Secondary malignant cardiac tumor

Secondary cardiac neoplasms or cardiac metastasis/es refer to a secondary malignant tumour of the heart, arising by lymphatic or haematogenous spread of a primary neoplasm ^3,5.

Epidemiology

Overall cardiac malignancy is an infrequent finding. Metastatic spread is much more common than primary cardiac malignancy, with a factor approximating 30 to 1. Series of autopsia cadaverum in patients with widespread disease burden revealed cardiac involvement in 12-25% of cases ³. Larger series (n=662) have demonstrated sole cardiac involvement by a metastasizing malignancy in no more than 1,5 % of cases ⁵.

Virtually any primary malignancy may metastasize to the heart, however the, the most often encountered primaries comprise:

• lung, breast, kidney, thyroid carcinomas and malignant melanomas, along with
• the lymphomyeloproliferative types lymphoma and leukemia.

As such, incidence of cardiac involvement reflects a combination of

• aggressiveness of the individual malignancy and 
• frequency in which the underlying malignancy occurs ⁵

Clinical presentation

Often missed during initial diagnostic work-up for primary diagnosis, secondary cardiac involvement may not be detected for many years. Not infrequently it is not diagnosed clinically at all and found at autopsy.

Potential presenting signs and symptoms may greatly vary, influenced by the location of tumor deposit(s) ^3,5:

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

Pathology

In most cases multiple metastatic tumor deposits are encountered. Locations and their frequency are as follows ³:

• right cavities, roughly one third of cases
• left cavities, another third
• bilateral involvement in the remaining cases

Pathways of spreading may occur ^3,5:

• predominantly lymphatic via mediastinal nodes and invasion of epicardial and pericardial lymphatics:
  • oesophageal
  • lung
  • breast carcinomas
• predominantly hematogenous:
  • melanomas
  • sarcomas
  • renal cell carcinomas
  • choriocarcinomas
  • lymphomas/leukemias
• superficial myocardial involvement
• intraluminal extension via 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 tumour is less commonly encountered ^3,5.

Histopathology

often resembles morphological features of the causative malignancy.

In cases of 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 (confer list of most common primaries) ^3,5.

Clinical manifestation

Often missed during initial diagnostic work-up for primary diagnosis, secondary cardiac involvement may not be detected for many years. Not infrequently it is not diagnosed clinically at all and found at autopsy.

Potential presenting signs and symptoms may greatly vary, influenced by the location of tumor deposit(s) ^3,5:

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

Radiographic features

Initial considerations

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

Useful imaging modalities include:

Chest radiograph

Findings are non-specific, but may include:

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

Importance of comparison with older films is obvious.

Ultrasound

Trans-thoracicTransthoracic 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 detection of ventricular masses.

Trans-oesophagealTransoesophageal ultrasound (TOE)

TOE usually offers a more detailed assessment, allowing for detection of sub-centimetre  masses or tumours located within the atria or near the valves.

The The lack of confident issuetissue characterization, however often necessitates 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 contour of the cardiac chambers and/or septum interventriculare

The latter finding may alert to theneed for pericardiocentesis.

MR

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 Typical characteristics of masses are:

• low signal on T1 and
• high signal on T2-weighted images
• 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 ^7,13, obviating the need for biopsy.

CT

As stated above. May depict calcifications. Masses typically show soft-tissue attenuation on CT ⁷.

Most frequent CT features of pericardial metastases include pericardial effusion, prepericardial lymph nodes, and pericardial thickening, enhancement, and nodules in order of decreasing frequency ².

Distribution is as follows ¹:

• 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 hematogenous spread
• only about 5% of cardiac metastases are endocardial/intracavitary lesions

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 ⁴.

MR/PET

Likely the imaging reference of the near feature, combining advantages of both modalities, i.e. excellent soft tissue contrast and molecular imaging ¹⁴.

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 ³.

Differential diagnosis

The distinction between primary and secondary cardiac neoplasms is, usually, easily made on clinical grounds since almost all cardiac metastases manifest in patients with known noncardiac primary malignant neoplasms ^1,3,5.

It is important to keep in mind that, although usually part of widespread metastatic disease, metastatic cancer may present as malignant pericardial effusion ⁵.

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 rarity section offers illustrative examples regarding the ratio of primary and secondary cardiac neoplasm, e.g.

• multiple cardiac metastases from a nonfunctioning pancreatic neuroendocrine tumor (pNET) ⁸
• squamous cell carcinoma of the bladder presenting as a metastatic right ventricular mass ⁹
• metastasis of a pulmonary undifferentiated pleomorphic sarcoma to the right ventricle ¹⁰
• extension of adrenocortical carcinoma into the right atrium ¹¹

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.