Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years

Accepted Manuscript Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years Katarina Kesty, MD, MBA, Omar P. Sangueza, MD, Barry Leshin, MD, John G. Albertini, MD PII:

S0190-9622(17)32814-1

DOI:

10.1016/j.jaad.2017.11.055

Reference:

YMJD 12174

To appear in:

Journal of the American Academy of Dermatology

Received Date: 4 September 2017 Revised Date:

18 November 2017

Accepted Date: 29 November 2017

Please cite this article as: Kesty K, Sangueza OP, Leshin B, Albertini JG, Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years, Journal of the American Academy of Dermatology (2018), doi: 10.1016/j.jaad.2017.11.055. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT 1 Article Type: Original Article Title: Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years

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Corresponding Author: John G. Albertini, MD The Skin Surgery Center 1450 Professional Park Drive Winston-Salem, NC, 27103 [email protected]

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Katarina Kesty1, MD, MBA, Omar P. Sangueza1, MD, Barry Leshin2,3, MD, John G. Albertini2,3, MD 1 Wake Forest Department of Dermatology, Wake Forest Baptist Health, Winston-Salem, NC 2 The Skin Surgery Center, Winston-Salem, NC 3 Wake Forest Department of Plastic and Reconstructive Surgery, Wake Forest Baptist Health, Winston-Salem, NC

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Funding Sources: None Conflicts of Interest: None declared IRB Status: Approved as exempt by IRB at Wake Forest Baptist Health (August 11, 2017, IRB # 00044678) Manuscript Word Count: 1,490 Abstract Word Count: 164 Capsule Summary Word Count: 50 References: 24 Figures: 1 Tables: 1 Attachments: IRB exemption memo

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Keywords: Mohs, cutaneous oncology, medical dermatology, dermatopathology, nonmelanoma skin cancer, melanoma

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Capsule Summary •

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Mohs micrographic surgery depends on the surgeon’s ability to correctly interpret intraoperative frozen sections

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We reviewed 1421 Mohs cases and 6407 slides for possible disagreement

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between fellowship trained-Mohs surgeons and dermatopathologists; the

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concordance rate was 99.79%

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Fellowship-trained Mohs surgeons are proficient at interpreting histopathology

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slides in the setting of Mohs micrographic surgery

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ACCEPTED MANUSCRIPT 3 Abstract

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Background: The success of Mohs micrographic surgery depends on the surgeon’s ability

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to correctly interpret intraoperative frozen sections.

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Objective: This retrospective study analyzed the rate of concordance between Mohs

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surgeons and dermatopathologists in reading slides from Mohs surgery cases.

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Methods: A dermatopathologist reviewed all the frozen sections and the corresponding

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Mohs map for every 30th Mohs case at a practice employing 6 different Mohs surgeons

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from 2001-2017. Cases in which the dermatopathologist and the Mohs surgeon disagreed

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on the interpretation were noted.

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Results: The concordance rate between Mohs surgeons and dermatopathologists was

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99.79%. The three discordant cases included one case each of squamous cell carcinoma,

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superficial basal cell carcinoma, and hypertrophic squamous cell carcinoma in situ.

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Limitations: This analysis is limited to fellowship-trained Mohs surgeons and therefore

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may not be applicable to all physicians who perform Mohs.

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Conclusions: Fellowship-trained Mohs surgeons show very high concordance with

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board-certified dermatopathologists in the accurate and precise interpretation of histology

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slides in the setting of Mohs micrographic surgery.

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Introduction An estimated 5.4 million cutaneous basal cell carcinomas and squamous cell carcinomas are diagnosed each year in the United States.1 Mohs surgery has a 99% cure

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rate for these non-melanoma skin cancers.2 The success of Mohs surgery is dependent

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upon the surgeon’s ability to interpret intraoperative frozen sections and correctly

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identify and remove any residual neoplasm. Several other studies have retrospectively

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analyzed small cohorts of Mohs cases for diagnostic reliability of the surgeon’s

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interpretation of frozen slides.3-9 We present an analysis of 6407 slides from 1421 cases

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of Mohs micrographic surgery in which all frozen sections for each case were

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independently reviewed by a fellowship-trained dermatopathologist and compared to the

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interpretation by the Mohs surgeon.

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Our study is a retrospective analysis of every 30th Mohs surgery case for 6

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fellowship-trained Mohs surgeons over a period of 17 years at an academically-affiliated

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practice as part of a quality assurance initiative. The frozen section slides from each of

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the numerically selected cases were collected by histotechnicians and reviewed monthly

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by a fellowship-trained dermatopathologist, whose interpretation of each slide was

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recorded in a log book. Since numerous physicians generated the cases over time, each

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Mohs surgeon was blinded to which cases were reviewed. Of the cases selected (every

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30th), those with the potential for disagreement with the Mohs surgeon (possible residual

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cancer, stage read as benign with additional stage taken, etc.) were flagged in the log

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book for an additional review. The frozen sections for these cases were then reviewed an

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ACCEPTED MANUSCRIPT 5 additional time by both a dermatopathologist and a Mohs surgeon. The results of this

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second slide review were compared to the interpretation by the Mohs surgeon who

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performed the case (according to the Mohs map) to evaluate for discordance in the

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interpretation of slides.

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All the Mohs surgeons involved in this study completed residency training in

dermatology and a fellowship in Mohs Micrographic Surgery (Procedural Dermatology)

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accredited by either the American College of Mohs Surgery (ACMS) and/or the

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Accreditation Council of Graduate Medical Education (ACGME). The

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dermatopathologists completed a residency in anatomic and surgical pathology and a

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fellowship in dermatopathology accredited by the ACGME. This study was approved as

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exempt from meeting the federal definition of research involving human subjects on

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August 11, 2017 (IRB number 00044678).

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Results

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1421 Mohs cases were reviewed by a dermatopathologist, with 6407 slides

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evaluated from 1444 unique sites and 1898 Mohs stages. All types of skin cancer treated

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by the Mohs surgeons during the 17 year period were included in the analysis as cases

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were added to the quality assurance logbook according to sequence (every 30th case) and

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not by type of cancer. Of note, the vast majority of the cases included in the analysis and

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all of the discordant cases were basal cell carcinoma, squamous cell carcinoma, or

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melanoma. Also, the presence or absence of perineural invasion was incorporated into the

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review of Mohs case slides by the dermatopathologist as part of the original quality

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assurance program. Of the 1421 cases, upon initial review of the quality assurance

ACCEPTED MANUSCRIPT 6 logbook, 36 were flagged for possible disagreement regarding the slide interpretation by

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the dermatopathologist and the Mohs surgeon. The slides and the Mohs map from these

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36 cases were re-evaluated by a dermatopathologist and a Mohs micrographic surgeon.

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After this further analysis, 31 of the 36 cases were found to be concordant. Some of these

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31 cases included pathology of residual actinic keratosis and squamous cell carcinoma in

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situ, which lead to them being flagged as possibly discordant upon initial review of the

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quality assurance logbook. This pathology, however, was noted by both the

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dermatopathologist and the Mohs surgeon on the Mohs map. Therefore, these cases were

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considered to be concordant in nature. When appropriate, a percentage of these cases

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were further treated with topical medication and/or referred back to their dermatologist

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for observation. The 31 concordant cases also included processing errors such as false

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edges that were recorded on the Mohs maps and noted by the dermatopathologist.

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In total, five cases were identified where the dermatopathologist and the Mohs

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surgeon disagreed in the interpretation of the frozen sections, or 0.35% of the total cases

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reviewed. These cases contain 13 slides out of the 6407 reviewed, amounting to 0.2% of

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the slides being discordant. Two of the five cases were squamous cell carcinomas and

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three were basal cell carcinomas. In two of these cases, the dermatopathologist read a

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layer as benign and the Mohs surgeon took an additional layer for what they noted on the

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Mohs map as a potential basal cell carcinoma vs. benign structure (hair follicle or benign

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follicular hamartoma). These were not regarded as clinically significant as the Mohs

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surgeon read the equivocal slides as suggestive of tumor and after clinicopathologic

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correlation decided to take another layer to ensure complete removal of the cancer. The

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other three of the five cases represented 5 slides that were discordant in their

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ACCEPTED MANUSCRIPT 7 interpretation. In these three cases the dermatopathologist interpreted the frozen sections

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as having residual cancer and the Mohs surgeon did not note this on the Mohs map.

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These included one case of squamous cell carcinoma, one case of superficial basal cell

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carcinoma, and one case of hypertrophic squamous cell carcinoma in situ. These

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represent 0.21% of the cases and 0.08% of the slides reviewed for this study. Therefore,

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the concordance rate pertaining to clinically significant decisions was 99.79%.

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Discussion

Overall, the concordance rate of our quality assurance program was 99.79% between

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the Mohs surgeons and dermatopathologists. This is higher or similar to the rate of

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agreement found in other studies (Table I).3-9 Our study demonstrates that fellowship-

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trained Mohs surgeons are sufficiently skilled in interpreting intraoperative frozen

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sections. This allows Mohs surgeons to achieve a high surgery success rate in terms of

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sparing non-involved tissue and achieving low tumor recurrence rates.

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In the two cases of basal cell carcinoma interpreted as tumor-free by the dermatopathologist and suggestive of tumor by the Mohs surgeon, the Mohs surgeon

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used the clinical exam together with the pathology to determine that another layer was

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warranted. Mohs surgery is unique in that the surgeon must correlate the clinical and

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pathologic data to achieve complete tumor removal. It is difficult to assess these

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decisions using only the pathology. Debate between dermatopathologists and Mohs

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surgeons regarding slides suggestive of tumor, but without definitive tumor, where the

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Mohs surgeon decided to proceed with another layer has been observed in other

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studies.3,5,7-9

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In the discordant case of squamous cell carcinoma, further review of the patient’s medical record by the Mohs surgeon and the dermatopathologist reflected that the

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residual squamous cell carcinoma was focally present in periosteum which was removed

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at the final Mohs stage. This resection was documented in the postoperative photograph,

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but inadvertently omitted from the map. The patient was examined 14 months

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postoperatively, and remains free of any clinical evidence of recurrence. In the discordant

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cases of superficial basal cell carcinoma and squamous cell carcinoma in situ, there was

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no recurrence evident at 5 week and 13 month follow up exams, respectively.

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Although other authors have evaluated Mohs slides and cases for concordance, this is

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the longest-running study to date with the highest number of slides reviewed. Also, our

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study is more clinically relevant than some previous studies on the topic because it

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compares Mohs maps with dermatopathologists’ interpretation of the slides. This is in

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contrast to studies that analyzed binary (tumor present/tumor not present) interpretations

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of slides by dermatopathologists and Mohs surgeons without the clinical correlation of

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the Mohs map.

Potential sources of error in our study include human error in recording the

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dermatopathologist’s initial interpretation of slides, and in reviewing the log book for

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potential cases of disagreement between the dermatopathologist and the Mohs surgeon.

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Volume is associated with better outcomes in many fields of study including surgery

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and pathology.10-21 Fellowship-trained Mohs surgeons have the benefit of significant

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volume of Mohs cases (a minimum of 400) performed and their pathology interpreted

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under the direct supervision and instruction of an experienced Mohs surgeon.22 Murphy

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et al demonstrated that it takes this volume and repetition gained in a Mohs fellowship to

ACCEPTED MANUSCRIPT 9 reliably interpret Mohs frozen sections to avoid recurrences and unnecessary tissue

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excision due to error in reading slides.23 Although our study demonstrates the highest

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concurrence rate and largest sample size of slides, we included only ACMS or ACGME

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fellowship-trained Mohs surgeons. Therefore, our results may not be applicable to all

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physicians who perform Mohs surgery, either in the United States or internationally. For

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example, the study that showed the lowest concordance rate of 94% included 11 variably

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experienced Mohs surgeons from the Netherlands, for whom only 100 cases are required

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during training for certification by The European Society of Micrographic Surgery.9,24

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The concordance rate between Mohs surgeons and dermatopathologists according to our data is 99.79%. This is consistent with previously published studies. Fellowship-

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trained Mohs surgeons demonstrate accurate and precise interpretation of histology slides

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in the setting of Mohs micrographic surgery.

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November 12, 2017.

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ACCEPTED MANUSCRIPT 14 Figure

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Figure 1. “1421 Mohs cases were analyzed as part of an ongoing quality assurance

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program. Three cases were determined to be discordant. The clinically significant

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concordance rate was 99.79%. BCC, basal cell carcinoma; SCCIS, squamous cell

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carcinoma in situ; SCC, squamous cell carcinoma.”

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ACCEPTED MANUSCRIPT 15 Table

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Table I. “Studies, including our analysis, of concordance between Mohs surgeons and

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dermatopathologists interpreting frozen sections. BCC: basal cell carcinoma, SCC:

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squamous cell carcinoma; NMSC: non-melanoma skin cancer.”

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1720 cases 170 slides

Grabski et al6 Macfarlane et al7 Tan et al8 Van Lee et al9

1000 slides 489 cases 99 slides 1653 cases

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BCC, SCC, melanoma BCC, SCC, other NMSC BCC, SCC BCC, SCC, sebaceous carcinoma, mucinous carcinoma BCC, SCC BCC, SCC, others BCC, SCC BCC

% Discordance 0.21%

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Highsmith et al.4 Semkova et al5

This study

Type(s) of cancer

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Mariwalla et al3

# Slides/cases reviewed 6407 slides/ 1421 cases 1156 slides

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0.26% 0.5% 0.58%

1.1% 1.2% 5% 6%

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