An Asymptomatic, Ectopic Mass as a Presentation of Adrenocortical Carcinoma Due to a Novel Germline <i>TP53</i> p.Phe338Leu Tetramerisation Domain Variant
Justyna Walenciak,
Zuzanna Urbanska,
Agata Pastorczak,
Katarzyna Babol-Pokora,
Kamila Wypyszczak,
Ewa Bien,
Aleksandra Gawlowska-Marciniak,
Jozef Kobos,
Wieslawa Grajkowska,
Joanna Smyczynska,
Wojciech Mlynarski,
Szymon Janczar
Affiliations
Justyna Walenciak
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Zuzanna Urbanska
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Agata Pastorczak
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Katarzyna Babol-Pokora
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Kamila Wypyszczak
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Ewa Bien
Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 80-210 Gdansk, Poland
Aleksandra Gawlowska-Marciniak
Department of Pediatric Surgery and Oncology, Central University Hospital, Medical University of Lodz, 91-738 Lodz, Poland
Jozef Kobos
Department of Normal and Clinical Anatomy, Chair of Anatomy and Histology, Medical University of Lodz, 92-213 Lodz, Poland
Wieslawa Grajkowska
Department of Pathology, The Children’s Memorial Health Institute, 04-736 Warsaw, Poland
Joanna Smyczynska
Department of Pediatrics, Endocrinology, Diabetology and Nephrology, Medical University of Lodz, 91-738 Lodz, Poland
Wojciech Mlynarski
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Szymon Janczar
Department of Pediatrics, Oncology and Haematology, Medical University of Lodz, 91-738 Lodz, Poland
Adrenocortical carcinoma (ACC) is a rare cancer in childhood. ACC is frequently associated with germline TP53 variants, with founder effects especially due to the p.Arg337His mutation. ACC leads to the secretion of adrenocortical hormones, resulting in endocrine syndromes, which is the usual trigger for establishing the diagnosis. We present a surprising ACC pathology in a non-secreting, ectopic retroperitoneal tumour in a 4-year-old boy, successfully controlled with chemotherapy and mitotane after microscopically incomplete tumour resection with spillage. Genomic analysis (gene panel sequencing and copy-number microarray) demonstrated a novel p.Phe338Leu tetramerisation domain (TD) TP53 variant in the proband and his cancer-free mother and a monoallelic deletion encompassing the TP53 locus in cancer tissue, consistent with cancer-predisposition syndrome. While the recurrent p.Arg337His variant translates into high ACC risk, residue 338 and, in general, TD domain variants drive heterogeneous clinical scenarios, despite generally being considered less disruptive than TP53 DNA-binding domain mutations.
