Anne Wandler1, Eva Spaun1, Torben Steiniche1, Patricia S Nielsen2. 1. Department of Pathology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark. 2. Department of Pathology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark. swittenp@gmail.com.
Abstract
BACKGROUND: Inability to distinguish melanomas from benign nevi is the most frequent reason for malpractice lawsuits in surgical pathology. Reliable diagnostic tools to support hematoxylin and eosin (H&E) stains and induce diagnostic vigilance are thus highly needed. Because high diagnostic performance recently was showed using automated image analysis, the immunohistochemical proliferation marker Ki67 seems a potential candidate. This study aimed to investigate if this previously presented automated algorithm could have prevented 10 false-negative melanoma diagnoses. In addition, diagnostic utility of another, but narrower, immunohistochemical proliferation marker, phosphohistone H3 (PHH3), was explored. METHODS: A total of 10 formalin-fixed paraffin-embedded melanocytic tumors, initially classified as benign or dysplastic but revised as melanomas at metastatic debut, were dual-stained for Ki67/MART1 and PHH3/MART1. A Ki67 index was automatically calculated in epidermis, dermis, a combination of such, and a dermal hot spot. Dermal PHH3/MART1 scores were established semi-automatically. RESULTS: The dermal Ki67 index identified all 10 melanomas, the hot-spot index 8 and the epidermal and combined indices only 2 and 5, respectively. Nine melanomas were PHH3 positive and scores correlated with Ki67. CONCLUSIONS: PHH3 added limited information, but supplemental automated Ki67 assessment could possibly have prevented the misdiagnosis of most melanomas had the algorithm been available at the time of diagnosis.
BACKGROUND: Inability to distinguish melanomas from benign nevi is the most frequent reason for malpractice lawsuits in surgical pathology. Reliable diagnostic tools to support hematoxylin and eosin (H&E) stains and induce diagnostic vigilance are thus highly needed. Because high diagnostic performance recently was showed using automated image analysis, the immunohistochemical proliferation marker Ki67 seems a potential candidate. This study aimed to investigate if this previously presented automated algorithm could have prevented 10 false-negative melanoma diagnoses. In addition, diagnostic utility of another, but narrower, immunohistochemical proliferation marker, phosphohistone H3 (PHH3), was explored. METHODS: A total of 10 formalin-fixed paraffin-embedded melanocytic tumors, initially classified as benign or dysplastic but revised as melanomas at metastatic debut, were dual-stained for Ki67/MART1 and PHH3/MART1. A Ki67 index was automatically calculated in epidermis, dermis, a combination of such, and a dermal hot spot. Dermal PHH3/MART1 scores were established semi-automatically. RESULTS: The dermal Ki67 index identified all 10 melanomas, the hot-spot index 8 and the epidermal and combined indices only 2 and 5, respectively. Nine melanomas were PHH3 positive and scores correlated with Ki67. CONCLUSIONS:PHH3 added limited information, but supplemental automated Ki67 assessment could possibly have prevented the misdiagnosis of most melanomas had the algorithm been available at the time of diagnosis.
Authors: Bart Sturm; David Creytens; Jan Smits; Ariadne H A G Ooms; Erik Eijken; Eline Kurpershoek; Heidi V N Küsters-Vandevelde; Carla Wauters; Willeke A M Blokx; Jeroen A W M van der Laak Journal: Diagnostics (Basel) Date: 2022-02-08