Atlas of Mohs and Frozen Section Cutaneous Pathology Second Edition Michael B. Morgan James M. Spencer John R. Hamill, Jr. Rebecca Thornhill Editors 123 Atlas of Mohs and Frozen Section Cutaneous Pathology Michael B. Morgan ∙ James M. Spencer John R. Hamill, Jr. ∙ Rebecca Thornhill Editors Atlas of Mohs and Frozen Section Cutaneous Pathology Second Edition Editors Michael B. Morgan, MD James M. Spencer, MD College of Medicine Suite 404 University of South Florida College of Medicine Spencer Dermatology Suite 404 TAMPA, Florida Saint Petersburg, Florida USA USA John R. Hamill, Jr., MD Rebecca Thornhill, MD Gulf Coast Dermatology Thomas Jefferson University Hudson, Florida Sidney Kimmel Medical College Thomas USA Jefferson University Philadelphia, Pennsylvania USA ISBN 978-3-319-74846-7 ISBN 978-3-319-74847-4 (eBook) https://doi.org/10.1007/978-3-319-74847-4 Library of Congress Control Number: 2018941239 © Springer Science+Business Media LLC 2010, 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by the registered company Springer International Publishing AG part of Springer Nature The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Dedication To Kerry, Poochie, and Bozie for your unconditional love and acceptance of the time and effort I have spent away from you in this endeavor. Michael B. Morgan, MD To Glicia and James, thank you for your love and encouragement. James M. Spencer, MD I would like to thank my mentor and friend in medical school, Robert Bookmyer, MD, from my dermatology training at the University of Chicago. I would like to thank Alan Lorincz, MD, for inspiring me to think creatively; Maria Medenica, MD, and David Fretzin, MD, for dermatopathology; and Keyoumaris Soltani, MD, for dermatological surgery. I also want to thank Frederick Mohs, MD, for being so generous and sharing his expertise with me. Most importantly, I want to thank my wife Sue and my children John, Sarah, Amy, and Gregory for their support and encouragement. John R. Hamill, Jr. MD To my mother, Mary Barber, who has always been my inspiration and to my husband, Christopher, for his unwavering love and support. Rebecca Thornhill, MD Preface This atlas is intended for practitioners in the fields of dermatologic surgery including Mohs cutaneous surgeons, pathologists who examine frozen section specimens derived from the skin, and dermatopathologists. This book will serve as a reference pictorial atlas detailing both common and challenging cutaneous neoplasms. It will also serve as a review for physicians- in-t raining preparing for certifying examinations in the fields of dermatology, dermatologic surgery, Mohs surgery, pathology, and dermatopathology. The central theme of the atlas entails the microscopic analysis, diagnosis, and discrimina- tion of common and problematic cutaneous neoplasms as encountered by the dermatologist, cutaneous surgeon, or pathologist employing the frozen section technique. The book includes coverage of (1) microscopic anatomy of the various cutaneous and mucosal sites of the body; (2) diagnosis of basic/routine dermatologic entities including basal cell carcinoma and its vari- ants as well as squamous cell carcinoma and its variants; (3) the discrimination of these forego- ing neoplasms from benign epidermal-derived or adnexal-derived neoplasms; (4) diagnosis and distinction of rare and/or deadly neoplasms from benign entities such as dermatofibrosar- coma protuberans and merkel cell carcinoma; (5) troubleshooting and dealing with quality control of the frozen section technique including cutting and staining; (6) new techniques including immunohistochemistry and molecular analysis. The underlying premise of this atlas is to provide its reader with a single reference atlas dealing with the frozen section microscopic diagnosis of cutaneous neoplasms. As these malig- nant entities are capable of presenting in a variety of microscopic guises potentially confused with benign mimics or in a subtle fashion easily missed by the examiner, it is important that pathologists or clinicians who interpret their own biopsies are apprised of this risk. This book should provide a shelf reference for dermatologic surgeons, Mohs cutaneous surgeons, pathologists who perform frozen section analysis of cutaneous specimens, and der- matopathologists. This book should also serve as a potential study source for dermatologists, pathologists, and dermatopathologists preparing for board examinations. Tampa, FL, USA Michael B. Morgan, MD Saint Petersburg, FL, USA James M. Spencer, MD Hudson, FL, USA John R. Hamill, Jr., MD Philadelphia, PA, USA Rebecca Thornhill, MD vii Prologue Skin cancer has reached epidemic proportions in the United States, and there is no evidence that this trend will decrease any time soon. Basal cell and squamous cell carcinomas, collec- tively referred to as nonmelanoma skin cancer, make up the vast majority of the estimated 1.5 million skin cancers seen annually in this country. There are many ways nonmelanoma skin cancer may be treated, ranging from topical medications for early thin tumors, destructive techniques such as cryosurgery or curettage and electrodessication, radiation therapy, surgical excision, and lastly excision utilizing the Mohs technique. Of all these techniques, the highest cure rates currently possible are with the Mohs technique, which relies on optimal preparation and interpretation of frozen sections. Therefore, frozen section analysis has become the gold standard for skin cancer therapy. When surgical excision is chosen as the treatment, frozen section analysis allows histologic information to become part of therapy, rather than preceding therapy (in the case of a biopsy) or confirming an already finished procedure (permanent sections read days after the surgery is over). Frozen sections may be utilized to sample a portion of a conventional surgical excision, or they may be used to examine all the exterior surface of the excised tumor during the Mohs technique. Cure rates with either conventional surgery or the Mohs technique can only be as good as the quality and interpretation of the frozen sections. Frozen section analysis is fundamentally different than permanent sections. Details from individual cells are difficult to assess, and pattern recognition becomes more important. Traditional permanent sections have vertical cuts, and thus structures of the skin are seen verti- cally oriented. Slides prepared as part of the Mohs technique produce sections with horizontal and tangential cuts on the same slide, and thus familiar structures are now altered in their appearance. Experience in reading vertically oriented permanent sections does not translate to expertise in reading frozen sections. In my opinion, the most difficult part in mastering Mohs surgery is not the excision or reconstruction, but rather developing expertise in reading hori- zontally and tangentially oriented frozen sections. It is our hope that this book provides a scholarly reference text to the student of frozen sec- tions for skin cancer therapy. The authors include pathologists and dermatologists practicing Mohs surgery. Mike Morgan, a dermatopathologist, has been the lead author and editor who has carried the lion’s share of getting this book done and deserves our thanks. Hopefully, der- matopathologists reading frozen sections, as well as practicing Mohs surgeons, will find this text a useful and handy reference to keep in the lab. Tampa, FL, USA James M. Spencer, MD ix The Early Days of Mohs Surgery Mohs surgery is an extremely effective method for eradicating skin cancers. The unique fea- ture of the technique is that it incorporates instant pathology while the patient waits. The value of the laboratory in producing frozen sections within a short period of time enables the physi- cian to determine if all of the tumor has been removed. Upon microscopic examination of excised tissue, the physician is able to pinpoint its exact location on the patient. Initially, the availability of cryostats was limited, and the freezing microtome stage was fed by a supply of CO gas that was stored in large containers. The gas was allowed to pass through 2 narrow tubing to reach the microtome stage and freeze the tissue. The CO containers were 2 often large and bulky, requiring substantial storage space. Furthermore, the dependence on timely deliveries of the CO led to many inconveniences in attempting to process the tissue 2 obtained from Mohs surgery. Shortly after, a new type of microtome was developed utilizing an electrical unit that provided a supply of cold air to freeze the specimen on the stage. In subsequent years, cryostats such as Leica became more practical and affordable and are among the most used in Mohs surgery practices today. Before the 1970s, the Mohs technique incorporated the application of a zinc chloride paste and was thus known as microscopically controlled chemosurgery. The final patented formula contained 45% zinc chloride by weight, with 40 g of stibnite antimony, 10 g of bloodroot (Sanguinaria canadensis), and a 34.5 mL zinc chloride saturated solution. The stibnite anti- mony acted as a granular support material, and the bloodroot kept the zinc chloride in suspen- sion so that it could freely move between the particles, yet not settle to the bottom. The product was not FDA approved and was prepared by the University of Wisconsin pharmacy, where at the time it could only be purchased under the authority of Fred Mohs. The zinc chloride paste was effective in fixing the tissue in situ. It was applied in a thin layer over the involved area and could not penetrate the skin unless keratin was removed. This was accomplished using dichloroacetic acid. It turned the affective area white due to precipitation of the proteins in the epidermis. Using the zinc chloride paste, Dr. Mohs created Z squares in which he impregnated a piece of gauze with the paste and cut into 1 cm2 pieces. Theses gauze pieces were then applied to the Mohs defect site to prevent the area from drying out. This entire process came to be known as the fixed tissue technique. Although Dr. Mohs had published work on the fresh tissue technique in the late 1950s, it was not until the mid-1970s that it became the favored method in Mohs surgery. In 1970, Dr. Tromovitch presented a paper at a chemosurgery meeting, reporting a 99% cure rate with close to a 5-year follow-up. The advantage of using the fresh tissue technique was that many stages of Mohs surgery could be performed in one day, and the defect could be repaired immediately following completion of the surgery. Today, there are some Mohs surgeons who continue to use the zinc chloride paste to treat malignant melanoma. They believe that the paste plays a role in killing melanocytes; however, this has not yet been substantiated. Therefore, the fresh frozen technique has become the preferred technique in the vast majority of Mohs surgery practices. In the early days, the favorite stain for basal cell carcinoma was toluidine blue. It caused the mucopolysaccharides to stain purple revealing the presence of tumor cells. The use of toluidine blue was less popular for squamous cell carcinoma as it was more difficult to differentiate xi xii The Early Days of Mohs Surgery tumor from normal tissue. Toluidine blue was taken off the market in its initial formulation as it was found to be carcinogenic at higher concentrations. Hematoxylin and eosin became the standard for both squamous cell and basal cell carcinomas as well as various tumors for which Mohs surgery is utilized as treatment. The toluidine blue used today is at a much lower con- centration and is preferred by many Mohs surgeons for visualizing basal cell carcinoma. However, its perceived advantage over hematoxylin and eosin is simply a matter of personal choice. New York, NY, USA Ritu Saini, MD New York, NY, USA Perry Robins, MD Contents Part I Introduction 1 Mohs and Frozen Section Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Michael B. Morgan and Terri Bowland 2 Quality Assurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Dennis H. Nguyen, Daniel M. Siegel, Deborah Zell, and Richard Spallone Part II Tumors of the Epidermis/Adnexae 3 Histology with Regional and Ethnic Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Michael B. Morgan and John R. Hamill Jr. 4 Benign Epidermal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Michael B. Morgan 5 Pseudotumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Martin Dunn 6 Squamous Cell Carcinoma: Variants and Challenges . . . . . . . . . . . . . . . . . . . . . . 59 Michael B. Morgan 7 Basal Cell Carcinoma: Variants and Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Michael B. Morgan 8 Adnexal Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Michael B. Morgan 9 Malignant Adnexal Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Ryan S. Jawitz and Jack C. Jawitz 10 Merkel Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Michael B. Morgan 11 Sebaceous Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 Michael B. Morgan 12 Paget’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Michael B. Morgan 13 Melanocyte Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Michael B. Morgan Part III Tumors of the Dermis 14 Benign Mesenchymal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Michael B. Morgan xiii