Discussion
We describe a case of paraneoplastic necrotizing myopathy in a patient with an undiagnosed lung adenocarcinoma. The patient had a history of ischemic heart disease, and was admitted to hospital for treatment of heart failure. His symptoms were initially attributed to a myocardial infarction because of his clinical history and electrocardiography and echocardiography findings, and the elevated serum muscle enzyme levels were attributed to myocardial ischemia. After admission, his heart failure resolved, but his muscle enzyme levels continued to increase. He developed symmetrical progressive proximal muscle weakness and was unable to mobilize. At this point, he already had advanced myopathy.
Initially, the diagnosis of necrotizing myopathy in a patient with ischemic heart disease and subacute onset of weakness with a high CK level led to investigation for drug-induced myopathy. The patient had never taken statins, proton pump inhibitors, or atypical antipsychotics that could have myotoxic effects. Of the drugs taken by the patient, to the best of our knowledge, only amiodarone is to be considered potentially myotoxic. Besides the more frequent peripheral neuropathy, amiodarone-associated myopathy has also been described (review by ), in most cases as a vacuolar autophagic myopathy with type II fiber atrophy, which was not seen in our patient. Although amiodarone-induced necrotizing myopathy has been previously reported, in the present case, peculiar pathological features, such as MAC capillary deposition and pipestem capillaries, are not consistent with amiodarone myopathy. Myotoxicity from salicylates has been reported anecdotally in one case of chronic abuse. Dermatomyositis may be associated with MAC deposition in capillaries, usually in a patchy pattern, but was ruled out because of the absence of skin lesions, perifascicular atrophy, and perivascular inflammation, and the rather diffuse MAC deposition pattern in capillaries. The pathological pattern also differed from that of polymyositis because of absence of significant endomysial infiltrates, lack of lymphohistiocytic invasion of non-necrotic fibers, and mild upregulation of MHC-I. As NAM has been reported in association with connective tissue disorders, and less frequently with cancer, immunologic and oncologic investigations were undertaken, leading to the diagnosis of lung cancer. Paraneoplastic necrotizing myopathies are rare and are known to be histopathologically heterogeneous, with myonecrosis ranging from occasional and scattered, to diffuse as in our patient. MAC deposition has been reported in NAM, both in paraneoplastic and non-neoplastic cases, but it may also be absent. Capillary loss in association with MAC deposition, as was observed in our patient, was morphometrically assessed in one group of cases. Few ultrastructural studies of microvessels in patients with NAM have been reported, and the pathogenic relationship between muscle necrosis and pipestem microangiopathy has yet to be elucidated. A subset of NAM is characterized by anti-SRP antibodies. SRP is a protein involved in protein trafficking in endoplasmic reticulum, and anti-SRP antibodies are classified as myositis-specific autoantibodies. Occasional cases of paraneoplastic anti-SRP+ NAM have been reported. No association between MAC deposition in capillaries and SRP antibodies has been detected, and there are no distinctive clinicopathological features that differentiate between SRP+ NAM and SRP– NAM. The role of anti-SRP antibodies in the pathogenesis of NAM is therefore unclear. Our patient was not tested for anti-SRP autoantibodies because testing was not available. Polyneuropathy may also occur in paraneoplastic NAM, in some cases associated with previous antiblastic treatment. It is probable that our patient had a mild pre-existing sensory-motor axonal polyneuropathy, as mild fiber type grouping consistent with reinnervation was observed. The moderate upregulation of MHC-I with neoexpression on some non-necrotic fibers is a consistent feature of NAM, in contrast to the diffuse upregulation observed in polymyositis, and a cytokine response inhibiting upregulation of MHC-I in NAM has been hypothesized.