Intrapulmonary ectopic thymoma with severe myasthenia gravis after thymoma surgery: A case report and literature review

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Case Report

Intrapulmonary ectopic thymoma with severe myasthenia gravis after thymoma surgery: A case report and literature review

https://doi.org/10.21203/rs.3.rs-2876816/v1

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Background: Ectopic thymoma are rare thymic tumorslocated in regions other than the anterior mediastinum. It is even rarer to find patients with intrapulmonary ectopic thymoma and myasthenia gravis . In particular, patients with pulmonary masses with pulmonary symptoms such as cough, sputum, and dyspnea are highly susceptible to misdiagnosis. Here, we report the clinical data, tumor pathology, treatment, and prognosis of a patient with intrapulmonary ectopic thymoma and myasthenia gravis after thymoma surgery and review the relevant literature.

Case presentation: Forty-five days ago, a 54-year-old female patient with a 12-year earlier clinical diagnosis of myasthenia gravis (type II) with thymoma (type B1) and thymoma resection presented with ptosis of the right upper eyelid with double vision. Enhanced chest computed tomography revealed a tumorous lesion in the supraglottic segment of the upper lobe of the left lung. After wedge resection of the upper lobe of the lung, the pathological biopsy and immunohistochemistry suggested pulmonary thymoma (mainly type B3). After surgery, the patient was treated with long-term oral pyridostigmine bromide combined with adjuvant radiation therapy.

Discussions and Conclusion: This case report and review of the related literature show that even after removal for thymoma, there is a possibility of recurrence and unexpected sites of recurrence, such as the lungs.It is also important to consider the possibility of other rare neurological diseases such as thymoma located in the lungs in addition to lung tumors in patients with pulmonary masses, whether the patient presents with or without myasthenia gravis.Early lung biopsy can lead to early identification and treatment of the disease.This case provide a reference for the clinical diagnosis of intrapulmonary ectopic thymoma and improve its clinical treatment.

Ectopic thymomas

intrapulmonary ectopic thymoma

myasthenia gravis

immunohistochemistry

case report

Ectopic thymoma is an uncommon type of thymoma that occurs at sites other than the anterior mediastinum. It accounts for less than 4% of all thymomas[1]. It has been recorded at various locations, including the neck[2], thyroid[3], middle mediastinum[4], pleura[5], pericardium[6], heart[7], and thoracic spine[8]. The thyroid gland is the most prevalent site of ectopic thymoma[9]. In contrast, primary thymoma in the lungs, a rare disease accounting for roughly 20% of ectopic thymomas, was first identified in 1951[10, 11]. According to a survey of pertinent clinical literature, only 214 cases of ectopic thymoma have been recorded, 23 of which occurred in the lung. Eight of these patients were without any symptoms, and 13 patients had pulmonary symptoms, such as cough or cough and chest tightness. Only a small proportion of these patients had neurological symptoms and myasthenia gravis, such as ptosis and diplopia. Here, we report the clinical data, tumor pathology, treatment, and prognosis of a patient with intrapulmonary ectopic thymoma and myasthenia gravis after thymoma surgery. Additionally, we also present a review of the relevant literature.

Our patient was a 54-year-old female freelancer. At 45 days before admission, she developed right upper eyelid ptosis and double vision, which was slight in the morning, and severe in the evening, without obvious cause. The patient had been clinically diagnosed with myasthenia gravis (type II) and thymoma (type B1) 12 years previously and had received long-term oral therapy with bromipyridamole after thymectomy, right upper eyelid ptosis and diplopia almost normalized. She did not have hypertension or diabetes mellitus or a history of cardiac, cerebrovascular, or psychiatric disease.

After admission to our hospital, examination revealed ptosis of the right eyelid, limited upward movement of the right eye, and diplopia of the right eye; however, no other abnormalities were observed. Repetitive nerve stimulation (RNS) showed 14.9–33.8% attenuation of low-frequency stimulation of the right and left oblique muscles. Quantification of serum anti-acetylcholine receptor (AChR) antibody enzyme-linked immunosorbent assay (ELISA) was 12.91 nmol/L (normal value < 0.45 nmol/L), while anti-muscle-specific receptor tyrosine kinase (MuSK) antibody was (0.07 U/mL; normal value < 0.4 U/mL). Anti-SOX1 antibody IgG and anti-linker Titin antibody IgG immunoblotting were all negative. Pulmonary function tests revealed mildly impaired pulmonary ventilation, an abnormal ratio of first and second expiratory volume to expiratory lung volume (FEV1/FVC), obstructive ventilation dysfunction, a low end-expiratory index, and abnormal small airway function.

A thymus computed tomography (CT) examination revealed no clear space-occupying lesion in the thymus area; however, a nodular shadow of approximately 24 mm × 23 mm was observed in the supraglottic segment of the left upper lobe of the lung. Considering the occurrence of a possible tumorigenic lesion, an enhanced CT scan was recommended. On the enhanced chest CT, a solid nodular shadow was observed in the supraglottic segment of the left upper lobe of the left lung (IM158), with a size of approximately 26 mm × 24 mm, a clear border, a lobulated shape in some areas, a heterogeneous interior density, and a CT value of approximately 24–40 HU. The lesion showed enhancement. The demarcation between the lesion and the left part of the mediastinum was neoplastic (Figure 1). Therefore, thoracoscopic wedge resection of the upper lobe of the left lung, thoracoscopic pleural adhesion release, and drainage closure of the thoracic cavity were performed.

Intraoperatively, the lingular segment of the upper lobe of the left lung was approximately 2.5 cm × 2.0 cm in size, with solid nodules and visceral pleural wrinkles. Non-invasion of the pleura, absence of intra-thoracic fluid, mild adhesions, chest implants, and enlarged lymph nodes were recorded in groups 5, 9, and 10, respectively. Intraoperative frozen pathology showed that the solid nodules of the left lung were considered to be a thymoma. Postoperative frozen paraffin sections also suggested that the nodules were a thymoma, pending immunohistochemical staining to aid diagnosis (9 items). No tumor involvement was observed in the lung sections.

Immunohistochemical staining was positive for CK19, P63, TdT, CD5, EMA, and Ki-67, with Ki-67 positivity at approximately 30%, while CD117 and CD20 were negative, which supported the diagnosis of thymoma (mainly B3 type) in the left lung (Figure 2). Pathological biopsies did not reveal metastases in the group 5, 9, and 10 lymph nodes. Postoperative contrast-enhanced CT showed the postoperative changes in the left lung as a dense shadow of striae and a few patches and cords of increased density around the operated area, a few striae with a low-density shadow, and a few gas shadows in the adjacent left subpleural area (Figure 3).

The patient continued to take pyridostigmine bromide orally for four months after lung tumor resection and has completed 25 rounds of radiotherapy. After 3 months of follow-up, the patient's general condition remains good, and the right upper eyelid ptosis and double vision are significantly improved. The patient can look forward horizontally, and the right eye opening is wider than before (Figure 4).

The thymus is a lymphoid organ usually located in the upper part of the anterior mediastinum. It originates from the ventral capsule of the third pharyngeal bursa in the sixth week of embryonic development. Then it begins to migrate[12], eventually extending from the posterior sternum, within the thorax, to below the thyroid gland. However, because some thymic tissue remains in other parts during the descent of the thymus, these residual thymic tissues can cause a number of diseases, such as thymic cysts and ectopic thymoma[13]. Intrapulmonary ectopic thymoma exhibits distinct histopathological features and is relatively rare[14]. The origin of intrapulmonary ectopic thymomas is not well understood. It may originate from ectopic thymic tissue during thymus development or from stem cells. It contains different proportions of tumor-like epithelial cells and lymphocytes[1].

Our patient's clinical history (including previous inpatient clinical records) was collected, and tests, such as the neostigmine test, RNS, CT of the lungs and thymus, serum AChR antibody and anti-MuSK antibody tests, tumor pathology biopsy, and immunohistochemistry tests, were performed. The tumor was surgically resected, and postoperative radiation therapy was performed. The results of the surgical resection, postoperative radiation therapy, and follow-up were reviewed.

Ten percent of patients with myasthenia gravis develop thymomas[15], and about one third of thymomas are associated with myasthenia gravis. However, the vast majority of ectopic thymomas are not In relation to myasthenia gravis[16]. In this case, the patient presented with symptoms of myasthenia, such as right upper eyelid ptosis and right eye diplopia, which was less severe in the morning than in the evening, and qualitatively positive ELISA results for serum AChR antibody, which is extremely rare in cases of intrapulmonary ectopic thymoma.

On reviewing the relevant literature, we found that ectopic thymoma of the lung usually occurs in middle-aged women (mean age: 55 years) and is generally located in the right lung and upper lung lobe, with a tumor size averaging 35 mm in diameter (range: 15–128 mm). Type B thymoma is more common than type A thymoma[11]. Our patient was a middle-aged female; the tumor occurred in the lingular segment of the upper left lung lobe and measured approximately 25 mm × 20 mm. The tumor was staged as type B on both occasions, which is broadly consistent with the reported epidemiology of ectopic thymoma of the lung.

Currently, the best treatment for thymoma is complete surgical resection. The recurrence rate of thymoma after resection is 10–30%[17, 18]. The overall recurrence rate of thymoma is approximately 20%, and it is related to tumor pathological staging and cell differentiation[19]. Type B thymoma belongs to type I malignant thymoma, and patients have a high recurrence and metastasis rate; type C thymoma belongs to type II malignant thymoma and has the highest recurrence rate. Regarding cell differentiation,the malignant potential and recurrence rate increases if the cells are cortical and predominantly epithelial, and the opposite if they are medullary and predominantly lymphocytic the malignant potential and recurrence rate increase if the cells are cortical rather than medullary and predominantly epithelial rather than lymphocytic[20, 21]. In this case, after thymoma resection in the year 2010, the patient had a recurrence of right eyelid ptosis with double vision in the right eye in 2022. The recurrent thymoma may represent a malignant transformation of the ectopic thymic tissue or a new primary focus, which requires further study. The patient's pathological stage was defined as B1 after the first thymoma resection; however, 12 years later, the recurrent intrapulmonary ectopic thymoma was staged as B3. Thus, the patient showed a shift in staging during the course of the disease. Because type B3 thymoma consists mainly of large polygonal cells with increased heterogeneity and less dispersed lymphocytes, its prognosis is worse than that of other thymomas[22]. Amplification of chromosome 1 has been associated with the histological staging of thymic epithelial tumors[23]. For patients with pulmonary masses, in addition to common primary bronchopulmonary carcinoma, clinicians need to be alert to the possibility of a thymoma lesion, although rare, which can be differentiated from pulmonary tumors by histopathological biopsy and immunohistochemical staining. Type B3 thymomas should be differentiated from thymic carcinomas and metastatic squamous cell carcinomas at other sites. The detection of chromosome 1 gain utilizing fluorescent in situ hybridization can assist in the differential diagnosis and prediction of the prognosis of patients with thymic epithelial tumors.

Through this case report, we should be alert to the possibility of thymoma recurrence in patients after thymoma resection;Although ectopic thymoma on the lung is rare, clinicians should be alert to the possibility of ectopic thymoma in the lung when the diagnosis of the etiology of the lung mass is unclear and when the symptoms of myasthenia gravis such as ptosis and diplopia are not treated well. And combine with pathological histology for its diagnosis and differential diagnosis, so that it can provide reference for clinical diagnosis and differential diagnosis.

Repetitive nerve stimulation (RNS)

Computed tomography (CT)

Enzyme-linked immunosorbent assay (ELISA)

Ethics Approval

The patient and his family gave informed consent to the content of this article.

Consent for Publication

Written informed consent was obtained from the patient’s family for publica‑

tion of this case report and any accompanying images.

Data Availability Statement

For data inquiries, please contact the corresponding author directly.

Competing Interests

The authors declare that they have no conflict of interest.

Funding

This work was supported by Sichuan Science and Technology Project (2023NSFSC0622)

Author Contributions

XY＆XmW contributed to the study conception and design, JyL＆WwH＆CXcollected and organized the data related to the case, ZqH ＆SfY followed up with the patient. All authors did extensive research and reading of relevant literature, completed the drafting of the article, and consented to the submission of the final version of the article.

Acknowledgments

We thank all the authors and the subjects who participated in this study, as well as the institutions involved, for their contributions.

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No competing interests reported.

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Intrapulmonary ectopic thymoma with severe myasthenia gravis after thymoma surgery: A case report and literature review

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