Sudden death due to acute hemoabdomen and hypovolemia from a ruptured splenic hemangiosarcoma in a German shepherd dog

Abstract

A 12-year-old neutered male German shepherd dog was evaluated after dying suddenly at home. A few hours prior to the unexpected death the dog displayed anorexia and lethargy. Post-mortem examination and histopathology led to a diagnosis of marked hemoabdomen and hypovolemia due to a single ruptured splenic hemangiosarcoma.

On July 30, 2019 a dead 12-year-old neutered male German shepherd dog was presented to Cheltenham Veterinary Centre (CVC) after dying suddenly at home. The previous evening the owner had picked the dog up from a boarding kennel, at which time the dog seemed quieter than usual. After arriving home, the dog refused to eat and remained quiet until the owner went to bed. A few hours later, the owner woke up and found the dog had died. The clinic submitted the dog to the Animal Health Laboratory (University of Guelph, Guelph, Ontario) for post-mortem examination.

The dog’s most recent previous presentation to CVC was in May 2019 for his annual wellness examination and vaccinations. He was reportedly doing quite well at home with no major health concerns at the time other than ongoing bilateral coxofemoral osteoarthritis, which was managed adequately with gabapentin (Apo Gabapentin; Apotex, Toronto, Ontario), 10 mg/kg body weight (BW), PO, q8h as needed, and meloxicam (Metacam 1.5 mg/mL; Boehringer Ingelheim, Burlington, Ontario), 40 mg PO, q24h. Results of the dog’s physical examination were unremarkable other than mild periodontal disease, pain and crepitus on coxofemoral extension bilaterally with mild muscle atrophy of the hind limbs, delayed proprioceptive knuckling of the hind limbs bilaterally with wearing of the medial nails, and alopecia on the dorsal aspect of the left manus. Medical history included mucocutaneous superficial lip pyoderma (intermittent) and an erythematous interdigital mass on the left manus between the 4th and 5th digits (ongoing for approximately 1 y, diagnostics not pursued). The most recent routine blood analysis [complete blood (cell) count (CBC) and serum biochemistry], performed in July 2018, was within normal reference ranges.

Initial observations on post-mortem examination revealed pale mucous membranes, a visible abdominal fluid wave and bilateral hyperkeratotic pigmented alopecic interdigital nodules between the 4th and 5th digits of both manus. Standard necropsy technique was utilized for gross examination. Upon inspection of the abdomen, a marked volume of blood (~1 L) was observed, including a hematoma approximately 10 cm in diameter. After removal of the blood, abdominal organs were inspected. The only grossly abnormal abdominal organs were the left kidney, the medulla of which was slightly hyperemic, and the spleen, which contained 3 circular, raised, moderately well-demarcated nodules which varied in diameter from 3 cm to 5 cm. One of the nodules had a linear rupture site along its center (Figure 1). Inspection of the thorax revealed no significant gross abnormalities other than mild endocardiosis of the mitral valve. Tissue samples for histopathology were collected from the splenic rupture site, diaphragm, peri-renal adipose tissue, kidneys, liver, lungs, heart (left and right atria and auricles), skeletal muscle, and interdigital skin nodules.

Figure 1.

Gross view of the spleen. A single splenic nodule with a linear rupture site running through its center is visible (arrow).

Histopathological assessment of the aforementioned tissue samples revealed a final diagnosis of splenic hemangiosarcoma with focal capsular invasion and acute rupture (Figure 2). No evidence of hemangiosarcoma was found in the right or left atria/auricles of the heart or any other common sites of metastasis. The interdigital skin nodules were found to contain marked regionally extensive acanthosis and hyperkeratosis with pigmentary incontinence, follicular keratosis, and superficial lymphoplasmacytic peri-vascular dermatitis. Evidence of osteoarthritis was noted in both the stifle and coxofemoral joints bilaterally. Other noted histological abnormalities were attributed to postmortem changes such as autolysis.

Figure 2.

View of the splenic hemangiosarcoma rupture site (40× magnification). Infiltrative neoplastic spindle cells are visible throughout (arrows).

Discussion

Hemangiosarcoma (HSA) is a neoplasm arising from vascular endothelial cells and is typically malignant. Common primary sites include the spleen, right atrium, liver, and subcutaneous tissues. Common sites of metastasis include the lungs and liver; however, any other organ or tissue in the same cavity as the primary tumor can be affected via intra-cavitary spread of neoplastic cells should the primary tumor rupture. Based on staging criteria, this dog had stage II HSA, as rupture had occurred but no distant metastases were detected (1). Up to 80% of dogs diagnosed with HSA have metastasis at the time of diagnosis (2), making this an unusual finding. However, it is possible that metastases were present but not represented in the tissue samples obtained during necropsy.

The etiology of HSA is unknown; however, it is more commonly seen in certain breeds, suggesting a potential underlying genetic component. While HSA accounts for approximately 5% of all visceral malignant neoplasms in dogs (1), it is more likely to be seen in German shepherd dogs than any other breed, with a reported odds ratio of 4.7 [95% confidence interval (CI): 2.7 to 7.8] (2). Other more commonly affected breeds include boxers, golden retrievers, and Labrador retrievers (1,3,4). Adult dogs (8 to 13 y) are overrepresented (2).

Clinical signs of HSA are often either nonspecific (lethargy, anorexia) or acutely severe if associated with hypovolemic shock and cavitary effusion caused by tumor rupture [pale mucous membranes, dyspnea, arrhythmias, cardiac murmur, muffled heart sounds, abdominal fluid wave, signs associated with disseminated intravascular coagulation (DIC) such as petechiae or ecchymoses, and collapse or sudden death]. A cranial abdominal mass may be palpated if it is large enough. In this dog’s case, the splenic masses were not palpable; prior to acute onset of clinical signs, only incidental discovery of the masses on abdominal ultrasound would have raised suspicion for HSA.

Diagnosis of HSA is often presumptive based on signalment, clinical signs, and the visualization of 1 or more splenic masses on ultrasound. However, HSA tumors share ultrasonographic characteristics with other splenic pathologies including hemangiomas, hematomas, and extramedullary hematopoiesis (5), and cytological evaluation is typically unrewarding (and contraindicated if coagulation deficiencies are present) (6). Other supplementary findings include CBC abnormalities (anemia, neutrophilia, thrombocytopenia, rubricytosis, acanthocytosis, poikilocytosis, Howell-Jolly bodies, schistocytes), electrocardiogram abnormalities (arrhythmias e.g., bundle branch block), hypoproteinemia and coagulation profile abnormalities (prolonged prothrombin time/partial thromboplastin time, increased fibrin degradation products) (1). Unfortunately, definitive diagnosis can only be achieved through histopathology of tissue samples obtained via exploratory laparotomy or necropsy (1). In addition, poorly differentiated HSA often requires subsequent immunohistochemistry to distinguish it from other splenic sarcomas (e.g., fibrosarcoma, leiomyosarcoma, histiocytic sarcoma, and undifferentiated sarcoma) (1). Other potential differential diagnoses include benign nodular hyperplasia, splenic lymphosarcoma, splenic congestion or metastatic neoplasia (7,8). Traumatic hemoabdomen is also a consideration if suggested by signalment or history.

Once a diagnosis of splenic HSA is reached, staging should be undertaken before developing a treatment plan. Thoracic radiographs are indicated to evaluate the lungs for metastasis as well as the cardiac silhouette for evidence of a concurrent heart-base mass or pericardial effusion. Echocardiography is not required but may be beneficial if clinical signs of cardiac compromise are present (murmur, arrhythmia, muffled heart sounds) or if the cardiac silhouette is abnormal on thoracic radiographs (9). Abdominal organs should be evaluated for metastasis via ultrasonography if not already completed. A therapeutic plan for HSA can then be developed based on findings in the aforementioned imaging modalities. If there is no gross evidence of pulmonary metastasis, splenectomy with adjuvant chemotherapy is indicated. Single agent doxorubicin is most frequently used (or epirubicin in patients with pre-existing cardiac disease); doxorubicin-based combination protocols have also been successful (10–12). Metronomic chemotherapy has more recently been used as an alternative protocol as it is easy to administer at home and is typically well-tolerated (13). Concurrent supportive care (IV fluids, transfusion, analgesia, DIC management) should be provided as indicated. Intra-operative and peri-operative monitoring is critical as ventricular arrhythmias, acid-base imbalances, and electrolyte and coagulation abnormalities can develop. A CBC should be repeated before each chemotherapy session to ensure adequate neutrophil and platelet counts; treatment should be delayed for 5 to 7 d if counts are < 2000/μL (neutrophils) or < 75 000/μL (platelets), respectively (1).

Prognosis for dogs treated with splenectomy and adjuvant chemotherapy (single agent doxorubicin, combination or metronomic) is generally better than for those treated with splenectomy alone. However, regardless of which therapeutic plan is used, the 1-year survival rate is < 10%, with death typically occurring due to secondary metastasis rather than the primary HSA itself (1).

Canine splenic hemangiosarcoma remains a challenging and often devastating diagnosis. This case is a prime example of the unpredictable and insidious nature of this neoplasm. Of particular interest is the juxtaposition between the acute onset of severe clinical signs resulting in sudden death and the relatively small size of the ruptured splenic mass. The absence of grossly and histologically detected metastasis is also unusual. Future investigation into diagnostic tests that may enable earlier detection of splenic HSA would likely be beneficial with regard to therapy and prognosis and may serve to prevent sudden death attributed to acute rupture of an undetected tumor.