Choroid Plexus carcinoma: a new case associated with a novel TP53 germ line mutation

The choroid plexus is a highly specialized structure projecting into the lateral ventricle and consisting of a vascularized fibrous stroma covered by epithelial cells of neuroectodermal origin. This specialized epithelium very rarely gives rise to neoplasms, which mainly affect young children and present in sporadic fashion. Choroid plexus tumours (CPT) are in fact rare epithelial brain neoplasms accounting for 0.4–0.8% of all brain tumours and for approximately 1% of paediatric brain tumours [1,2]. Histologically, CPT are classified into benign choroid plexus papilloma (CPP), atypical CPP and malignant choroid plexus carcinoma (CPC) [3]. The survival rate of patients with CPP is significantly higher; nevertheless, a few cases of CPP have been reported to pursue a more aggressive course with intracranial and/or spinal seeding; progression from CPP to CPC has also been reported [1,4]. Most CPT occur sporadically; nevertheless, they can also occur in association with hereditary syndromes such as Aicardi's syndrome [5] or, more frequently, Li–Fraumeni syndrome (LFS) [3]. The p53 tumour suppressor gene (TP53) is the most commonly mutated gene in human cancers. It regulates cell proliferation and DNA repair by inhibiting the cell cycle at G1/S, so that loss of its function may lead to aberrant cell kinetics and tumour growth [6]. Germline mutations in TP53 characterize patients with LFS, a rare hereditary tumour syndrome commonly associated with a variety of malignancies including sarcoma, breast cancer, leukaemia and adrenal cortical carcinoma [7]. Among the paediatric cancers arising within the LFS, rhabdomyosarcoma and CPC are the two most frequent histotypes [8]. Up to date, 17 cases of CPC have been described in the literature occurring in association to a TP53 germline mutation [8–19]. We have identified a hitherto undescribed TP53 germline mutation associated with CPC in a 3-month-old boy, in the absence of a clear tumour predisposition syndrome. The infant presented with vomiting, weight loss and somnolence. The first, non-enhanced, CT scan demonstrated marked and active hydrocephalic enlargement of the supratentorial ventricular system and a lobulated hyperdense mass, with rare and minute calcified foci, arising within the occipital horn and the posterior atrium of the right lateral ventricle; magnetic resonance imaging (MRI) confirmed the intraventricular lobular neoplasm, occupying and enlarging the aforementioned ventricular sections and showing transverse largest diameters of about 3.4 × 2.9 × 2.9 cm (Figure 1). Moderate peri-trigonal vasogenic oedema was also present. The mass appeared iso-intense on T1 weighted images (T1 WI) and of intermediate signal, with multiple areas of signal void, on T2 gradient recalled echo images (GRE-T2*), showing marked and spreading enhancement after administration of paramagnetic contrast material. Diffusion weighted imaging (DWI) and MR spectroscopy (MRS) complemented MRI: DWI revealed an iso-intense mass with multiple small hypo-intense ‘cystic-like’ areas; MRS demonstrated a pathological alteration of the spectral pattern, with complete absence of N-Acetyl Aspartate, marked depletion of Creatine compounds, elevated levels of Choline and lipids.