Original StudyC4d as a Practical Marker for Cutaneous AmyloidosisYaman, Banu MD; Kumbaracı, Banu Sarsık MD; Gómez González, Claudia A. MD; Akalın, Taner MD; Şen, Sait MDAuthor Information Department of Pathology, Medical Faculty, Ege University, Izmir, Turkey. Correspondence: Banu Sarsik Kumbaraci, MD, Department of Pathology, Ege University Faculty of Medicine, Bornova 35100, İzmir, Turkey (e-mail: [email protected]). S. Şen, B. Yaman, and B. S. Kumbaraci contributed to the conception of the study, designed the study, and performed the histopathological examination of cases. B. Yaman and C. A. Gomez Gonzalez were major contributors in writing the manuscript and analyzed and interpreted the patients' data. T. Akalın and B. S. Kumbaraci helped perform the analysis with constructive discussions; all authors read and approved the final manuscript. The authors declare no conflicts of interest. The study was approved by the Ethics Committee of Ege University Faculty of Medicine, Izmir, Turkey (Approval No.: 21-2.1T/43), and conducted according to the principles of the Declaration of Helsinki. The American Journal of Dermatopathology: January 2022 - Volume 44 - Issue 1 - p 28-32 doi: 10.1097/DAD.0000000000002057 Buy Metrics Abstract Cutaneous amyloidosis (CA) is defined by the accumulation of amyloid in the dermis; it might be primary or secondary. The diagnosis is based on histopathological findings with the demonstration of amyloid deposits, confirmed by Congo red stain under the polarized light. Studies on other diagnostic markers are ongoing in the literature. The aim of this study was to demonstrate the utility of C4d staining in the recognition of amyloid in CA and using it as an alternative or substitute marker for the diagnosis. In this retrospective study, 199 skin biopsies with a clinical provisional diagnosis of CA were analyzed, the Congo red stain was performed, and, in a subgroup (n = 97) with histopathological findings probably for CA, C4d immunohistochemistry was assessed. Forty-eight cases of CA were detected. Congo red birefringence was positive in all cases, whereas in 14 cases, it was faded. In these 14 cases, the diagnosis of CA was made by means of Congo red fluorescence and Thioflavin T because the histopathological findings were highly suggestive for CA. All CA cases were positive with C4d, and in 12 of the 49 inflammatory dermatoses, C4d was positive. The interpretation of C4d immunohistochemistry can be performed more easily and rapidly than Congo red evaluation. The sensitivity and specificity of C4d were 100% and 75.5%, respectively. In our experience, C4d staining was a useful method for detecting amyloid deposits in CA. Although Congo red staining is the gold standard for amyloid detection, we propose C4d immunohistochemistry as a routine screening method or hybrid transition while further investigations are completed. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.