Antoine Legras, Anne Talet, Audrey Didelot, Aurélie Cazes, Angela Hin, Raphaël Borie, Bruno Crestani, Yves Castier, Françoise Le Pimpec-Barthes, Marc Riquet, Hélène Blons, Pierre Mordant
Institution : Service de chirurgie thoracique et vasculaire et transplantation pulmonaire, hôpital Bichat, Paris
Objectives : Mediastinal unicentric Castleman disease is a very rare condition, poorly known due to small number of cases and the absence of genomic study. We sought to characterize the clinical, radiological, histological and genomic patterns associated with unicentric mediastinal CD in the frame of a substantial case series.
Methods : We retrospectively reviewed cases from 2 French thoracic surgery departments (1988-2012). Clinical, radiological, surgical and pathological data were recorded. On available paraffin-embedded blocks were performed mutation screening by next generation sequencing, with AmpliSeq™ Cancer Hotspot v2 (Life Technologies) and immunohistochemistry (AKT mTOR pathway).
Results : Eleven patients were identified (mean age: 41, range 17-69; sex-ratio 0.8). Surgical approach was thoracotomy (n=6), VATS (n=1) or sternotomy (n=4). Bilobectomy was needed in 1 case and radical mediastinal lymphadenectomy in 2 cases. One patient presented local relapse as follicular dendritic cell sarcoma, leading to death. Within 9 patients, 2 mutations were found: VHL (p.F119L, 35%, n=1) and JAK3 (p.V718L, 53%, n=1). Stainings for phospho-AKT and phospho-mTOR were negative. Phospho-S6K staining was observed in 5 cases, mainly in cytoplasm of interfollicular cells.
Conclusion : Here we presented the largest series of mediastinal unicentric Castleman disease, with genomic and cellular pathway data. We observed 2 potential driver mutations and phospho-S6K activation not related to mTOR nor AKT pathway. Knowledge may be improved by addressing all pathological specimens to a unique reference national centre.