Secondary malignant cardiac tumor

Secondary malignant cardiac tumors or cardiac metastases refer to a secondary malignant tumor involving any structural component of the heart. It represents spread of a primary neoplasm via lymphatic, haematogenous, or endovascular pathways, or potentially by direct extension from an adjacent tissue .

Epidemiology

Overall, cardiac malignancy is uncommon. Metastatic spread is much more common than primary cardiac malignancy (~30:1) . In patients with widespread metastatic disease, autopsy series have reported 12-25% incidence of cardiac metastasis . One larger autopsy series showed that findings of isolated cardiac metastasis are unusual (10/662 cases of cardiac metastasis) .

Virtually any primary malignancy may metastasize to the heart; however, the most common metastases are:

• lung, breast, kidney, ovarian carcinoma
• pleural mesothelioma
• malignant melanoma
• lymphomyeloproliferative types lymphoma and leukemia
• pancreatic adenocarcinoma
• gastric carcinoma
• colonic carcinoma
• mixed germ cell testicular cancer

The incidence of cardiac involvement may reflect a combination of:

• the aggressiveness of the individual malignancy
• frequency in which the underlying malignancy occurs

Clinical presentation

Often missed during the initial evaluation of the primary malignancy, secondary cardiac involvement may not be detected for many years. Not infrequently, the diagnosis is only made at autopsy.

Potential presenting signs and symptoms may greatly vary, influenced by the location of tumor deposit(s) :

• dyspnea and congestive heart failure, hypotension:
  •  malignant pericardial effusion
• infarction, arrhythmias, hypoxia, and hypotension:
  • involvement of myocardium or conductive system
  • intracavitary mass
  • valvular implants

Pathology

From a surgical pathology perspective, most presentations of cardiac metastasis comprise multifocal tumor deposits. In order of frequency, the distribution is as follows :

• pericardial (70%)
  • mesothelioma
  • lung carcinoma
  • ovarian carcinoma
  • gastric carcinoma
  • prostate adenocarcinoma
• epicardial (34%)
  • melanoma
  • lung carcinoma
• myocardial (32%)
  • melanoma
  • lymphoma/leukemia
• endocardial (5%) - usually ventricular; right ventricle more common. Associated with tumors with endovascular growth potential
  • melanoma
  • renal carcinoma
  • hepatocellular carcinoma
• valvular (rare)

Primary malignancies have predilections for pathways of spread :

• predominantly lymphatic via mediastinal nodes and invasion of epicardial and pericardial lymphatics
  • esophageal
  • lung
  • breast carcinomas
• predominantly haematogenous
  • melanomas
  • sarcomas
  • renal cell carcinomas
  • choriocarcinomas
  • lymphomas/leukaemias
• superficial myocardial involvement
• intraluminal extension via the inferior vena cava and right atrium
  • hepatocellular carcinoma
  • renal cell carcinoma
  • Wilms tumor
• extension via the pulmonary vein
  • pulmonary malignancies

Gross pathology

Typical features include:

• diffuse studding and thickening of the pericardium
• nodular, white-tan infiltrations on cut section
• associated desmoplastic reaction resulting in pericarditis constrictiva (frequently caused by directly extending lung malignancy)

A singular mass, endocardial involvement, or intracavitary tumor is less common .

Histopathology

Often resembles morphological features of the causative malignancy.

In cases of an unknown primary or long interval between primary malignancy and diagnosis of cardiac involvement, immunohistochemical analysis may be necessary.

Encountering a high-grade, undifferentiated tumor may necessitate extensive use of immunohistochemical stains, a preliminary panel of which should include keratinic, melanocytic and lymphoid markers (cf. list of most common primaries) .

Radiographic features

Masses are rarely amenable to biopsy. Knowledge of the often characteristic imaging features is a prerequisite for providing a meaningful list of differential diagnosis.

Plain radiograph

Findings are non-specific on chest x-ray, but may include:

• cardiomegaly (e.g. indicating pericardial effusion and/or cardiac congestion)
• gross mediastinal lymphadenopathy

Comparison with previous films is important.

Ultrasound

Transthoracic echocardiography (TTE)

Very often the initial imaging method of choice, albeit both operator-dependent and influenced by patient-related factors. The limited field-of-view may preclude complete assessment of an invading mass, but depicting pericardial effusion is usually straightforward. It may also allow for the detection of ventricular masses.

Transesophageal ultrasound (TOE)

TOE usually offers a more detailed assessment, allowing for detection of subcentimeter masses or tumors located within the atria or near the valves. The lack of confident tissue characterization, however, often necessitates the use of cross-sectional imaging.

Cross-sectional imaging

General features comprise:

• multiple masses or nodules with heterogeneous enhancement pattern, best diagnostic clue
• diffuse infiltration may also occur
• epicardial and pericardial masses with associated effusion, usually complex
• changes in the contour of the cardiac chambers and/or intraventricular septum 

The latter finding may alert to the need for pericardiocentesis.

MRI

Cardiac MR (ECG-gated MR) is the imaging modality of choice due to:

• high temporal resolution (30–50 ms)
• excellent soft-tissue contrast

Imaging features are as listed above. Typical characteristics of masses are:

• T1: hypointense
• T2: hyperintense
• almost always significant contrast enhancement post gadolinium injection

In addition, malignant melanoma deposits typically show high T1 signal caused by paramagnetic properties of melanin, thus allowing for a specific diagnosis of the primary malignancy , obviating the need for biopsy.

CT

As stated above. May depict calcifications. Masses typically show soft-tissue attenuation on CT .

Most frequent CT features of pericardial metastases include pericardial effusion, prepericardial lymph nodes, and pericardial thickening, enhancement, and nodules in order of decreasing frequency .

Distribution is as follows :

• pericardium is by far the most commonly affected site
• myocardium can be involved through direct tumor extension from the pericardium. However, malignant melanoma may result in diffuse myocardial involvement through haematogenous spread
• only about 5% of cardiac metastases are endocardial/intracavitary lesions

Nuclear medicine

PET/CT

18F-FDG PET/CT with state-of-the-art CT may aid in differentiation between benign and malignant cardiac tumors. 
Likely the best present imaging modality to assess the widespread nature of the causative primary malignancy .

PET/MRI

Likely the imaging reference of the near feature, combining advantages of both modalities, i.e. excellent soft tissue contrast and molecular imaging .

Treatment and prognosis

As mostly encountered in widespread disease, treatment is often palliative and addresses the underlying malignancy. Pericardiocentesis may be indicated to relieve symptoms caused by effusion (see also imaging features indicating cardiac tamponade). Although a rare finding, single nodules may be resectable .

Differential diagnosis

The distinction between primary and secondary cardiac neoplasms is typically made empirically, since almost all cardiac metastases manifest in patients with known non-cardiac primary malignancies .

It is important to keep in mind that metastatic cancer may present as malignant pericardial effusion .

In cases of doubt, or on encountering findings suggestive of malignant cardiac disease without known primary malignancy, general differential diagnostic considerations may include:

• other causes of pericardial effusion
• anatomic variants
• thrombi and pseudothrombi (flow-related changes)
• primary cardiac neoplasms (albeit much less common)

A walk through the rarity section offers illustrative examples regarding the ratio of primary and secondary cardiac neoplasm:

• multiple cardiac metastases from a non-functioning pancreatic neuroendocrine tumor (pNET) 
• squamous cell carcinoma of the bladder presenting as a metastatic right ventricular mass
• metastasis of a pulmonary undifferentiated pleomorphic sarcoma to the right ventricle
• extension of adrenocortical carcinoma into the right atrium

Practical points

Caveat emptor! Calculating a priori probability of synchronous primary cardiac neoplasm in these rare primaries might provide the end of the calculator on Occam's desk.