Necrotizing myopathy secondary to multifocal infarctions from disseminated neoplasia
Contributed by Dr. Marguerite F. Knipe
University of California, Davis
Davis, California
Clinical History
A 7-year-old spayed female Rhodesian Ridgeback dog (19kg) presented to the UC Davis William R. Pritchard Veterinary Medical Teaching Hospital (VMTH) for further evaluation of elevated liver enzymes, elevated creatine kinase (CK) activity, inappetance, and labored breathing. About 10 days prior to presentation, the dog had an acute onset of weakness and inability to jump onto the bed. Abnormalities found on diagnostic testing performed by the referring veterinarian included elevated ALT (1447 IU/L, reference 19-67), elevated CK (56,508 IU/L, reference 51-399), and bacteriuria. Treatment included marbofloxacin 50 mg PO q 24 hr and Rimadyl 100 mg PO q 24hr. Improvement was not noted so the dog was referred .
Physical and Neurological Examination
Abnormalities noted on physical examination included hyperpnea (rate 60 at rest) with abdominal effort noted, and no crackles or wheezes. The dog was apparently painful on opening the mouth. On neurological examination, the dog was mildly obtunded, and had generalized weakness and was reluctant to walk. Proprioceptive placing and segmental reflexes were normal. The neuroanatomical localization was to the neuromuscular system, most likely a myopathic process with the historical marked elevation of CK. Possiible causes for myopathy with markedly elevated CK included immune-mediated (polymyositis), infectious (protozoal), neoplastic (lymphoma) and toxic. The increased respiratory effort was interpreted as secondary to muscular weakness, pain, or possibly aspiration pneumonia.
Diagnostic Tests
CBC
WBC 24,500
(6,000-13,000)
Bands 735 with few slightly toxic
(rare)
Neutrophils 19,355
(3,000-10,500)
Lymphocytes 2205 with few reactive (1,000-4,000)
Chemistry
Chloride 103 mmol/l (108-118)
Phosphorus 6.9 mg/dl (3.0-6.2)
Calcium 9.5 mg/dl (9.7-11.5)
ALT 1318 IU/L (19-67)
AST 1464 IU/L (9-42)
CK 30,734 IU/L (51-399)
GGT <3IU/L (0-6)
Total bilirubin 0.3 mg/dl (0-0.2)
Thoracic radiographs – normal
Abdominal ultrasound – Ascites was noted and a sample was determined to be a modified transudate.
Electrodiagnostic testing and muscle biopsies – Scheduled for the following day.
Outcome
The following morning the respiratory rate and effort had increased, mucous membranes were pale and the pulse quality was poor. The dog was treated for hypovolemic shock, but arrested during treatment and the owner declined resuscitation. Muscle specimens were collected post-mortem. On gross-examination of the appendicular muscles, there were large, well-defined pale regions throughout the muscles (Figure 1).
Figure 1. Well-defined pale regions (arrow) within the triceps muscle. Similar lesions were present in the cranial tibial and quadriceps muscles.
Necropsy showed multiple irregular oval dark red foci with thin, pale pink to white well-demarcated rims present in the myocardium, diaphragm, intercostals, and skeletal muscles, consistent with infarcts (Figure 2). Well-defined regions of myonecrosis were present within the tricpes, quadriceps and cranial tibial muscles. Myonecrosis was the cause of the markedly and persistently elevated CK activities. Inflammatory cell infiltrate was most severe at the periphery of the lesions, with edema and necrosis with loss of normal enzymatic activity throughout the lesions (Figures 4-7). The largest lesion with the myocardium involved about 70% of the right ventricular free wall. Infiltrates of neoplastic histiocytes were found in both cardiac and skeletal muscles, and were likely the cause of the infarcts. Cause of death was myocardial failure due to infarction secondary to disseminated histiocytic sarcoma.
Figure 2. Gross Images of myocardial infarctions (arrows)
Figure 3. H&E stained frozen sections of the quadriceps muscle (magnification 5X on left and 20X on right) showing well-demarcated necrotic area (left) with extensive cellular infiltrates at the periphery of the necrotic region (right).
Figure 4. Myofibers within necrotic areas are degenerating and have lost enzymatic activity. Frozen sections of the quadriceps muscle are reacted for myofibrillar ATPase (left, ATPase, pH 4.3, magnification 5X) or for succinic dehydrogenase activities (right, magnification 5X).
Figure 5. Frozen sections from the quadriceps muscle reacted with acid phosphatase for macrophage localization. Macrophages are concentrated at the periphery of the necrotic area (left, magnification 5X and right, magnification 20X).
