Myasthenia gravis and prostatic neoplasia: a rare association

Abstract

An 88-year-old male patient presented with left ptosis, diplopia, muscle weakness of the lower limbs, dysphagia for solids, dysphonia and constipation. On investigation, he was found to have myasthenia gravis (MG). Further evaluation for the possible cause of MG, with CT scan, revealed that the patient had concomitant prostatic cancer. The patient was given steroids and pyridostigmine, with consequent resolution of his neurological symptoms. This is a rare case of MG associated with prostatic cancer.

Background

Myasthenia gravis (MG) is an autoimmune disease, affecting the neuromuscular junction through autoantibodies to postsynaptic acetylcholine receptors (AChRs), blocking acetylcholine attachment at the postsynaptic junction. This process results in a lack of the excitatory effects of acetylcholine, leading to varying degrees of weakness of skeletal muscles and fatigability. This disease is commonly associated with autoimmune conditions, including autoimmune thyroiditis, Graves’ disease, rheumatoid arthritis and systemic lupus erythematosus, but it can present itself as a paraneoplastic syndrome, such as in 15% of thymomas.

Extramediastinic malignancies have also been reported but are rare, the association with prostatic cancer has been reported as extremely rare. We present a case of a man with MG as a presenting symptom of prostate carcinoma.

Case presentation

An 88-year-old male patient presented to the emergency department with left ptosis and occasional diplopia of 1 week duration, with progressive worsening.

The patient’s medical history revealed muscle weakness of the lower limbs (impairing his walking for over 6 months), dysphagia for solids, dysphonia and constipation for the last 4 months. The patient had also a history of hypertension, dyslipidaemia, obesity (body mass index 33 kg/m²) and ischaemic cardiomyopathy. He had never smoked in the past and had no significant occupational/environmental exposures.

Physical examination revealed bilateral ptosis, more severe on the left side; left ophthalmoparesis, with fatigability and horizontal binocular diplopia in the levo and dextroversion. We also found moderate dysarthria, hypophony and dysphonia. The physical examination was otherwise unremarkable, and the patient was haemodynamically stable.

Investigations

A complete blood count and metabolic panel were ordered and were significant for a slight leukocytosis (white cell count: 13.1×10⁹/L, polymorphonucleates: 73.7%) and a high C reactive protein 11.83 mg/dL; the other laboratory tests were unremarkable.

Cranial CT showed signs suggestive of lacunar stroke in both cerebral hemispheres, chronic infarct in the right cerebellum and diffuse cerebral atrophy.

The patient was hospitalised with the initial presumptive diagnosis of ischaemic vertebrobasilar stroke. An MRI of the brain was performed, and it showed no signs of acute ischaemic stroke.

Therefore, it was considered the possibility of a neuromuscular disorder. To quickly confirm this diagnosis, a bedside ice test was performed, holding ice packs over the patient’s closed eyes for 1 min, after which, the ptosis showed a marked improvement, in particular on the left, and the improvement persisted for several minutes.

In the next days, the patient was submitted to further investigations. An edrophonium test was performed, injecting intravenously 10 mg edrophonium. The patient showed significant ptosis improvement, and decreased fatigability, quickly after edrophonium administration, and it lasted around 10 min.

Subsequently, he was submitted to electromyography whose result was compatible with neuromuscular dysfunction, suggestive of MG. Serology tests were negative for antibodies against AChRs and antibodies against the tyrosine kinase muscle-specific kinase (MuSK) protein.

He was admitted as a seronegative MG syndrome. Investigation for hidden malignancy was completed with CT of the chest, abdomen and pelvis, revealing signs of prostatic adenocarcinoma, with local invasion and bone metastases.

Treatment

After confirmation of MG with edrophonium test, the patient immediately started treatment with oral corticosteroids (prednisolone 60 mg/day) and acetylcholinesterase inhibitor (pyridostigmine 30 mg, three times a day), showing progressive improvement of all symptoms.

Considering the advanced stage of the prostate cancer (stage IV), and after discussion with both the patient and his family, it was decided not to proceed with further diagnostic investigation.

The patient started hormonal treatment with leuprolide 7.5 mg monthly.

Outcome and follow-up

The patient was evaluated in consultation, showing signs of remission of his neurological symptoms—resolution of ptosis, diplopia and dysphonia. The patient continued to be followed-up in oncology consultation as well.

Discussion

MG is an autoimmune disorder, resulting from the production of antibodies to AChRs at the neuromuscular junction, being characterised by skeletal muscle weakness, with easy fatigability, diplopia, dysphagia and even respiratory compromise.

MG is considered a paraneoplastic phenomenon, frequently associated with thymomas, present in 10%–15% of patients with MG.¹ It may also be present in other malignant neoplasms, and there are several large series of reports of MG associated with extrathymic tumours, with a frequency between 1.7% and 9%.^2–8 Leukaemia, lymphoma, breast cancer and colon cancer were the most common extrathymic malignant tumours found in these patients. However, the presence of prostate cancer in patients with MG has been reported as extremely rare.

We reported a case of prostate cancer that presented itself with seronegative MG. The patient had symptoms of MG for over 6 months, and no indication of the underling neoplasm.

The definitive diagnosis of MG depends on a combination of clinical, serological and electrophysiological findings.^{9 10} In this case, an ice test was initially performed that quickly supported this diagnosis, subsequently confirmed by the edrophonium test and electromyography.

In approximately 80% of patients with MG, autoantibodies to AChR are present.¹¹ These antibodies are specific for MG, thus presenting an additional diagnostic test. In patients with negative AChR antibodies, almost half present autoantibodies against the MuSK protein. In this patient, serology tests were negative for both anti-MuSK and anti-AChR antibodies. Nevertheless, autoantibodies such as anti-LRP4 could be present, and were not examined.

The treatment of MG includes corticosteroids, acetylcholinesterase inhibitors, high dose intravenous immunoglobulin, plasma exchange, thymectomy or, in cases of extrathymic tumours, treatment of underling condition. This patient started treatment of MG with prednisolone and pyridostigmine, showing good results.

Although we suspect this case could be a paraneoplastic phenomenon, we cannot be certain. We would only be able to prove this causality effect by observing a resolution of neurological symptoms after treating the prostatic cancer. Since this patient has advanced prostatic cancer, he was only subjected to non-curative hormonal therapy. However, we consider this possibility very plausible, as it is quite unusual for MG to start after the age of 80.

Even though the association with prostatic cancer is rare, this case shows the importance of a thoroughly search for neoplasia though the entire body, allowing its early diagnose, and proper treatment.

The timely and appropriate treatment of cancer is critical, not only to improve the patient prognosis, but also in controlling the symptoms of MG.

Learning points.

• Myasthenia gravis (MG) is often a paraneoplastic phenomenon, not exclusively associated with thymomas.

• A patient with MG should undergo a thorough investigation for association with neoplasms.

• Starting treatment of an underlying neoplasia early is important for both prognoses and in controlling the symptoms of MG.