LAUSR

Abstract Background Thymic Epithelial Tumors (TETs) are rare entities, which can be diagnostic challenges for Pathologists. It has been proven that patients’ referral to a Center with an expert Pathologist is a key factor in obtaining the correct diagnosis. As therapeutic options vary widely for the different entities of TET spectrum, an accurate diagnosis is essential in the therapeutic planning. We aimed at investigating this topic, analyzing pathologic second opinions in a single reference Centre. Methods We retrospectively reviewed all the cases which obtained a pathologic second opinion, after being diagnosed elsewhere with a TET or for a suspicion of TET, at the Istituto Nazionale dei Tumori (INT), Milan, Italy, between 2010 and 2019. Descriptive statistics were used for qualitative variables. Concordance between diagnoses was estimated through Cohen’s k. Results We identified 278 cases; 72 of them received a pathologic revision in INT. Among these cases, initial diagnosis was thymoma A in 5 cases, thymoma AB in 3 cases, thymoma B1 in 5 cases, thymoma B2 in 15 cases, thymoma B3 in 7 cases, thymoma Not Otherwise Specified (NOS) in 8 cases, thymic carcinoma in 17 cases, carcinoma NOS in 8 cases, carcinoma with different histology in 3 cases, lymphoblastic lymphoma in one case. INT pathologic revision changed the diagnosis in 41 (56.9%) cases, with a potential shift in therapeutic approach in 32 (44.4%). In particular, 12 cases of carcinoma NOS or lymphoma were reviewed as thymic carcinoma (10 cases) or thymoma (2 cases); 9 cases of thymic carcinoma were reviewed as cases of thymoma (7 B3, 2 B2); 11 cases of thymoma were reviewed as different thymoma subtypes (9 cases), or thymic carcinoma (one case), or diffuse large B cell lymphoma (one case). Concordance between Pathologists was moderate when the initial diagnosis was thymoma (74.7%, k 0.447), only slight when the initial diagnosis was thymic carcinoma (60.5%, k 0.139). Conclusions A change in histological characterization was documented in a significant percentage of cases initially diagnosed in other Centers, not rarely with potential therapeutic implications. Therefore, in the approach to TETs as well as for other rare diseases, patients’ referral to a reference Centre with high pathology expertise is strongly recommended. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure C. Proto: Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly. D. Signorelli: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS. F.G.M. de Braud: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer-Ingelheim; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: F. Hoffmann-La Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp and Dohme; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer. M.C. Garassino: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD International GmbH; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim Italia S.p.A; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Inivata; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MedImmune; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (institution): Tiziana; Honoraria (institution): Foundation Medicine; Research grant / Funding (institution): AIRC; Research grant / Funding (institution): AIFA; Research grant / Funding (institution): Italian Moh; Research grant / Funding (institution): Transcan. G. Lo Russo: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly. All other authors have declared no conflicts of interest.