Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development

Abstract

The aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not a complication of this condition. The present paper reports a high frequency of monoclonal B-cell populations (6 of 18 cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm with a B-cell-rich stroma, while B cells were consistently polyclonal in TFH (25 cases) and other types of thymomas (15 cases) (p < 0.001). An intratumoural lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and thymic mucosa-associated lymphoid tissue (MALT) lymphomas. The neoplastic epithelium of MNTs, but not of TFH and other types of thymoma, expressed high levels of dendritic cell, T-cell, and B-cell chemoattractants, such as CCL18, CCR6, and CCL20. It is concluded that abnormal chemokine expression in an epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of monoclonal B cells, and, eventually, the subsequent development of mediastinal lymphomas. More generally, the concept that expression of a 'high-risk' spectrum of chemokines due to local or genetic factors may interfere with B-cell homeostasis and may contribute to MALT lymphoma development in chronic inflammatory states is proposed.

Micronodular thymic carcinoma with lymphoid hyperplasia: a clinicopathological and immunohistochemical study of five cases

“…Of note, no tumor deaths were reported for any of the patients with micronodular thymoma despite obvious cytological malignancy in a small number of cases, 3,4,[6][7][8] nor was there mortality in any of the cases described by Nonaka et al…”

“…4,5 Since the first description of this neoplasm by Suster, 3 only few series and case reports have been presented in the literature. [4][5][6][7][8] Micronodular thymomas with prominent lymphoid hyperplasia are usually encapsulated or minimally invasive tumors histologically characterized by a proliferation of small tumor nodules separated by an abundant lymphoid stroma with prominent germinal centers. The individual tumor nodules are composed of spindle cells containing oval nuclei that lack cytological atypia or mitotic activity.…”

“…3 Although in the original description the lymphoid component comprised almost exclusively B-cells with only few scattered immature T-cells in the tumor nodules, 3 in subsequent series, the lymphoid elements were found to be composed of a mix of B-and T-cells. 4 follicles with germinal centers. Contrary to our cases, in Nonaka's series the tumors were classified as 'undifferentiated large cell carcinomas' in some areas resembling lymphoepithelioma-like carcinoma.…”

Thymome

“…Seltene "atypische Fälle" kön-nen schlecht umschrieben und nekrotisch sein [10]. A-oder -AB-Thymome häufig MNTAnteile auf [25].…”

Two neoplasms rich in small lymphocytes, B1B2 thymoma and small lymphocytic lymphoma, intermingled in one tumor mass. A case report

“…Histological classifications of the World Health Organization (WHO) [4,6] were used to establish thehistologicaltypeoftheneoplasms,andthestage of the thymic epithelial tumor was determined by employingtheMasaoka-Kogastagingsystem.…”