Somatic malignant transformation (SMT) arising in germ cell tumours (GCTs) is an infrequent, but clinically relevant event. There is only limited knowledge on the morphological spectrum of SMT, and therapeutic management of these patients is poorly defined. In this work we revisit two consecutive case series (n=756) of GCTs. Clinicopathological data of SMT arising in GCT were determined, with focus on the histopathological spectrum, and molecular aspects were obtained by Fluorescence in situ Hybridization (FISH) and Next Generation Sequencing (NGS).
30 male patients (28 primary testicular, 2 primary extragonadal) were included. These patients represent 4% of GCT patients diagnosed in two institutes (University Hospital Zurich and IPO Porto). The most common SMT were adenocarcinoma (n=8), embryonic-type neuroectodermal tumours (ENETs, n=8) and rhabdomyosarcoma (n=6), but a wide range of challenging morphologies were depicted, including low-grade neuroglial tumour, adenosquamous carcinoma, neuroblastoma and neuroendocrine carcinoma. SMT was found in 15 primary tumour samples and in 27 metastatic samples of these 30 patients, the latter showing poorer overall-survival. Adenocarcinoma occurred only in metastasis post-chemotherapy and in one primary retroperitoneal GCT with SMT, but not in GCT of the testis. 12p gains were identified by FISH in all cases. NGS results were available in 6 patients. Clinical trials and/or targeted treatments based on the molecular profile of SMT were recommended in 4 patients.
SMT arising in GCTs represents a diagnostic challenge and should be confirmed by a specialized uropathologist. NGS based treatment recommendations may improve outcome of these patients.
Histopathology. 2022 Apr 19 [Epub ahead of print]
João Lobo, Ângelo Rodrigues, Rui Henrique, Ailsa Christiansen, Jörg Beyer, Holger Moch, Peter Karl Bode
Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal., Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH, 8091, Zurich, Switzerland., Universitätsklinik für Medizinische Onkologie, Inselspital, Universitätsklinik der Universität Bern, Bern University, Switzerland.