Thymic Hyperplasia with Lymphoepithelial Sialadenitis (LESA)-Like Features: Strong Association with Lymphomas and Non-Myasthenic Autoimmune Diseases.

Štefan Porubský ,Timo Gaiser,Philipp Ströbel,Fabian Lötscher,Thomas Graeter,Burkhard Möller,Monika Brüggemann,Dietmar Borchert,Yara Banz,Andreas Rosenwald,Andreas Kreft,Sabina Berezowska,Sunil Badve,German Ott,Alexander Marx,Katrin S Huettl,Zoran V Popović ,Peter H Hollaus ,Eric Dominic Roessner ,Michaela Kotrová ,Gerhard Preißler ,Christian Kügler

doi:10.3390/cancers13020315

Abstract

Simple SummaryThymic epithelial tumors and lymphomas are the most frequent mediastinal mass lesions. Thymic hyperplasia with “lymphoepithelial sialadenitis (LESA)-like features” (LESA-like TH) was initially described as one form of thymic hyperplasia and was thought not to be associated with autoimmune and lymphoproliferative diseases. Our systematic analysis of patients with LESA-like TH shows that 14% have associated lymphomas and 33% partially overlapping autoimmune diseases. This implies a hematologic and rheumatologic workup in patients with LESA-like TH. In addition, LESA-like TH should enter the list of differential diagnoses of mediastinal mass lesions, in particular in patients with autoimmune diseases.Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32–80; lesion diameter 7.0 cm, 1–14.5; median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sjögren syndrome, pure red cell aplasia, Grave’s disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases.

Highlights

Thymic epithelial tumors and lymphomas represent the two most frequent types of mediastinal neoplasms in adults [1]
”conventional” TFH: the association with lymphoma and mainly non-myasthenic autoimmune diseases, and the near total absence of thymic cortical structures even in corticosteroid-naïve patients. These current new findings have the following implications for patient care: First, the classification of lymphoepithelial sialadenitis (LESA)-like Thymic hyperplasia (TH) as benign should be complemented by the fact that diseases, and the near total absence of thymic cortical structures even in corticosteroidnaïve patients
The classification of LESA-like TH as benign should be complemented by the fact that more than 10% of patients have a concomitant lymphoma at the time of surgery

Summary

Introduction

Thymic epithelial tumors (thymomas and thymic carcinomas) and lymphomas represent the two most frequent types of mediastinal neoplasms in adults [1]. (i) true thymic hyperplasia of unknown etiology that shows normal-looking histology and a thymus weight that mostly exceeds 100 g, (ii) rebound hyperplasia that follows the cessation of various “stressors” such as infection or chemotherapy and shows normal-forage or juvenile histology and organ weights usually below 100 g, (iii) diseases with the unifying histological hallmark of lymphofollicular hyperplasia In this group, the paradigmatic and most frequent disease is the “conventional thymitis” with lymphofollicular hyperplasia that typically occurs in early-onset myasthenia gravis (EOMG) and rarely other settings and is labelled here as “thymic follicular hyperplasia” ( abbreviated as TFH). Until now, systematic investigations into a relationship between LESA-like TH and lymphomas as well as autoimmune diseases have not been undertaken

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