DICER1 screening in 15 paediatric paratesticular sarcomas unveils an unusual DICER1‐associated sarcoma

Abstract

Individuals with DICER1 syndrome, a genetic disorder caused by pathogenic germline variants in DICER1 , are at increased risk of developing a wide array of predominantly childhood onset conditions, including genitourinary sarcomas. However, data on DICER1 involvement in paratesticular sarcomas have not been published. Herein, we analyse a series of 15 paediatric paratesticular sarcomas and describe in detail the case of a male infant with a paratesticular myxoid tumour, considered to be a low‐grade sarcoma, who also manifested a cystic nephroma, a classic DICER1 syndrome phenotype. He harboured a pathogenic germline DICER1 variant and different somatic hot‐spot mutations in each tumour. The paratesticular tumour showed strong and diffuse expression for WT1 and CD10, an unusual immunophenotype in paediatric sarcomas, but typical of tumours of Müllerian origin. The tumour was postulated to arise from the appendix testis, a Müllerian remnant located in the paratestis. Such an origin would be analogous to other DICER1‐associated non‐epithelial gynaecological tumours, thought to arise from Müllerian derivatives. These findings point towards a key role of DICER1 in Müllerian‐derived structures. Supporting this hypothesis is the fact that the other paratesticular sarcomas from the series were either negative or focally positive for WT1 and for CD10, and none had any DICER1 mutations. In summary, we present the first case of a paratesticular sarcoma associated with DICER1 syndrome, emphasising that paratesticular tumours with an unusual histological appearance may suggest an underlying DICER1 mutation, especially in the presence of a personal or family history of DICER1‐associated disease. In this context, DICER1 mutation testing could lead to changes in clinical care including implementation of cancer care surveillance strategies.

DICER1‐associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing

“…Another study, revealed that inactivated Dicer1 in Müllerian duct mesenchyme‐derived tissues resulted in the down‐regulation of specific miRNAs predicted to regulate Wnt and Hox genes, important for Müllerian duct differentiation and mesenchyme‐derived structures 98 . Interestingly, we recently reported a case of a paratesticular sarcoma with DICER1 mutations that we postulated arose from the appendix testis, a Müllerian remnant located in the paratestis 99 …”

Phenotypic Similarities Within The Morphologic Spectrum Of DICER1-Associated Sarcomas and Pleuropulmonary Blastoma -- Histopathologic Features Suggesting Genetic Testing and Counselling

“…7,8,12,13 However, rare cases have been reported in males as well, including the para-testicular region. 14 The PPB-like morphologic spectrum ranging from benign to overtly malignant sarcoma, is also noted in DICER1 associated renal cystic nephromas and anaplastic sarcoma of kidney, both of which also show rhabdomyoblastic differentiation. 7,15 Like in cystic nephromas and type 1 PPB, the spindle cell morphology in some DICER1 associated tumours can be very bland and hypocellular in some tumours and can be misinterpreted on a small biopsy as fibrotic tissue (as with the recurrent vaginal tumour case 3), even though the cells express RMS markers on IHC.…”

Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature

“…DICER1 mutations (germline and/or somatic) were identified in 33/35 tested cases ( Table 5 ). This included 12 patients with confirmed germline DICER1 mutations (or 14q32 deletion in one case); six of them also had a somatic DICER1 mutation in the tumor [ 48 , 49 , 50 , 51 , 52 , 53 ]. This was not assessed or described in the remaining five patients [ 54 , 55 , 56 ].…”