Spinal Mast Cell Tumor in a Dog

Case Report

A 6-year-old, 32-kg, spayed female rottweiler was referred to the Kansas State University Veterinary Medical Teaching Hospital (KSU-VMTH) with a 1-month history of left forelimb lameness followed by tetraparesis. The referring veterinarian had examined the dog 5 days previously, at which time the dog was found to be febrile (temperature, 103.4°F), lame in the left forelimb, and generally stiff. Enrofloxacin^a (9 mg/kg body weight, intramuscularly [IM], followed by 2.1 mg/kg body weight, per os [PO] q 12 hours) and carprofen^b (2.3 mg/kg body weight, PO q 12 hours) were prescribed. The owner did not note any improvement. The dog became recumbent and unable to walk 2 days prior to presentation. Upon presentation, the dog had been unable to urinate or defecate and was anorectic and adipsic for 24 hours.

Complete physical examination was normal except for findings related to the nervous system. Neurological examination revealed normal mentation and cranial nerve function. The dog was tetraparetic with significantly decreased hopping, placing, and proprioceptive responses in all four limbs. Severe proprioceptive ataxia was noted when the dog was assisted to walk, but positive motor responses were seen. All spinal reflexes were exaggerated, with clonus observed bilaterally with the patellar reflex. The urinary bladder was distended and difficult to express. The previous lameness was interpreted as a root signature, as no abnormalities were detected on musculoskeletal examination. Funduscopic examination was unremarkable. The anatomical localization of the lesion was within the sixth cervical to first thoracic (C₆–T₁) vertebral spinal cord segments. Differential diagnosis included Hansen’s Type II disk disease, neoplasia, discospondylitis, inflammatory disorders, and other degenerative disorders.

The dog was admitted to the hospital, and a complete blood count (CBC), serum biochemical profile, urinalysis (UA), urine culture, and thoracic radiographs were performed. Results of the CBC revealed a mild lymphopenia (1.2 × 10³/μL; reference range, 1.5 to 5.0 × 10³/μL) consistent with a stress response and an eosinophilia (1.8 × 10³/μL; reference range, 0.1 to 0.8 × 10³/μL). The serum biochemistry profile showed mildly elevated creatine kinase (CK) activity (613 U/L; reference range, 58 to 241 U/L) consistent with a recent IM injection. The UA was within reference ranges, and the urine culture was negative. Thoracic radiographs revealed mild spondylosis of the midthoracic vertebrae, osteochondral fragments in the area of the left scapulohumeral joint, and no evidence of metastatic disease. Due to the history of anorexia and adipsia, the dog was maintained on intravenous (IV) fluids (i.e., lactated Ringer’s solution with 16 mEq KCl/L at 60 mL per hour). The dog’s bladder was expressed, and she was turned every 6 hours.

On day 2, cervical radiographs, a cerebrospinal fluid (CSF) tap from the cisterna magna, and cervical myelography were performed with the dog under general anesthesia. Survey cervical radiographs were unremarkable. The CSF was collected prior to the myelogram. Analysis revealed normal protein, glucose, and cellularity. Iohexol^c (10 mL) was administered into the subarachnoid space via an injection at the fourth to fifth lumbar (L₄–L₅) space. Attenuation of the dorsal and ventral contrast columns was seen over the midbody of C₆ to the caudal end of the seventh cervical (C₇) vertebra on the lateral view [Figure 1A]. The contrast columns were attenuated on the right and left, with the cord deviated to the left from the midbody of C₆ to the caudal edge of C₇ on ventrodorsal projections [Figure 1B], consistent with a right-sided extradural lesion. No change was seen in the lesion with flexion, extension, and traction views. Differentials for the myelogram findings included neoplasia and disk herniation. The dog recovered uneventfully from anesthesia and the myelogram.

The option of surgery was presented to the owners but was declined. The owners elected euthanasia and granted postmortem examination. At necropsy, an ovoid, 3-cm × 1-cm, green mass was identified in the extradural spinal canal from the level of C₆ to T₁. The mass was firmly adhered to the right dorsal dura mater, and tendrils of similar tissue extended into the right intervertebral foramen at C₆ to C₇. Grossly apparent compression and deformity of the spinal cord in a left ventrolateral direction were present adjacent to the mass. Histopathology of the mass revealed a grade III mast cell tumor (MCT) [Figure 2] with multifocal infiltration into the dura and adjacent connective tissue. Eosinophils were present in the mass in higher numbers than neoplastic cells, which can be seen in canine MCT.¹ Neoplastic cells had distinct cell margins with minimal to moderate amounts of eosinophilic cytoplasm and rare metachromatic granules. Nuclei were round to oval, with moderate anisokaryosis; occasional binucleate and multinucleate cells were present. Mitotic figures were frequent, and occasional, very large, bizarre nuclei were observed. Microscopic changes in the spinal cord consisted of diffuse, scattered axonal sheath dilatation. Dilated sheaths contained necrotic axons, gitter cells, and eosinophilic debris. There was scattered wallerian degeneration of spinal nerves. The microscopic changes in the spinal cord and peripheral nerves were consistent with compressive lesions of prolonged duration.

Discussion

To the authors’ knowledge, this is the first report of a MCT within the spinal canal affecting the spinal cord of a dog. Other extracutaneous MCTs have been reported. Locations include the nasopharynx, pharynx with secondary hypophyseal involvement, oral cavity (including tongue), larynx, trachea, hepatopancreatic lymph nodes, ileocecal valve, mandibular salivary gland, conjunctiva, and orbit.^2–11 No reports of MCTs of the spinal canal in humans could be found, although MCTs are rare in humans.¹² It is possible that the spinal tumor was a metastatic lesion, but the dog had no history of previous skin masses, nor were any found at necropsy. If systemic mastocytosis was present, mast cells would have been found in other tissues. In one study of systemic mastocytosis, the criteria used to establish systemic disease included two of the following: mast cells on peripheral blood smears or buffy coat; bone-marrow involvement; hepatic or splenic involvement; and involvement of lymph nodes distant from the primary mass.¹³ As no mast cells were found in other tissues (i.e., liver, spleen, lymph nodes, and blood smear), the likelihood is that this was a primary tumor. A bone-marrow evaluation was not done in this case. Fine-needle aspirates (FNA) can confirm the diagnosis of mast cell neoplasia antemortem in the majority of cases.¹⁴ Fluoroscopy-guided FNA of this lesion could have provided a presurgical or antemortem diagnosis had the owner chosen to pursue further diagnostics and therapy. However, cytopathology may not be able to distinguish between round cell tumors that are poorly differentiated.

The extent and chronicity of the compressive spinal cord damage seen on histopathology would have made recovery of this patient questionable, even with successful treatment of the tumor. If the lesion had been identified earlier, a better prognosis for spinal cord recovery may have been possible. However, dogs with grade III, or poorly differentiated MCT, typically die of disease within 6 months due to local recurrence or distant metastases.^15–18 Treatment options for this patient would have included surgical removal, chemotherapy, radiation therapy, or a combination thereof. The poor long-term prognosis expected with a grade III MCT needs to be considered before clients pursue treatment of such a malignancy. Tumor grade would require a surgical biopsy; however, treatment options can be considered based on the cytopathological findings of a MCT. Surgical therapy alone in this case would not have been ideal, since adequate margins could not have been obtained. Surgical removal of visible neoplastic tissue followed by adjunctive therapy would have been the treatment option most likely to provide a long-term remission. Adjunctive radiation therapy for microscopic dermal MCT has recently been shown to provide a median disease-free interval of 54 months, with the majority of these being grade II, or intermediate grade, tumors.¹⁹ Two other studies of radiation therapy for microscopic, intermediate-grade tumors showed 86% to 93% of the patients disease free at 3 years posttreatment.²⁰²¹ Poorly differentiated MCTs are unlikely to have such prolonged survivals.¹⁵ Adjunctive chemotherapy has also been shown to increase disease-free intervals in dogs with residual microscopic MCT, but the durations of such remissions are not as high as with radiation therapy. Vinblastine and prednisone for microscopic MCT provided 1-and 2-year disease-free intervals of 67% for dogs with intermediate-grade tumors and 50% for dogs with poorly differentiated tumors.²² In another study, CCNU therapy caused a response in eight of 19 (42%) dogs with measurable cutaneous MCTs that had previously been treated with prednisone.²³ One dog obtained a complete remission for 440 days, while seven dogs had a partial response for a median duration of 77 days. Radiation as a single modality therapy could also have been considered. Mast cells are sensitive to radiation, and several reports have shown local remissions of gross disease with radiation therapy. However, disease-free intervals and survival times for dogs receiving only radiation therapy for visible disease are significantly shorter than for dogs treated for microscopic disease postsurgery.¹⁵¹⁹ Also, the high potential for systemic disease developing with a grade III MCT would make chemotherapy an integral part of the treatment protocol.

The peripheral eosinophilia seen in the dog of this report was interesting. Differentials for the eosinophilia included internal parasitism (e.g., gastrointestinal, heartworms), mast cell disease, and allergic or other inflammatory conditions. No evidence of parasitism or other inflammation was found at necropsy. The eosinophilia may have been related to the MCT. However, in one study, only 13% of dogs with systemic mastocytosis had peripheral eosinophilia, while 31% had peripheral basophilia.¹³ The eosinophilia could also have been due to an inflammatory or allergic condition that was not evident on necropsy.

Conclusion

Mast cell tumors in dogs may occur in a variety of extracutaneous sites. This is the first report of a MCT in the spinal canal of a dog. While very uncommon, mast cell neoplasia should be considered as a differential for a spinal compressive lesion. A FNA of such a compressive mass should be considered in an attempt to obtain a presurgical diagnosis, which may change the prognosis of the patient as well as the owner’s treatment decisions.