Suspected disseminated histiocytic sarcoma in a 3-year-old Perro de Presa Canario dog

Abstract

A 3-year-old intact male Perro de Presa Canario dog was presented with acutely inflamed and edematous right hind limb, scrotum, prepuce, and an enlarged left carpus. Two weeks later the dog returned with weight loss, draining tracts in the right hind limb, dermal nodules, a palpable abdominal mass, and uveitis in the left eye. The dog succumbed to his illness 2 days later and a widely disseminated round cell tumor compatible with histiocytic sarcoma was diagnosed following postmortem examination.

Case description

A 3-year-old intact male Perro de Presa Canario dog was presented to Norwich Veterinary Service with acutely edematous right hind-limb, scrotum, and prepuce. The left carpus was inflamed and firm. The dog had previously been taken to another practice in the area and was prescribed cephalexin and meloxicam, followed by clindamycin, marbofloxacin, and furosemide a week later. During this first visit to Norwich, the veterinarian on the case performed a SNAP 4Dx (IDEXX Laboratories, Markham, Ontario) test, which was negative for Ehrlichia, Anaplasma, Borrelia, and Dirofilaria immitis. A fine-needle aspirate from the edematous leg revealed a large number of red blood cells and a few white blood cells. Further diagnostics were declined.

Approximately 2 wk later, the dog returned to Norwich Veterinary Service in poorer condition. He had been placed on tetracycline (250 mg, PO, q8h) and prednisone (50 mg, PO, q12h) by his other clinic 5 d earlier. The dog was quiet, alert, and responsive. He was still eating and drinking, was urinating, and was reported to be still having bowel movements. He had gone from 53 to 51.3 kg in 2 wk since the first visit. The owner described an episode of collapse 5 d earlier. Physical examination revealed a severe uveitis and mild exophthalmia of the left eye, with scleral vascularization and periorbital swelling. The dog exhibited pain when attempts were made to open the mouth, potentially due to the lesions associated with the left eye. Mucous membranes were pink and the capillary refill time was < 2 s. The right submandibular lymph node was slightly enlarged. The right carpus was visibly inflamed and firm on palpation. Mildly increased lung sounds were ausculted bilaterally with a respiratory rate of 28 breaths/min. The heart rate was 124 beats/min and the heart rhythm was normal. A firm, round mass ~10 cm in diameter was palpated in the caudal abdomen. There was a tri-lobed dermal nodule ~3 cm × 6 cm in size on the craniodorsal thorax, and a single dermal nodule approximately 1 cm in diameter on the medial axilla. There was severe and diffuse edema of the right hind limb, scrotum, and prepuce. The left hind limb was normal. The edematous limb had 1 to 3 draining tracts along the medial aspect of the leg from which a clear, colorless fluid was leaking. The animal’s body temperature was 39°C. A rectal examination was performed but the abdominal mass could not be palpated rectally. Generalized muscle wasting with a body condition score of 3 (on a scale of 1 to 9) was noted. Given the history and findings of the physical examination, neoplasia and systemic blastomycosis (Blastomyces dermatitidis) were considered. The dog was admitted for in-patient care that day and remained in hospital overnight.

During his 24-hour stay in hospital, the patient was administered Lactated Ringer’s solution (Baxter, Mississauga, Ontario) intravenously at 200 mL/h to correct his dehydration and meet maintenance requirements. During his hospitalization he became pyrexic (39.6°C) and anorexic. The diagnostic plan while hospitalized included radiographs, fine-needle aspirates, and blood collection.

Radiographs of the thorax and abdomen were taken. A generalized perihilar soft tissue opacity was seen on the left lateral thoracic radiograph. A radiopaque focal soft tissue opacity caudal to the base of the heart was also present. The lobar pulmonary arteries appeared enlarged. On the ventrodorsal (VD) projection, the caudal half of the thoracic cavity and the cranial half of the abdominal cavity were included. There was a circumscribed, soft-tissue opacity in the right caudodorsal lung lobes adjacent to the cardiac silhouette. The remainder of the radiograph was not of diagnostic value due to poor image quality. Unfortunately no repeat VD projection was taken.

The left lateral abdominal radiograph revealed a large mass in the caudal abdomen that displaced the intestines cranially. It was unclear whether the mass was an enlarged prostate or a tumor, but given that the mass was not detected during rectal palpation an enlarged prostate was less likely. The small intestine was distended with moderate amounts of gas and the colon appeared to be distended with fecal material. On the VD radiograph of the abdomen, there was a loss of serosal detail within the mid-abdomen. The mass could not be clearly seen in this view. The small intestine appeared to be displaced cranially and laterally on the right side, with moderate to severe gas distension.

A fine-needle aspirate of the craniodorsal thoracic nodule was submitted to the Animal Health Laboratory (AHL), University of Guelph, Guelph, Ontario for cytology. The samples, stained with Wright’s stain and evaluated by clinical pathologists, were found to contain necrotic cell debris and poorly preserved cells. Rare neutrophils and macrophages were seen on 1 slide, but otherwise there was no evidence of inflammation. The cell preservation was very poor and precluded cytologic diagnosis. It was suspected that a necrotic center was aspirated, and intact cells suggested a possible neoplastic process. Stained impression smears revealed suppurative inflammation, with low to moderate numbers of mildly lytic neutrophils and numerous extracellular bacteria. The bacteria were likely either an overgrowth of residential flora or secondary bacterial infection. No fungal agents were observed.

A complete blood (cell) count (CBC) and biochemical profile were conducted at the AHL. The CBC revealed a moderate to marked leukocytosis [53.6 × 10⁹/L; reference interval (RI): 4.9 to 15.4 × 10⁹/L], a moderate neutrophilia (37.52 × 10⁹/L; RI: 2.9 to 10.6 × 10⁹/L) with a marked left shift (5.36 × 10⁹/L; RI: 0.0 to 0.3 × 10⁹/L), and a marked monocytosis (9.11 × 10⁹/L; RI: 0.0 to 1.1 × 10⁹/L). Mild-moderate toxic changes in neutrophils were noted mostly in the band cells. These findings indicated chronic, ongoing inflammation. A mild, macrocytic, hypochromic regenerative anemia was also revealed in the CBC. The biochemistry profile showed a mild hypocalcemia (2.30 mmol/L; RI: 2.50 to 3.00), a mild hyperphosphatemia (1.91 mmol/L; RI: 0.90 to 1.85 mmol/L), and high-normal hypermagnesemia (1.1 mmol/L; RI: 0.7 to 1.0 mmol/L). A high anion gap was present (27 mmol/L; RI: 13 to 24 mmol/L), and alkaline phosphatase was mildly elevated (160 U/L; RI: 22 to 143 U/L). Creatine kinase was mildly elevated (275 U/L; RI: 40 to 255 U/L). All other parameters were within normal limits.

Interpretation of the fine-needle aspirate sample was inconclusive due to the likelihood that a necrotic center was aspirated. Blastomycosis could not be ruled out despite the lack of fungal agents in the samples obtained. Since infection was still possible, blastomycosis and neoplasia remained on the differential diagnoses list, given the history and clinical signs. The option was given to the owner to treat the dog empirically with itraconazole (Sporanox; Janssen, Toronto, Ontario), 5 mg/kg body weight (BW), PO, q12h since further diagnostics were declined. The client elected to take the dog home to care for him over the weekend and itrazonazole was started the following day. The dog’s condition deteriorated and death ensued 2 d after being discharged from the clinic.

The owners consented to a postmortem examination of the dog, which was performed at the Department of Pathobiology, Ontario Veterinary College. There were generalized, multifocal to coalescing, firm nodules ranging between 1 and 4 cm in diameter in the caudoventral abdominal wall, kidneys (Figure 1), mesentery, lung parenchyma, and myocardial tissue. Within the caudal abdomen there was a 5 cm × 10 cm round mass that contained caseous and also suppurative material.

Figure 1.

The kidney of the dog with a round cell tumor which appeared to be a histiocytic sarcoma. There are numerous nodules, 1 to 4 cm in diameter.

Nodules in the kidneys extended into the cortex. Occasional nodules had cavitated centers of either purulent debris or liquefaction necrosis. One kidney exhibited a large medullary infarct. The right adrenal gland appeared to have diffuse necrosis.

Within the mesentery, the nodules had occasional fibrous adhesions to the small intestine. One nodule extending from the serosa of the jejunum was found to communicate with the lumen of the intestine. The liver and spleen appeared grossly normal.

Two 3- to 4-cm masses were found in the pericardium and were not adhered to the heart itself. The heart had 1 firm pedunculated nodule within the right atrial lumen that was approximately 3 cm × 5 cm. A nodule was also found to protrude into the lumen of the left ventricle near the apex.

The right hind leg had severe generalized, multifocal, coalescing nodules within the muscles proximal to the stifle. Edema of the limb was noted distally to the nodules, and likely resulted from impaired drainage. The scrotum had severe edema as well.

The left eye showed corneal edema and possible uveitis. The bone marrow appeared reactive.

Samples of all grossly affected organs and tissues as well as liver, spleen, and brain were submitted for histopathology. Within multiple tissues there were nodular, expansile, poorly circumscribed, moderately cellular masses composed of sheets and streams of round or spindle-shaped cells supported by fine strands of fibrous connective tissue. Neoplastic cells had well-defined cellular membranes, a moderate amount of foamy eosinophilic cytoplasm, an eccentric round nucleus with coarse chromatin and a single nucleolus. Cells measured 20 to 30 μm and the N:C ratio was 1:2. There were 22 mitotic figures in ten 400× fields and there was 3-fold anisokaryosis. There were numerous individual dead cells and there were multifocal, sharply demarcated areas of necrosis accounting for 30% to 40% of the sections examined. In the lung and kidney, clusters of neoplastic cells were also found within the lumen of small and medium-sized blood vessels. Neoplastic cells were found within the anterior chamber of the eye and appeared to block the iridocorneal angle. The histological diagnosis was a round cell tumor with suspicion of histiocytic sarcoma, requiring immunohistochemistry for confirmation.

Discussion

Blastomycosis is a fungal infection that proliferates in the lungs following inhalation of hyphae from soil. In Ontario, dogs affected with blastomycosis are most commonly found in the Ottawa Valley area. Infection induces granulomatous inflammation, forming multifocal pale nodules similar to those found during gross necropsy of the dog in discussion. Blastomycosis can disseminate hematogenously and cause skin nodules, uveitis, draining tracts in limbs, and osteomyelitis (1). The dog in this case came from a rural property with abundant dark, rich soils. Given his young age, rapid disease progression, and clinical signs, blastomycosis was a top differential diagnosis, despite the failure to detect fungal organisms on cytology. No yeast was found, however, in any of the histological samples taken during necropsy and blastomycosis was therefore ruled out based on postmortem examination.

Canine histiocytic sarcoma (HS) is a rare neoplasm which can present as a localized lesion or a disseminated, multi-organ disease (2). The cell of origin of canine HS is most likely a myeloid dendritic antigen-presenting cell (3). Disseminated histiocytic sarcomas are aggressive, rapidly progressive, and carry a poor prognosis (2,4). Histology demonstrated a round cell tumor in this patient that had metastasized to many major organs and tissues. It is possible that this neoplasm, with immunohistochemistry, would be classified as a disseminated HS. Evidence suggests that rottweilers, Bernese mountain dogs, and retrievers are the breeds most commonly affected with HS (3).

Presentations of histiocytic sarcomas similar to that for the dog in this case have been documented. In dogs with disseminated HS, tumor masses have been identified in a number of organ systems but primarily in the lung, spleen, and bone marrow (3). Intraocular HS has been shown to present as an exophthalmia, buphthalmia, and hyphema. One study of rottweilers and retriever breeds showed that the majority of tumors were located in the anterior uvea, similar to the dog in the present case, and carried a poor prognosis (5). The authors concluded that intraocular HS likely represented metastatic disease since most dogs developed systemic signs of illness and short survival time following enucleation.

A retrospective evaluation of histiocytic-like sarcomas in flat-coated retrievers revealed that most cases presented with a swelling or mass in skeletal muscle or surrounding a joint, with lameness and pain (6), as did the case herein. One case report in a golden retriever documented a similar initial presentation of swelling and lameness of the proximal right forelimb (7).

Both localized and disseminated histiocytic sarcomas can resemble other neoplasms such as synovial cell tumors, lymphoma, and malignant fibrous histiocytoma (which is actually a soft tissue sarcoma) (2,8). They can also resemble more benign histiocytic diseases such as canine cutaneous histiocytoma. Definitive diagnosis can be accomplished by immunohistochemical staining for the leukocyte surface markers CD1 and CD11c (9). This is of great importance when making treatment plans and predicting prognosis since the nature of these diseases varies widely (2).

Localized HS, such as those arising in the subcutis, respond well to surgical excision and radiation therapy (3). Even with aggressive therapy, however, disseminated histiocytic sarcomas rapidly progress. Systemic chemotherapy is currently the recommended treatment, and responses to lomustine have been documented. In a study involving 59 dogs, improvement was observed in approximately half the animals exhibiting gross metastatic disease. The median survival time of grossly affected dogs was 109 d. Dogs with solitary tumors or minimal residual disease lived 433 d or more (4).

This case describes a neoplastic disease of very rapid progression which, based on histopathology, appeared to be a round cell tumor. Early diagnosis of this disease would be critical to instituting a treatment plan. The dog in this case, based on the aggressive nature of the disease, would likely have had a poor prognosis even with therapy.