Journal of Clinical & Experimental OncologyISSN: 2324-9110

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Case Report, J Clin Exp Oncol Vol: 3 Issue: 2

Unexpected Vocal Cord Paralysis and Myasthenia Gravis in a Patient with Squamous Cell Lung Cancer

Francesca De Iuliis1, Lucrezia Amoroso2, Luciana Blasi1, Stefania Vendittozzi2, Ludovica Taglieri1, Gerardo Salerno1, Giuseppe Buongiorno4, Giorgio Bandiera4, Rosina Lanza3 and Susanna Scarpa1*
1Experimental Medicine Department, School of Medicine, University Sapienza of Rome, Viale Regina Elena 324, 00162, Rome, Italy.
2Radiology, Oncology and Anatomo-pathology Department, School of Medicine, University Sapienza of Rome. S. Andrea Hospital, via di Grottarossa 1035, 00189 Rome, Italy
3Gynecology and Obstetrics Department. School of Medicine, University Sapienza of Rome. Viale Regina Elena 324, 00162, Rome, Italy
4NESMOS Department, School of Medicine, University Sapienza of Rome. S. Andrea Hospital, via di Grottarossa 1035, 00189 Rome, Italy.
Corresponding author : Susanna Scarpa
Experimental Medicine Department, Viale Regina Elena 324, University of Rome 'Sapienza', 00161 Rome, Italy
Tel: +393395883081
Received: February 07, 2014 Accepted: April 15, 2014 Published: April 18, 2014
Citation: De Iuliis F, Amoroso L, Blasi L, Vendittozzi S, Taglieri L, et al. (2014) Unexpected Vocal Cord Paralysis and Myasthenia Gravis in a Patient with Squamous Cell Lung Cancer. J Clin Exp Oncol 3:2. doi:10.4172/2324-9110.1000122


Vocal cord paralysis is a voice disorder that occurs when one or both the vocal cords don’t open or don’t close properly. This often determines difficulty in swallowing and coughing by the patient, because food or liquids slip into the trachea and the lungs. Vocal cord paralysis may be caused by trauma, cancer, surgery, or intubation and it has been sometimes described to follow vinca alkaloid treatment. Myasthenia gravis is an autoimmune disorder that can represent a paraneoplastic syndrome in cancer patients. We report a 55-years-old male with an advanced squamous cell lung carcinoma, presenting a unilateral vocal cord paralysis immediately after the treatment with gemcitabine, and myasthenia gravis one week after. To date, there aren’t any data in the literature describing causal relationship between non small cell lung cancer and myasthenia gravis; here we suggest that myasthenia gravis simultaneous to lung cancer might be a rare form of paraneoplastic syndrome. It is impossible to find a single cause for our patient vocal cord paralysis: it could in fact have a multifactorial pathogenesis, not excluding the possibility of a single rare paraneoplastic syndrome, which includes both myasthenia gravis and vocal cord paralysis.

Keywords: Non small cell lung cancer (NSCLC); Vocal cord paralysis; Paraneoplastic syndrome; Myasthenia gravis; Quality of life; Lung cancer


Non small cell lung cancer (NSCLC); Vocal cord paralysis; Paraneoplastic syndrome; Myasthenia gravis; Quality of life; Lung cancer.


Advanced lung cancer is one of the most aggressive tumors and one of the less responsive to treatments. The primary goal in the management of these patients is the improvement of their quality of life, since this is often compromised because of underlying disease and of chemotherapy side effects [1]. Neurological complications frequently occur in patients with cancer as side effects of therapy, compression or tumor invasion of nerves or lymph nodes. In 20% of lung cancers, neurological symptoms can be associated with various paraneoplastic syndromes (encephalomyelitis, sensory neuropathy, myasthenia). Paraneoplastic neurologic syndromes (PNS) can generally precede the cancer or, sometimes, can be the presenting symptom of the tumor. The cause of all paraneoplastic disorders is related to the release of substances into the blood stream which can have negative effects on the body, sometimes triggering autoimmune humoral or cellular responses, with the presence of multiple kind of antibodies also in the same patient [2,3].
PND can affect all regions of nervous system and the diagnosis of PND should be taken in consideration in every insidiously progressive neurologic condition, when no clear alternate diagnosis is possible.
Several antineoplastic drugs (cisplatin, taxanes, vinca alkaloids) widely used in the treatment of lung cancer can cause neurological toxicity related to impaired nerve transmission, especially in predisposed patients or patients with neurological comorbidities.
Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG) are well known classical paraneoplastic syndromes of small cell lung carcinoma (SCLC), but not of NSCLC.

Case Report

A 55-year-old man, with 40 pack-year history of smoking, was referred to our hospital describing a sharp chest pain that spread to the left side of the chest continuously for one week and weight loss during the two last months. The pain was not associated with cough and physical exercise and it didn’t change location. He complained of hemoptysis, hoarseness and dyspnea, swelling of the lower extremities and loss of appetite. His medical history described past myocardial infarction, diabetes mellitus and hypertension. Blood tests were normal except for hemoglobin (9.5 g/dl); serum tumor markers (CEA, CA125, CA19.9) were negative. A chest CT revealed a 4.5 cm circumscribed mass in the left lung hilum that infiltrated the middle and posterior mediastinum, the left pulmonary artery and the left main bronchus, with lymphadenopathy in the hilum and aortopulmonary window (Figure 1). The diagnosis of poorly differentiated squamous cell lung carcinoma was performed on the bronchoscopic biopsy.
Figure 1: Contrast-enhanced CT showing a 4,5 cm circumscribed mass in left lung hilum.
Bone scintigraphy was negative; after cardiological evaluation and echocardiogram (ejection fraction was 45%), the patient underwent 3 cycles of carboplatin (AUC 5) + vinorelbine 30 mg/mq d1, 8 q21. The patient didn’t report any side effect from the chemotherapy.
At the end of chemotherapy, a CT scan was performed, showing an increase of the left lesion and other new small lesions in the lung left lower lobe. So the patient underwent three cycles of docetaxel 75 mg/mq d1 q21 without significant toxicity. Unfortunately, a CT scan assessment showed progression of lung disease.
Considering the good general condition of the patient and the absence of side effects associated with the treatment, the patient was submitted to a third-line chemotherapy with gemcitabine 1000 mg/mq d1, 8, 15 q28.
At the end of the first infusion, the patient developed hoarseness, stridor and dysphonia, progressing to nearly total aphonia. An endoscopy was performed showing the left vocal cord in adducted position with loss of movement (Figure 2) Otolaryngology evaluation and flexible laryngoscopy performed the diagnosis of unilateral irreversible left vocal cord paralysis (VCP).
Figure 2: Endoscopic images of left vocal cord paralysis.
A contrast enhanced CT scan of soft tissue neck was performed and it firstly showed that the left vocal cord was hypotonic and rigid, as compared to the right one, secondly it showed that there wasn’t any metastatic compression from adenopathy along the course of the recurrent laryngeal nerve (Figure 3). In parallel, the images of the chest demonstrated enlargement of the lung cancer and metastatic nodes in the aortopulmonary window (Figure 4).
Figure 3: Contrast-enhanced CT of neck soft tissues.
Figure 4: Contrast-enhanced CT showing enlargement of the lung cancer and metastatic nodes in the aortopulmonary window.
Complete blood chemistry, electrolytes and serum proteins were normal, anti-lue antibodies were negative. At that time the patient was recommended to have further investigations but he refused any procedure (laryngeal electromyography, thyroid ultrasonography, esophageal transit, MRI of the neck). After one week he described symptoms of muscle weakness, diplopia, dysphagia, and fatigue; also a bilateral asymmetric ptosis was noted. A new neurologic examination was performed, which confirmed bilateral ptosis, moderate weakness in proximal muscles and low weakness in distal muscles, normal reflexes and normal sensory function. A test with 2 mg of intravenous edrophonium was performed, and it was positive. The presence of serum autoantibodies against muscle proteins titin (positivity range 0.6-1.5 ng/ml) and ryanodin receptor (positivity range 0.3-20 ng/ml) resulted positive, while antibodies against acetylecholine receptor (AChR-MG) and muscle-specific receptor tyrosine-kinase (MuSKMG) were negative. The diagnosis of myasthenia gravis was determined. We then suggested to the patient to perform a standard repetitive nerve stimulation (RNS) test, but the patient refused to follow our indication. Furthermore, the patient refused any other kind of examination and treatment, therefore a supportive care was proposed to him. After 3 months, a CT scan showed liver metastasis and disease progression, the patient had a progressive deterioration of general medical conditions, and he died two weeks later.


We present the case of a patient affected by an advanced NSCLC who reported a VCP suddenly arosen after the first infusion of gemcitabine and then, after one week, symptoms related to MG. Both VCP and MG determined a negative impact on the clinical history of our patient. Literature doesn’t describe any causal relationship between NSCLC and MG, we suggest for the first time that MG simultaneous with lung cancer might be a rare form of paraneoplastic syndrome. Also for what regards to VCP in our patient, it could have a multifactorial pathogenesis, not excluding the possibility of a single rare paraneoplastic syndrome.
Paraneoplastic syndromes are frequently associated with lung cancer [4-7]; the symptoms can be different, depending on the substance or the hormone which is secreted (ectopic ACTH, parathyroid-like hormone, antidiuretic-like hormone). Paraneoplastic neurological syndromes (PNS) are rare and occur as a remote effect of tumors, not directly caused by mass lesions, metastases, infections, nutritional factors or anti-tumor treatment. Small cell lung cancers (SCLC) are the tumors most frequently associated with PNS, while paraneoplastic syndrome is rarely correlated to NSCLC [8-10].
Our patient had a left lung collapse due to an enlarged mass in the left hilum, with an evidence of metastatic node in the aortopulmonary window near the pathway of the left recurrent laryngeal nerve that might justify VCP, but not its fast onset. The neoplastic compression of laryngeal nerve could be a valid theory [11-13], although no diagnostic evidence of compression was performed. The most interesting feature was the sudden appearance of dysphonia immediately after the end of the infusion of chemotherapy: the suddenness of this dysphonia suggested an acute event (paraneoplastic syndrome?), rather than the result of a much slower invasive process. MG is an autoimmune neuromuscular disorder, considered as a paraneoplastic syndrome when associated with thymoma (in 15% of cases) or other malignancies. The manifestations of MG are muscle fatigability and weakness, caused by antibody-mediated reaction against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction [14]. The first clinical signs of MG are diplopia and ptosis, characteristic of the ocular form of the disease. In generalized MG, the weakness extends to bulbar muscles (with consequent dysarthria, dysphonia, chewing and swallowing difficulties), trunk muscles (respiratory difficulties) and limb muscles. A recent paper has described the VCP as the first and only manifestation of MG in some patients [15]. The Myasthenia Gravis Foundation of America Clinical Classification divides MG into 5 main classes and several subclasses [16]: our patient corresponded to Class IIa, predominantly affected limbs, axial muscles and lesser involvement of oropharyngeal muscles. Many factors may trigger or worsen exacerbations of MG, we suggest that chemotherapy could have permitted the onset of a paraneoplastic myasthenia-like syndrome in our patient. To better evaluate our patient's muscle weakness and to confirm the diagnosis of MG, we asked him to perform a standard repetitive nerve stimulation (RNS) test, which is one of the most sensitive diagnostic test in patients with presynaptic neuromuscular junction (NMJ) disorders, but he refused the proposed examination. The patient did not agree to have further investigations, so it was impossible to perform an efficient investigation for the lack of compliance. Whether the patient should have made a therapy with pyridostigmine, he could have quickly improved myasthenic symptoms, as demonstrated by the positive test with edrophonium. The steroid therapy should have been proposed only at low doses and with strict control of blood glucose, considering the diabetes. The lack of compliance had worsened significantly the clinical outcome.
Vocal cord paralysis (VCP) is a common disorder. The severity of voice and swallowing problems depends on the position where the nerve damage occurs and symptoms range from mild to life threatening. It can be due to head and neck injuries, viral infections, neck or chest tumors, complications from endotracheal intubation, neurologic insults, such as a stroke, or neurologic diseases, such as multiple sclerosis or Parkinson’s disease. In many cases, however, the cause is unknown [17,18]. Our patient had been analyzed for anti-lue antibodies in order to rule out any lue-correlated paralysis and he resulted negative. Metabolic diseases, such as diabetes mellitus, can cause VCP: our patient had neither previous clinical symptoms nor positive history for inherited neuropathy, furthermore the performed neurological examinations did not reveal any deficiency or peripheral neuropathy. In fact our patient’s diabetes was totally controlled by therapy, without showing any side effect, as demonstrated by blood tests, with normal values of glycemia and glycosylated hemoglobin.
Treatment of VCP may include voice therapy, bulk injections, surgery or a combination of treatments. In some cases, the voice returns normal without treatment during the first year after damage. For this reason, doctors often delay corrective surgery for at least one year, to be sure that the voice does not recover spontaneously. During this time, the suggested treatment is usually voice therapy, which may involve exercises to strengthen the vocal cords or improve breath control during speech. The surgery technique adds bulk to the paralyzed vocal cord or changes its position; there was certainly no indication to surgery for our patient, due to the advanced stage of disease.
Rare side effects of cisplatin and vincristine [19-21] therapy can be the one-sided paralysis of the vocal cord and this has never been described for other chemotherapeutic agents, not even for the gemcitabine. Gemcitabine is an antimetabolite, mainly responsible for hematological (thrombocytopenia, neutropenia) and gastrointestinal (nausea, vomiting, diarrhea) toxicities. Neurotoxic side effects have not been described in relation to gemcitabine, except rare cases of reversible CNS symptoms [22]. In addition, our patient previously treated with carboplatin and vinorelbine, showed good tolerance and no neurological deficits.
Patients with lung cancer are very heterogeneous, and this case report demonstrates how the presence of a disabling health condition can have a serious impact on compliance and outcomes. Seemingly, severe symptoms, as in our case, can often determine a psychological distress and a consequent poor quality of life.


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