Testicular Germ Cell Tumors: Revisiting a Series in Light of the New WHO Classification and AJCC Staging Systems, Focusing on Challenges for Pathologists - Beyond the Abstract

Testicular germ cell tumors (TGCTs) represent the most common neoplasms diagnosed in Caucasian men aged between 15-44 years, accounting for about 60% of malignancies in this age group. Despite the decline of mortality rates incidence is rising due to changes in lifestyle. Also, still 15-20% of patients with disseminated disease relapse with poor prognosis disease, and some patients develop resistance to standard cisplatin-based chemotherapy. Moreover, matters like quality of life, chemo- and radiotherapy side effects and fertility cannot be overlooked in these highly curable neoplasms, as they preferably afflict young patients with high life expectancy. All in all, there are more than reasons to stay focused on TGCTs.

TGCTs are hallmarked by striking heterogeneity, reflecting a complex tumorigenesis which was only recently more clearly understood. A new classification for TGCTs was proposed by WHO in 2016 and constituted a paradigm shift, moving from a merely morphological-based model into a pathogenesis-based classification, around the basilar concept of germ cell neoplasia in situ (GCNIS). Also, concerning staging purposes, the new AJCC 8th Edition manual has introduced some novelties, namely concerning Seminomas. Hence, now more than ever, Pathologists should assume a central role in TGCTs diagnostic approach and need to be up-to-date with these recent modifications in classification and staging.
In this study we aimed to revise a series of consecutively diagnosed TGCTs at a single cancer institution (2005-2016), in light of the new proposed classification and staging systems, exploring some of the most challenging issues faced by Pathologists in their daily routine. Thorough reviews of consecutive series of TGCTs are lacking in the literature, especially those taking into account this new input introduced by the new classification and staging systems.

Throughout the paper, we have systematically compared clinical, macroscopic and histological features between Seminomas and Non-seminomatous tumors, the two major subtypes of TGCTs, with distinct behavior and prognosis. We have also explored the composition of Mixed Tumors, looking for the most frequent combinations of tumor subtypes. Regarding pathological factors taken into account in the Pathologist’s report and that can alter the prognosis, we have looked into possible atypical features of Seminomas, and also into the value of lympho-vascular invasion and the amount of embryonal carcinoma. Finally, we have focused on changes established in the most recent AJCC staging system, namely concerning stage IA Seminomas.

TGCTs are challenging neoplasms, posing many dilemmas to Pathologists in their daily routine. Referral for tertiary institutions with expertise in TGCTs is a way of ensuring an accurate diagnosis. Multidisciplinary teams composed of dedicated pathologists, urologists, oncologists, radiotherapists, and other professionals are crucial for achieving more patient-centered care in testicular cancer.

Written by: João Lobo, MD, Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal; Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto, Porto, Portugal; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal

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