Thymolipoma as a Rare Cause of Myasthenia Gravis

ABSTRACT

We present two cases of a rare thymic tumor presenting with ocular myasthenia gravis. Patient A was a male in his 40s who presented with bilateral diplopia. Investigations revealed negative myasthenic antibodies and positive jitter on single fiber electromyography. Patient B was a female in her 20s who presented with bilateral and fluctuating ptosis and diplopia, and was found to have positive acetylcholine receptor antibodies. Both patients demonstrated thymic hyperplasia on computed tomography chest and underwent robotic thymectomy. Pathology of the excised thymic tissue confirmed thymolipoma. We discuss the incidence, presentation, and management of thymolipomatous myasthenia gravis and present robotic thymectomy as a minimally invasive surgical treatment for thymolipoma.

Introduction

Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, resulting in muscle weakness and fatigability.¹ Thymolipoma is a rare, benign thymic tumor that has been associated with autoimmune diseases, including myasthenia gravis, in up to 50% of patients.² Although the precise pathophysiology underlying thymolipoma and the development of myasthenia gravis is unclear, there is evidence to support symptom improvement following tumor resection.³ We present two cases of ocular myasthenia gravis associated with thymolipoma who successfully underwent robotic thymectomy.

Case report

Patient A

Patient A was a 40-year-old male who presented with a two-month history of diplopia on eye movements and a right eyelid droop. His symptoms were worse with prolonged screen use. He denied any bulbar symptoms, limb weakness, or respiratory weakness. He was otherwise well and had no significant past medical history. There was a maternal family history of autoimmune disease, including type 1 diabetes mellitus and vitiligo.

On examination, the patient had variable right sided ptosis. There was restricted abduction in the right eye, however the remainder of the extraocular movements were full. There was full power in the orbicularis oculi, neck, and limbs. Fatiguability of the right eyelid was demonstrated, but there was no fatiguability in the limbs. Reflexes were intact.

Initial investigations included acetylcholine receptor (AChR) and muscle-specific kinase antibodies, which were negative. A magnetic resonance imaging (MRI) brain was normal. Single fiber electromyography demonstrated increased jitter in the right and left orbicularis oculi, with blocking shown in 13% and 23%, respectively. Three pairs had jitter, with one of these pairs demonstrating block in up to 53% of the sampled pairs. Computed tomography (CT) chest identified a soft tissue density in the anterior mediastinal fat suggestive of residual thymic tissue (Figure 1). There was no discrete anterior mediastinal mass.

Figure 1.

CT chest demonstrating a wispy soft tissue density in the anterior mediastinal fat (arrow).

The patient was commenced on prednisolone 10 mg daily for myasthenia gravis. Steroids were increased to 20 mg daily after a week and then weaned to 5 mg daily over the next 4 months. The patient underwent robotic thymectomy 6 months after his initial diagnosis. Histopathology confirmed thymolipoma. The patient’s steroids were weaned postoperatively over a period of 3 months.

One year after steroid cessation, the patient experienced disease relapse, developing sudden onset ptosis and diplopia. MRI chest showed no residual thymic tissue. He was commenced on prednisolone 50 mg daily and received intravenous immunoglobulin, following which his symptoms completely resolved. Steroids were weaned over the next 4 months, and the patient was commenced on mycophenolate. At follow-up 12 months later, the patient remained asymptomatic.

Patient B

Patient B was a 24-year-old female who presented with several months of diplopia and ptosis. She had recently been diagnosed with hyperthyroidism, with elevated thyroglobulin, thyroid peroxidase, and thyroid receptor antibodies, for which she was taking carbimazole and prednisolone. The patient was otherwise well and had no significant past medical history or family history.

On examination, the patient had significant fatigable right sided ptosis. There was impairment in right eye abduction and adduction with preserved elevation and depression. Extraocular movements of the left eye were full. Saccades were of normal velocity. There was no Cogan’s lid twitch. Upper and lower limb examination revealed normal power, reflexes, and no fatiguability.

Repeat thyroid function tests were normal. AChR antibodies were positive at 3.24 nmol/L (reference range: <0.5) using AChR radioimmunoassay. MRI orbits showed no evidence of thyroid eye disease. CT chest demonstrated thymic hyperplasia without a focal mass lesion (Figure 2).

Figure 2.

CT chest demonstrating thymic hyperplasia in the anterior mediastinum (arrow).

The patient continued prednisolone and commenced pyridostigmine. Repeat AChR antibodies were positive. The patient underwent robotic thymectomy 12 months after diagnosis, with histopathology confirming thymolipoma. Postoperative MRI chest demonstrated no residual thymic tissue. Six months postoperatively, the patient was asymptomatic on a weaning dose of prednisolone.

Discussion

Thymolipoma is a rare thymic lesion that accounts for 2–9% of all thymic tumors.³ It is a benign, slow-growing tumor that histologically comprises a combination of normal thymic tissue and mature adipose tissue, with no features of atypia or mitotic activity.² Worldwide, the incidence of thymolipoma is estimated at 0.12 cases per 100 000 per year.³

The exact pathogenesis of thymolipoma is uncertain, although several theories have been proposed for its development. The most commonly accepted theory is that thymolipoma is a neoplasm of thymic fat containing involuting thymic remnants.⁴ Another theory describes thymolipoma formation secondary to fatty replacement of diffuse thymic hyperplasia.^4,5 Furthermore, it has more recently been suggested that long-term use of steroids may stimulate transformation from thymoma into thymolipoma via fatty degeneration.⁵

The rate of myasthenia gravis in association with thymolipoma is variable, reported in 2.8–50% of patients with thymolipoma.² Myasthenia gravis is thought to develop due to the presence of thymic myoid cells, which express AChR, and may stimulate the formation of ectopic germinal centers and subsequent autoantibody production in the thymus.⁶ In addition, thymolipoma has been implicated in other autoimmune conditions, including Graves’ disease, aplastic anemia, and lichen planus.²

The clinical presentation of thymolipoma is diverse. Often, thymolipoma is identified incidentally, as patients are asymptomatic in 30–50% of cases.⁵ Compressive symptoms, including cough, chest pain, dyspnea, and cyanosis, may occur in the setting of large tumors.⁴ When associated with myasthenia gravis, typical symptoms include ptosis, diplopia, limb weakness, fatiguability, dysphonia, and dysphagia.³ In the present study, both patients initially presented with features of ocular myasthenia gravis.

A recent systematic review by Alghamdi et al. identified 36 patients with thymolipomatous myasthenia gravis who underwent thymectomy.³ In this study, the mean age was 46.4 years (range 18–76 years) at time of myasthenia gravis diagnosis, and 47.7 years (range 16–76 years) at time of thymolipoma diagnosis. There was no gender predilection. Of patients tested for AChR antibody status, 81% were positive and 19% were negative. In half of cases, there was no mediastinal mass present on imaging.

Treatment of myasthenia gravis associated with thymolipoma involves both medical and surgical management, although, at present, there is no standardized treatment guideline. Medical therapy is the same as non-thymolipomatous myasthenia gravis, involving symptomatic management with acetylcholinesterase inhibitors, corticosteroids, and other immunosuppressants.^2,7 Importantly, surgical treatment via thymectomy is the only curative management option.^3,5 In the literature, surgical approaches for thymolipoma resection include sternotomy thymectomy, thoracotomy thymectomy, and video-assisted thoracoscopic thymectomy.³ Robotic thymectomy is a minimally invasive approach that has been shown to be a safe and effective method of complete thymic resection in patients with thymomatous myasthenia gravis.^8,9 Hospital stays may be as short as 3 days and patients can usually return to normal activities after 2 weeks.

Reported outcomes following thymectomy are varied. In a retrospective study comparing surgical outcomes in 267 myasthenia gravis patients, the rate of myasthenic complete stable remission was significantly higher in the thymolipomatous (41.7%) and non-thymomatous (42.3%) groups compared with the thymomatous group (28.8%, p = .029). None of the 12 thymolipoma patients included in this analysis experienced tumor recurrence or worsening of symptoms post-thymectomy.¹⁰ In the study by Alghamdi et al., 14% of thymolipoma patients experienced complete stable remission, and a further 53% had improvement in myasthenia gravis symptoms postoperatively. The remaining patients experienced no improvement or late recurrence of symptoms. There was a significant association between age and symptom improvement after thymectomy, with younger patients more likely to experience a positive outcome after surgery.³ However, the mechanisms underlying disease relapse and persistence of symptoms after thymectomy are not well understood.²

In conclusion, thymolipoma is a rare benign thymic lesion that may be associated with myasthenia gravis. Thymectomy is the only definitive treatment, with outcomes shown to be more favorable in younger patients. Robotic thymectomy is a safe and effective technique enabling minimally invasive surgical treatment of thymolipoma. Further studies will better inform clinician understanding of the presentation, management, and prognosis of thymolipoma associated myasthenia gravis.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The manuscript does not contain clinical studies or patient data.

Informed consent

Patients gave informed consent for inclusion in this report.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01658107.2025.2449873