Juan Rosai as master of our comprehensive understanding of thymus and thymoma

Abstract

Summary In this study, the authors report on the activity of Juan Rosai, one of the pathologists most engaged in the definition of cells, diseases and tumors occurring in the thymus and in the mediastinum during the last 60 years. With his morphological skills and tireless interest in clarification of disease patterns, he contributed extraordinarily to expand our knowledge of the mediastinal diseases and to improve our diagnostic approach. He determined extraordinary advances also in trasmission electron microscopy and in immunohistochemistry as powerful diagnostic tools. Moreover, he proposed and promoted, together with an international panel of Pathologists, the World Health Classification of Thymic tumors as a definite progress in our comprehension and diagnostics of thymic epithelial tumors (TET). Our purpose is to review J. Rosai’s achievements in thymic normal structure, in TET and particularly in the entity now definied as “thymoma”, in distinction from the thymic carcinoma. To do this, our narrative will also be based on personal memories, longstanding collaborations and/or friendship with J. Rosai.

Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells

“…In particular, the upregulation of TP53 and downregulation of oncogenes, such as MYC/Max, MYB, and FOXM, characterize the A-like cluster, while the downregulation of TP53 and upregulation of MYC/Max, MYB, FOXM1, and E2F1 in AB-, B-, and C-like clusters are consistent with the high aggressiveness of B3 and TC tumors. Furthermore, this study highlighted that types A, AB, B, and TC are not a continuum of diseases, but are instead distinct biological entities (5,19), Recently, metaplastic thymomas were reported to harbor the YAP1-MAML2 translocation, whereas 6% of pretreated types B2 and B3 and a combined TC and B3 thymoma (but not in thymoma and "pure" TCs) may be associated with KMT2A-MAML2 translocation (7).…”

“…Type A thymomas are tumors with a component of spindle-oval EC but lack lymphocytes, whereas type B thymomas are characterized by large EC with dendritic or plump (epithelioid) morphology, forming networks where lymphocytes are attracted. Notably, the combination of these two morphologies has been designated as type AB (5). Thymic carcinoma (type C) is a rare malignancy, representing less than 1% of thymic tumors, and is characterized by cytological atypia, more aggressive behavior, and local and distant metastases (liver, lymph nodes, or bones) (6).…”

Histogenetic and disease‐relevant phenotypes in thymic epithelial tumors (TETs): The potential significance for future TET classification

“…14 In contrast, another group of pathologists was reluctant to adopt the above "histogenetic" classification, claiming there was a lack of solid evidence, and described thymomas based on their morphological features, for example, spindle thymoma (for current type A thymoma) and epithelial thymoma (for current type B2 thymoma). 15 Against this background, Dr. Rosai, the co-editor of the 1999 WHO fascicle on thymic tumors 13 and a pathologist who significantly advanced our understanding of mediastinal tumors more than anyone else, 16,17 proposed "labels" that reflected neither histogenesis nor morphological features to solve the conflict and enhance constructive discussions (although he pointed out that types A and B had some functional meanings, namely, atrophic and bioactive, respectively 16 ). This compromise was possible because the subtyping of thymomas was nearly concordant between the two groups even though the nomenclatures differed.…”

“…Against this background, Dr. Rosai, the co‐editor of the 1999 WHO fascicle on thymic tumors 13 and a pathologist who significantly advanced our understanding of mediastinal tumors more than anyone else, 16,17 proposed “labels” that reflected neither histogenesis nor morphological features to solve the conflict and enhance constructive discussions (although he pointed out that types A and B had some functional meanings, namely, atrophic and bioactive, respectively 16 ). This compromise was possible because the subtyping of thymomas was nearly concordant between the two groups even though the nomenclatures differed.…”