Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing Paul W. Harms, Alexandra C. Hristov, David S.

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Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing Paul W. Harms, Alexandra C. Hristov, David S. Kim, Tobenna Anens, Michael J. Quist, Javed Siddiqui, Shannon Carskadon, Rohit Mehra, Douglas R. Fullen, Timothy M. Johnson, Arul M. Chinnaiyan, Nallasivam Palanisamy Human Pathology: Case Reports Volume 1, Issue 2, Pages 21-28 (June 2014) DOI: 10.1016/j.ehpc.2014.07.002 Copyright © 2014 The Authors Terms and Conditions

Fig. 1 Morphologic and immunohistochemical features of melanoma metastatic to soft tissue. A) Frankly malignant, epithelioid cells with scattered mitotic figures form sheets and vague aggregates; lymphocytes are not conspicuous (H&E, ×400). B) Higher magnification shows tumor cells with faint cytoplasmic pigmentation and intermixed melanophages (H&E, ×600). C) The malignant cells are highlighted by Melan-A immunohistochemical staining (×400). Human Pathology: Case Reports 2014 1, 21-28DOI: (10.1016/j.ehpc.2014.07.002) Copyright © 2014 The Authors Terms and Conditions

Fig. 2 Morphologic and immunohistochemical features of follicular lymphoma. A) Low magnification shows lymph node effacement by abnormal, closely-packed follicle structures (H&E, ×100). B) On higher magnification, abnormal follicles are predominantly composed of centrocytic cells, with few scattered centroblasts; they lack appropriate polarization and tingible body macrophages (H&E, ×400). C) Abnormal follicles are highlighted by BCL2 (×100). D) No Melan-A positive cells are identified (×100). Human Pathology: Case Reports 2014 1, 21-28DOI: (10.1016/j.ehpc.2014.07.002) Copyright © 2014 The Authors Terms and Conditions

Fig. 3 EZH2 mutational status and expression in index case. A) Sanger sequencing chromatogram of heterozygous A to C mutation resulting in EZH2 (Y641S) mutation. B) Sanger sequencing chromatogram of GT to AA mutation resulting in BRAF (V600K) mutation. C) Transcript expression of EZH2 in index case relative to other melanoma tumors in Michigan Center for Translational Pathology sequencing compendium. D) Protein expression of EZH2 in index case by immunohistochemistry (400× magnification). Human Pathology: Case Reports 2014 1, 21-28DOI: (10.1016/j.ehpc.2014.07.002) Copyright © 2014 The Authors Terms and Conditions