Photo of Lyn McDivitt Duncan,  MD

Lyn McDivitt Duncan, MD

Massachusetts General Hospital

Massachusetts General Hospital


duncan@helix.mgh.harvard.edu

Lyn McDivitt Duncan, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Chief of Dermatopathology Unit, Pathology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our work in skin cancer is focused on cutaneous lymphomas and malignant melanoma. The cutaneous low grade B-cell lymphomas, follicular lymphoma and marginal zone B-cell lymphoma (MALT lymphoma), may be difficult to distinguish from benign reactive infiltrates (cutaneous lymphoid hyperplasia). Using immunohistochemistry, in situ hybridization and PCR techniques, these tumors are being characterized and the current classification schemes revised accordingly.

Our work in melanoma concerns molecular phenotypes of the primary and metastatic tumors that may predict prognosis and response to therapy. In collaboration with investigators at Millennium Pharmaceuticals, Inc., we identified a novel melanocyte specific gene, melastatin (TRPM1/MLSN-1), which appears to be a melanoma prognostic factor. Multivariate analysis reveals Melastatin mRNA expression as predictor of melanoma metastasis that is independent from the current gold standard, tumor thickness. MLSN-1 expression is one of the genes studied in the CALGB 500105 clinical trial and the Harvard Skin SPORE projects. The results of sentinel lymph node sampling also factor into melanoma patient prognosis. In the examination of over 2700 tissue sections from patients with cutaneous melanoma we found that immunohistochemical techniques and deeper sectioning leads to the detection of melanoma in 12% of cases diagnosed as negative using routine techniques. The methods used in this study have been adopted by the MGH Department of Pathology for the analysis of sentinel lymph nodes in patients with melanoma. CALGB 500105 will study the correlation of MLSN-1 mRNA expression with sentinel node status in patients with primary cutaneous melanoma.

Publications

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  • Luo S, Lobo AZ, Tanabe KK, Muzikansky A, Durazzo T, Sober A, Tsao H, Cosimi AB, Lawrence DP, Duncan LM. Clinical Significance of Microscopic Melanoma Metastases in the Nonhottest Sentinel Lymph Nodes. JAMA Surg 2015. PubMed
  • Enamandram M, Duncan LM, Kimball AB. Delivering value in dermatology: insights from skin cancer detection in routine clinical visits. J Am Acad Dermatol 2015; 72:310-3. PubMed
  • Goyal A, Moore JB, Gimbel D, Carter JB, Kroshinsky D, Ferry JA, Harris NL, Duncan LM. PD-1, S-100 and CD1a expression in pseudolymphomatous folliculitis, primary cutaneous marginal zone B-cell lymphoma (MALT lymphoma) and cutaneous lymphoid hyperplasia. J Cutan Pathol 2015; 42:6-15. PubMed
  • Gerami P, Busam K, Cochran A, Cook MG, Duncan LM, Elder DE, Fullen DR, Guitart J, Leboit PE, Mihm MC, Prieto VG, Rabkin MS, Scolyer RA, Xu X, Yun SJ, Obregon R, Yazdan P, Cooper C, Weitner BB, Rademaker A, Barnhill RL. Histomorphologic Assessment and Interobserver Diagnostic Reproducibility of Atypical Spitzoid Melanocytic Neoplasms With Long-term Follow-up. Am J Surg Pathol 2014. PubMed
  • Nazarian RM, Primiani A, Doyle LA, Linskey KR, Duncan LM, Odze RD, Zukerberg LR. Cytokeratin 17: an adjunctive marker of invasion in squamous neoplastic lesions of the anus. Am J Surg Pathol 2013; 38:78-85. PubMed
  • Aboutalebi A, Korman JB, Sohani AR, Hasserjian RP, Louissaint A, Le L, Kraft S, Duncan LM, Nazarian RM. Aleukemic cutaneous myeloid sarcoma. J Cutan Pathol 2013; 40:996-1005. PubMed
  • Dekker J, Duncan LM. Lack of standards for the detection of melanoma in sentinel lymph nodes: a survey and recommendations. Arch Pathol Lab Med 2013; 137:1603-9. PubMed
  • Linskey KR, Gimbel DC, Zukerberg LR, Duncan LM, Sadow PM, Nazarian RM. BerEp4, cytokeratin 14, and cytokeratin 17 immunohistochemical staining aid in differentiation of basaloid squamous cell carcinoma from basal cell carcinoma with squamous metaplasia. Arch Pathol Lab Med 2013; 137:1591-8. PubMed
  • Nemlich Y, Greenberg E, Ortenberg R, Besser MJ, Barshack I, Jacob-Hirsch J, Jacoby E, Eyal E, Rivkin L, Prieto VG, Chakravarti N, Duncan LM, Kallenberg DM, Galun E, Bennett DC, Amariglio N, Bar-Eli M, Schachter J, Rechavi G, Markel G. MicroRNA-mediated loss of ADAR1 in metastatic melanoma promotes tumor growth. J Clin Invest 2013; 123:2703-18. PubMed
  • Schlegel J, Sambade MJ, Sather S, Moschos SJ, Tan AC, Winges A, DeRyckere D, Carson CC, Trembath DG, Tentler JJ, Eckhardt SG, Kuan PF, Hamilton RL, Duncan LM, Miller CR, Nikolaishvili-Feinberg N, Midkiff BR, Liu J, Zhang W, Yang C, Wang X, Frye SV, Earp HS, Shields JM, Graham DK. MERTK receptor tyrosine kinase is a therapeutic target in melanoma. J Clin Invest 2013; 123:2257-67. PubMed
  • Hanna SC, Krishnan B, Bailey ST, Moschos SJ, Kuan PF, Shimamura T, Osborne LD, Siegel MB, Duncan LM, O'Brien ET, Superfine R, Miller CR, Simon MC, Wong KK, Kim WY. HIF1留 and HIF2留 independently activate SRC to promote melanoma metastases. J Clin Invest 2013; 123:2078-93. PubMed
  • Chan MP, Duncan LM, Nazarian RM. Subcutaneous Sweet syndrome in the setting of myeloid disorders: A case series and review of the literature. J Am Acad Dermatol 2013. PubMed
  • Lobo AZ, Tanabe KK, Luo S, Muzikansky A, Sober AJ, Tsao H, Cosimi AB, Duncan LM. The distribution of microscopic melanoma metastases in sentinel lymph nodes: implications for pathology protocols. Am J Surg Pathol 2012; 36:1841-8. PubMed
  • Ho J, Barbi de Moura M, Lin Y, Vincent G, Thorne S, Duncan LM, Lin HM, Kirkwood JM, Becker D, van Houten B, Moschos S. Importance of glycolysis and oxidative phosphorylation in advanced melanoma. Mol Cancer 2012; 11:76. PubMed
  • Le LP, Garibyan L, Lara D, Finberg KE, Iafrate AJ, Duncan LM, Kay J, Nazarian RM. Fibrosis-Associated Single-Nucleotide Polymorphisms in TGFΒ1 and CAV1 Are Not Associated With the Development of Nephrogenic Systemic Fibrosis. Am J Dermatopathol 2012. PubMed
  • Hawryluk EB, Sober AJ, Piris A, Nazarian RM, Hoang MP, Tsao H, Mihm MC, Duncan LM. Histologically challenging melanocytic tumors referred to a tertiary care pigmented lesion clinic. J Am Acad Dermatol 2012; 67:727-35. PubMed
  • Piris A, Lobo AC, Duncan LM. Melanoma staging: where are we now? Dermatol Clin 2012; 30:581-92. PubMed
  • Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, Xu W, Tan L, Hu Y, Zhan Q, Lee CW, Hu D, Lian BQ, Kleffel S, Yang Y, Neiswender J, Khorasani AJ, Fang R, Lezcano C, Duncan LM, Scolyer RA, Thompson JF, Kakavand H, Houvras Y, Zon LI, Mihm MC, Kaiser UB, Schatton T, Woda BA, Murphy GF, Shi YG. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 2012; 150:1135-46. PubMed
  • Hung T, Piris A, Lobo A, Mihm MC, Sober AJ, Tsao H, Tanabe KK, Duncan LM. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanocytic tumors. Hum Pathol 2012. PubMed
  • Piris A, Mihm MC, Duncan LM. AJCC melanoma staging update: impact on dermatopathology practice and patient management. J Cutan Pathol 2011; 38:394-400. PubMed
  • Luo S, Chaplin AC, Langley RG, Njauw CN, Duncan LM, Miller RA, Tsao H. Agminated segmental nevi demonstrating intranevic concordance of BRAF status. J Invest Dermatol 2011; 131:788-90. PubMed
  • Kolman O, Hoang MP, Piris A, Mihm MC, Duncan LM. Histologic processing and reporting of cutaneous pigmented lesions: recommendations based on a survey of 94 dermatopathologists. J Am Acad Dermatol 2010; 63:661-7. PubMed
  • Pless ML, Kroshinsky D, LaRocque RC, Buchbinder BR, Duncan LM. Case records of the Massachusetts General Hospital. Case 26-2010. A 54-year-old man with loss of vision and a rash. N Engl J Med 2010; 363:865-74. PubMed
  • Nazarian RM, Prieto VG, Elder DE, Duncan LM. Melanoma biomarker expression in melanocytic tumor progression: a tissue microarray study. J Cutan Pathol 2010; 37 Suppl 1:41-7. PubMed
  • Jané-Valbuena J, Widlund HR, Perner S, Johnson LA, Dibner AC, Lin WM, Baker AC, Nazarian RM, Vijayendran KG, Sellers WR, Hahn WC, Duncan LM, Rubin MA, Fisher DE, Garraway LA. An oncogenic role for ETV1 in melanoma. Cancer Res 2010; 70:2075-84. PubMed
  • Kabbarah O, Nogueira C, Feng B, Nazarian RM, Bosenberg M, Wu M, Scott KL, Kwong LN, Xiao Y, Cordon-Cardo C, Granter SR, Ramaswamy S, Golub T, Duncan LM, Wagner SN, Brennan C, Chin L. Integrative genome comparison of primary and metastatic melanomas. PLoS ONE 2010; 5:e10770. PubMed
  • Wilbur DC, Madi K, Colvin RB, Duncan LM, Faquin WC, Ferry JA, Frosch MP, Houser SL, Kradin RL, Lauwers GY, Louis DN, Mark EJ, Mino-Kenudson M, Misdraji J, Nielsen GP, Pitman MB, Rosenberg AE, Smith RN, Sohani AR, Stone JR, Tambouret RH, Wu CL, Young RH, Zembowicz A, Klietmann W. Whole-slide imaging digital pathology as a platform for teleconsultation: a pilot study using paired subspecialist correlations. Arch Pathol Lab Med 2009; 133:1949-53. PubMed
  • Koreishi AF, Nazarian RM, Saenz AJ, Klepeis VE, McDonald AG, Farris AB, Colvin RB, Duncan LM, Mandal RV, Kay J. Nephrogenic systemic fibrosis: a pathologic study of autopsy cases. Arch Pathol Lab Med 2009; 133:1943-8. PubMed
  • Mandal RV,Duncan LM,Austen WG Jr,Nielsen GP. Infiltrating intramuscular spindle cell lipoma of the face. J Cutan Pathol 2009; 36 Suppl 1:70-3. PubMed
  • Nazarian RM, Van Cott EM, Zembowicz A, Duncan LM. Warfarin-induced skin necrosis. J Am Acad Dermatol 2009; 61:325-32. PubMed
  • Shah SM, Konnikov N, Duncan LM, Tannous ZS. The effect of 595 nm pulsed dye laser on superficial and nodular basal cell carcinomas. Lasers Surg Med 2009; 41:417-22. PubMed
  • Erickson LA,Letts GA,Shah SM,Shackelton JB,Duncan LM. TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas. Mod Pathol 2009; 22:969-76. PubMed
  • Rothberg BE, Moeder CB, Kluger H, Halaban R, Elder DE, Murphy GF, Lazar A, Prieto V, Duncan LM, Rimm DL. Nuclear to non-nuclear Pmel17/gp100 expression (HMB45 staining) as a discriminator between benign and malignant melanocytic lesions. Mod Pathol 2008; 21:1121-9. PubMed
  • Robertson GT, Bonventre EJ, Doyle TB, Du Q, Duncan L, Morris TW, Roche ED, Yan D, Lynch AS. In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Studies of the Mode of Action in Staphylococcus aureus. Antimicrob Agents Chemother 2008; 52:2313-23. PubMed
  • Robertson GT, Bonventre EJ, Doyle TB, Du Q, Duncan L, Morris TW, Roche ED, Yan D, Lynch AS. In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Microbiology Profiling Studies Undertaken in Staphylococci and Streptococci. Antimicrob Agents Chemother 2008; 52:2324-34. PubMed
  • Mittal S, Marshall NA, Duncan L, Culligan DJ, Barker RN, Vickers MA. Local and systemic induction of CD4+CD25+ regulatory T cell population by non-Hodgkin's lymphoma. Blood 2008; 111:5359-70. PubMed
  • Walsh K, Moss C, Lawless J, McKelvie R, Duncan L. Puzzling practice: a strategy for working with clinical practice issues. Int J Nurs Pract 2008; 14:94-100. PubMed
  • Duncan L, Jacob S, Hubbard E. Evaluation of p16INK4a as a diagnostic tool in the triage of Pap smears demonstrating atypical squamous cells of undetermined significance. Cancer 2008; 114:34-48. PubMed
  • Kuffova L, Netukova M, Duncan L, Porter A, Stockinger B, Forrester JV. Cross presentation of antigen on MHC class II via the draining lymph node after corneal transplantation in mice. J Immunol 2008; 180:1353-61. PubMed
  • Duncan L, Shelmerdine H, Hughes MP, Coley HM, Hubner Y, Labeed FH. Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells. Phys Med Biol 2008; 53:N1-7. PubMed
  • Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH. Identification of cells initiating human melanomas. Nature 2008; 451:345-9. PubMed
  • Duncan LK, Jinschek JR, Vikesland PJ. C60 colloid formation in aqueous systems: effects of preparation method on size, structure, and surface charge. Environ Sci Technol 2008; 42:173-8. PubMed
  • Nahmias C, Carlson ER, Duncan LD, Blodgett TM, Kennedy J, Long MJ, Carr C, Hubner KF, Townsend DW. Positron emission tomography/computerized tomography (PET/CT) scanning for preoperative staging of patients with oral/head and neck cancer. J Oral Maxillofac Surg 2007; 65:2524-35. PubMed
  • Kim M, Gans JD, Nogueira C, Wang A, Paik JH, Feng B, Brennan C, Hahn WC, Cordon-Cardo C, Wagner SN, Flotte TJ, Duncan LM, Granter SR, Chin L. Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell 2006; 125:1269-81. PubMed
  • Koehler JE, Duncan LM. Case records of the Massachusetts General Hospital. Case 30-2005. A 56-year-old man with fever and axillary lymphadenopathy. N Engl J Med 2005; 353:1387-94. PubMed
  • Polisson RP, Crocker JT, Mueller PR, Harris NL, Duncan LM. Case records of the Massachusetts General Hospital. Case 29-2005. A 68-year-old man with periorbital swelling, rash, and weakness. N Engl J Med 2005; 353:1275-84. PubMed
  • Quinn TR, Duncan LM, Zembowicz A, Faquin WC. Cutaneous metastases of follicular thyroid carcinoma: a report of four cases and a review of the literature. Am J Dermatopathol 2005; 27:306-12. PubMed
  • Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, Ralfkiaer E, Chimenti S, Diaz-Perez JL, Duncan LM, Grange F, Harris NL, Kempf W, Kerl H, Kurrer M, Knobler R, Pimpinelli N, Sander C, Santucci M, Sterry W, Vermeer MH, Wechsler J, Whittaker S, Meijer CJ. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105:3768-85. PubMed
  • Tannous ZS, Mihm MC, Sober AJ, Duncan LM. Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol 2005; 52:197-203. PubMed
  • Zand S, Lio PA, Mackool BT, Duncan LM. A slightly erythematous, firm papule on the upper arm--quiz case. Arch Dermatol 2005; 141:93-8. PubMed
  • Zubovits J, Buzney E, Yu L, Duncan LM. HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Hum Pathol 2004; 35:217-23. PubMed
  • Ahmed AR, Avram MM, Duncan LM. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 23-2003. A 79-year-old woman with gastric lymphoma and erosive mucosal and cutaneous lesions. N Engl J Med 2003; 349:382-91. PubMed
  • Santucci M, Pimpinelli N, Massi D, Kadin ME, Meijer CJ, Muller-Hermelink HK, Paulli M, Wechsler J, Willemze R, Audring H, Bernengo MG, Cerroni L, Chimenti S, Chott A, Diaz-Perez JL, Dippel E, Duncan LM, Feller AC, Geerts ML, Hallermann C, Kempf W, Russell-Jones R, Sander C, Berti E. Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop. Cancer 2003; 97:610-27. PubMed
  • de Leval L, Harris NL, Longtine J, Ferry JA, Duncan LM. Cutaneous b-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification. Am J Surg Pathol 2001; 25:732-41. PubMed
  • Duncan LM, Deeds J, Cronin FE, Donovan M, Sober AJ, Kauffman M, McCarthy JJ. Melastatin expression and prognosis in cutaneous malignant melanoma. J Clin Oncol 2001; 19:568-76. PubMed
  • Deeds J, Cronin F, Duncan LM. Patterns of melastatin mRNA expression in melanocytic tumors. Hum Pathol 2000; 31:1346-56. PubMed
  • Tannous ZS, Lerner LH, Duncan LM, Mihm MC, Flotte TJ. Progression to invasive melanoma from malignant melanoma in situ, lentigo maligna type. Hum Pathol 2000; 31:705-8. PubMed
  • Su LD, Duncan LM. Lymphoma- and leukemia-associated cutaneous atypical CD30+ T-cell reactions. J Cutan Pathol 2000; 27:249-54. PubMed
  • Yu LL, Flotte TJ, Tanabe KK, Gadd MA, Cosimi AB, Sober AJ, Mihm MC, Duncan LM. Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 1999; 86:617-27. PubMed
  • Tannous Z, Baldassano MF, Li VW, Kvedar J, Duncan LM. Syringolymphoid hyperplasia and follicular mucinosis in a patient with cutaneous T-cell lymphoma. J Am Acad Dermatol 1999; 41:303-8. PubMed
  • Duncan LM. Cutaneous lymphoma. Understanding the new classification schemes. Dermatol Clin 1999; 17:569-92. PubMed
  • Wrone DA, Duncan LM, Sober AJ. Melanoma and pregnancy: eight questions with discussion. J Gend Specif Med 2001; 2:52-4. PubMed
  • Gadd MA, Cosimi AB, Yu J, Duncan LM, Yu L, Flotte TJ, Souba WW, Ott MJ, Wong LS, Sober AJ, Mihm MC, Haluska FG, Tanabe KK. Outcome of patients with melanoma and histologically negative sentinel lymph nodes. Arch Surg 1999; 134:381-7. PubMed
  • Duncan LM. Prognostic Indicators in Melanoma. Harrison's Principles of Internal Medicine. 1999; 15:489-518.
  • Baldassano MF, Bailey EM, Ferry JA, Harris NL, Duncan LM. Cutaneous lymphoid hyperplasia and cutaneous marginal zone lymphoma: comparison of morphologic and immunophenotypic features. Am J Surg Pathol 1999; 23:88-96. PubMed
  • Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res 1998; 58:1515-20. PubMed
  • Duncan LM, Richards LA, Mihm MC. Increased mast cell density in invasive melanoma. J Cutan Pathol 1998; 25:11-5. PubMed
  • Duncan LM, Bouffard D, Howard C, Mihm MC, Byers HR. In situ distribution of integrin alpha 2 beta 1 and alpha-actinin in melanocytic proliferations. Mod Pathol 1996; 9:938-43. PubMed
  • Bailey EM, Ferry JA, Harris NL, Mihm MC, Jacobson JO, Duncan LM. Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients. Am J Surg Pathol 1996; 20:1011-23. PubMed
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