Comparative Neuromuscular Laboratory

NEUROMUSCULAR CASE OF THE MONTH – NOVEMBER 2007

Myopathic Presentation of Malignant Histiocytosis
Contributed by Joan R. Coates, DVM, MS, DACVIM (Neurology)
Jill Luther, DVM
Catherine Tonks, DVM
University of Missouri Veterinary Medical Teaching Hospital (MU-VMTH)
Columbia, MO 65211

Clinical History
A 5 year-old female spayed Labrador retriever mixed breed was presented for evaluation of generalized weakness. Limb weakness was first manifested 2 months prior to presentation and had progressively worsened.

Physical and Neurological Examination
Routine physical examination revealed moderate masticatory muscle atrophy and asymmetrical loss of muscle mass in varying muscle groups on whole body palpation. Abnormal findings on neurologic examination were most obvious on gait evaluation. Gait revealed episodic weakness manifested by a shortened stride that was most severe in the pelvic limbs
(go to video clip). Weakness would progress to the point of no longer being able to support weight but improve with rest. Muscle hypertrophy and firmness was noted in the quadriceps, semi-tendinosus and membranous muscle groups. Heat and pain was evident on muscle palpation after exercise. Rectal temperature increased with exercise. Cranial nerve examination, postural reaction testing and spinal reflexes were within normal limits. The differential diagnosis included myopathic disease (e.g. myositis, exercise induced myopathy).

Diagnostic Tests
CBC - Mature neutrophilic leukocytosis 22.13 x 10³ (reference range: 3-11.5 x 10³ /mm³ ) and lymphocytosis 3.29 x 10³ (reference range: 0.15-1.35 x 10³ /mm³ )
Serum Chemistry Profile
ALT 172 U/L (reference range: 9-58 U/L)
CK 5004 U/L (reference range: 10-274 U/L)
Urinalysis – WNL
Thoracic radiographs – A 1.5 cm soft tissue nodule at the level of the third intercostals space was identified on the right lateral view (Fig. 1)
Abdominal radiographs – WNL
Abdominal ultrasound – Multiple enlarged and heterogenous masses were present surrounding the aortic bifurcation and distal portion of the caudal vena cava. These masses probably corresponded to lymph nodes. Aspirates of the lymph nodes were taken.
Cytology of abdominal lymph node aspirate (Fig. 2,3) – Aspirates were performed under general anesthesia. The lymphoid population was a mixture of mature lymphocytes and immature lymphoid cells. Occasional plasma cells were seen. Some of the lymphocytes appeared reactive. Other cells were monocytic in appearance. Also present were mononuclear cells with morphology somewhere in between that of normal macrophages and the monocytoid cells. The nuclei of some macrophage and monocyte-like cells occasionally contained one or two nucleoli. Malignant histiocytosis was suspected.

Figure 1 - Right lateral view of thorax
Figure 2 - Low field magnification(100X) of lymph node aspirate
Figure 3 - High field magnification(600X) of lymph node aspirate

Electromyography EMG of selected major muscle groups revealed mild to severe fibrillation potentials and positive sharp waves, and sporadic complex repetitive discharges (Fig. 4). Distribution of findings was considered generalized and scattered. Sciatic-tibial nerve conduction studies showed waveforms were normal in shape but had lower amplitudes (Fig. 5). Nerve conduction velocity was 61 m/sec.

Figure 4- Electromyography Figure 5- Measurement of motor nerve conduction velocity and amplitude

Diagnosis
The presumptive diagnosis was malignant histiocytosis preimarily affecting the skeletal muscles or secondasrily causing a paraneoplastic myopathy. Metastatic disease to the thorax and abdomen were also suspected. The owner declined muscle biopsies.

Outcome
The dog was palliatively managed with an anti-inflammatory dosage of prednisone; the owner declined other forms of chemotherapy. The owner elected euthanasia 4 months later. The body was returned to the MU-VMTH for complete necropsy. Multiple muscles were submitted to the Comparative Neuromuscular Laboratory for analysis(Fig 6,7). Multifocal macrophaghic cellular infiltrations were present within all muscles. Post-mortem examination confirmed malignant histocytic cellular infiltrates in the liver, lung, lymph node, subcutis, and skeletal muscles.

Figure 6- H&E stained frozen muscle biopsy section showing foci of mononuclear cell infiltration Figure7- Esterase stain highlighting lysosomes in macrophages in area of cellular infiltration

Discussion
Malignant histiocytosis was suspected in this case due to the rapid progression and involvement of multiple organ systems. Breeds predisposed to malignant histiocytosis include the Bernese Mountain dog, Rottweiler, and Golden and Flat-coated retriever. It is characterized by proliferation or infiltration of histiocytic cells in multiple organs with occasional involvement of the CNS. Primary sites for disseminated histiocytic sarcoma are spleen, lung, bone marrow, liver and lymph nodes. This case was unique due to it myopathic presentation in a mixed-breed dog.