Paraneoplastic Necrotizing Myopathy in Lung Cancer
Paraneoplastic Necrotizing Myopathy in Lung Cancer
Introduction: Inflammatory myopathies (such as dermatomyositis and polymyositis) are well-recognized paraneoplastic syndromes. However, paraneoplastic necrotizing myopathy is a more recently defined clinical entity, characterized by rapidly progressive, symmetrical, predominantly proximal muscle weakness with severe disability, and associated with a marked increase in serum muscle enzyme levels. Paraneoplastic necrotizing myopathy requires muscle biopsy for diagnosis, which typically shows massive necrosis of muscle fibers with limited or absent inflammatory infiltrates.
Case Presentation: We report the case of an 82-year-old Italian-born Caucasian man who was admitted to hospital because of heart failure and two drop attacks. Over the following days, he developed progressive severe weakness, dysphagia, and dysphonia. Testing showed increasing serum muscle enzyme levels. Electromyography showed irritative myopathy of the proximal muscles and sensorimotor polyneuropathy. Muscle biopsy (left vastus lateralis) showed massive necrosis of muscle fibers with negligible inflammatory infiltrates, complement membrane attack complex deposition on endomysial capillaries, and moderate upregulation of major histocompatibility complex-I. Computed tomography of the thorax showed a nodular mass in the apex of the right lung. The patient was diagnosed with paraneoplastic necrotizing myopathy. In spite of high-dose corticoid therapy, he died 1 month later because of his aggressive cancer. Subsequent electron microscopic examination of a muscle biopsy specimen showed thickened walls and typical pipestem changes of the endomysial capillaries, with swollen endothelial cells. Poorly differentiated adenocarcinoma of the lung was confirmed on post-mortem histological examination.
Conclusions: Paraneoplastic necrotizing myopathy is a rare syndrome with outcomes ranging from fast progression to complete recovery. Treatment with corticosteroids is often ineffective, and prognosis depends mainly on the characteristics of the underlying cancer. This case shows that paraneoplastic necrotizing myopathy may have an atypical appearance, and should be considered in elderly patients with neoplastic disease. In this case, the diagnosis was delayed by the unusual clinical picture that suggested heart disease rather than muscle disease.
Paraneoplastic necrotizing myopathy is a rare condition associated with cancer and characterized by massive necrosis of muscle fibers in the absence of significant inflammation. It is part of the distinct disease entity of necrotizing myopathy, which has been added as an independent new domain to idiopathic inflammatory myopathy. As autoimmunity is considered to play a role in the development of this condition, it is currently known as necrotizing autoimmune myopathy (NAM). An association between myopathy and cancer has been reported for the past century. This myopathy occurs in less than 1% of patients with cancer, and often precedes diagnosis of the cancer itself. Paraneoplastic necrotizing myopathy differs from primary myositis in that the prognosis is dependent on the underlying malignancy. Diagnosis of the underlying cancer is therefore crucial to the management of these patients. Paraneoplastic myopathy presents with symmetrical proximal muscle weakness, with acute or subacute onset of other symptoms such as dysphagia. Compared with non-neoplastic myopathy, paraneoplastic myopathy is much more likely to be associated with a marked increase in serum creatine kinase (CK) level and electromyographic changes characteristic of irritative myopathy. This condition is associated with many neoplasms, including gastrointestinal adenocarcinoma, non-small cell lung carcinoma, and breast cancer.
Paraneoplastic necrotizing myopathy is diagnosed on histological examination of biopsy specimens, and is characterized by massive necrosis of muscle fibers and very few inflammatory changes. Some cases have focal or general capillary depletion and complement membrane attack complex (MAC) deposition in a significant proportion of endomysial capillaries. Thickened and hyalinized capillaries, called pipestem capillaries, are an ultrastructural finding associated with necrotizing myopathy which has also been described in paraneoplastic cases. The minimal inflammatory infiltrate allows necrotizing myopathy to be distinguished from other cancer-related myopathies.
Here we report the case of a man who presented with heart failure and elevation of serum muscle enzyme levels; he was diagnosed with paraneoplastic necrotizing myopathy. He had a poorly differentiated lung adenocarcinoma, which had not previously been identified. This case highlights the difficulty of diagnosing paraneoplastic necrotizing myopathy, which may be underreported.
Abstract and Introduction
Abstract
Introduction: Inflammatory myopathies (such as dermatomyositis and polymyositis) are well-recognized paraneoplastic syndromes. However, paraneoplastic necrotizing myopathy is a more recently defined clinical entity, characterized by rapidly progressive, symmetrical, predominantly proximal muscle weakness with severe disability, and associated with a marked increase in serum muscle enzyme levels. Paraneoplastic necrotizing myopathy requires muscle biopsy for diagnosis, which typically shows massive necrosis of muscle fibers with limited or absent inflammatory infiltrates.
Case Presentation: We report the case of an 82-year-old Italian-born Caucasian man who was admitted to hospital because of heart failure and two drop attacks. Over the following days, he developed progressive severe weakness, dysphagia, and dysphonia. Testing showed increasing serum muscle enzyme levels. Electromyography showed irritative myopathy of the proximal muscles and sensorimotor polyneuropathy. Muscle biopsy (left vastus lateralis) showed massive necrosis of muscle fibers with negligible inflammatory infiltrates, complement membrane attack complex deposition on endomysial capillaries, and moderate upregulation of major histocompatibility complex-I. Computed tomography of the thorax showed a nodular mass in the apex of the right lung. The patient was diagnosed with paraneoplastic necrotizing myopathy. In spite of high-dose corticoid therapy, he died 1 month later because of his aggressive cancer. Subsequent electron microscopic examination of a muscle biopsy specimen showed thickened walls and typical pipestem changes of the endomysial capillaries, with swollen endothelial cells. Poorly differentiated adenocarcinoma of the lung was confirmed on post-mortem histological examination.
Conclusions: Paraneoplastic necrotizing myopathy is a rare syndrome with outcomes ranging from fast progression to complete recovery. Treatment with corticosteroids is often ineffective, and prognosis depends mainly on the characteristics of the underlying cancer. This case shows that paraneoplastic necrotizing myopathy may have an atypical appearance, and should be considered in elderly patients with neoplastic disease. In this case, the diagnosis was delayed by the unusual clinical picture that suggested heart disease rather than muscle disease.
Introduction
Paraneoplastic necrotizing myopathy is a rare condition associated with cancer and characterized by massive necrosis of muscle fibers in the absence of significant inflammation. It is part of the distinct disease entity of necrotizing myopathy, which has been added as an independent new domain to idiopathic inflammatory myopathy. As autoimmunity is considered to play a role in the development of this condition, it is currently known as necrotizing autoimmune myopathy (NAM). An association between myopathy and cancer has been reported for the past century. This myopathy occurs in less than 1% of patients with cancer, and often precedes diagnosis of the cancer itself. Paraneoplastic necrotizing myopathy differs from primary myositis in that the prognosis is dependent on the underlying malignancy. Diagnosis of the underlying cancer is therefore crucial to the management of these patients. Paraneoplastic myopathy presents with symmetrical proximal muscle weakness, with acute or subacute onset of other symptoms such as dysphagia. Compared with non-neoplastic myopathy, paraneoplastic myopathy is much more likely to be associated with a marked increase in serum creatine kinase (CK) level and electromyographic changes characteristic of irritative myopathy. This condition is associated with many neoplasms, including gastrointestinal adenocarcinoma, non-small cell lung carcinoma, and breast cancer.
Paraneoplastic necrotizing myopathy is diagnosed on histological examination of biopsy specimens, and is characterized by massive necrosis of muscle fibers and very few inflammatory changes. Some cases have focal or general capillary depletion and complement membrane attack complex (MAC) deposition in a significant proportion of endomysial capillaries. Thickened and hyalinized capillaries, called pipestem capillaries, are an ultrastructural finding associated with necrotizing myopathy which has also been described in paraneoplastic cases. The minimal inflammatory infiltrate allows necrotizing myopathy to be distinguished from other cancer-related myopathies.
Here we report the case of a man who presented with heart failure and elevation of serum muscle enzyme levels; he was diagnosed with paraneoplastic necrotizing myopathy. He had a poorly differentiated lung adenocarcinoma, which had not previously been identified. This case highlights the difficulty of diagnosing paraneoplastic necrotizing myopathy, which may be underreported.
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