Myasthenia gravis that has developed long after radical resection of lung cancer: A case report

  • Authors:
    • Shinichiro Okauchi
    • Ayako Shioya
    • Kesato Iguchi
    • Kinya Furukawa
    • Hiroaki Satoh
  • View Affiliations

  • Published online on: July 5, 2022
  • Article Number: 554
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Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission and is a heterogeneous disorder generally caused by auto‑antibody to the nicotinic acetylcholine receptor. The current study presented a rare case of MG that occurred a long time after surgical resection of lung cancer. A 58‑year‑old man with lung adenocarcinoma underwent upper lobectomy and mediastinal lymph node dissection. Severe myasthenic symptoms began 7 years after the operation, and emergent mechanical ventilation was needed because of myasthenic crises. Levels of serum anti‑acetylcholine receptor antibody were high and typical decremental responses to repetitive stimulation on electromyography were observed. Appropriate therapies for a severe acute condition were performed, and MG has been controlled for 6 years since then. There is no recurrence of lung cancer or appearance of thymoma. In conclusion, although very rare, physicians should be aware of MG as a potential comorbidity developing in patients with a history of lung cancer.


Clinically, myasthenia gravis (MG) and Lambert-Eaton syndrome are characterized by muscle weakness and easy fatigability. These symptoms are brought about by an impairment of nerve and muscle synaptic transmission (1). MG is often caused by autoantibodies to the acetylcholine receptors on the postsynaptic membrane (2), whereas, Lambert-Eaton syndrome develops mainly due to autoantibodies to calcium channels in the presynaptic membrane (3). Numerous patients with MG also develop thymic abnormalities such as thymoma and thymus hyperplasia (2). In contrast, Lambert-Eaton syndrome frequently occurs concomitantly with lung cancer, especially small cell lung cancer (3). Patients with lung cancer who develop MG are extremely rare (4-17). Furthermore, there have been no reports of MG developing several years after the lung cancer was completely resected. We herein report a rare case of MG that occurred seven years after a surgical resection of lung cancer. This patient developed myasthenic crisis, a critical condition in which rapidly occurred severe weakness of the pharyngeal and respiratory muscles. After successful treatment with mechanical ventilation, plasma exchange and methylprednisolone, the patient has been followed up for more than 6 years.

Case report

A 58-year-old man underwent upper lobectomy and mediastinal lymph node dissection due to T2aN0M0, stage IB lung adenocarcinoma (Fig. 1) at Ibaraki Medical Center, Tokyo Medical University (Ami, Ibaraki, Japan) in January 2008. He had neither thyroid nor other autoimmune disorders, nor a family history of neuromuscular or autoimmune disorder. He did not have any postoperative recovery difficulties that might have suggested pre-existing neuromuscular transmission disorder. Fifteen months after resection, there was swelling of the left lower tracheal bronchial lymph node, which was irradiated with 60 Gy. Six years after the end of irradiation, he presented at Mito Medical Center, University of Tsukuba (Mito, Ibaraki, Japan) with a chief complaint of double vision, bilateral eyelid drooping, and difficulty swallowing for one month. He was not taking any antiarrhythmic agents or other drugs impairing neuromuscular transmission. Development of thymic disease and recurrence of lung cancer were ruled out on imaging studies. Neurologic examination showed ptosis and gaze palsy with facial muscle weakness and reduced gag reflex. The repetitive nerve stimulation test (RNS) showed abnormal (>10%) decrement in facial, accessory, median nerve (Fig. 2; median nerve, stimulation frequency 10 Hz). Waning was observed in the repeated stimulation test, and the serum anti-acetylcholine receptor (AchR) antibody level was 67.0 nmol/l (normal: up to 0.2 nmol/l). With these findings, we diagnosed generalized MG of Ossermann II type. In addition to cholinesterase inhibitors (180 mg/day, oral), we started plasma exchange and treatment with prednisolone (2.5 mg/day, oral) which was gradually increased. On day 26 after hospitalization, he had acute respiratory failure and needed mechanical ventilation for myasthenic crisis. He had pulse therapy with methylprednisolone at 1,000 mg/day (three days) and plasma exchange six times within a month, and was successfully discharged from the hospital. Prednisolone (60 mg/day) gradually decreased to 10 mg/day, and pyridostigmine (180 mg/day, oral) continued at the same dose for 16 weeks. However, the symptoms of MG worsened 17 and 25 months after the start of treatment for MG, and the dose of prednisolone was increased up to 30 mg/day and plasma exchange was performed again. Symptoms of MG were improved, and these drugs gradually decreased. Six years have passed since the end of treatment, but neither recurrence of lung cancer nor development of thymoma has been confirmed. AchR antibody level in recent years has been 6.5-8.2 nmol/l, which are higher than the normal value, but the symptoms associated with MG are controlled. At present, prednisolone has been tapered down to 60 mg/day and 13 mg/day, respectively. Fig. 3 shows a timeline with relevant data from the episode of care.


When symptoms such as double vision, eyelid drooping, and difficulty in swallowing occur in patients with a history of thymic disease, a patient may have developed MG and should be diagnosed and treated accordingly. When such myasthenic symptoms manifest in patients with lung cancer, Eaton-Lambert syndrome should be included in the differential diagnosis. In our patient, whole-body imaging studies, including of the chest, showed no recurrence and no development of thymoma for 14 years after the diagnosis of lung cancer. MG was diagnosed on the basis of elevated serum AchR level, a typical decreasing response to repeated stimulation of EMG, and positive findings on the tensilon test.

The first case with MG associated with lung cancer was reported by Hazard et al in 1986(4). Since then, to our best knowledge, 14 lung cancer patients with MG have been reported (4-17). Of these 14 cases, six were small cell lung cancer, one was LCNEC, and seven were non-small cell lung cancer. Previous reports have reported that MG onset was more common in patients with small cell lung cancer (4-6,13,16,17), but there were cases of non-small cell lung cancer that also developed MG (7-12,14,15). Regarding the onset time of lung cancer and MG, nine patients were diagnosed with lung cancer at the time of MG onset (4,5,9,10,12-16). In three cases, however, the onset of MG preceded the diagnosis of lung cancer by eight months to six years (6,8,17). On the other hand, in two cases, the onset of MG anteceded the diagnosis of lung cancer by two to three years (7,11). One patient developed MG when lung cancer recurred (11). In this patient, chemotherapy, radiation therapy, and surgical resection were performed, but two years later, lung cancer recurred with pleural effusion and MG developed (11). Interestingly, in one case, as in our patient, the diagnosis of lung cancer preceded the onset of MG (7). This patient had developed MG three years after the diagnosis of lung cancer. Due to invasion of the vertebral body at the time of his diagnosis of lung cancer, complete resection was not performed. The pathological diagnosis of lung cancer in this patient was poorly differentiated anaplastic malignancy with a number of atypical cells and multiple mitoses consistent with large-cell carcinoma of the lung (7). One year later, the patient developed adenocarcinoma of the other lung and he died of systemic complications of MG ~2 years after the initial diagnosis of MG (7). Considering this course, the possibility of residual lung cancer and involvement of new lung cancer in the onset of MG could not be ruled out in this patient. In our patient with completely resected stage IB lung cancer, there had been no lung cancer recurrence and no development of thymoma until the onset of MG six years after irradiation. Although the mechanism was unknown, considering that AchR antibody levels were higher than normal even in recent years, we speculated that the memory of immunocompetent cells was involved in the onset of MG (18), not the residual lesions of lung cancer.

Treatment of advanced lung cancer has made great strides in the last decade; particularly, treatment with immune checkpoint inhibitors (ICPIs) has significantly improved prognosis. Alongside, the immune-related side effects (irAEs) caused by ICPI have attracted attention, including ICPI-related MG (19,20). Safa et al reported that MG is a life-threatening irAE of acute onset and rapid progression after ICPI initiation (19). In a previous review of the 23 reported cases of ICPI-associated MG, 72.7% were de novo presentations, 18.2% were exacerbations of pre-existing MG and 9.1% were exacerbations of subclinical MG (20). Our patient did not receive any ICPI treatment, therefore, the possibility of developing ICPI-related MG can be completely ruled out. However, ICPI-related MG is an interesting irAE from the viewpoint of pathogenesis and treatment method, and future research will be expected.

Survival time was described in 6 lung cancer patients with MG (7,8,10,15-17). Three of them died within two years after initiation of therapy for these diseases (7,16,17). Only one patient was followed up for more than 3 years (10). This patient had lung cancer and MG found at the same time, and the symptoms of MG disappeared after lung cancer resection, and he had been taking pyridostigmine bromide for 4 years and 2 months (10). In our patient, recurrence occurred at the mediastinal lymph nodes 15 months after the resection, and radical irradiation was performed on the mediastinum. MG developed 6 years after the irradiation. No additional treatment for lung cancer was subsequently given, but there has been no recurrence of lung cancer for 6 years. To the best of our knowledge, this was the longest survived patient, and is interesting in terms of treatment of lung cancer and MG.

In our patient, recurrence of lung cancer or development of thymic disease could be ruled out on imaging studies for more than six years after MG was controlled. We must carefully follow up the patient not to overlook the recurrence of lung cancer and the development of thymic disease, even if MG is controlled. This case indicates that physicians should be aware that MG as a potential comorbid disease can develop in patients with a history of lung cancer.


Not applicable.


Funding: No funding was received.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

SO, AS, KI, KF and HS contributed to the planning, conduct, reporting, conception, design and acquisition of data and drafting the manuscript. All authors read and approved the final manuscript. SO and HS confirm the authenticity of all the raw data.

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of the Mito Medical Center, University of Tsukuba-Mito Kyodo General Hospital (approval no. 16-39).

Patient consent for publication

Written informed consent from the patient for the publication of their data was obtained from the patient.

Competing interests

The authors declare that they have no competing interests.



Rodríguez Cruz PM, Cossins J, Beeson D and Vincent A: The neuromuscular junction in health and disease: Molecular mechanisms governing synaptic formation and homeostasis. Front Mol Neurosci. 13(610964)2020.PubMed/NCBI View Article : Google Scholar


Dresser L, Wlodarski R, Rezania K and Soliven B: Myasthenia gravis: Epidemiology, pathophysiology and clinical manifestations. J Clin Med. 10(2235)2021.PubMed/NCBI View Article : Google Scholar


Huang K, Luo YB and Yang H: Autoimmune channelopathies at neuromuscular junction. Front Neurol. 10(516)2019.PubMed/NCBI View Article : Google Scholar


Hazard PB, Bertorini TE and Griffin JP: Myasthenia gravis associated with small cell carcinoma of the lung. J Tenn Med Assoc. 79:273–276. 1986.PubMed/NCBI


Fujita J, Yamadori I, Yamaji Y, Yamagishi Y, Takigawa K and Takahara J: Myasthenia gravis associated with small-cell carcinoma of the lung. Chest. 105:624–625. 1994.PubMed/NCBI View Article : Google Scholar


Miyoshi R, Yamaji Y, Shima S, Fujita J, Okada H and Takahara J: A case of small cell lung cancer that developed during therapy for myasthenia gravis. Nihon Kyobu Shikkan Gakkai Zasshi. 33:456–462. 1995.PubMed/NCBI(In Japanese).


Leavitt JA: Myasthenia gravis with a paraneoplastic marker. J Neuroophthalmol. 20:102–105. 2000.PubMed/NCBI View Article : Google Scholar


Sakamaki Y, Yoon HE and Oda N: Non-small-cell lung cancer associated with non-thymomatous myasthenia gravis. Jpn J Thorac Cardiovasc Surg. 54:207–211. 2006.PubMed/NCBI View Article : Google Scholar


Takagi M and Akiba T: A case of surgically treated primary lung cancer with myasthenia gravis. Nihon Kokyuki Gakkai Zasshi. 45:198–201. 2007.PubMed/NCBI(In Japanese).


Kataoka K, Fujiwara T, Matsuura M and Seno N: A case of simultaneously operated primary multiple lung cancers with nonthymomatous myasthenia gravis. Jpn J Lung Cancer. 49:273–277. 2009.(In Japanese).


Peltier AC, Black BK, Raj SR, Donofrio P, Robertson D and Biaggioni I: Coexistent autoimmune autonomic ganglionopathy and myasthenia gravis associated with non-small-cell lung cancer. Muscle Nerve. 41:416–419. 2010.PubMed/NCBI View Article : Google Scholar


Shaygannejad V, Ghasemi M and Rajaee Z: Myasthenia gravis as a presenting feature in a patient with lung cancer: A case report. J Res Med Sci. 16:229–232. 2011.PubMed/NCBI


Ohira M, Jeong D and Oh SJ: Seropositive myasthenia gravis associated with small-cell lung carcinoma. J Clin Neurol. 7:43–46. 2011.PubMed/NCBI View Article : Google Scholar


Takizawa M, Oda M, Matsumoto I, Waseda R, Tanaka N and Watanabe G: Myasthenia gravis complicated with lung cancer and middle mediastinal thymoma. Asian Cardiovasc Thorac Ann. 20:486–488. 2012.PubMed/NCBI View Article : Google Scholar


Niimi K, Nagata E, Murata N, Sato M, Tanaka J, Horio Y, Takiguchi H, Tomomatsu H, Tomomatsu K, Hayama N, et al: Lung cancer associated with seronegative myasthenia gravis. Intern Med. 54:1381–1384. 2015.PubMed/NCBI View Article : Google Scholar


Yamasaki M, Funaishi K, Saito N, Yonekawa T, Yamawaki T, Ihara D, Daido W, Ishiyama S, Deguchi N, Taniwaki M and Hattori N: Acetylcholine receptor antibody-positive myasthenia gravis associated with small-cell lung cancer: A case report. Medicine (Baltimore). 97(e0541)2018.PubMed/NCBI View Article : Google Scholar


Jia R, Chen J, Ge R, Zheng Q, Chen F and Zhao Z: Coexistence of myasthenia gravis and Lambert-Eaton myasthenic syndrome in a small cell lung cancer patient: A case report. Medicine (Baltimore). 97(e10976)2018.PubMed/NCBI View Article : Google Scholar


Stathopoulos P, Kumar A, Heiden JA, Pascual-Goñi E, Nowak RJ and O'Connor KC: Mechanisms underlying B cell immune dysregulation and autoantibody production in MuSK myasthenia gravis. Ann NY Acad Sci. 1412:154–165. 2018.PubMed/NCBI View Article : Google Scholar


Safa H, Johnson DH, Trinh VA, Rodgers TE, Lin H, Suarez-Almazor ME, Fa'ak F, Saberian C, Yee C, Davies MA, et al: Immune checkpoint inhibitor related myasthenia gravis: Single center experience and systematic review of the literature. J Immunother Cancer. 7(319)2019.PubMed/NCBI View Article : Google Scholar


Makarious D, Horwood K and Coward JI: Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors. Eur J Cancer. 82:128–136. 2017.PubMed/NCBI View Article : Google Scholar

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Okauchi S, Shioya A, Iguchi K, Furukawa K and Satoh H: Myasthenia gravis that has developed long after radical resection of lung cancer: A case report. Exp Ther Med 24: 554, 2022
Okauchi, S., Shioya, A., Iguchi, K., Furukawa, K., & Satoh, H. (2022). Myasthenia gravis that has developed long after radical resection of lung cancer: A case report. Experimental and Therapeutic Medicine, 24, 554.
Okauchi, S., Shioya, A., Iguchi, K., Furukawa, K., Satoh, H."Myasthenia gravis that has developed long after radical resection of lung cancer: A case report". Experimental and Therapeutic Medicine 24.3 (2022): 554.
Okauchi, S., Shioya, A., Iguchi, K., Furukawa, K., Satoh, H."Myasthenia gravis that has developed long after radical resection of lung cancer: A case report". Experimental and Therapeutic Medicine 24, no. 3 (2022): 554.