P156 Muscle biopsy findings in a large cohort of patients affected by valosin containing protein disease: preliminary analysis of the international multicentric VCP study

• Published in: Neuromuscular disorders : NMD 2023-10, Vol.33, p.S138-S139
• Main Authors: Schiava, M., Nishino, I., Inoue, M., Nishimori, Y., Saito, Y., Polvikoski, T., Charlton, R., Parkhurst, Y., Henderson, M., Marini-Bettolo, C., Guglieri, M., Straub, V., Weihl, C., Stojkovic, T., Villar-Quiles, R., Romero, N., Evangelista, T., Pegoraro, E., De Bleecker, J., Monforte, M., Malfatti, E., Souvannanorath, S., Severa, G., Alonso-Jiménez, A., Baets, J., De Ridder, W., De Jonghe, P., Kierdaszuk, B., Claeys, K., Muelas, N., Oldfors, A., Rodolico, C., Quin, C., Dominguez, C., Lain, A Herández, Pál, E., Papadimas, G., Kushlaf, H., Alfano, L., Alonso-Pérez, J., Luo, S., Badrising, U., Bevilacqua, J., Nedkova-Hristova, V., Cetin, H., Gelpi, E., Klotz, S., Plana, M Olivé
• Format: Article
• Language: English
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2023.07.288

Valosin-containing protein (VCP) disease is an adult autosomal dominant multisystem proteinopathy (MSP) with a heterogeneous phenotype including myopathy, Paget's disease of bone, fronto temporal dementia, motor neuron disease and peripheral neuropathy. We describe the muscle biopsy features of 72 patients enrolled in the VCP International Multicentre Study. Muscle biopsies were retrospectively reviewed by experts in muscle pathology at each centre following the recommendation of the "Common Data Elements for Muscle Biopsy Reporting" publication. Experts entered relevant data into a database that was used for the overall biopsy analysis. Representative images from each biopsy were also collected. The mean age at muscle biopsy was 53.0 SD 11 years (SD, standard deviation) and the mean time between first symptom and biopsy was 7.0 SD 5.0 years. Fifty percent of the biopsies had a myopathic pattern while 29.2% showed combined myopathic and neurogenic changes. The most frequent findings were the presence of atrophic fibres, 98.6% (involving both fibre types in the 54.9%); myophagocytosis, 80.6%; rimmed vacuoles, 80.6%; areas of healthy tissue mixed with extensive areas of fat replacement, fibrosis and/or necrosis, 62.5%; fibre hypertrophy, 57.7% and fibre grouping, 23.6%. Only 16.7% of the samples showed focal endomysial inflammatory infiltrates. Protein aggregates were reported in 62.0% of the patients of which p-62 was identified in 54.4% and VCP in 29.5%. No significant differences were identified in the biopsy findings among the four most frequent mutations in the cohort and among the clinical phenotypes (myopathy, motor neuron, and others). This preliminary analysis confirms that muscle biopsies of patients with VCP-MSP depict a myopathic or mixed pattern with rimmed vacuoles, p-62 and VCP immunoreactive inclusions. The myopathologic findings in VCP-MSP are highly similar and consistent irrespective of the clinical phenotype. However, some biopsies might not show rimmed vacuoles, which increases the challenge in the diagnosis of VCP-MSP.