Thymic Epithelial Tumors: An Evolving Field

Abstract

Despite their rarity, thymic epithelial tumors (TETs) have attracted much interest over the years, leading to an impressive number of histological and staging classifications. At present, TETs are divided by the WHO classification into four main subtypes: type A, type AB, and type B thymomas (subdivided into B1, B2, and B3), and thymic carcinomas, going from the more indolent to the most aggressive ones. Among many debated staging proposals, the TNM and the Masaoka–Koga staging systems have been widely accepted and used in routine practice. The four-tiered histological classification is symmetrically mirrored by the molecular subgrouping of TETs, which identifies an A-like and an AB-like cluster, with frequent GTF2I and HRAS mutations; an intermediate B-like cluster, with a T-cell signaling profile; and a carcinoma-like cluster comprising thymic carcinomas with frequent CDKN2A and TP53 alterations and a high tumor molecular burden. Molecular investigations have opened the way to tailored therapies, such as tyrosine kinase inhibitors targeting KIT, mTOR, and VEGFR, and immune-checkpoints that have been adopted as second-line systemic treatments. In this review, we discuss the crucial events that led to the current understanding of TETs, while disclosing the next steps in this intriguing field.

Immunotherapy in thymic epithelial tumors: tissue predictive biomarkers for immune checkpoint inhibitors

“…TMs are the most common neoplastic type accounting for more than 50% of TETs, while TCs and TNENs represent approximately 14-22% and 2-5%, respectively [23]. TMs are characterized by thymus-like differentiation as they variably show organotypical features such as lobulated architecture, perivascular spaces, medullary differentiation and intratumoral infiltration of immature Tlymphocytes while Hassall corpuscles are only occasionally identified [6,24,25]. TMs are a heterogeneous group of neoplasm with different molecular, histopathological, immunophetypical and clinical features [26].…”

“…TMs are characterized by thymus-like differentiation as they variably show organotypical features such as lobulated architecture, perivascular spaces, medullary differentiation and intratumoral infiltration of immature T-lymphocytes while Hassall corpuscles are only occasionally identified [ 6 , 24 , 25 ]. TMs are a heterogeneous group of neoplasm with different molecular, histopathological, immunophetypical and clinical features [ 26 ]. TMs are variably encapsulated and well circumscribed masses, except for type B3 TM which shows smooth invasive fronts with invasion in mediastinal fat or adjacent organs; neoplastic proliferation shows lobulated architecture due to the presence of thick fibrous septa and it is organized according to several growth patterns, with bland and spindle/oval cytomorphology and few or no admixed immature T-cells in type A TM, except for s atypical type A TM, and variably atypical polygonal neoplastic cells, as single cellular elements or arranged in clusters (≥ 3 contiguous cells), with dense immature T-lymphocyte infiltrate or few and scattered immature T lymphocytes in type B TMs (B1–B3).…”

Survival Outcomes and Prognostic Factors of Thymic Epithelial Tumors a Single Center Experience

“…They sporadically develop ectopically, primarily in the neck. Reaching its height in the fourth and sixth decades (2) .…”