Extragonadal germ cell tumors (EGGCTs) are uncommon neoplasms, which arise in anatomical locations other than gonads. The pathogenesis of these neoplasms is still poorly understood and it is a matter of debate if they really represent extragondal primary neoplasms or rather extragondal metastasis from occult gonadal neoplasms. The actual observations suggest that EGGCTs represent a unique entity, so their biology and behavior are substantially different from gonadal counterparts. The diagnosis of EGGCTs is often challenging, and differential diagnosis is particularly wide. Nevertheless, a correct diagnosis is essential for the correct management of the patient. We summarize the state of art about EGGCTs, with particular emphasis on diagnosis and prognosis.
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of '"cancer immunoediting"'. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response. Areas covered: In this review, the authors summarize the most relevant knowledge related to TILs. This includes their prognostic and predictive significance in various types of tumour and the recent findings about their potential role in the cancer immunotherapy. Expert opinion: TILs evaluation could lead to a predictive biomarker for immunotherapy effectiveness in several cancer types. Furthermore, typing of TILs subpopulation could have clinical relevance in patient selection for treatment with immune checkpoint inhibitors. However further studies are still needed.
In the era of precision medicine, the identification of several predictive biomarkers and the development of innovative therapies have dramatically increased the request of tests to identify specific targets on cytological or histological samples, revolutionizing the management of the tumoral biomaterials. The Food and Drug Administration (FDA) has recently approved a selective neurotrophic tyrosine receptor kinase (NTRK) inhibitor, larotrectinib. Contemporarily, the development of multi-kinase inhibitors with activity in tumors carrying TRK fusions is ongoing. Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes result in constitutive activation and aberrant expression of TRK kinases in numerous cancer types. In this context, the identification of tumors harboring TRK fusions is crucial. Several methods of detection are currently available. We revise the advantages and disadvantages of different techniques used for identifying TRK alterations, including immunohistochemistry, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, and next generation sequencing-based approaches. Finally, we propose a diagnostic algorithm based on histology and the relative frequency of TRK fusions in each specific tumor, considering also the economic feasibility in the clinical practice.
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