Paraneoplastic Necrotizing Myopathy Associated With Neuroendocrine Carcinoma
Inflammatory myopathy, especially dermatomyositis and polymyositis, is known to be associated with many neoplasms. The necrotizing noninflammatory paraneoplastic myopathy is rarely seen and has not been reported in neuroendocrine carcinoma.
We report a case of severe myopathy that is associated with neuroendocrine carcinoma. The patient is a 77-year-old man who presented with dyspnea while walking, difficulty in chewing, and generalized weakness for 1 month. He, then, developed respiratory failure in 2 weeks before transfer to the hospital. Despite a stable clinical condition, he was not able to wean from the ventilator. Physical examination showed severe weakness in both upper and lower limbs (Medical Research Council (MRC) grade 1-2/5 in proximal and 2-3/5 in distal groups). Sensory examination was normal. Reflexes were absent.
Investigations that included blood chemistry, creatine kinase, autoimmune antibody panel, paraneoplastic antibody screening, myositis antibody profile, and acetylcholine receptor antibody were unremarkable. Nerve conduction study showed very low motor amplitudes with normal sensory study. Repetitive nerve stimulation was unsuccessful because of inexcitable nerves and muscles (trapezius, orbicularis oculi, and abductor digiti minimi). Electromyography showed nonirritative, severe generalized myopathy in both upper and lower limbs. Muscle biopsy showed mild type 2 muscle atrophy and necrotic fibers without lymphocytic infiltration. Myosin ATPase was present. Immunohistochemistry staining showed negative major histocompatibility complex class I staining and absence of cluster of differentiation 68-positive cells. Computed tomography (CT) of chest revealed bilateral pleural effusion, multiple-matted mediastinal, paratracheal, subcarinal, supraclavicular lymphadenopathies. CT-guided biopsy of mediastinal lymph node showed large-cell neuroendocrine tumor (NET) with many necrotic cells. Immunohistochemical stains revealed the presence of cluster of differentiation 56 cells, positive synaptophysin, borderline chromogranin and thyroid transcription factor-1, and negative leukocyte common antigen staining.
At that time, the immunotherapy was not given. After supportive treatment and radiation therapy, he was slowly weaned off the ventilator in 1 month and was discharged home in a partially dependent state.
Paraneoplastic inflammatory myopathy, especially dermatomyositis and polymyositis, are well recognized.1 However, paraneoplastic necrotizing myopathy is a rare entity. It is now thought to be part of necrotizing autoimmune myopathy. It often presents with acute or subacute onset of severe proximal myopathy and has been associated with gastrointestinal tumor, lung cancer, and breast cancer, among others.2,3 Muscle pathology demonstrates prominent necrosis with alkaline phosphatase staining of connective tissue and little inflammation.2 Diagnosis of the underlying cancer is therefore crucial to the management of these patients. Whole body positron emission tomography/CT screening has been proposed to localize affected muscles and an underlying malignancy.4
NETs comprise a heterogenous group of neoplasms derived from peptide- and amine-producing cells of the neuroendocrine system. The evaluation of NET is initially focused on obtaining tissue diagnosis and then identifying potentially resectable disease.5 The preferred treatment is surgical resection. The paraneoplastic manifestations are scarce, mainly related to the overproduction of certain hormones or physiologically active tumor products. Its association with necrotizing myopathy has not been reported.
In summary, our case represents another end of the spectrum of the noninflammatory paraneoplastic myopathy with less active disease. Respiratory insufficiency as a presenting symptom is unusual. Recognition of this manifestation in association with neuroendocrine carcinoma is crucial, as early and aggressive treatment can lead to substantial recovery.