An unusual ectopic thymoma clonal evolution analysis: A case report

Abstract

Thymomas and thymic carcinomas are rare and primary tumors of the mediastinum which is derived from the thymic epithelium. Thymomas are the most common primary anterior mediastinal tumor, while ectopic thymomas are rarer. Mutational profiles of ectopic thymomas may help expand our understanding of the occurrence and treatment options of these tumors. In this report, we sought to elucidate the mutational profiles of two ectopic thymoma nodules to gain deeper understanding of the molecular genetic information of this rare tumor and to provide guidance treatment options. We presented a case of 62-year-old male patient with a postoperative pathological diagnosis of type A mediastinal thymoma and ectopic pulmonary thymoma. After mediastinal lesion resection and thoracoscopic lung wedge resection, the mediastinal thymoma was completely removed, and the patient recovered from the surgery and no recurrence was found by examination until now. Whole exome sequencing was performed on both mediastinal thymoma and ectopic pulmonary thymoma tissue samples of the patient and clonal evolution analysis were further conducted to analyze the genetic characteristics. We identified eight gene mutations that were co-mutated in both lesions. Consistent with a previous exome sequencing analysis of thymic epithelial tumor, HRAS was also observed in both mediastinal lesion and lung lesion tissues. We also evaluated the intratumor heterogeneity of non-silent mutations. The results showed that the mediastinal lesion tissue has higher degree of heterogeneity and the lung lesion tissue has relatively low amount of variant heterogeneity in the detected variants. Through pathology and genomics sequencing detection, we initially revealed the genetic differences between mediastinal thymoma and ectopic thymoma, and clonal evolution analysis showed that these two lesions originated from multi-ancestral regions.

Keywords: case report; clonal evolution; ectopic pulmonary thymoma; heterogeneity; immunohistochemical.

Graphical abstract

Figure 1

Imaging findings of the patient. (a–d) PET/CT showed a mass in the mediastinal portion. (e and f) PET/CT showed nodules (red arrow) in lung. (g and h) MRI examination showed a 4.5 cm × 3.0 cm × 3.8 cm mass (red arrow) in the mediastinal portion. (i) MRI examination showed multiple nodules in the lung. The red arrow indicated a 1.9 cm × 1.8 cm nodule in the left lower lobe of the lung.

Figure 2

(a) Histopathological result showed a type A thymoma pattern (hematoxylin and eosin staining; magnification: ×100). (b) Microscopic view of thymoma type A in the anterior mediastinum. (c) Microscopic view of ectopic pulmonary thymomas type A in the left lower lung. Magnification: ×40. (d) Serum CA724 and NSE expression levels in patients (normal level of CA724 is less than 6.9 U/mL and the normal value of NSE is less than 16.3 μg/L).

Figure 3

Imaging findings of the patient. CT examination showed masses (red arrows) in the multiple nodules in the lung.

Figure 4

Clone phylogenies and sample clone mixtures. A clone phylogeny is shown for the patient, with distinct clonal genotypes color-coded. The clonal composition of each sample was depicted as a schematic tumor, with the coloring of “cells” proportional to the prevalence of each clone. Samples were arrayed in a circle, with constituent clones from the overall clone phylogeny represented in an outer circle.