Cardiac osteochondrolipoma in a cheetah

Abstract

A 13-y-old captive female cheetah (Acinonyx jubatus) succumbed following the acute onset of respiratory distress. Autopsy revealed bacterial bronchopneumonia as the primary cause of death. Additionally, splenic myelolipomas and systemic amyloidosis were identified postmortem. Interestingly, a solitary, firm nodule was found in the right atrial wall, consisting histologically of mature adipocytes with partial osseous and cartilaginous differentiation, consistent with osteochondrolipoma. Hepatic congestion suggested right heart failure. Although the direct impact of the cardiac mass on heart function remains unclear, its potential contribution to the fatal outcome cannot be discounted. To our knowledge, cardiac osteochondrolipoma has not been reported previously in cheetahs or other animals.

Cheetahs (Acinonyx jubatus) are classified as an endangered and vulnerable species, and there are <7,000 worldwide. ⁷ Similar to domestic felids, cheetahs have heightened susceptibility to chronic kidney disease and gastritis.^8,16,18,21 However, spontaneous tumors in cheetahs are relatively rare; the few documented tumors include splenic myelolipomas, exocrine pancreatic adenomas, visceral mast cell tumors, hepatic lymphomas, cutaneous hemangiosarcomas, mesotheliomas, and cutaneous basal cell tumors.^{4,6,10,12,13,18,20}

A 13-y-old female cheetah housed in an outdoor exhibit died suddenly after developing coughing and rhinorrhea. Postmortem examination was performed immediately after death. No significant pleural, abdominal, or pericardial effusions were found. Upon incising the heart and major vessels, a tan, firm, 1.5 × 1.0 × 0.6-cm nodule was found protruding into the right atrial chamber, adjacent to the cranial vena cava near the sinoatrial node (Fig. 1A, 1B). Additionally, we found congested and consolidated lungs with foamy froth in the trachea; shrunken, indented kidneys; and numerous white nodules in the spleen (Fig. 1C, 1D). Representative samples of heart, spleen, lung, kidney, and liver were fixed in 10% phosphate-buffered formalin, processed routinely, and sections stained with H&E for histologic examination.

Figure 1.

Cardiac osteochondrolipoma and splenic myelolipomas in a cheetah (Acinonyx jubatus). A, B. Gross images of the cardiac mass. The 10-mm mass is located at the terminal ridge (crista terminalis) of the right atrium and near the cranial vena cava. This solitary mass protruded into the atrial lumen and had a greasy yellow-to-white appearance with a chalky texture. Ao = aorta; CVC = cranial vena cava; LA = left atrium; PT = pulmonary trunk; RA = right atrium. Bar = 5 mm. C, D. Gross images of the splenic masses. White, often raised, 2–15-mm nodules are scattered randomly throughout the spleen. On section, the masses bulge and have hemorrhagic foci.

Histologically, the well-defined cardiac mass was composed of lobules of well-differentiated mature adipocytes in a fine fibrovascular stroma with regions of osseous and cartilaginous differentiation (Fig. 2A, 2B). No histologic criteria for malignant adipocytic tumors were observed. Degeneration, necrosis, and focally extensive fibrosis were observed in both ventricles, particularly in the papillary muscle of the right ventricle. The soft white nodules in the spleen were myelolipomas (fully differentiated adipocytes and extramedullary hematopoietic cells), which are encountered commonly in cheetahs (Fig. 2C, 2D).^4,23 The consolidated cranial lobes of the lungs were congested, with 80–90% of alveoli and bronchioles filled with degenerate neutrophils, macrophages, and intralesional bacterial colonies. Renal lesions included lymphoplasmacytic interstitial nephritis and fibrosis consistent with chronic renal disease; medullary interstitial amyloid deposition was observed in both kidneys. Hepatic congestion and sinusoidal amyloid deposition were confirmed.

Figure 2.

Cardiac osteochondrolipoma and splenic myelolipomas in a cheetah (Acinonyx jubatus). H&E. A. The well-circumscribed cardiac mass is positioned centrally within the muscle layer, and consists predominantly of well-differentiated adipocytes plus multifocal osseous and cartilaginous differentiation. Bar = 2 mm. B. At high magnification, chondrocytes within lacunae, surrounded by a chondroid matrix, and osteocytes encircled by osteoid matrix with mineralization, are dispersed randomly within the adipose tissue of the cardiac mass. Bar = 100 µm. C. Well-differentiated adipocytes with extramedullary hematopoietic cells are found in the splenic masses. Bar = 2 mm. D. Mature adipocytes and hematopoietic cells at high magnification in the splenic masses. Bar = 50 µm.

In veterinary medicine, cardiac lipomas are rare, with only a few reported cases. Our searches in Google, PubMed, CAB Direct, Web of Science, and Scopus using the search terms “cardiac osteochondrolipoma in cheetahs” found no reported cases of cardiac osteochondromatosis in cheetahs, suggesting that the disease has not been reported in cheetahs. Three cases of cardiac lipoma have been documented in dogs: 2 cases of pericardial lipomas, and 1 case of a right atrial lipoma.^3,11,26 Clinical signs in the canine cases were associated with respiratory distress and circulatory disturbances, including exercise intolerance, dyspnea, cardiac murmurs, effusions, and decreased capillary refill time. Only one case of pericardial lipoma underwent surgical removal and fully recovered from clinical signs of heart failure. ²⁶ A right ventricular cardiac lipoma associated with the tricuspid valve and right atrium was found incidentally in a horse at autopsy and was not associated with respiratory or circulatory disturbances. ¹

In humans, cardiac tumors are rare and are generally found incidentally in 0.2–0.4% of autopsies. ²⁵ Studies have suggested a correlation between the location of the tumor within the heart chambers and its histologic subtype. For instance, myxomas are the most commonly found primary cardiac tumors and are often located in the left ventricle. ²⁸ Lipomas, the second most frequently encountered primary cardiac tumors, can develop in any anatomic region within the heart; however, they are often found in the right atrium and left ventricle.^25,28 By integrating tumor location with factors such as age, medical history, and findings from cardiac MRI scans, a presumptive diagnosis can potentially be made without resorting to invasive procedures. ²⁸ The size and location of the mass dictate clinical symptoms, primarily through the compressive effect of the tumor on the heart and surrounding parenchymal structures. ²⁸

Given the limited literature on cardiac lipomas in veterinary medicine, understanding their pathophysiology and clinical significance is challenging. Hemangiosarcomas and aortic body tumors are reported frequently in dogs, whereas lymphomas are common in cats; however, cardiac lipomas are generally rare in either species. ²⁷ Considering that nearly 38% of human cardiac lipoma patients are asymptomatic and their tumors are found incidentally during routine medical checkups or autopsies, the prevalence of cardiac lipomas in veterinary practice may be underestimated. ²⁸ Unlike in human medicine, access to computed tomography or MRI in zoo animals is limited given the high costs and associated anesthesia risks. Therefore, identification of cardiac lipomas in animals is less likely than in humans, especially when clinical signs are absent. As in the case of the cardiac lipoma diagnosed in the horse at autopsy, ¹ subclinical cardiac lipomas will remain undetected unless postmortem examinations are performed.

In our case, the cheetah, which exceeded the typical cheetah lifespan of 12 y, was considered geriatric with a reduced activity level. Apart from respiratory signs, no notable abnormalities were detected before it died. Although chronic renal failure and gastritis have been documented in cheetahs, cardiac diseases are relatively uncommon. This is attributed to the unique physiologic characteristics of cheetahs, including their large cardiac output facilitating high-speed running and their proportionally large hearts, which often mask subclinical valvular issues, unlike in other feline species.^5,24

The cause of cardiac lipomas in cheetahs remains unclear, although chondrometaplasia may occur during tissue repair in traumatic injury, leading to the differentiation of pluripotent mesenchymal cells into adipocytes and chondrocytes. ¹⁵ Replacement myocardial fibrosis generally results from myocardial infarction, which could be linked to cardiovascular diseases. ⁹ Bone and cartilage formation in the heart has been observed in chimpanzees and rats following myocardial infarction.^14,17 In such cases, damaged cells were replaced by cardiac fibroblasts derived from resident cardiac stem cells or bone marrow–derived mesenchymal stem cells. ²⁹ These multipotent stem cells can differentiate into adipocytes, chondrocytes, and osteocytes. ²² Additionally, the developmental processes associated with os cordis or cartilago cordis, commonly found in the Bovidae family and occasionally in certain orders of Artiodactyla and Carnivora, such as dogs, otters, sea lions, and cats, could be related. ² In our cheetah case, considering that the cardiac lipoma was well-defined from the surrounding intact cardiomyocytes, the spontaneous origin of the lipoma with osseous and cartilaginous differentiation from mesenchymal stem cells appears more plausible.

In addition to pneumonia as the primary cause of death in our case, lesions were observed in various parenchymal organs, including the cardiac osteochondrolipoma, chronic interstitial nephritis, and systemic amyloidosis, and may have contributed to the cheetah’s death. There were no clinical signs or diagnostic results indicating a cardiac lipoma in the cheetah. Therefore, it is unclear whether the cardiac lipoma affected cardiac function, but several possibilities can be considered. The expansion of the mass into the cardiac chamber may have disrupted hemodynamics during cardiac contraction, as evidenced by hepatic congestion. Additionally, a cardiac mass could interfere with preferential sinoatrial conduction pathways and induce dysrhythmias.

We found renal and hepatic amyloidosis in our case. In cheetahs, renal amyloidosis is found concurrently with chronic inflammatory lesions in other organs, including gastritis and chronic renal disease. ²¹ Because the stomach was not examined histologically, we cannot exclude chronic gastritis as a potential cause of systemic amyloidosis. However, given the susceptibility of captive cheetahs to chronic renal failure and systemic amyloid deposition, the renal and hepatic amyloidosis in our case is presumed to be a consequence of chronic renal disease. ²¹ Additionally, fecal–oral transmission of amyloidosis has been reported in cheetahs and other animals. ¹⁹