Hibernoma: a case report of a rare cardiac tumour

Abstract Background A cardiac hibernoma is a rare phenomenon, with just a handful of reports in the literature. They are difficult to characterize with conventional imaging including echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or positron emission tomography (PET). Their definitive diagnosis relies primarily on histopathology via either endovascular or surgical biopsy. Previous case reports have entailed surgical excision followed by histopathology; however, surgery may be unfavourable in some patients with increased perioperative risk. Case summary We present the case of a 57-year-old woman who was referred to our cardiology service with an interatrial lipomatous mass found incidentally on chest CT for assessment of rib fractures. She had 6 months of unexplained syncope, which was attributed to superior vena cava (SVC) compression demonstrated by chest CT. The mass had benign characteristics on echocardiography, CT, and CMR but was glucose-avid on PET, which indicated a possible malignancy such as liposarcoma. Her comorbid and very significant airways disease precluded her from surgical excision, so instead, endovascular biopsy was performed. Histopathology showed brown fat which was negative for mouse double minute 2 amplification on fluorescence in situ hybridisation testing; hence, a diagnosis was made of hibernoma, a rare benign tumour of brown fat. Given the benign diagnosis and her surgical risk with severe chronic obstructive pulmonary disease, a multidisciplinary recommendation was made favouring conservative management, with careful ongoing follow-up and the consideration of SVC stenting if symptoms progressed. Discussion The definitive diagnosis of a cardiac hibernoma is complex and relies heavily on histopathology due to the contradictory findings on chest imaging. Careful consideration of management within a multidisciplinary team setting is essential to achieve a successful outcome.


Background
A cardiac hibernoma is a rare phenomenon, with just a handful of reports in the literature.They are difficult to characterize with conventional imaging including echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or positron emission tomography (PET).Their definitive diagnosis relies primarily on histopathology via either endovascular or surgical biopsy.Previous case reports have entailed surgical excision followed by histopathology; however, surgery may be unfavourable in some patients with increased perioperative risk.

Case summary
We present the case of a 57-year-old woman who was referred to our cardiology service with an interatrial lipomatous mass found incidentally on chest CT for assessment of rib fractures.She had 6 months of unexplained syncope, which was attributed to superior vena cava (SVC) compression demonstrated by chest CT.The mass had benign characteristics on echocardiography, CT, and CMR but was glucose-avid on PET, which indicated a possible malignancy such as liposarcoma.Her comorbid and very significant airways disease precluded her from surgical excision, so instead, endovascular biopsy was performed.Histopathology showed brown fat which was negative for mouse double minute 2 amplification on fluorescence in situ hybridisation testing; hence, a diagnosis was made of hibernoma, a rare benign tumour of brown fat.Given the benign diagnosis and her surgical risk with severe chronic obstructive pulmonary disease, a multidisciplinary recommendation was made favouring conservative management, with careful ongoing follow-up and the consideration of SVC stenting if symptoms progressed.

Discussion
The definitive diagnosis of a cardiac hibernoma is complex and relies heavily on histopathology due to the contradictory findings on chest imaging.Careful consideration of management within a multidisciplinary team setting is essential to achieve a successful outcome.

Learning points
• Although multimodal imaging including echocardiography, cardiac magnetic resonance (CMR), and positron emission tomography (PET) are generally useful for guiding the diagnosis and management of most intracardiac masses, lipomatous intracardiac masses can produce contradictory findings.
• Hence, histopathology, in particular the presence of mouse double minute 2 (MDM2), is important for confirming the diagnosis of liposar- coma.Conversely, the absence of MDM2 is more suggestive of a benign lipoma or hibernoma.
• Non-operative management of cardiac hibernoma is a potentially viable option for patients with unacceptably high surgical risk, where CMR has significant utility for monitoring and surveillance.
There are no reported guidelines on the management of cardiac lipomas, let alone hibernomas. 1 In the scarce case reports, surgical resection was universally performed due to the risk for lipomas to grow or even infiltrate/compress nearby structures. 1 In this case, a multidisciplinary decision was made for non-operative management given concurrent comorbid severe airways disease, which represents the first cardiac hibernoma, to our knowledge, managed conservatively.

Case presentation
A 57-year-old female of Indigenous Australian descent was referred to our cardiology service for evaluation of a large interatrial mass incidentally identified on chest imaging performed for assessment of rib fractures, occurring in the context of unexplained syncope.She is an ex-smoker (cigarettes, 28 pack/years) and used marijuana daily.Both were stopped 6 months before presentation and resulted in severe chronic obstructive airways disease (FEV1 0.74 L, 29% predicted; FEV1/FVC 0.32; DLCO 29% predicted).Her only other previous medical history was of Caesarean procedure and depression.Her regular medications were duloxetine, and the following inhalers: budesonide-formoterol, tiotropium, and salbutamol as required.
The patient described 6 months of multiple syncopal episodes.These occurred after periods of recumbency, and there were no symptoms preceding these episodes.An invasive coronary angiogram demonstrated minor coronary disease, while echocardiography showed normal bi-ventricular function and telemetry ruled out significant rhythm disturbances.
A computed tomography (CT) chest without contrast performed May 2021 reported rib fractures as was clinically suspected, but also superior vena cava (SVC) obstruction from a 57 × 41 × 40 mm predominantly fat signal mass.A whole-body positron emission tomography (PET) performed at her local centre demonstrated marked avidity for fluorodeoxyglucose (FDG) by a fat density mass in the interatrial septum (IAS), most consistent with a malignant liposarcoma.There was no lymphadenopathy or distant metastases.She was subsequently referred to our centre for further investigations and management.
On presentation to our centre, she was 82 kg, blood pressure 125/ 87 mmHg, and heart rate was 92 b.p.m. in an ectopic atrial rhythm on electrocardiogram (ECG).There was no right heart strain.Oxygen saturations were between 90% and 98% on room air throughout the entire admission.She had markedly hyperexpanded lungs and no clinical features of pulmonary hypertension.There were no palpable lymph nodes.She had mildly positive Pemberton's sign.
Echocardiography at our centre identified the IAS and mass in both transthoracic and transoesophageal views (see Supplementary material online, Videos S1 and S2, respectively).The patient underwent a CT venogram of the chest and neck, which demonstrated normal flow down the SVC.She then proceeded to have dedicated cardiac magnetic resonance (CMR) imaging to further delineate the IAS and mass.Figure 1A demonstrates the interatrial septal mass was lobulated, extending posteriorly and superiorly into the pericardial space.On black blood and cine imaging, it was markedly hyperintense and hypointense on fatsaturated T2-weighted imaging, relative to the myocardium.There was mild enhancement noted post administration of gadolinium contrast.These signal characteristics were more consistent with a benign process.
As shown in Figure 1B, repeat PET using a cardiac dedicated protocol (i.e.avoiding pre-scan carbohydrate) found only moderately increased metabolism compared with the previous PET imaging (SUV 6.5 vs. 12.7).Importantly, there was no brown fat uptake; however, given moderate metabolism shown in the mass, our cardiothoracic surgeons were consulted for feasibility of biopsy.As she was too high risk for surgical management and biopsy, a multidisciplinary team (MDT) discussion determined that biopsy would be crucial to ascertain whether the mass was benign or malignant.The mass was deemed not anatomically feasible Hibernoma: a case report of a rare cardiac tumour for CT-guided biopsy, and hence, we proceeded to a transoesophageal echocardiogram (TOE) guided endovascular biopsy of the IAS mass.The biopsy result demonstrated two fragments of cardiac muscle and one of a fatty process that included brown fat and mature appearing adipocytes, as seen in Figure 1C.There was no lymphoid process identified nor was there amyloid or iron deposition seen on Congo Red and Perls staining, respectively.Figure 1D demonstrates that fluorescence in situ hybridisation testing (FISH) testing for mouse double minute 2 (MDM2) was negative (sensitivity of about 99% in atypical lipomatous tumours or well-differentiated and de-differentiated liposarcoma). 11We hence conclude that the lesion is a hibernoma based on morphology and negative MDM2 FISH.
She was discharged home with a plan for serial surveillance imaging and telehealth to accommodate her regional residence.Aspirin 100 mg daily was added to her medications to reduce her risk of thrombotic events.A progress CT chest in May 2022 demonstrated no significant interval changes of the mass, while a telephone interview in July 2023 found she had no further syncopal episodes, especially after following advice on adequate levels of oral intake and hydration.She may be considered for SVC stenting if her symptoms progress.

Discussion
This case presents an uncommon cardiac tumour in which there are both difficulties in discerning the diagnosis and the optimal management approach.
][3][4][5][6][7][8][9][10] A recent systematic review by Shu et al. 1 described 255 case reports of cardiac lipomas, with only 4 hibernoma.[6][7][8][9][10] Diagnosis of hibernoma is challenging with conventional chest imaging be it echocardiography, CT, CMR, or PET.Based on this case and previous reports, hibernomas are most often well-demarcated lesions with heterogeneous characteristics.3][14] Interestingly, previous imaging studies of brown adipose tissue have found methods of reducing its uptake of glucose, such as keeping the patient warm, using a high-fat/low-carb diet, and administering agents like propranolol or fentanyl. 12Our case demonstrates the importance of appropriate pre-PET scan preparation with a low-carbohydrate diet to avoid the possibility of false-positive findings.
Histological findings of a hibernoma are similar regardless of location. 2,3It entails a predominance of multivacuolated cells with eosinophilic cytoplasm and small central nuclei, which represents the brown adipocytes. 2,3[6][7][8][9][10] Hibernoma-like areas can be seen in liposarcomas, hence the importance of MDM2 FISH testing. 3All previous case reports have relied heavily on open biopsy to confirm a diagnosis of cardiac hibernoma.
The seemingly contradictory findings in imaging modalities of this case created a significant diagnostic dilemma.The mass had benign characteristics on echocardiogram, chest CT, and CMR, which were suggestive of a lipoma.However, the glucose-avid findings of PET imaging raised suspicion of malignancy such as liposarcoma.Ultimately, biopsy proved to be the most important investigation for diagnosis, with the absence of MDM2 markers ruling out malignant sarcomatous disease.
There are no reported guidelines on the management of cardiac lipomas, let alone hibernomas. 1 Shu et al. 1 suggest consideration of all patients for surgical resection because of the potential for lipomas to grow and compress nearby structures.They also suggest close follow-up with imaging to monitor growth or recurrence.][6][7][8][9][10][11] Currently, there are insufficient past cases of cardiac hibernoma to provide a thorough understanding of natural history.Fatal pulmonary embolism has been reported in an elderly woman, 10 as well as fatal cardiogenic shock in a neonate, 5 both of which were diagnosed post-mortem.][6][7][8][9][10] In our case, the patient's significant airways disease was a contraindication to surgical management; hence, a percutaneous biopsy was performed for diagnostic/prognostic purposes.
Cardiac hibernoma is a rare phenomenon.Diagnosis is aided significantly by multimodal imaging and histopathology with negative MDM2 FISH.This case report demonstrates a successful outcome with conservative management.

Lead author biography
David Cistulli completed his BMedSci in 2016, followed by his MD in 2020.In 2023, he is working as a surgical senior resident medical officer at Royal Prince Alfred Hospital, Sydney, Australia.He is currently completing his Masters and has a strong interest in cardiothoracic surgery.

Figure 1
Figure 1 and histopathology.(A) Cardiac magnetic resonance demonstrating lobulated interatrial mass (white arrow); (B) Positron emission tomography scan demonstrating moderate fluorodeoxyglucose (FDG) uptake within the interatrial septum (black arrow).The scan was performed 60 min post intravenous administration of 282 MBq of FDG; (C) Haematoxylin and eosin stain demonstrating brown adipose and native mature adipose tissue; (D) Fluorescent in situ hybridisation demonstrating normal signal without amplification of mouse double minute 2 locus.