Difference in the distribution of tumor‐infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma

Abstract

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients′ antitumor immune response.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Experimental model of micronodular thymic neoplasm with lymphoid stroma

“…MNT with lymphoid stroma was originally described by Suster and Moran 1 as a characteristic of multiple micronodular thymoma epithelial cell nests with abundant B cell stroma, often with lymphoid follicles. Interestingly, several variations have been added to the concept of micronodular thymic neoplasm with lymphoid stroma; epithelial components varied from thymoma to thymic carcinoma, and lymphoid stroma was also associated with T cells 2–6 . The thymic tumor was composed of AE1/AE3 anticytokeratin cocktail positive epithelial cells, which showed autonomous growth, whereas the lymphoid stroma consisted of T cells, which declined in number, due to apoptosis, as a consequence of absent epithelial cell nests.…”

“…MNT was first reported by Suster and Moran, 1 and since then accumulated case reports have indicated that this tumor represents a spectrum of micronodular thymic epithelial tumor cell proliferations, varying from micronodular thymoma to thymic carcinoma with lymphoid stroma and with intratumorous lymphoma. [2][3][4][5][6] The biological properties of thymic epithelial cells, including their ability to attract and harbor lymphocytes to promote lymphocyte development, 7 might be related to the lymphoid stroma formation of micronodular thymic neoplasm. However, the pathobiological and molecular mechanisms (e.g., humoral factor pathway) underlying abundant lymphoid stroma formation in micronodular thymic neoplasm remain to be elucidated.…”

“…Micronodular thymic neoplasm with lymphoid stroma (MNT) is a rare subtype of thymic neoplasm that is histopathologically characterized by micronodular thymic epithelial cell nests with lymphoid stroma. MNT was first reported by Suster and Moran, 1 and since then accumulated case reports have indicated that this tumor represents a spectrum of micronodular thymic epithelial tumor cell proliferations, varying from micronodular thymoma to thymic carcinoma with lymphoid stroma and with intratumorous lymphoma 2–6 …”

Micronodular Thymic Carcinoma with Lymphoid Stroma: A Case Report

“…MTC is a rare subtype of thymic carcinoma, and the histological characteristic of MTC or MT is the formation of tumor nodules accompanied by lymphoid stroma, unlike other common thymomas [1]. To date, 23 cases of MTC have been reported (Table 1) [2][3][4][5][6][7][8][9]. The mean age of the patients was 62.9 years (range 42-82 years) and the mean tumor size was 3.7 cm (range 1.1-10 cm).…”

“…MT, which was rst described in 1999 by Suster et al, is a rare subtype of thymoma, accounting for 5% of thymomas, and comprising neoplastic epithelial nests and surrounding hyperplastic lymphoid tissue containing a germinal center [2]. Since MT and MTC share a similar morphology, MTC is considered a malignant form of MT; there have been a few cases of malignant transformation from MT to MTC [2][3][4][5][6][7][8][9]. Herein, we describe a case of MTC accompanied by a benign histological component of thymoma and review the literature.…”