIR ROBSON, MB, CHB, BSC (HONS), FRCPATH , DIPRCPATH,‡ AND IOULIOS PALAMARAS, MD, PHD†
BACKGROUND Mohs micrographic surgery (MMS) is the preferred treatment modality for high-risk nonmelanoma skin cancer because of the high cure rates and tissue-sparing effect. Its outcome is highly dependent on the expertise and accuracy of the Mohs surgeon in the interpretation of frozen sections. OBJECTIVE This retrospective study evaluated the level of concordance between Mohs surgeons and dermatopathologists in reading histology slides from MMS procedures. METHODS AND MATERIALS A Mohs surgeon read 170 randomly selected slides for a quality assurance audit during excision, and then a dermatopathologist blindly read them at a separate time. Absence or presence of tumour and the final diagnosis were recorded on a standardized form. RESULTS An overall concordance of 99.4% was demonstrated. True discordance was recorded in only one of 170 cases. Intraepidermal atypia was the most challenging scenario for Mohs surgeons. CONCLUSIONS The high rate of agreement in this study confirms that adequately trained MMS surgeons have sufficient expertise and training for accurate and precise frozen sections interpretation. The authors have indicated no significant interest with commercial supporters.
onmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common malignancy worldwide, and its incidence is increasing on an epidemic scale.1,2 The main treatment modality for these tumors is excision, performed conventionally or, if appropriate, with Mohs micrographic surgery (MMS). MMS achieves a high cure rate for BCC and SCC through an optimal margin excision.1,2 Additionally, MMS has a tissue-sparing effect with less loss of normal surrounding tissue than conventional excision. It is currently the treatment of choice for recurrent skin cancers and for primary skin cancers with anatomic distribution that demands tissue preservation for functional or cosmetic reasons.3,4
The reliability and the rate of success of the Mohs technique rest primarily on the diagnostic accuracy of the frozen section evaluation by the Mohs surgeon. The surgeon excises, maps, and examines the slides personally, simultaneously acting as a surgeon and pathologist. This process ensures precise identification of tumor and consequent resection during the stages of MMS. Few studies in the literature have compared the histopathology expertise of MMS surgeons in the assessment of Mohs sections with that of pathologists with special training in dermatopathology.5–7 A quality assurance dermatopathology audit of frozen section interpretation by MMS surgeons was conducted in the Dermatological Surgery and Laser
*Department of Dermatology and Venereology, Medical University-Sofia, Sofia, Bulgaria; †Dermatological Surgery and Laser Unit, St Thomas’ Hospital, London, UK; ‡Department of Dermatopathology, St John’s Institute of Dermatology, St Thomas’ Hospital, London, UK The work was carried out at St John’s Institute of Dermatology, St Thomas’ Hospital, London, United Kingdom.; © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2013;39:1648–1653 DOI: 10.1111/dsu.12320 1648
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Care Unit at St John’s Institute of Dermatology, St Thomas’ Hospital, London. The aim of the audit was to examine the diagnostic concordance between the Mohs surgeons and a dermatopathologist with experience in reading Mohs sections and to analyze its possible clinical implications. Our study is a retrospective analysis of the randomly selected cases for the audit over 3 years (2009–2011).
Materials and Methods Two MMS surgeons (IP, RM), one accredited dermatopathologist (AR), and a dermatology trainee (KS) were involved in this study. The MMS surgeons had completed residency training in dermatology and fellowship training in MMS, involving more than 500 cases. They were trained by Mohs surgeons, and the trainer consistently checked their assessment of slides in each case, with input from dermatopathologists in challenging cases. One hundred seventy randomly selected frozen sections from Mohs procedures performed in the Dermatological Surgery and Laser Care Unit from 2009 to 2011 were analyzed retrospectively. Mohstrained histotechnicians processed all sections, which were stained with hematoxylin and eosin (HE) during the MMS procedure. The surgeon reviewed the slides at the time of the procedure and recorded “tumor” or “no tumor” and his diagnosis on a specifically designed standardised quality assurance form (Figure 1). The histotechnician then randomly selected slides and sent them to the Department of Dermatopathology to be reviewed within 3 months by the dermatopathologist, who used the same form to record lack or presence of Slide No
tumor and was blind to the results of the Mohs surgeon. The information from the two readings was then converted into a data set using Excel software (Microsoft, Corp., Redmond, WA) and analyzed for concordance. In case of diagnostic discordance, the MMS surgeon who initially interpreted the sections identified and reviewed the slides again together with the dermatopathologist. The purpose of this interactive review was to elucidate the nature of the discordance and its effect on the patient’s treatment. The comments and outcome of this session were recorded in the data set.
Results Of the 170 slides reviewed, initial concordance as to the presence or absence of tumor was found in 167 cases. Because of the random selection, these slides represented tumor or clear stages. Sixty-nine (41.3%) cases were concordantly recorded as “tumor” and 98 (58.7%) as “no tumor.” Tumor types included BCC (superficial, nodular, infiltrative), SCC, sebaceous carcinoma, and mucinous carcinoma. The MMS surgeon read one of the discordant slides as tumor free, but the dermatopathologist noted a small residual focus of BCC cells within a hair follicle (Figure 2). Further review of deeper sections revealed total clearance, and this discordance therefore had no relevance as to the patient’s final outcome. The dermatopathologist noted SCC in situ on two slides and actinic keratosis (AK) on four other slides, in addition to the BCC undergoing excision. Because
Tumor No tumor Premalignant lesion: AK Bowen’s disease
Figure 1. The quality assurance form used for the audit (modified from Mariwalla and colleagues6). The surgeon’s diagnosis and the agreement sections were completed at the Dermatological Surgery and Laser Care Unit after the Pathology reading.
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Figure 2. A small basaloid nest attached to the follicular epithelium. Note the peripheral palisading, the retraction artefact, and the cytologic atypia (hematoxylin-eosin stain, original magnification: (A) 9200; (B) 9400).
the BCC was concordantly identified as excised in clear margins, the additional findings did not represent a true discrepancy because the MMS surgeon and the dermatopathologist identified the cases as “no tumor.” The MMS surgeon and the dermatopathologist read three slides as being suggestive but not conclusive of tumor features. In all three cases, the surgeon proceeded with resection until complete clearance. In total, diagnosis agreement was found in 169 of 170 reviewed cases between the MMS surgeons and the dermatopathologist, a concordance rate of 99.4% (Table 1).
Discussion When available, MMS is the preferred treatment option for high-risk NMSC because of its remarkable cure rates and tissue preservation. Because the evaluation of frozen sections by the MMS surgeon is an important step in the procedure, the surgeon’s expertise in identifying the pathology on histology is crucial for the final outcome of the surgery. This retrospective quality assurance study of diagnostic concordance between MMS surgeons and a trained dermatopathologist in frozen section interpretation showed a high
overall rate of agreement (99.4%). These results are consistent with previous studies carried out in the United States and Australia.5–7 Grabski and colleagues5 were the first to correlate the interpretation of frozen sections by MMS surgeons with the interpretation by pathologists and dermatopathologists. Their study included 1,000 slides and showed 98.9% agreement, suggesting that Mohs surgeons are sufficiently qualified to interpret the histologic slides prepared during MMS. A second study by Mariwalla and colleagues6 analyzed 1,156 cases of NMSC slides from MMS procedures read separately and blindly by a surgeon and a histopathologist within the Quality Assurance Programme of the Section of Dermatologic Surgery and Cutaneous Oncology at the Yale University School of Medicine. The observed concordance rate regarding clinically significant decisions was 99.7%, with a slightly higher rate for cases of BCC than for SCC. Only three cases were truly discordant and considered to contain tumor by the MMS surgeon but not the dermatopathologist. These cases represented infiltrative, morpheic, and recurrent multifocal BCC, and the Mohs surgeon, being more cautious, took an additional layer to ensure complete excision.
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TABLE 1. Reviewed Cases for Histopathological Concordance Between the MMS Surgeons and the Dermatopathologist Cases, n Type of tumor
All cases Tumor No tumor Basal cell carcinoma Squamous cell carcinoma Sebaceous carcinoma Mucinous carcinoma
170 69 101 58 9 1 1
170 70 100 59 9 1 1
99.4 98.57 99.00 98.31 100 100 100
A similar study by Tan and colleagues7 evaluated concordance between a MMS surgeon and a dermatopathologist in the correct identification of NMSC on frozen sections and marking its location on a Mohs map. A dermatopathologist randomly selected and reviewed 99 archival MMS slides from a private dermatologic surgery practice in Australia. The concordance was 94.9%. As also shown in this study, making a clear distinction between lesions in the spectrum of solar damage to SCC in situ is the most challenging scenario for the MMS surgeon. This is consistent with other studies in which the identification of SSC in situ was the main area of discordance between the pathologist and the MMS surgeon.6 Nevertheless, a unanimous diagnosis of AK or SCC in situ is not always achieved even among dermatopathologists, and the threshold for determining invasive malignancy in this setting remains debatable.8,9 In addition, the observed discordance should be interpreted with the consideration that the Mohs surgeon has the advantage of the clinicopathologic correlation. The surgeon might consider keratinocyte atypia in the setting of severe solar damage in the absence of a clinical lesion to be less relevant and therefore not to record it. In three of our cases, a definitive diagnosis of tumor on frozen sections was not possible for both the MMS surgeon and the dermatopathologist. The risk:benefit ratio of not proceeding with further excision in such cases is high, and a larger defect
might be preferable to residual tumor nests, with the risk of recurrence. Hence, a decision to continue with a further stage of excision was made in all suspicious cases. The difficulty in precise evaluation is most likely due to the limitations of HE staining. HE is the most preferred routine staining method for MMS and is used in as many as 83% of all cases.10 Although this method is usually sufficient to detect NMSC, there are still circumstances in which the tumor cells are difficult to differentiate from normal structures regardless of the quality of staining. These include poorly differentiated cancers, single cell spread, perilesional dense inflammatory infiltrate, nerve or vessel involvement, and embedding in fibrotic or connective tissue.11 In such ambiguous cases, immunohistochemical staining may facilitate tumor type or presence distinction and reduce the number of MMS stages performed.11 Our study represents the first correlation between a MMS surgeon and a dermatopathologist in reading MMS frozen HE sections in Europe. The high concordance in this and similar studies demonstrates a satisfactorily high level of training and expertise of the involved MMS surgeons. Accurate histologic examination of excision margins is a prerequisite for a good outcome of the MMS procedure and, as Lane and colleagues emphasized,12 MMS fellowship programs should pay particular attention to achieving histopathology proficiency with a high volume of cases and mentoring by Mohs surgery trainers with feedback during the procedure.
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It would be advisable that other MMS centers in the United Kingdom and in other European countries perform similar quality assurance audits to ensure that the same high quality of training and expertise is being offered in dermatologic centers across Europe.
Acknowledgments The authors would like to thank Nisith Sheth and Catherine Gleeson for their assistance in collecting part of the data.
5. Grabski WJ, Salasche SJ, McCollough ML, Berkland ME, et al. Mohs micrographic frozen sections: a peer review comparison study. J Am Acad Dermatol 1989;20:670–4. 6. Mariwalla K, Aasi SZ, Glusac EJ, Leffell DJ. Mohs micrographic surgery histopathology concordance. J Am Acad Dermatol 2009;60:94–8. 7. Tan E, Elliott T, Yu L, Litterick K. Mohs surgery histopathology concordance in Australia. Australas J Dermatol 2011;52:245–7. 8. Hurwitz RM, Buckel LJ. Actinic keratosis on a continuum with squamous cell carcinoma. Arch Dermatol 2010;146:923–4. 9. Ko CJ. Actinic keratosis: facts and controversies. Clin Dermatol 2010;28:249–53. 10. Silapunt S, Peterson SR, Alcalay J, Goldberg LH. Mohs tissue mapping and processing: a survey study. Dermatol Surg 2003;29:1109–12.
References 1. Wood LD, Ammirati CT. An overview of Mohs micrographic surgery for the treatment of basal cell carcinoma. Dermatol Clin 2011;29:153–60. 2. Belkin D, Carucci JA. Mohs surgery for squamous cell carcinoma. Dermatol Clin 2011;29:161–74. 3. Telfer NR, Colver GB, Morton CA. Guidelines for the management of basal cell carcinoma. Br J Dermatol 2008;159:35–48. 4. Motley RJ, Preston PW, Lawrence CM. Multi-professional Guidelines for the Management of the Patient with Primary Cutaneous Squamous Cell Carcinoma; 2009. Available from: http://www.bad.org.uk Accessed April 30, 2012.
11. Miller CJ, Sobanko JF, Zhu X, Nunnciato T, et al. Special stains in Mohs surgery. Dermatol Clin 2011;29:273–86. 12. Lane JE, Chiller KG, Baucom MF, Kent DE. Mohs micrographic surgery histopathology concordance in fellowship-trained surgeons. J Am Acad Dermatol 2010;62:148.
Address correspondence and reprint requests to: Ioulios Palamaras, MD, PhD, Dermatological Surgery and Laser Care Unit, St John’s Institute of Dermatology, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK, or e-mail: [email protected]
Commentary: Mohs Micrographic Surgery Concordance Between Mohs Surgeons and Dermatopathologists GARY D. MONHEIT, MD*
The authors have indicated no significant interest with commercial supporters.
his report further documents the expertise of the Mohs surgeon in evaluating cancer slides and interpreting the results. For the last 10 years, our Mohs surgery practice has sent slides to our
referral pathologist for review to further back up and credential our work. Every tenth slide is sent to our referral pathologist as an unknown and examined as an unknown for a histologic diagnosis. The
*Total Skin and Beauty Dermatology Center, PC, Departments of Dermatology and Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2013;39:1652–1653 DOI: 10.1111/dsu.12331 1652