Title: Replacement and desmoplastic histopathological growth patterns: Prediction of outcome in patients with uveal melanoma liver metastases

Barnhill Raymond

Institut Curie,France


Raymond L. Barnhill is currently Professor of Pathology at the Institut Curie, and the Faculty of Medicine, University of Paris Descartes, Paris, France. Dr. Barnhill received his MD degree from Duke University and was a postdoctoral fellow and graduate student in the University of Oxford. He has trained as a dermatologist, anatomic pathologist, and dermatopathologist. His academic and research interests have largely been associated with the biology of melanocytic lesions and melanoma, but also all aspects of dermatopathology and more recently ophthalmic pathology. He has held major academic leadership appointments including Director of Dermatopathology at Brigham and Women’s Hospital and Children’s Hospital, Harvard Medical School, and Director of Dermatopathology (tenured professor) at Johns Hopkins University. Pr Barnhill has founded both the North American Melanoma Pathology Study Group and in 2007 the International Melanoma Pathology Study Group, of which he is currently President. He has also been an active member of the WHO Melanoma Program and the EORTC Melanoma Group and many other professional societies. In 2011, he received the Founder’s Award from the American Society of Dermatopathology. Pr Barnhill is the author of a substantial number of original articles, chapters and reviews, and the author, co-author, or editor of five books, including three leading textbooks in dermatopathology and the pathology of melanoma.


Up to 50% of uveal melanomas (UM) metastasize to the liver within 10 years of diagnosis, and these almost always prove rapidly fatal.  Since histopathological growth patterns (HGP) of liver metastases of the replacement and desmoplastic type, particularly from colon and breast carcinoma, may import valuable biological and prognostic information, we have studied HGP in a series of 41 UM liver metastases originating from 41 patients from the period 2006-2017.  Twenty patients underwent enucleation while 21 had radiation therapy.  Analysis of UM by array comparative genomic hybridization revealed:  25 (64%) patients with high risk (monosomy3/8q gain); 13 (33%) intermediate risk (M3/8normal or disomy3/8q gain); and 1 low risk (disomy3/8normal).  The principal HGP was replacement in 30 (73%) cases and desmoplastic in 11 (27%) cases.  Cases with replacement demonstrated striking vascular co-option/angiotropism. With the development of liver metastasis, only the replacement pattern, largest primary tumor diameter, and R2 (incomplete resection) status predicted diminished overall survival (p<0.041, p<0.017, p<0.047 respectively). On multivariate analysis, only HGP (HR= 6.51, p=0.008) and resection status remained significant. The genomic high-risk variable had no prognostic value at this stage of liver metastasis. Chi-square test showed no association of HGP with monosomy 3 or 8q gain. Eighteen of 41 (44%) patients are alive with disease and 23 (56%) patients died with follow-up ranging from 12 to 318 months (mean: 70 months, median: 47 months).  In conclusion, we report for the first time the frequency of the replacement and desmoplastic HPG in liver UM metastases resected from living patients, and their potential important prognostic value for UM patients, as in other solid cancers.  These results may potentially be utilized to develop radiologic correlates and therapeutic targets for following and treating patients with UM metastases.