Paediatric ovarian tumours and their associated cancer susceptibility syndromes

Abstract

Non-epithelial ovarian tumours are rare neoplasms that occasionally arise in childhood and adolescence. They can be associated with various cancer susceptibility syndromes. The morphological overlap seen across these tumours and their rarity can make the diagnosis challenging. In the case of an incorrect diagnosis, the underlying genetic susceptibility may be missed. In this review, we outline the genetic background of ovarian non-epithelial tumours arising in children, emphasizing the genes harbouring pathogenic germline variants associated with each tumour type. Specifically, juvenile granulosa cell tumours, Sertoli-Leydig cell tumours, sex cord tumours with annular tubules, Sertoli cell tumours, germ cell tumours and small cell carcinoma of the ovary of hypercalcaemic type are discussed in this review. For each tumour type, we detail the personal and family history features and the presenting characteristics of the ovarian tumour as well as the pathological features and molecular markers that point towards a cancer predisposition syndrome. Throughout, we stress the need for specialised pathological review in difficult cases.

Management of ovarian cysts in children and adolescents

“…Ollier disease, Maffucci syndrome, Peutz–Jeghers syndrome, Frasier syndrome and DICER1 syndrome). If such syndromes are identified, patients should be offered the possibility of surveillance …”

Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines

“…Please see https://smallcellovariancancer.com/contact-us/ for more details.The Consortium recommends referral of all patients with SCCOHT to a clinical genetics service or provider, with an offer for testing for germline SMARCA4 PVs (Table 1). It is important to use a clinical laboratory that offers full gene sequencing, including copy number calling, as PVs are typically scattered throughout the gene, and whole or partial gene deletions have been reported(40).The incidence of germline pathogenic PVs could be high (up to 43%), and the family history is not generally informative, especially if the germline PV was inherited from the proband's father(36). There are several different approaches to genetic testing for diagnostic confirmation and with the increasing use of matched tumor-normal sequencing, both germline and somatic mutations can be identified.…”

Is genetic testing required in a child with an ovarian germ cell tumour?

“…The family history was particularly focused on the probability of occurrence of mutations in BRCA1 and BRCA2 genes in the patient's family. Mutations in these genes predispose predominantly to ovarian cancer, and in the case of BRCA 2 also to acute lymphoblastic leukaemia, which was diagnosed in several of the girl's relatives [2,12]. Molecular diagnostics including next-generation sequencing of the whole coding region of the two genes, excluded the presence of mutations.…”

“…Primary ovarian cancer develops only in about 1.5% of cases [1], whereas malignant germ cell tumours account for 75% of ovarian neoplasms arising in the first 20 years of life and 15% of all neoplasms diagnosed in young individuals aged 15-19 years. These neoplasms are characterised by good prognosis associated with a survival probability reaching from 89% to 98% [2]. Gonadoblastoma is a potentially malignant mixed germ cell tumour that develops particularly frequently as a disorder secondary to dysgenetic gonads.…”

“…The genetic predisposition to develop germ cell neoplasms also refers to carriers of germline mutations within the WT1 gene the phenotype of which corresponds to such conditions as Frasier syndrome, Denys-Drash syndrome, and WAGR syndrome [2]. However, the highest risk of malignant transformation occurs in patients suffering from complete gonadal dysgenesis (CGD) with 46,XY (Swyer syndrome), and it reaches 30-45% throughout the lifetime and increasing even up to 80% in the fifth decade of life [3,5,[7][8][9].…”