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DF Clinical Symposia: DF Honors Dr A DE RMATOL OGY FO UNDA TION PUBLICAT IO N SPONSORED BY MEDICIS, A DIVISION OF VALEANT PHARMACEUTICALS VOL. 32 NO. 1 SPRING 2013 DERMATOLOGYDERMATOLOGY ™ DF Also In This Issue DF: Strong Specialty FFOOCCUUSS Support Continues $3.2 Million in Research Funding Awarded for 2013 DF Clinical Symposia: DF Honors Dr. Robert A. Silverman and Proceedings 201 3–Part I Dr. C. William Hanke inadequately excised. The adventure had a happy ending because ADVANCES IN DERMATOLOGY “accurate diagnosis was at the time of biopsy rather than a decade The Dermatology Foundation presented its annual later, after a catastrophe had occurred.” The basis for molecular diagnosis. Cancer is a disease 3-day symposia series in February. This highly regarded of the genome. Most typically, DNA—either whole chromosomes cuttin g-edge CME program provides the most clinically or specific segments—has been lost and/or multiplied. Losses tend relevant knowledge and guidance for making the to involve tumor suppressors and pro-apoptotic genes. Gains, or newest research advances accessible and usable. A repetitions, frequently involve oncogenes and anti-apoptotic daily provocative keynote talk precedes topic-focused, genes. The amplified sequences may involve normal or mutant peer-reviewed caliber presentations. This year’s DNA. Not all such changes, however, signify a malignant process. topics were: Women’s & Children’s Dermatology; Cancer is commonly associated with multiple rather than single CPC; Emerging Therapies; Revisiting Old Therapies; Medical Dermatology; and Cutaneous Oncology & Copy Number Changes in Immunology. The Proceedings appear in the Spring Melanocytic Neoplasm s—Assumptions (Part I) and Summer (Part II) issues. • Cancer is a disease of the genome Janet A. Fairley, MD, and • Most cancers have gains/losses of whole Jack S. Resneck, Jr., MD —Program Co-Chairs chromosomes, or focused gains/losses • CGH may not be able to detect either small gains/losses or translocations WERNER K. STIEFEL LECTURESHIP • Multiple aberrations favor cancer more than Molecular Diagnosis of Melanocytic Neoplasms: single ones do • Amplifications (ie, high level gains) are stronger Adventures and Misadventures evidence of malignancy than are low level gains Philip E. LeBoit, MD Background. Although the high degree of correlation be - • Gains/losses that have “edges” at important cancer tween morphology and outcome enables H&E staining to determine genes are more significant than random ones the nature of roughly 99% of melanocytic lesions, morphology for the remaining 1%—the borderline melanocytic neoplasms—is inconclu - sive or misleading. “These are the most difficult cases in melanocytic CGH Points to Genetic Hotspots neoplasms, and cannot be solved by even the best expert,” Dr. in Melanoma Progression LeBoit said. Relying on H&E staining here is highly vulnerable to serious, sometimes catastrophic, diagnostic error. Accuracy requires • Gains/amplifications can lead to increased molecular diagnosis, which is based on the lesion’s DNA fingerprint. protein expression LeBoit discussed the two most common molecular tech - • Losses reflect loss of function niques, then presented several illustrative cases referred to his lab. • Loci identified by CGH can be investigated Two misadventures involved the metastatic consequences of an with more refined techniques earlier melanoma erroneously diagnosed as a dysplastic nevus and Who Inspired You? DF Accepting Nominations for 2013 Honorary Awards Each year, the Foundation honors those extraordinary dermatologists who have left a lasting imprint on the specialty. The DF’s honorary awards provide an opportunity to recognize dermatology’s formative teachers and clinicians—true role models—who have inspired and trained generations of dermatologists. Clark W. Finnerud Award. This award honors the exceptional clinician who has also been a dedicated and highly effective volunteer or part-time teacher for residents and medical students. Practitioner of the Year. This dermatologist is an exemplary clinician in private practice with significant involvement in professional organizations, and participation in medical teaching and/or research. Your nomination letter, along with the nominee’s . CV, are due at the Dermatology Foundation by August 1, 2013. The 2013 Honorary Awards will be presented at the DF Annual Meeting of Membership in March 2014. Contact the DF staff with any questions: 847-328-2256 or [email protected] Malignant n=133 Skin 2008 Small Bowel 2011 Benign n=54 Case: an excised lesion diagnosed by H&E as a dysplastic nevus in 2008 was retrospectively diagnosed as a primary melanoma 3 years later, when CGH analysis matched the more re cent bowel melanoma. Pooled CGH plots: 133 melanomas vs 54 nevi. Each lane represents a chromosome. 6), gain of 1q—noting their significance, then contrasting this to The melanoma plot reveals characteristic widespread DNA gains and losses. The benign the changes that characterize Spitz nevi. nevi show only 2 minimal gains, which characterize the Spitz nevi subset. FISH and CGH. The molecular dermatopathology lab at aberrations; many rather than few repeats; gains and losses that UCSF (founded by Dr. Boris Bastian) relies on FISH (fluorescent in have “edges” at important cancer genes. In addition, “the genomic situ hybridization) and CGH (comparative genomic hybridization) damage in melanoma is not random.” LeBoit enumerated the for detecting changes in DNA copy number. FISH appeared in the most common melanoma-associated aberrations—loss of 9p (the early 1980s, and CGH roughly a decade later. Although they both short arm of chromosome 9), loss of the entire chromosome 9, use fluorescent-labeled DNA probes that bind with relevant areas loss of chromosome 10, loss of 6q (the long arm of chromosome of DNA, FISH uses focused probes that home in on a narrowly 2 Spring 2013 Dermatology Foundation defined area of the genome and bind to complementary se - quences. CGH, on the other hand, can screen the entire genome in a single session and is also better than FISH at detecting DNA DERMA TOLOGY FOCUS losses. LeBoit describes CGH as a competitive binding assay in A PUBLICATION OF THE DERMATOLOGY FOUNDATION DF Sponsored by which the tumor DNA is microdissected out and fluorescently labeled with an identifying color, then hybridized with a refer - Medicis, A Division of Valeant Pharmaceuticals ence sample of normal DNA—or more frequently now, a DNA Editors-in-Chief array—that has been fluorescently labeled with a different identi - David J. Leffell, MD— Professor of Dermatology fying color, and with control DNA. Yale School of Medicine, New Haven, CT Misadventures. A 22-year-old woman with intussuscep - Mary M. Tomayko, MD, PhD— Assistant Professor of Dermatology tion of her small bowel was found to have a large tumor mass. Al - Yale School of Medicine, New Haven, CT though it stained positively for the melanoma marker HMB-45, Heidi A. Waldorf, MD— Director, Laser and Cosmetic Dermatology she denied any history of melanoma but mentioned a dysplastic The Mount Sinai Medical Center, New York, NY nevus removed from her shoulder 3 years earlier. A slide from the excisional biopsy lacked any clear melanoma indicators, Executive Director making the diagnosis of dysplastic nevus “very understandable.” Sandra Rahn Benz With immunohistochemical stains, this melanocytic tissue Deputy Executive Director showed a high proliferation rate and the absence of protein from Christine M. Boris the tumor suppressor p16. CGH analyses of both this tissue and Please address correspondence to: the bowel tumor produced strikingly similar chromosomal pro - Editors-in-Chief files, “proof that this bowel tumor metastasized from the misdi - Dermatology Focus agnosed skin lesion.” c/o The Dermatology Foundation A 65-year-old woman—who had had what was interpreted as a 1560 Sherman Avenue, Evanston, Illinois 60201 Tel: 847-328-2256 Fax: 847-328-0509 dysplastic nevus removed 11 years earlier—now had a huge peri - e-mail: dfgen@de rmatologyfoundation.org anal mass that was obviously a melanoma. The highly unlikely pos - sibility that it was a metastasis to this site rather than a primary Published for the Dermatology Foundation by tumor had to be explored, because treatment would differ signifi - Robert B. Goetz— Designer, Productio n cantly. Reviewing tissue from the 11-year-old biopsy, morphology Sheila Sperber Haas, PhD— Managing Editor, Writer was similar—except for the presence of melanoma-associated giant This issue of Dermatology Focus is distributed without charge through melanocytes that should have sounded the alarm. Now, CGH on tis - an educational grant from Medicis, A Division of Valeant Pharmaceuticals. sue from both lesions showed “an almost identical pattern” of gains The opinions expressed in this publication do not necessarily reflect those of and losses. Thus the perianal melanoma was metastatic disease, the Dermatology Foundation or Medicis, A Division of Valeant Pharmaceuticals. and the original surgical plan—to remove the patient’s anus and © Copyright 2013 by the Dermatology Foundation rectum—would not provide benefit. Adventures. After discussing the typical histology and Spitz nevus or not.” He illustrated this with H&E-stained tissue from clear-cut variants for Spitz nevi, LeBoit noted those uncertain a 31-year-old man that was typical except for a nest of cells with cases—especially in adults—with very subtly aberrant features by “dusty looking melanin”—a tip-off to look further. CGH analysis H&E staining. “CGH can determine whether the lesion is really a identified melanoma. (Continued on page 6) Deferred Giving: The Benefits of a Bequest to the DF Contributing to There are a variety of ways to establish a be - the Dermatology quest, and your attorney and/or financial advisor Foundation this year is the best way to ensure can recommend the best option for you. Once that the newest generation of physician scientists you have determined the best approach, be sure and investigators has the support they need to identify the Dermatology Foundation, a 501(c)3 now to initiate work that will ultimately advance organization, as the recipient of this gift in your patient care.
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