In this review, we summarize the current understanding of the genetic renal neoplasia syndromes, the clinical and pathologic presentations, their molecular pathogenesis, the advances in therapeutic implications and targeted therapy.

Eosinophilic solid and cystic RCC and RCC with TFEB alterations (translocation or amplification) show some histological, immunohistochemical and molecular overlap. Both tumours frequently express Melan A, and both can express CK20 and can show TSC mutations. FISH for TFEB can aid in differential diagnosis of challenging cases.

The graphical abstract was build with biorender.com

Somatic malignant transformation (SMT) occurred in 4% of germ cell tumour (GCT) patients, with most common histologies being adenocarcinoma, embryonic-type neuroectodermal tumour (ENET) and rhabdomyosarcoma, but a wide range of morphologies was seen. Patients with evidence of SMT in the metastatic mass showed significantly poorer overall-survival compared to those with SMT exclusively in the primary testicular tumour. Clinical trials and targeted treatments based on molecular profile assessed by NGS were recommended in 4 patients.

A limited form of Rosai-Dorfman disease can present in the clinical setting of chronic sinusitis. These histologic findings are associated with recurrent chronic sinus symptoms but no risk of systemic disease.

After filigree reclassification, diagnostic sensitivity of micropapillary pattern on frozen section increased from 43.2% to 65.3% in study cohort. The presence of filigree was significantly associated with worse RFS. Identification of filigree may improve the diagnostic sensitivity of micropapillary pattern on frozen section.