Anterior mediastinal seminoma with myasthenia gravis: A rare case report and literature review

doi:10.21203/rs.3.rs-1562197/v1

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Case Report

Anterior mediastinal seminoma with myasthenia gravis: A rare case report and literature review

https://doi.org/10.21203/rs.3.rs-1562197/v1

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Background:

Myasthenia gravis may be associated with thymic follicular hyperplasia or thymomas. We present a case of an anterior mediastinal tumor with myasthenia gravis, which turned out to be seminoma. We also review the literature on seminoma with myasthenia gravis in this article.

Case presentation:

A 34-year-old man presented to our hospital with a complaint of diplopia. Single fiber electromyography revealed ocular myasthenia gravis; chest computed tomography showed a 1.5 cm anterior mediastinum nodule suspected as thymoma. The patient underwent video-assisted thoracoscopic thymectomy. Histopathological findings revealed seminoma with thymic follicular hyperplasia.

Conclusion:

Anterior mediastinal seminoma with thymic follicular hyperplasia is rare and extremely rare with associated myasthenia gravis. Though rare, young male patient with anterior mediastinal tumor and myasthenia gravis, thymic seminoma is one possible cause. Testicular examination can be taken into consideration before operation.

seminoma

thymic follicular hyperplasia

myasthenia gravis

Myasthenia gravis may be associated with thymic follicular hyperplasia or thymomas [1]. Seminoma mimicking myasthenia gravis with anterior mediastinal tumor is rare. Germ cell tumors account for less than 4% of mediastinal tumors [2]. Non-seminomatous tumors are more common than seminomas [3]. Due to the indolent behaviour of seminomas, most of them are bulky when diagnosed. Patients with seminoma may present with symptoms, such as dyspnea, chest pain, cough, hemoptysis, hoarseness or even superior vena cava syndrome, caused by large anterior mediastinal tumor masses [2, 4]. These symptoms are non-specific; therefore, the diagnosis of seminomas is often incidental.

We present a case with double-seronegative myasthenia gravis and a 1.5 cm nodule in the upper anterior mediastinum (suspected as thymoma) revealed on chest computed tomography. After thymectomy, the histopathological findings revealed seminoma with thymic hyperplasia.

A 34-year-old man experienced intermittent diplopia for 6 months. Serum test was negative for acetylcholine receptor antibody in Cheng Ching Hospital on 03/2021, where the patient was diagnosed with an unknown virus infection. He had diplopia again on 08/2021 and reported to Shin Kong Wu Ho-Su Memorial Hospital for further evaluation. Serum test was negative for muscle-specific receptor tyrosine kinase test; however, single fiber electromyography revealed ocular myasthenia gravis. Double-seronegative myasthenia gravis was suspected, and chest computed tomography was performed, which showed a 1.5 cm nodule in the upper anterior mediastinum, suspected as thymoma (Fig. 1). The patient reported to Chung Shan Medical University Hospital for a second opinion.

Physical examination revealed a male in apparent good health and no distress. His temperature was 36.4 ℃, pulse rate was 66 per minute and regular, and blood pressure was 128/78 mmHg. The findings were within normal limits. There was no tracheal shift, and the thyroid gland was normal to palpation. Both lungs were clear to auscultation.

Laboratory data revealed a white blood cell count of 8,050 per microliter with 67% polymorphonuclear leukocytes; hemoglobin, 14.5 grams per deciliter; hematocrit, 43.1%. Serum electrolytes were normal. A pre-operative survey, including ultrasonography of the abdomen and whole-body bone scan, showed no liver or bone metastasis. Ultrasonography of the abdomen revealed mild fatty changes in the liver with bright echogenicity. A whole-body bone scan revealed no significant abnormal uptake.

The patient underwent video-assisted thoracoscopic thymectomy. Diplopia resolved after surgery, and the patient was discharged in stable condition on postoperative day 4.

In 12/2021, follow-up physical examination showed no epididymal or testicular lesions. Follow-up positron emission tomography showed no active lesion. Follow-up tumor markers, such as lactate dehydrogenase, alpha-fetoprotein and beta-human chorionic gonadotropin, were within normal range.

Pathology

Macroscopically, the thymus (with tumor) measured 20.0 × 7.0 × 2.0 cm and weighed 124.6 grams. A soft to solid, mild irregular and well-defined tumor (about 1.5 × 1 × 1 cm) in the high body of thymus was noted (Fig. 2A). The tumor measuring 1.3 × 1.0 × 0.8 cm showed a homogeneous yellow-white to flesh cut surface with a rubbery consistency (Fig. 2B).

Histologically, the lesion shows the characteristic appearance of nests of large, uniform polygonal cells with clear or eosinophilic cytoplasm and distinct cell membranes. Marked thymic follicular hyperplasia with numerous germinal centers is seen (Fig. 3A). High-power field shows squared-off nuclei and prominent central nucleoli (Fig. 3B).

Immunohistochemical staining shows positive CD117 with strong and diffused circumferential cytoplasmic membrane reactivity (Fig. 3C). Positive SALL4 with strong, uniform nuclear staining (Fig. 3D). Negative for CK, P63, CD20, CD3, CD68, CD79a and Tdt stain.

Overall, the appearance is consistent with primary mediastinal seminoma with thymic follicular hyperplasia. The surgical margins are free.

Mostly, symptoms of anterior mediastinal seminoma, such as dyspnea, chest pain and cough, are tumor-size dependent [2, 4]. We reviewed previous literature on anterior mediastinal seminoma with thymic follicular hyperplasia and found only 12 case reports of mediastinal seminoma with lymphoid hyperplasia. In 1985, a paper by Williams et al. [5] described a case with symptoms of ocular myasthenia gravis. In 1986, Burns et al. [6] described 3 case reports. In 2015, Weissferdt et al. [7] described 6 case reports with a median tumor size of 4 cm (ranging from 3 ~ 5 cm), mostly presenting symptoms of chest pain. In 2016, Lee et al. [8] described a case with asymptomatic synchronous thymoma. In 2021, Holmes et al. [9] described a case report with symptoms of breathlessness on lying down. Among the case reports mentioned above, only one patient presented ocular myasthenia gravis symptoms, similar to our patient.

The most common association of thymic pathology with myasthenia gravis is thymus follicular hyperplasia or thymoma. The association between seminoma and follicular lymphoid hyperplasia is still uncertain. Willis et al. [10] found that the microenvironment of seminoma produced specific antigens, which could be associated with follicular lymphoid hyperplasia. Weissferdt and Moran hypothesised that the mechanism of thymus follicular hyperplasia was associated with a characteristic distribution of antigen-presenting dendritic cells in mediastinal seminomas [7]. Further research is needed.

Mediastinal seminomas are morphologically similar to testicular seminomas. However, secondary changes are noticed in mediastinal seminomas sometimes, including the presence of thymic remnants, prominent cystic changes, reactive follicular lymphoid hyperplasia and epithelioid granulomas [6, 11, 12]. These secondary changes lead to more differential diagnoses. For example, differential diagnosis of anterior mediastinal cyst should include thymic cyst, cyst formation of thymoma or Hodgkin lymphoma and seminoma with cystic change [11]. Similarly, in the case of anterior mediastinal tumors with symptoms of myasthenia gravis, thymoma, thymus hyperplasia and seminoma with reactive follicular lymphoid hyperplasia should be considered for differential diagnosis.

For small, resectable anterior mediastinal seminomas, surgical removal of the tumor with thoracoscopic or thoracotomy is the first-line treatment. The decision to use postoperative radiotherapy depends on histopathological features of surgical resection margins [13, 14]. Patients with advanced disease should receive chemotherapy and radiotherapy because seminomas are highly sensitive to chemotherapy and radiotherapy [14]. Moreover, monitoring tumor markers of human chorionic gonadotropin and alpha-fetoprotein for detecting recurrence of advanced seminoma has been recommended by Gilligan et al. However, they did not recommend using markers for detecting recurrence of stage I seminoma [15].

Anterior mediastinal seminoma with thymic follicular hyperplasia is rare and extremely rare with associated myasthenia gravis. The clinical presentation was attributed to the secondary changes in the thymic seminoma. For anterior mediastinal tumors with myasthenia gravis symptoms, thymic seminoma with thymic follicular hyperplasia should be included in differential diagnoses, especially in young male patients.

CD117: Cluster of differentiation 117

SALL4: Spalt like transcription Factor 4

CK: Cytokeratins

P63: Tumor protein 63

CD20: Cluster of differentiation 20

CD3: Cluster of differentiation 3

CD68: Cluster of differentiation 68

CD79a: Cluster of differentiation 79a

TdT: Terminal deoxynucleotidyl transferase

Ethics approval and consent to participate:

This case is in accordance with the ethical standards of the Ethics Committee of Chung Shan Medical University Hospital, Taiwan (R.O.C.) (date: March 4, 2022, approval number: CS2-22027) and the Declaration of Helsinki and its later amendments.

Consent for publication:

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Availability of data and materials:

Not applicable.

Competing interests:

All authors declare that they have no competing interests.

Funding:

Not applicable.

Authors' contributions:

YCW, first author, reviewed the medical record and drafted the manuscript.

JYH, corresponding author, performed the operation, carried out clinical treatments and drafted the manuscript.

TYK and JDH reviewed the medical record and carried out histopathological studies.

All authors read and approved the final manuscript.

Acknowledgements:

Not applicable.

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No competing interests reported.

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You are reading this latest preprint version

Anterior mediastinal seminoma with myasthenia gravis: A rare case report and literature review

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Version 1

Abstract

Figures

Background

Case Presentation

Discussion

Conclusion

Abbreviations

Declarations

References

Competing Interests

Status:

Version 1