Mark C Mochel1, Marc R Hammond2, Dennie T Frederick2, Maria B Alora-Palli3, Adriano Piris4, Keith T Flaherty5, Mai P Hoang6. 1. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. 2. Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts. 3. Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 4. Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 5. Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 6. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: mhoang@mgh.harvard.edu.
Abstract
BACKGROUND: There are limited descriptions of histopathology and immune profiles of new or changing melanocytic nevi in the setting of B-Raf proto-oncogene (BRAF) inhibitor therapy. OBJECTIVE: We sought to identify their distinctive features. METHODS: Clinical charts and histologic review, neuroblastoma RAS viral (v-ras) oncogene homolog genotyping, and immunohistochemistry for HMB-45, BRAFV600E, phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated protein kinase B, CD4, and CD8 were performed on 19 melanocytic nevi from 10 patients and 23 control nevi. RESULTS: BRAF inhibitors were administered for metastatic melanoma (7), colonic adenocarcinoma (2), and papillary thyroid carcinoma (1). The average duration of BRAF inhibition before lesion excision was 8 months. Frequently associated histologic features included pigmentation of the stratum corneum, hyperpigmented keratinocytes, dermal melanophages, and deep HMB-45 expression. The lesions were BRAFV600E and neuroblastoma RAS viral (v-ras) oncogene homolog wild-type, expressed diffuse weak-moderate pERK, and possessed a predominance of CD8(+) in comparison with CD4(+) T lymphocytes within the dermal infiltrates. LIMITATION: This is a retrospective study of a small and heterogeneous group. CONCLUSION: The nevi associated with BRAF inhibitor therapy invariably lack BRAFV600E mutation. BRAF inhibition appears to cause an increased cytotoxic T-cell response and increased mitogen-activated protein kinase activity in BRAF wild-type lesions, supported by pERK expression, possibly resulting in an activated phenotype characterized by increased melanin pigmentation and deep HMB-45 expression.
BACKGROUND: There are limited descriptions of histopathology and immune profiles of new or changing melanocytic nevi in the setting of B-Raf proto-oncogene (BRAF) inhibitor therapy. OBJECTIVE: We sought to identify their distinctive features. METHODS: Clinical charts and histologic review, neuroblastoma RAS viral (v-ras) oncogene homolog genotyping, and immunohistochemistry for HMB-45, BRAFV600E, phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated protein kinase B, CD4, and CD8 were performed on 19 melanocytic nevi from 10 patients and 23 control nevi. RESULTS:BRAF inhibitors were administered for metastatic melanoma (7), colonic adenocarcinoma (2), and papillary thyroid carcinoma (1). The average duration of BRAF inhibition before lesion excision was 8 months. Frequently associated histologic features included pigmentation of the stratum corneum, hyperpigmented keratinocytes, dermal melanophages, and deep HMB-45 expression. The lesions were BRAFV600E and neuroblastoma RAS viral (v-ras) oncogene homolog wild-type, expressed diffuse weak-moderate pERK, and possessed a predominance of CD8(+) in comparison with CD4(+) T lymphocytes within the dermal infiltrates. LIMITATION: This is a retrospective study of a small and heterogeneous group. CONCLUSION: The nevi associated with BRAF inhibitor therapy invariably lack BRAFV600E mutation. BRAF inhibition appears to cause an increased cytotoxic T-cell response and increased mitogen-activated protein kinase activity in BRAF wild-type lesions, supported by pERK expression, possibly resulting in an activated phenotype characterized by increased melaninpigmentation and deep HMB-45 expression.
Authors: Subashini Sharon Gnanendran; Lauren Maree Turner; James Austin Miller; Shelley Ji Eun Hwang; Andrew Charles Miller Journal: Curr Treat Options Oncol Date: 2020-03-19
Authors: Vishwas Parekh; Joseph Sobanko; Christopher J Miller; Giorgos Karakousis; Wei Xu; Richard Letrero; Rosalie Elenitsas; Xiaowei Xu; David E Elder; Ravi Amaravadi; Lynn M Schuchter; Katherine L Nathanson; Melissa A Wilson; Emily Y Chu Journal: J Cutan Pathol Date: 2018-12-27 Impact factor: 1.587