Background

Metastatic cardiac tumours are uncommon with an estimated prevalence of 0.002%–0.3% during autopsy and can be the first manifestation of an undiagnosed malignant neoplasm.1 Limited literature is available regarding the incidence of cardiac metastasis; however, the Department of Pathologic Anatomy, University of Trieste, Italy carried out 18 751 postmortem examinations out of which 622 had cases of cardiac metastasis with 8% of those being prostatic carcinoma in origin.2 Diagnosis of isolated cardiac masses is challenging when a primary malignancy has not been established. Cardiac metastases are usually clinically silent, but symptoms depend mostly on the location and the invaded structures.3 The metastasis of prostate adenocarcinoma to the heart is an exceedingly rare occurrence with a precise incidence rate remaining unestablished in the contemporary literature. Regrettably, the clinical prognosis associated with this condition is notably unfavourable.

Case presentation

A man in his late 80s presented with a 2-week history of right heart failure symptoms including progressive peripheral oedema and mild dyspnoea on exertion. He underwent a transthoracic echocardiogram (TTE), which revealed a severely dilated heart’s right ventricle with a large mass occupying the majority of the right ventricular cavity causing restrictive filling and decreased systolic function. He was referred to our institution for further evaluation and management. Physical examination was notable for normal vital signs and elevated jugular vein pulsations. Cardiac auscultation demonstrated a soft S2 and a grade III/VI systolic ejection murmur in the pulmonic area. Laboratory investigations demonstrated an elevated N-terminal brain natriuretic peptide: 1928 pg/mL (normal range 0–125 pg/mL). Complete blood count, renal function (creatinine, blood urea nitrogen and estimated glomerular filtration rate) and liver function (Alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, albumin and platelet count) were normal.

The patient’s medical history was notable for Lynch syndrome complicated by transverse colon adenocarcinoma (T3 N0 M0) requiring laparoscopic extended right hemi-colectomy 8 years prior. A year later, he was diagnosed with prostate adenocarcinoma (T3b N0 M0) Gleason score 9 with involvement of the left seminal vesicle, for which he subsequently underwent radical prostatectomy. Recent treatment for his prostate cancer included 3 months of androgen deprivation therapy with bicalutamide and leuprorelin with the most recent dose given prior to his admission to the hospital.

Investigations

Two months prior to the development of symptoms, a surveillance whole-body 18-fluorodeoxyglucose positron emission tomography-CT (18-FDG PET-CT) scan did not reveal any active malignancies. But 18F-Fluciclovine (Axumin) PET-CT did demonstrate high uptake in the right ventricle cavity (figure 1). TTE at presentation demonstrated a dilated right ventricle with paradoxical septal motion and a giant intracardiac right ventricular mass (8.5×4.4×4.5 cm). The morphological characteristics were suggestive of a neoplastic process. Cardiac MRI (CMR) showed a hyperintense T2/isointense T1 large sessile mass with irregular borders attached from the base to the apex of the right ventricle free wall, occupying the entire cavity, sparing only the medial aspect of the basal and middle segments (figure 2). End-diastolic volume was 54 mL/m² (normal range: 55–103 mL/m²), stroke volume index 27 mL/m² (normal range: 36–70 mL/m²) with akinesis of the entire right ventricle free wall. The mass demonstrated heterogeneous gadolinium uptake on first-pass perfusion images and heterogeneous late gadolinium enhancement (LGE). An incidental left-superior mediastinum lesion was also identified. Initially, Fluciclovine F18 PET-CT images were not available for review by our multidisciplinary cardiac team; therefore, endomyocardial biopsy (EMB) was performed but histological examination showed normal myocardium with focal interstitial fibrosis and no neoplastic process. This represented a false negative result, given the low diagnostic yield of EMB in these scenarios.4 5 Coronary angiogram showed normal anatomy without evidence of obstructive coronary artery disease.

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Figure 1

FDG and Fluciclovine F18 PET-CT. (A) Normal findings without evidence of active malignancy. Left pleural effusion is noted. (B) Fused axial view with normal FDG uptake. (C) PET images showing high uptake of Fluciclovine F18 in the right ventricular cavity (yellow arrow). FDG, fluorodeoxyglucose; PET, positron emission tomography.

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Figure 2

Multiparametric CMR. Representative end-diastolic (A) and end-systolic short axis (B) cine images demonstrate a large mass (*) occupying the right ventricular cavity. The mass was iso-intense to the myocardium on dark-blood turbo-spin-echo T1-weighted images (C) and hyperintense on fat-saturated T2-weighted images (D). Native T1 (E) and T2 maps (F) showed long T1 and T2 relaxation times relative to the myocardium. On first-pass perfusion images (G) there are areas of delayed contrast uptake (yellow arrowhead) in the mass representing loss of vascularity. On late gadolinium enhanced images (H) there is heterogeneous enhancement (yellow arrowhead) indicative of tumour necrosis. CMR, cardiac MRI.

Differential diagnosis

Primary cardiac tumours (5% of cardiac tumours): (1) benign (75% of cases): myxoma, lipoma, fibroelastoma, rhabdomyoma, fibroma, haemangioma, teratoma and other less common4 5; and (2) malignant (25% of cases): angiosarcoma, rhabdomyosarcoma, mesothelioma fibrosarcoma, leiomyosarcoma and other less common.4 5 Metastatic malignancies (95% of cardiac tumours): breast, lung, melanoma, renal cell and lymphoma. Pseudotumour: intracardiac thrombus, vegetation, cysts, lipomatous hypertrophy of the atrial septum and normal variant structures.

Treatment

The patient underwent palliative partial resection of the right ventricle tumour and tricuspid valve replacement with a 31 mm Magna bioprosthesis due to tumour invasion to the anterior and septal leaflets. Postoperative course was complicated by haemodynamic instability requiring transient inotropic support, prolonged respiratory failure requiring tracheostomy and complete heart block with implantation of a dual-chamber pacemaker. After a prolonged recovery phase, the patient was discharged in stable condition with medical management, including metoprolol succinate and torsemide, in addition to sildenafil for pulmonary artery hypertension noticed during his postoperative course. No hormonal or radiation treatment was started inpatient.

Heart and mediastinal lymph nodes were collected during open heart surgery. Histologically, abundant pericardium and myocardium tissues were obtained. Most of the myocardium in the samples were effaced and replaced by a metastatic adenocarcinoma of prostatic origin that displayed a Gleason’s grade 4+4=8. Immunohistochemical stains revealed that tumour cells were strongly positive for prostatic specific antigen stain and keratin. This correlated with the patient’s most recent elevated Prostate-Specific Antigen (PSA) levels at 44 ng/dL (normal: 2.5–4.0 ng/dL). The stains for intestinal differentiation cytokeratin-20 and Caudal-type homeobox transcription factor 2 (CDX2) failed to support a colonic origin (figure 3). Identical findings were observed in the metastasis to the mediastinal lymph node.

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Figure 3

Histological findings. (A, B) Nest of tumour composed of a monotonous population of cells whose nuclei show prominent nucleoli (H&E stain; 100× and 200×). (C) Tumour cells are positive for cytokeratin; myocardial fibres are negative (immunoperoxidase; 100×). (D) Tumour cells show positive staining in the cytoplasm for prostatic specific antigen (immunoperoxidase; 100×).

Outcome and follow-up

Heart failure symptoms improved after surgical mass reduction over the next 4 months. Given that the mass was only partially resected, adjuvant hormonal therapy with leuprorelin and enzalutamide (non-steroidal antiandrogen medication) was continued for 6 months after surgery. Unfortunately, the patient did not respond as his PSA continued to rise along with worsening heart failure symptoms. Subsequently, enzalutamide was discontinued, and the patient’s overall performance status was too poor for any other therapies such as docetaxel and the patient transitioned to hospice care. He died 11 months after the operation.

The role of multimodality imaging for intracardiac masses

TTE is the initial non-invasive imaging modality of choice as it is easily available at low cost, with many cardiac tumours detected incidentally.8 TTE and Transesophageal echocardiogram (TEE) are excellent for determining cardiac mass location, morphology, and assessment of the functional and haemodynamic consequences.9

CMR is an advanced complimentary imaging modality due to its ability to visualise all cardiac chambers without acoustic window limitations and it offers superior definition of disease burden.10 More importantly, with the use of multiparametric tissue characterisation, CMR can differentiate thrombus versus tumour and benign versus malignant masses with high accuracy.11 12 The use of T1-weighted and T2-weighted imaging helps with identification of tissue composition such as solid, fluid or fat. First-pass perfusion and LGE imaging define mass vascularity.13 CMR also identifies myocardial infiltration and involvement of adjacent structures. Limitations include claustrophobia, patient difficulty with breath holds and arrhythmias which may lead to acquisition artefacts, diminishing the diagnostic accuracy. However, recent advances in CMR pulse sequences such as free-breathing motion corrected reconstruction and single-shot acquisitions, mitigate breathing motion and poor ECG gating artefacts, and provide high quality diagnostic images. Beyond diagnosis and surgical planning, LGE patterns have been shown to have prognostic value; tumours with heterogeneous enhancement, indicative of loss of vascularity and necrosis, portend worse prognosis among a cohort of cancer patients.13 14

ECG-gated cardiac CT may be used in the evaluation of cardiac masses; however, it has lower temporal resolution and limited tissue characterisation ability compared with CMR. Cardiac CT is a valid alternative in patients with contraindications to CMR or patients with inadequate images from other imaging modalities. Imaging protocols must be tailored for imaging cardiac masses, specifically including delayed imaging to maximise tissue characterisation. The use of dual energy imaging can prove useful to differentiate tumour versus thrombus.

The role of metabolic imaging for prostate adenocarcinoma

The utility of cardiac CT is enhanced when coupled with 18-FDG PET imaging. 18-FDG PET/CT can detect increased glucose metabolism of tissue, helping to distinguish between malignant and benign tumours with a sensitivity of 80% and a positive predictive value of 87% for the detection of primary prostate cancer but studies for cardiac metastases are lacking.15

18F-FDG is one of the most common PET tracers used in oncology but its use can be limited when it comes to malignancies of certain origins, including recurrent prostate cancer. The relatively low sensitivity, compared with other tracers, has been proposed to be due to the small size of recurrent lesions, and prostate cancer utilising non-glucose metabolic pathways.16 On the other hand, 18F-Fluciclovine (Axumin) is a tracer approved in 2016 for suspected prostate cancer recurrence based on elevated PSA level following treatment; this tracer can detect both bony and soft tissue lesions that indicate tumoral proliferation.

In our case, the diagnosis of prostate cancer was made after the excision of the mass. An EMB was attempted based on recommendations of the joint statement by the AHA/ACC/ESC 2007 guidelines recommending a cardiac biopsy if the diagnosis cannot be demonstrated by other non-invasive modalities, and if the pathological diagnosis can influence the treatment plan but in our patient, the result of the EMB was found to be a false negative given that the initial report showed no evidence of a neoplastic process. Usual biopsy forceps may not always yield adequate tissue samples for histological analysis. In this case, the 18F-Fluciclovine PET-CT would have been helpful given the patient’s history of Lynch syndrome and prostate cancer had we known the results prior in time.