Dermatopathology Lyn M

Chapter  Dermatopathology Lyn M. Duncan and Martin C. Mihm Jr.

he history of dermatopathology at role of pathological investigation was doubtless Tthe Massachusetts General Hospital (MGH) imparted to Dr. White during his time in Vienna. is a rich and long one, dating back to the second Dr. White returned to Boston, and his versatility half of the nineteenth century and continuing as a physician is illustrated by the fact that he to the present day. It features close interaction began his career at MGH as a clinical chemist, between the Dermatology and Pathology depart- serving in that capacity from 1863 to 1872; but ments, beginning in Dermatology and then he was interested primarily in dermatology and becoming a specifi c Dermatopathology Unit in devoted his practice to it after 1872. Once he had the department of Pathology in the 1960s. Th e opened the outpatient clinic, he began a two-year history includes luminaries in the fi eld, such as debate with other MGH physicians and surgeons Drs. James C. White, John T. Bowen, Walter F. on the need for a special “Skin Ward”; this special Lever, Wallace H. Clark Jr., and Martin C. Mihm ward was formed, but it closed in only a year, Jr., and major discoveries, perhaps most notably and Dr. White was appointed to the Out-Patient in the area of skin neoplasia. A number of epony- Department, as Physician to Out-Patients with mous skin diseases and tumor staging systems are Diseases of the Skin. He was a prolifi c writer, associated with individuals who worked at the served as an Editor of the Boston Medical and Sur- MGH, attesting to the infl uential role of MGH gical Journal (the precursor to the New England Dermatopathology over the years. Journal of Medicine), and was the fi rst professor of dermatology in the United States (at HMS). The Early Years: White and Bowen In keeping with his training under von Hebra, Th e roots of dermatopathology at MGH can be some of his works contained detailed descrip- traced to its companion clinical discipline, der- tions of cutaneous pathology (34). His family matology, which itself dates to 1869 at MGH, would also go on to prominent positions at the when Dr. James Clarke White began an outpa- MGH, his son Charles J. White (see below) serv- tient clinic for patients with diseases of the skin ing as Chief of Dermatology and his grandson, (fi gure 18.1). He graduated from Harvard Medi- also named James C. White, becoming Chief of cal School (HMS) in 1856 and then studied in Neurosurgery. Vienna with the great dermatologist Ferdinand One of Dr. White’s trainees was Dr. John Tem- von Hebra. Von Hebra is considered the fi rst pleton Bowen (fi gure 18.2). Dr. Bowen had gradu- person to bring careful pathological study to ated from HMS in 1884 and studied in Germany diseases of the skin, and an appreciation for the and Vienna before returning to the MGH in 1889

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Figure 18.1 James Clarke White Figure 18.2 John Templeton Bowen

as Assistant Physician to Out-Patients with Dis- much preferred this type of life to the public area eases of the Skin. He went on to become the fi rst of hospital practice and teaching” (32). In a his- Edward Wigglesworth Professor of Dermatology torical sense, therefore, Dr. Bowen can justifi ably at HMS in 1907 and was Chief of the Derma- be considered the fi rst dermatopathologist at the tology Service at MGH from 1911 to 1913. Dr. MGH. Bowen did seminal and extremely careful work in After Dr. Bowen’s tenure, Chiefs of Dermatol- understanding the microscopic pathology of skin ogy included Drs. Charles J. White (son of Dr. diseases, the most notable being his descriptions James C. White; 1913–1927), Harvey P. Towle of in situ squamous cell carcinoma (3), known (1913–1925, with Dr. White), E. Lawrence Oli- subsequently as Bowen’s disease. He collaborated ver (1927–1936), and C. Guy Lane (1936–1947). and published with pathologists, including Dr. Some of these individuals did clinicopathologi- S. Burt Wolbach, the Chair of HMS Pathology, cal correlations of dermatological disease and and was a member of the American Association published interesting case reports on a variety of of Pathologists and Bacteriologists. Indeed, some conditions. For example, Dr. White published felt that this quiet man may have liked his micro- an article with Dr. Oscar Richardson of Pathol- scope better than his patients. According to Dr. ogy (chapter 3) on cutaneous leprosy in 1909 that Charles J. White, “Dr. Bowen was by nature a included detailed histopathological and bacte- student. He loved quiet: he loved his microscope, riological examinations and that acknowledged and he loved to ponder over things—to ‘mull’ Dr. Bowen’s help with the case (33). A promi- over them was a frequent word on his lips. He nent MGH dermatologist from 1921 to 1937 was

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Arthur M. Greenwood, who also worked at New England Deaconess Hospital. He published a number of papers that had dermatopathological correlates, including ones with the MGH Pathol- ogy department and on the skin of diabetics with Dr. Elliott Joslin (chapter 3). His papers refl ect close interactions with MGH Pathology, such as his acknowledgment in a 1922 paper on hemangiosarcoma of the skin of “indebtedness to Dr. J. Homer Wright and to Dr. Charles J. White for their valuable suggestions and aid in interpre- tation of the sections” and his reference to Dr. Wright in the text (14). Dr. Wright himself had also published on dermatopathology, including one of the detailed early histological descriptions of cutaneous leishmaniasis, an article in which he acknowledged his close interactions with Dr. White on the case (36). The Lever Era Walter F. Lever was born on December 13, 1909, in Germany and obtained his medical degree in Leipzig (fi gure 18.3). His father, Alexander Lever, Figure 18.3 Walter F. Lever was a prominent dermatologist in Germany. In the 1930s Walter Lever became one of many phy- together he agreed to it. In working with him in sicians who left Germany in an exodus to the dermatopathology I learned a great deal of gen- United States because of the rise of Nazism. He eral pathology. With only brief interruptions the joined the MGH in 1936 as a research fellow and Pathology Laboratory at the Massachusetts Gen- resident on the Dermatology Service. In that year eral Hospital was a ‘second home’ to me for more Guy Lane had become Chief of Dermatology than 20 years” (19). and had expanded the training program to two Dr. Lever was appointed to the Dermatology years and doubled the number of residents, giv- faculty in 1944, and he continued his close rela- ing Dr. Lever “some spare time” that he “spent in tionship with Pathology, reviewing the skin biop- the Pathology Laboratory” (19), thus beginning sies with the residents. He is best known for his his long association with MGH Pathology. His widely read textbook, Histopathology of the Skin, description of his early interactions with Pathol- originally published in 1949 and now in its ninth ogy attests to the novelty of a dedicated dermato- edition (20). Th is successful text is a refl ection pathologist: “Th e members of the Pathology Lab- of Dr. Lever’s important role in the forging of oratory were not used to seeing a dermatologist a strong relationship between the departments among them. Th ey frankly admitted that their of Pathology and Dermatology at the MGH. In know-how in dermatopathology was not exactly 1949 this close bond was portrayed in the pref- overwhelming. When I suggested to Ben Castle- ace to the fi rst edition of his textbook: “I wish to man [who was fi nishing his pathology training express my deep gratitude to Dr. Tracy B. Mallory in the mid-1930s] that perhaps we might learn it and Dr. Benjamin Castleman of the Pathology

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Laboratory at the Massachusetts General Hospi- and M.D. in 1947 from Tulane University, where tal for the training in pathology they have given he continued to work, rising to become Professor me. It has been invaluable to me. Th eir teaching of Pathology before his move to Boston. Upon is refl ected in this book.” joining the MGH in 1962, with the support of Dr. Lever was also known for his original work the Chief of Dermatology, Th omas B. Fitzpat- in the fi eld, including his description of bul- rick, Dr. Clark set up an electron microscopy lous pemphigoid in 1953 (21). In 1959 Dr. Lever research laboratory on the Dermatology fl oor left the MGH to become the Chairman of the of the Warren Building. His work in this facility Department of Dermatology at Tufts Univer- yielded descriptions of dermal-epidermal separa- sity Medical School; despite this move, he was tion in bullous pemphigoid, dermatitis herpeti- retained as a consultant to the MGH and Hon- formis, and erythema multiforme, as well as the orary Dermatologist for more than 20 years. Dr. ultrastructural mechanisms of melanin synthesis. Lever had an infectious enthusiasm about derma- Dr. Clark’s contributions to clinical dermatopa- topathology diagnosis and teaching. He was con- thology over the next seven years included the sidered by many in Boston to be a type of Red publication of the fi rst classifi cation of mela- Baron: he attended and supported the citywide noma and the identifi cation of histopathologi- dermatopathology review sessions, driving his cal prognostic factors, including the anatomical open convertible in the winter, a red scarf fl ut- extent of invasion, now termed the Clark level. tering behind him in the wind. Dr. Walter Lever Th e original melanoma classifi cation remains in married a young German student in Dermatol- use a half century later (5, 30). Benjamin Castle- ogy, Gundula Schaumburg, who was on elective man’s 1967 Annual Report noted: “Dr. Wallace in Dermatology at the MGH. Dr. Schaumburg- Clark’s electron microscopic studies have been Lever was an electron microscopist, and she and directed toward accumulating evidence regarding her husband worked on several editions of his the abnormal formation of melanin by the malig- textbook as well as scientifi c papers on skin dis- nant melanocyte. He has shown that the large ease. Dr. Lever died in 1993. epithelioid melanoma cell of superfi cial spread- Dr. Lever trained an entire generation of ing melanoma forms melanin in a distinctively pathology and dermatology residents in der- diff erent structural way than do the normal epi- matopathology at the MGH. Of note was Dr. dermal melanocytes. He has further found that Alexander Breslow, who was a resident in MGH the melanosome, used as a cytogenetic marker, Pathology from 1955 to 1959. Dr. Breslow went indicates that a given tumor nodule may contain on to a highly successful career in surgical pathol- more than one type of melanocyte.” Th is early ogy at George Washington University, where he understanding of melanocytic heterogeneity published seminal papers correlating melanoma serves as the foundation of translational science depth of invasion with prognosis. Th is measure- in the melanoma fi eld today, including drug dis- ment of the primary tumor thickness came to be covery and investigations of melanoma initiat- known as the Breslow measurement and remains ing cells (13, 25). Dr. Clark also established the the most relied-on staging factor for patients fi rst multidisciplinary pigmented lesion clinic, in with localized melanoma at presentation (4, 27). collaboration with Drs. Th omas B. Fitzpatrick (Dermatology), John Raker (Surgery), and Mar- The Clark Era tin C. Mihm Jr. (Dermatology). Wallace H. Clark came to the MGH in 1962 During Dr. Clark’s tenure, he trained and men- (fi gure 18.4). He was born in 1924 in LaGrange, tored several future leaders in dermatopathology, Georgia. He received his bachelor’s degree in 1944 including Drs. Richard W. Sagebiel, Martin C.

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a gradual transition from benign to malignant neoplasms, a biologic evolution, and focused his work on identifying prognostic factors. Dr. Ackerman, on the other hand, believed that there was a clear-cut distinction between benign nevi and malignant melanoma, and that the job of the dermatopathologist was diagnosis rather than determining prognosis. Dr. Ackerman continued to teach these concepts after leaving MGH and became an internationally recognized albeit controversial fi gure in the fi eld. He published an algorithmic approach to diagnosis in Histologic Diagnosis of Infl ammatory Skin Diseases, founded on Dr. Clark’s reaction patterns of the skin. Th is reference became a necessary part of every dermatopathologist’s library, alongside Dr. Lever’s Histopathology of the Skin. A number of other trainees of the program in the late 1960s and early 1970s went on to serve the MGH or other institutions as derma- topathologists. Dr. Joel Umlas was a resident in Figure 18.4 Wallace H. Clark MGH Pathology from 1964 to 1967; he served in the Army for two years and returned to become a Mihm Jr., A. Bernard Ackerman, and N. Scott faculty member in 1969. A year later, Dr. Umlas McNutt. Dr. Sagebiel, a clinical research fellow left the MGH for Mount Auburn Hospital in in Pathology in 1962, was one of many MGH Cambridge; he has continued his collaborative Pathology trainees to become a dermatopatholo- relationship with the MGH over the past four gist. He moved from Boston to join the Univer- decades (chapter 22). In 1968 Dr. Neil Scott sity of California–San Francisco (UCSF) in 1970, McNutt came to the MGH as a clinical and where he helped establish the USCF Melanoma research fellow in Pathology to study intercellular Clinic in 1971 with Dr. M. Scott Blois, embark- communication. Using the freeze-fracture tech- ing on a career as a world-renowned melanoma nique in collaboration with Dr. Ronald Wein- expert. In 1964 Dr. Mihm joined the MGH as stein, Dr. McNutt was able to obtain high-reso- a resident in Dermatology. Th e ensuing decade lution images of the internal structure of plasma marked an exciting time for dermatopathology, membranes. Th ey found that the nexus, or “gap as he and Clark made groundbreaking progress junction,” was lost in early stages of malignant in the classifi cation and diagnosis of cutaneous transformation and that contact inhibition was melanoma. In 1967 Bernard Ackerman came to correlated with the presence of aggregates of the MGH as a clinical assistant in Dermatology cytoplasmic microfi laments that are involved in to complete his dermatology residency training cell motility. In 1969 and 1970 Eugene Mark, with the aim of studying dermatopathology with Bruce Ragsdale, Th omas M. Chesney, and John Dr. Clark. Drs. Clark and Ackerman had active Kaiser were residents in pathology and went on debates regarding the diagnosis and classifi cation to train in dermatopathology. of melanoma. Dr. Clark taught that there was In 1969 Dr. Clark left the MGH to join the

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faculty at Temple University as a Professor of In the 1970s multidisciplinary melanoma cen- Pathology, serving as chairman of that depart- ters evolved through the Malignant Melanoma ment from 1974 to 1978. Concerning who would Cooperative Group, supported by the National be Dr. Clark’s successor in Dermatopathology, Institutes of Health as part of President Nixon’s Dr. Castleman favored Dr. Ackerman, but Dr. “war on cancer.” In one of the fi rst multidisci- Clark and Dr. Th omas B. Fitzpatrick, Chief of plinary trials, the investigators studied the natu- Dermatology, favored Dr. Mihm (Th omas B. ral history of cutaneous melanoma in over 1,100 Fitzpatrick, personal communication with Lyn patients from the MGH, New York University, Duncan). According to Dr. Castleman’s report Temple University, and later the University of for that year, “With the support of Dr. Th omas Pennsylvania and UCSF. Dr. Mihm was pivotal B. Fitzpatrick, Chief of the Dermatology Service, in this eff ort, as was Dr. Arthur Sober, whom Dr. Martin C. Mihm, a graduate of the Derma- Fitzpatrick recruited to coordinate this project, tology Service and recently in charge of research which led to more than 30 publications regarding and teaching dermatology at the USPHS Hospi- the diagnosis and prognosis of patients with mel- tal in Staten Island, returned to the hospital to anoma. In 1973 Drs. Mihm, Fitzpatrick, and oth- obtain training in General Pathology.” Dr. Mihm ers published an atlas of early detection of cuta- quickly became the liaison member with the neous melanoma in the New England Journal of Dermatology Service, succeeding Dr. Clark. Medicine, which was the fi rst time that color had been used in the journal (22). Indeed, the Ameri- The Mihm Years can Cancer Society distributed 100,000 copies of Martin Charles Mihm Jr. was born in Pittsburgh this landmark publication as a melanoma educa- on March 15, 1934 (fi gure 18.5). He graduated tion eff ort, the fi rst of many endeavors in early from Duquesne University in 1955 and the Uni- melanoma screening and detection. versity of Pittsburgh School of Medicine in 1961. In addition to his interest in melanocytic After training in internal medicine at Mount tumors, Dr. Mihm was also fascinated by the Sinai Hospital in New York, he joined MGH as a biology of host response. In the early 1970s he trainee in Dermatology in 1964. His training was collaborated with Drs. Harold Dvorak and Rob- followed by early, pioneering work in collabora- ert Colvin of MGH Pathology in studies that tion with Drs. Clark and Fitzpatrick that had focused on cutaneous basophil hypersensitivity. a global eff ect on the diagnosis of melanocytic After developing suitable embedding and sec- tumors. Dr. Mihm continued to make weekly tioning techniques, they found that basophils visits to the MGH during his years in the mili- represented 10–15 percent of the infi ltrate in tary service at Staten Island. He served as a liai- allergic contact dermatitis to poison ivy—in a son between the departments of Pathology and biopsy from Dr. Dvorak’s own arm (10). With Dermatology and expanded the teaching pro- the support of an NIH grant for human studies, gram so that residents in both Dermatology and this work was expanded to examine a variety of Pathology were exposed to special instruction in immunological lesions in the skin of 100 human dermatopathology. He returned to the MGH to volunteers, since the hypersensitivity-associated complete his training in Pathology, and in 1974 changes observed in human skin were not appar- he was appointed by Benjamin Castleman to suc- ent in animal models and required a human clini- ceed Dr. Clark as the Chief of the MGH Derma- cal study. Drs. Ann Dvorak and Richard A. John- topathology Unit and to continue as the Codi- son collaborated in this work, which described rector of the MGH Pigmented Lesion Clinic, basophil infi ltration, mast cell and basophil with Dr. Th omas Fitzpatrick. degranulation, obliterative endothelial changes,

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autoantibodies against skin components, as seen in pemphigus and bullous pemphigoid.” The Founding of the HMS Dermatopathology Fellowship In 1974 the fi rst certifying board examination in dermatopathology was given to 205 dermatologists and pathologists who were allowed to take the examination on the basis of their experience rather than formal training. Th e idea for a more formal, accredited training program stemmed from discussions predominantly among two groups of physicians, the American Society of Dermatopathology (ASD) and the Dermatopa- thology Club. Th e ASD was established in 1962 by members of the Pathology Committee of the American Academy of Dermatology (AAD), including Dr. Walter Lever. Th is group held their fi rst scientifi c meeting in 1963 and was populated largely by dermatologists. Th e Dermatopathol- ogy Club, on the other hand, was composed of a group of pathologists, including Drs. Clark, Figure 18.5 Martin Charles Mihm Jr. Mihm, and Richard Reed, who met regularly throughout the early 1970s to discuss and review and deposition of fi brin in the dermis as charac- dermatopathology cases. At a meeting held in the teristic of delayed-type hypersensitivity (11). Ether Dome at the MGH, led by their President, Th e increasing volume of dermatopathology Dr. Reed, the members voted to join the ASD to specimens as the 1970s progressed led to a need help found dermatopathology training programs. for additional faculty members. By 1974 Drs. Th e Harvard Dermatopathology Training Pro- Eugene Mark and A. Jane Lingeman had joined gram was founded in 1975 by the chairs of the the service. After a few years in Dermatopathol- HMS Pathology departments, and Dr. Mihm ogy, Dr. Mark decided to focus his eff orts on was named Director. Its roots at the MGH, the pulmonary pathology and went on to become Harvard Dermatopathology Training Program the Director of the Autopsy Service. Dr. Linge- was one of fi ve accredited programs in the United man was an expert in melanoma diagnosis, hav- States. Drs. Antoinette Hood and Th eodore Kwan ing trained at the Royal Prince Alfred Hospital in were the fi rst two clinical trainees in the program; Australia; she served on the MGH faculty for over Dr. David McLean was the fi rst research fellow a decade. In addition, as Robert McCluskey, the (fi gure 18.6). Drs. Hood, Kwan, and Mihm pub- new Chief of Pathology at MGH, recorded, der- lished one of the fi rst systematic approaches to matopathology had begun to provide “expanded diagnosis in dermatopathology (17). diagnostic immunofl uorescence service for der- Th e late 1970s, the 1980s, and the early 1990s matology, including direct immunofl uorescence witnessed extensive activity in MGH Dermato- studies of skin biopsies and measurements by pathology that involved clinical service, research, indirect immunofl uorescence of circulating and teaching. Dr. Terence J. Harrist, after training

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in pathology and dermatopathology at MGH, Harrist left MGH in 1982 to focus his eff orts on joined the faculty in 1980 when Eugene Mark the development of a private dermatopathology decided to pursue a career in pulmonary pathol- group in Boston, Pathology Services. ogy. In collaboration with Drs. George Murphy, Th at year George F. Murphy, another graduate Atul Bhan, and Mihm, Dr. Harrist investigated of the MGH Pathology and Dermatopathology the ultrastructural and antigenic features of programs, became the fi rst Director of Derma- benign and proliferative Langerhans cells, provid- topathology at Brigham and Women’s Hospital ing key contributions to studies that ultimately (BWH); he nonetheless continued to take regu- established CD1a (then called T6) as a specifi c lar rotations in signing out the MGH dermato- immunohistochemical marker (15, 23). His work pathology specimens. Dr. Murphy received the in melanoma focused on early-stage disease and Benjamin Castleman Award (chapter 8) for his included the description of microscopic satellites work on cell surface antigens in Langerhans cells. as an important prognostic factor (6). Addition- Dr. Murphy went on to a highly successful career ally, with Drs. Calvin Day and Arthur Sober, he in academic dermatopathology. In 1989 he left participated in a landmark analysis of prognostic for Philadelphia, joining the faculty of the Uni- factors for patients with thin melanomas (7). Dr. versity of Pennsylvania and later becoming the

Figure 18.6 Th e ﬁ rst class of the Harvard Dermatopathology Training Program. Left to right: David McLean (research fellow), Eugene Mark (faculty), Antoinette Hood (fellow), Th eodore Kwan (fellow), Martin C. Mihm Jr. (Program Director).

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head of Dermatopathology at Th omas Jeﬀ erson University, returning to head Dermatopathology at BWH in 2002. His investigations in cutaneous immunology have led to an understanding of melanoma initiation and tumor cell escape from immune surveillance. Other notable graduates of the MGH Der- matopathology Training Program in the 1980s included Drs. Th omas Flotte (see below) and Ste- ven Tahan, Chief of Dermatopathology at Beth Israel Deaconess Medical Center and later Direc- tor of the Harvard Dermatopathology Train- ing Program. MGH Dermatopathology graduates who joined the MGH faculty in the 1980s included Drs. Ben Bronstein, Randall Margolis, Michael Imber, and Hugh Randolph Byers. Dr. Bronstein left the MGH for a business career in a Boston-based biotechnology ﬁ rm, and Dr. Mar- golis left to join the Dermatopathology group at Boston University and later served as a dermatopathology consultant to Harvard Commu- nity Health Plan. While at the MGH, Dr. Byers pursued melanoma research at the Charlestown Figure 18.7 Thomas J. Flotte Navy Yard laboratory (8); in the early 1990s he left the MGH to become the Director of Derma- of Dermatology at the Lahey Clinic since 1969, topathology Research at Boston University, and was an active participant in the Dermatopa- in 2010 he moved to California to join the der- thology Conferences at the MGH. He achieved matopathology practice of Dr. Bruce Ragsdale, great fame, particularly as an expert in leprosy; an MGH Pathology alumnus. he became President of the American Academy Th roughout the 1980s Dr. Mihm enriched the of Dermatology and was named a Master in teaching program with his consultation material Dermatology. In the 1980s, Dr. Moschella trav- and through visits to the other HMS hospitals. eled to MGH for the weekly Th ursday evening Many remember driving with Dr. Mihm in his dermatopathology reviews with Drs. Mihm, dark gray Mercedes to each hospital to read der- Murphy, Harrist, and Flotte. He continues as a matopathology cases set aside for his review. He regular participant at MGH Dermatology Grand also initiated a dermatopathology postgraduate Rounds and the annual MGH Dermatopathol- course in the early 1980s that ran for four years. ogy postgraduate course. And in the late 1980s he established an annual Th e Harvard Dermatopathology Training Pro- visiting dermatopathology professorship; among gram was a two-year fellowship. Trainees with the guest lecturers were Drs. Wallace Clark, a background in pathology spent six months in Richard Reed, Wayne Streilein, Bernard Acker- dermatology and attended nine clinic sessions man, and Steven Katz. at the MGH each week, including the famous Dr. Samuel Moschella, Professor of Dermatol- Friday morning Pigmented Lesion Clinic. Th ose ogy at HMS and Chairman of the Department with a background in dermatology completed six

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months of surgical pathology training, including the performance of autopsies; the remaining 18 months of fellowship were devoted to diagnostic dermatopathology and research endeavors. Th e trainees were based at MGH; they traveled throughout the HMS system in Dr. Mihm’s Mer- cedes. In the early 1990s, however, there was a move to broaden the scope of experience and allow more interaction with the many expert faculty who had developed clinical and academic programs at BWH, Children’s, Beth Israel, New England Deaconess, the Veterans Administration hospitals, and Pathology Services (which had a close affi liation with Beth Israel). In the early 1990s the training program shifted to a one-year format. Shortly thereafter, as Wallace Clark was consid- ering a return to Boston from Philadelphia, Ter- ence Harrist (who held a faculty appointment at Beth Israel) and Harold Dvorak (then the Chair of Pathology at Beth Israel) proposed a separate HMS dermatopathology training program to be based at Beth Israel Hospital. Around this time Figure 18.8 Lyn McDivitt Duncan Dr. Raymond Barnhill was the head of Derma- topathology at BWH, Steven Tahan was head of clinical activities in the Dermatopathology Unit. Dermatopathology at New England Deaconess, In 1995, with the support of Dr. John Parrish, and Th eodore Kwan was the chief dermatopa- Chief of MGH Dermatology, Dr. Flotte became thologist at Beth Israel. Ultimately, it was agreed the Director of MGH Dermatopathology, and that there would remain one HMS Dermatopa- Dr. Duncan remained the Director of the Har- thology Training Program, Dr. Mihm remaining vard Dermatopathology Training Program. Program Director, and with the provision that Dr. Flotte is a graduate of Albany Medical trainees could be based at MGH, BWH, or Beth College and trained in anatomic pathology at Israel Hospital. the New York University Medical Center (fi g- Recent Years ure 18.7). Shortly after completing his dermatopathology training at the MGH in 1984, he Martin Mihm was presented the opportunity became involved in research supported by the to start a department of dermatology at Albany Wellman Laboratories of Photomedicine in the Medical Center in 1993. He moved to Albany MGH Department of Dermatology. In 1984 Drs. at the end of the year. With his departure, Lyn Mihm, Flotte and Margolis, with the enthusias- McDivitt Duncan (see below) was appointed as tic support of Dr. John Parrish in Dermatology, Interim Director of the Harvard Dermatopathol- founded the fi rst Photopathology Laboratory ogy Training Program and Interim Chief of the Service as part of the Wellman Laboratories. MGH Dermatopathology Unit. Dr. Duncan Flotte joined the Dermatology Department in invited Dr. Th omas Flotte (see below) to return to 1989 as Director of Photopathology and full-time

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with Millennium Pharmaceuticals led to the discovery of the melanoma prognostic marker, Melas- tatin (TRPM1/MLSN) (9, 12). Dr. Duncan’s fi nding that routine pro- cessing of sentinel lymph nodes is associated with a 12 percent false- negative rate in detecting meta- static melanoma led to a revision of the sentinel lymph node ana- lytical platform at MGH (37), and her collaboration with the MGH hematopathologists Dr. Nancy Harris and Dr. Judith Ferry led to revised diagnostic criteria for cutaneous B-cell lymphomas (2, 35). In the mid-1990s Dr. Duncan and her codirectors of the Har- vard Dermatopathology Fellow- ship (Drs. Barnhill, Harrist, and Tahan) made a series of changes in the program that would provide a more equal experience Figure 18.9 Th e Harvard Dermatopathology Training Program celebrates Martin Mihm’s seventy-fi fth birthday. Lyn Duncan, George for all trainees in the program, Murphy (center), Steven Tahan (right), and Martin C. Mihm Jr. regardless of their home institu- with a Festschrift copy of the Journal of Cutaneous Pathology tion. Th ey established rotations at each institution for all trainees, researcher in the Wellman Laboratories. He was including opportunities to partici- responsible for landmark studies of laser-tissue pate in the consultative practices of Drs. Mihm interactions, including the eff ects of pulsed CO2- (after his return to the MGH in 1996), Clark laser and ER YAG laser on tissue ablation and (then at Pathology Services), Harrist, and Barn- the use of Q-switched ruby laser and Q-switched hill; the MGH Pigmented Lesion Clinic with ND-YAG laser for the removal of tattoos (18, 26, Drs. Arthur Sober and Hensin Tsao; the Cutane- 28, 31). ous Oncology Clinic at the Dana-Farber Cancer Dr. Duncan (fi gure 18.8) had joined the Institute, which included Dr. Th omas Kupper’s MGH in 1990 as a trainee in dermatopathology cutaneous lymphoma patients; clinics at Chil- after completing anatomic pathology training at dren’s Hospital; Friday afternoon sessions with Washington University in St. Louis, where she Dr. Harley Haynes at the Veterans Administra- was involved in a research program with Dr. Emil tion Hospital; and selected rotations providing Unanue. She became a faculty dermatopathologist exposure to subspecialty experts in pathology, in 1991, joining Drs. Barnhill, Byers, and Mihm. including Drs. Nancy Harris (hematopathology) Her collaborations with Drs. Mihm and Barnhill and Ben Pilch (ENT pathology) at the MGH, led to the largest U.S. study of pregnancy-associ- and Christopher Fletcher (soft tissue pathology) ated melanoma (29). Her work in collaboration at BWH. Dr. Duncan enlisted codirectors at each

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Figure 18.10 MGH Dermatopathology faculty, 2010–2011. Standing, left to right: Stephan Kraft, Mai P. Hoang, Rosalynn M. Nazarian, Adriano Piris. Seated: Lyn M. Duncan, Martin C. Mihm Jr.

institution; these included Drs. Flotte at MGH, faculty, Dr. Duncan established an annual post- Phillip McKee at BWH, Steven Tahan at Beth graduate course in the early 1990s that continues Israel Deaconess, and Terence Harrist at Pathol- to serve as a yearly teaching (and social) oppor- ogy Services. In 2003, after Dr. Duncan had tunity for trainees, faculty, and alumni. Th e served 10 years as training program director, Dr. Harvard Dermatopathology Training Program Tahan was appointed director, and it was decided has continued its record of success, its graduates that the directorship would rotate thereafter. including endowed full professors, department In 2011 Dr. George Murphy at BWH will take chairs, heads of commercial dermatopathology the helm of the fellowship program. Notably, laboratories and pharmaceutical companies, a all the program directors to date (Drs. Duncan, university president, and numerous NIH-funded Tahan, and Murphy) have been trained by Mar- investigators. tin Mihm and have aimed to carry forward his In addition to Dr. Duncan, graduates from legacy of excellence in teaching, investigation, the fellowship who joined the MGH Dermato- and patient care (ﬁ gure 18.9). To further the col- pathology faculty in the 1990s included Drs. T-Y laboration among the HMS Dermatopathology Wong and Lisa Lerner. Dr. Lerner, after several

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years on the MGH Dermatopathology faculty, Program and Codirector of the Melanoma Pro- joined Dr. Lisa Cohen to cultivate a highly suc- gram at the Dana-Farber Cancer Institute. cessful private dermatopathology laboratory in In 2007 Th omas Flotte moved to direct derma- Boston. In 2003 Dr. Vincent Liu graduated from topathology at the Mayo Clinic in Rochester, and the program and joined the faculty of MGH Dr. Duncan was appointed head of MGH Der- Pathology and Dermatology; after a few years matopathology. Since then Drs. Adriano Piris, of MGH service, he moved to Iowa to continue Rosalynn Nazarian, and Stefan Kraft have gradu- his clinical practice in dermatology and derma- ated from the training program and joined the topathology and recently coedited a dermatopa- MGH Dermatopathology faculty. Additionally, thology textbook for trainees. After completing Dr. Mai Hoang was recruited to join the group in his pathology and dermatopathology training 2007, after beginning her career at the University as a BWH-based trainee, Dr. Artur Zembowicz of Texas Southwestern Medical Center. Today joined the faculty of MGH Dermatopathology the faculty of MGH Dermatopathology includes in 2000 and became the director of the annual expert diagnosticians with specifi c research pro- MGH Dermatopathology Continuing Medi- grams in the areas of melanocytic tumors, cuta- cal Education Course. Dr. Zembowicz left the neous fi brosing disorders, adnexal tumors, and MGH in 2008 to serve as a consultant to the evolving diagnostic technologies (fi gure 18.10). Lahey Clinic. Dr. Cynthia Magro, a graduate of Dr. Hoang is the director of the postgraduate MGH training programs in anatomic pathology, course started in 1996, and she has expanded cytology, and dermatopathology, spent two years the curriculum to include virtual microscopic practicing pathology in her hometown in Winni- diagnosis online and maintenance of certifi ca- peg, Canada, then returned to the United States; tion modules. All faculty are actively engaged she currently serves as the Chief of the Derma- in teaching, research, and diagnosis, continuing topathology Service at Weill Cornell Medical the models set by Drs. Bowen, Lever, Clark, and College in New York City, replacing Dr. Scott Mihm. McNutt, who retired to focus on his research eff orts after 20 years of clinical service. When Dr. Mihm returned to the MGH in References 1996, he did so freed of administrative duties. He spent the next 14 years embracing the joys 1. Balch CM, Soong SJ, Bartolucci AA, Urist MM, of teaching, research, and consultative diagnosis Karakousis CP, Smith T, Temple WJ, Ross MI, locally and abroad; the Dermatopathology Unit Jewell WR, Mihm MC, Barnhill RL, Wanebo HJ. at the MGH was his home base (1, 16). His enthu- Effi cacy of an elective regional lymph node dissec- siasm at the microscope and his contributions as tion of 1 to 4 mm thick melanomas for patients 60 an internationally recognized senior statesman years of age and younger. Ann Surg 224:255–266, 1996. continue to inspire students and colleagues. In 2. Baldassano MF, Bailey EM, Ferry JA, Harris NL, 1998 he established the fi rst multidisciplinary Duncan LM. Cutaneous lymphoid hyperplasia Vascular Malformations Clinic at MGH (24). and cutaneous marginal zone lymphoma. Com- Th is monthly clinic has become an internation- parison of morphologic and immunophenotypic ally recognized clinical management resource. features. Am J Surg Pathol 23:88–96, 1999. Dr. Mihm has recently started another chapter 3. Bowen J. Precancerous dermatosis. A study of two of his academic career: in 2010 Dr. Th omas Kup- cases of chronic atypical epithelial proliferation. J per recruited him to join the BWH Dermatol- Cutan Dis Syph 30:241–255, 1912. ogy Department as Director of the Melanoma 4. Breslow A. Th ickness, cross-sectional area and

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depth of invasion in the prognosis of cutaneous as a marker for Langerhans cells and indeterminate melanoma. Ann Surg 172:902–908, 1970. cells in normal epidermis. A monoclonal antibody 5. Clark WH Jr., From L, Bernardino EA, Mihm study. J Invest Dermatol 80:100–103, 1983. MC. Th e histogenesis and biologic behavior of 16. Hodi FS, Butler M, Oble DA, Seiden MV, primary human malignant melanomas of the skin. Haluska FG, Kruse A, Macrae S, Nelson M, Can- Cancer Res 29:705–727, 1969. ning C, Lowy I, Korman A, Lautz D, Russell S, 6. Day CL Jr., Harrist TJ, Gorstein F, Sober AJ, Lew Jaklitsch MT, Ramaiya N, Chen TC, Neuberg D, RA, Friedman RJ, Pasternack BS, Kopf AW, Fitz- Allison JP, Mihm MC, Dranoff G. Immunologic patrick TB, Mihm MC Jr. Malignant melanoma. and clinical eff ects of antibody blockade of cyto- Prognostic signifi cance of “microscopic satellites” toxic T lymphocyte-associated antigen 4 in previ- in the reticular dermis and subcutaneous fat. Ann ously vaccinated cancer patients. Proc Natl Acad Surg 194:108–112, 1981. Sci USA 105:3005–3010, 2008. 7. Day CL Jr., Mihm MC Jr., Sober AJ, Harris 17. Hood AF, Kwan TH, Burnes DC, Mihm MC MN, Kopf AW, Fitzpatrick TB, Lew RA, Harrist Jr. Primer of Dermatopathology. Boston: Little, TJ, Golomb FM, Postel A, Hennessey P, Gum- Brown, 1984. port SL, Raker JW, Malt RA, Cosimi AB, Wood 18. Kilmer SL, Lee MS, Grevelink JM, Flotte TJ, WC, Roses DF, Gorstein F, Rigel D, Friedman RJ, Anderson RR. Th e Q-switched Nd:YAG laser Mintzis MM. Prognostic factors for melanoma eff ectively treats tattoos. A controlled, dose- patients with lesions 0.76–1.69 mm in thickness. response study. Arch Dermatol 129:971–978, 1993. An appraisal of “thin” level IV lesions. Ann Surg 19. Lever W. Reminiscences about dermatopathology. 195:30–34, 1982. Am J Dermatopathol 1:313–322, 1979. 8. Duncan LM, Bouff ard D, Howard C, Mihm 20. Lever W. Histopathology of the Skin. Philadelphia: MC Jr., Byers HR. In situ distribution of integrin Lippincott, 1949. alpha 2 beta 1 and alpha-actinin in melanocytic 21. Lever W. Pemphigus. Medicine 32:1–123, 1953. proliferations. Mod Pathol 9:938–943, 1996. 22. Mihm MC Jr., Fitzpatrick TB, Brown MM, Raker 9. Duncan LM, Deeds J, Cronin FE, Donovan M, JW, Malt RA, Kaiser JS. Early detection of pri- Sober AJ, Kauff man M, McCarthy JJ. Melastatin mary cutaneous malignant melanoma. A color expression and prognosis in cutaneous malignant atlas. N Engl J Med 289:989–996, 1973. melanoma. J Clin Oncol 19:568–576, 2001. 23. Murphy GF, Bhan AK, Sato S, Harrist TJ, Mihm 10. Dvorak HF, Mihm MC Jr. Basophilic leukocytes MC Jr. Characterization of Langerhans cells by in a case of poison ivy. N Engl J Med 285:54–55, the use of monoclonal antibodies. Lab Invest 1971. 45:465–468, 1981. 11. Dvorak HF, Mihm MC Jr., Dvorak AM, Johnson 24. North PE, Waner M, Mizeracki A, Mihm MC Jr. RA, Manseau EJ, Morgan E, Colvin RB. Mor- GLUT1. A newly discovered immunohistochemi- phology of delayed type hypersensitivity reactions cal marker for juvenile hemangiomas. Human in man. I. Quantitative description of the infl am- Pathol 31:11–22, 2000. matory response. Lab Invest 31:111–130, 1974. 25. Schatton T, Murphy GF, Frank NY, Yamaura K, 12. Erickson LA, Letts GA, Shah SM, Shackelton Waaga-Gasser AM, Gasser M, Zhan Q, Jordan JB, Duncan LM. TRPM1 (Melastatin-1/MLSN1) S, Duncan LM, Weishaupt C, Fuhlbrigge RC, mRNA expression in Spitz nevi and nodular mela- Kupper TS, Sayegh MH, Frank MH. Identifi ca- nomas. Mod Pathol 22:969–976, 2009. tion of cells initiating human melanomas. Nature 13. Flaherty K. Advances in drug development. BRAF 451:345–349, 2008. validation in melanoma. Clin Adv Hematol Oncol 26. Schomacker KT, Domankevitz Y, Flotte TJ, 8:31–34, 2010. Deutsch TF. Co:MgF2 laser ablation of tissue. 14. Greenwood A, Lawless TK. Hemangiosarcoma of Eff ect of wavelength on ablation threshold and the skin. Arch Dermatol Syphilol 6:10–20, 1922. thermal damage. Lasers Surg Med 11:141–151, 1991. 15. Harrist TJ, Muhlbauer JE, Murphy GF, Mihm 27. Sokoloff L. Obituary. Alexander Breslow, M.D. MC Jr., Bhan AK. T6 is superior to Ia (HLA-DR) Am J Surg Pathol 4:603–604, 1980.

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28. Taylor CR, Gange RW, Dover JS, Flotte TJ, Gon- 33. White C, Richardson O. A deceptive case of lep- zalez E, Michaud N, Anderson RR. Treatment of rosy. JAMA 52:18–23, 1909. tattoos by Q-switched ruby laser. A dose-response 34. White J. Dermatitis Venenata. An Account of the study. Arch Dermatol 126:893–899, 1990. Action of External Irritants on the Skin. Boston: 29. Travers RL, Sober AJ, Berwick M, Mihm MC Jr., Cupples and Hurd, 1887. Barnhill RL, Duncan LM. Increased thickness of 35. Willemze R, Jaff e ES, Burg G, Cerroni L, Berti pregnancy-associated melanoma. Br J Dermatol E, Swerdlow SH, Ralfkiaer E, Chimenti S, Diaz- 132:876–883, 1995. Perez JL, Duncan LM, Grange F, Harris NL, 30. Viros A, Fridlyand J, Bauer J, Lasithiotakis K, Kempf W, Kerl H, Kurrer M, Knobler R, Pimpi- Garbe C, Pinkel D, Bastian BC. Improving mela- nelli N, Sander C, Santucci M, Sterry W, Vermeer noma classifi cation by integrating genetic and MH, Wechsler J, Whittaker S, Meijer CJ. WHO- morphologic features. PLoS Medicine/Public EORTC classifi cation for cutaneous lymphomas. Library of Science 5:e120, 2008. Blood 105:3768–3785, 2005. 31. Walsh JT Jr., Flotte TJ, Deutsch TF. Er:YAG laser 36. Wright J. Protozoa in a case of tropical ulcer ablation of tissue. Eff ect of pulse duration and (“Aleppo boil”). J Cutaneous Dis 22:1–9, 1904. tissue type on thermal damage. Lasers Surg Med 37. Yu LL, Flotte TJ, Tanabe KK, Gadd MA, Cosimi 9:314–326, 1989. AB, Sober AJ, Mihm MC Jr., Duncan LM. Detec- 32. White C. Obituary: John Templeton Bowen. Arch tion of microscopic melanoma metastases in senti- Dermatol Syphilol 43:386–388, 1941. nel lymph nodes. Cancer 86:617–627, 1999.

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