Paraneoplastic necrotizing myopathy associated with adenocarcinoma of the lung - a rare entity with atypical onset: a case report

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.

Figure 1

Vastus lateralis muscle biopsy. Myopathic changes with increased variability of muscle fiber diameter and sporadic centralized nuclei. Necrotic fibers (*) and regenerating fibers with basophilic cytoplasm (°). Hematoxylin and eosin staining, ×100.

Figure 2

Vastus lateralis muscle biopsy. Immunohistochemical staining for complement membrane attack complex (MAC) on a section adjacent to that shown in Figure 1. The necrotic fibers (*) show MAC deposition in the membrane and cytoplasm. MAC: immunoperoxidase staining, ×100.

Figure 3

Vastus lateralis muscle biopsy. Endomysial capillaries with complement membrane attack complex (MAC) deposition. MAC: immunoperoxidase staining, ×400.

Figure 4

Vastus lateralis muscle biopsy. Lowered density of endomysial capillaries: several fibers have no capillaries in the endomysial space (number of capillaries/mm² of cross-sectional area: 148.2; normal value 393.2). CD31: immunoperoxidase staining, ×200.

Figure 5

Vastus lateralis muscle biopsy. Necrotic fibers (*) with macrophage invasion show strong major histocompatibility complex (MHC)-I expression. Global MHC-I upregulation is very mild, with neoexpression on a limited subset of intact fibers (°). MHC-I: immunoperoxidase staining, ×200.

Figure 6

Vastus lateralis muscle biopsy. Thickened endomysial capillary wall, surrounded by a thick layer of amorphous material including the pericytes, and collagen fibers. Transmission electron microscopy, ×5200.

Figure 7

Vastus lateralis muscle biopsy. A swollen endothelial cell of an endomysial capillary, with loss of organelles and cytoplasmic material. Transmission electron microscopy, ×11,500.

Figure 8

Pulmonary hilar lymph node biopsy. Regional lymphadenopathy (metastases). Hematoxylin and eosin staining, ×25.

Figure 9

Lung biopsy. Adenocarcinoma with a necrotic component and surrounding edema. Bronchopneumonia and emphysema are observed. Hematoxylin and eosin staining, ×25.