Rare Disease of the Heart Highlights Imaging's Role

A 58-year-old man presents to an emergency department (ED) in Houston after experiencing worsening lightheadedness over a period of several months. He notes that although he had seizures many years ago, they have not returned.

He explains that the previous summer when he initially told his family doctor that he had been feeling faint, the physician ordered a neurologic workup including magnetic resonance imaging and an electroencephalogram, but the results were normal.

Diagnosis

ED clinicians perform an echocardiogram, which reveals mild enlargement of the left atrium, with numerous suspicious mobile masses and preserved ejection fraction (60%-65%). A follow-up transesophageal echocardio­gram confirms the findings and raises suspicion of a primary cardiac tumor.

Two days later, the patient undergoes surgery, resulting in partial debulking of multiple fragments of the left atrial masses infiltrating the anterior cham­ber surface and aortic leaflet, with aortic valve repair. Based on the pathology report, clinicians diagnose intermediate- to high-grade unclassified pleomorphic sarcoma of the left atrium (largest mass is 5.5 × 5.0 × 2 cm) involving the endocardium -- moderately cel­lular with evidence of pleomor­phic and atypical cells, myxohyaline stroma, and inflammatory cells.

Treatment

December 2015 – April 2016

Clinicians start the patient on chemotherapy with doxorubicin 75 mg/m² and ifosfamide 10 g/m², six cycles over the course of the next 4 months. Follow-up computed tomography (CT) scan of the chest shows that the mass detected in the left atrium is reduced in size.

May 2016

Clinicians perform a second resection of the left atrial sarcoma using cardiac auto-transplantation tech­nique, reconstruction of the left atrium using bovine pericar­dium, total cardiopulmonary bypass, and cold del Nido cardio­plegia for myocardial protection. Pathology tests show pleomorphic sarcoma (5.3 × 4.7 × 0.6 cm) with left and right pulmonary vein involvement and positive margins.

July 2016 – September 2016

About 2 months after surgery, a CT scan shows no sign of residual disease. The patient is managed with salvage chemotherapy -- two cycles of gemcitabine (Gemzar) 675 mg/m² and docetaxel 75 mg/m². However, the patient subsequently develops symptomatic pneumonitis and has to stop treatment.

October 2016 – June 2017

CT imaging shows no indications of recurrence or metastatic disease.

September 2017

Disease recurrence: CT imaging detects a new nodule within the left superior pulmonary vein and a new scle­rotic lesion in the right posterior ilium that clinicians believe indicates metasta­sis.

October 2017 – December 2017

The doxorubicin/ifosfamide regimen is resumed for two cycles; imaging suggests the disease is stable, but the patient's kidney function is declining.

December 2017 – May 2018

Treatment is switched to doxorubicin 75 mg/m² and olaratumab (Lartruvo) 15 mg/kg -- six cycles. Cardiac imaging shows an enlarging left superior pulmonary vein lesion; right iliac metastasis shows no sign of response and remains unchanged. In May 2018, the patient reports pain in his pelvis; clinicians biopsy the right iliac bone lesion, and assessment confirms metastatic sarcoma.

June 2018

CT scan shows that the size of the left superior pulmonary vein lesion has increased, with evidence of new extension into the left atrium. Treatment is initiated with pazopanib 800 mg daily.

September 2018

Imaging shows that the tu­mor is progressing.

January 2019

Treatment is initiated with pembrolizumab every 3 weeks.

May 2019

After five cycles of pembrolizumab, interval imaging reveals that the pulmonary nodules have advanced slightly; cardiac tu­mor and right iliac bone lesions are stable.

July 2019

After seven cycles of pembrolizumab, perihilar disease progresses. Treatment is initiated with liposomal doxorubicin (Caelyx) 30 mg/m².

August 2019

After two cycles of doxorubicin, the patient has further perihilar disease progression; metastatic disease spreads to involve new bone. Clinicians discuss the situation with the patient, and subsequently refer him for hospice care.

Discussion

Clinicians reporting this case of a patient with undifferentiated pleomorphic sarcoma describe the various lines of treatment used to manage this sarcoma of the heart, which led to sur­vival of more than 4 years. The authors note that due to the rarity of the disease, management is multidisci­plinary and generally extrapolated from case re­ports and case series.

That the tumor is undifferentiated means that it lacks immunohistochemical or morphologic find­ings to suggest a specific type of sarcoma. About 12% of all primary cardiac sarcomas are classified as undifferentiated pleomorphic sarcoma, also referred to as malig­nant fibrous histiocytoma.

Most cardiac tumors have metastasized from another site – they are identified in the autopsies of about one in 10 patients who die of cancer. In contrast, tumors that originate in the heart account for only 0.001% to 0.02% of all cardiac neoplasms, affect less than 0.1% of the population, and are mostly benign atrial myxo­mas.

The most common sarcomas of the heart are angiosarcomas, which arise from vascular components. About 20% of primary cardiac neoplasms are cardiac rhabdomyosarcomas; these often affect children and are associated with tuberous sclerosis.

Factors determining cardiac tumor symptoms include:

• Tumor location

• Degree of flow obstruction

• Size of the tu­mor

• Extent of myocardial invasion

Presentation

Clinically, this cancer may cause no symptoms and may be identified incidentally or present with symptoms such as shortness of breath, chest pain, pericarditis, or acute heart failure with tamponade.

Left-sided tumors may cause arrhythmias and interfere with or obstruct blood flow, resulting over time in pulmonary hyperten­sion and heart failure. Heart auscultation may demon­strate murmurs similar to those associated with mitral valve dis­ease.

Up to 12% of left-sided myxomas may cause tumor embolic strokes, which in some cases are the tumor's initial presentation. Right-sided tumors often present with symptoms suggestive of right-sided heart failure, increased right-sided pres­sures, and pulmonary emboli.

Imaging

Imaging is central to diagnosing primary cardi­ac sarcomas. Transthoracic echocardiography is of­ten used first to assess for cardiac-related symptoms. Transesophageal echocardiography is more invasive but may offer higher resolution to help identify spa­tial localization of the tumors.

Where available, cardiac MRI can help determine the vascularity of the masses and is preferred over CT. Positron emission tomogra­phy (PET) imaging is used in patients with suspected cardiac metastasis from an unknown origin, to look for a primary tu­mor and occasionally to assess for distant metastases from primary cardiac tumors.

The case authors stress the importance of including pan-body imag­ing in the diagnostic staging workup for cardiac sarcomas, to rule out distant metastases.

A 2019 review of 39 patients diagnosed with primary cardiac sarcoma (median age of 41) at the University of Michigan between 1992 and 2017 found that 18 patients presented with metastases involving lung (10 patients), bone (seven), liver (five), and brain (four).

At a median of 8.5 months (range 0-75) from diagnosis, brain metastases occurred in 12 patients (31%), nine (75%) of whom had left heart tumors. Those researchers suggested that clinicians should be aware of the increased risk of brain metastases with cardiac sarcomas, and consider brain imaging at diagnosis and follow-up.

Treatment

The locally aggressive nature of these sarcomas makes complete excision rare -- resection for cure or complete remission is reported in just 12% of patients with cardiac tumors. Furthermore, as noted, they generally recur locally, and metastasize to distant sites over time.

Even with aggressive treatment, patients with cardiac sarcomas have a median overall survival of only 6 to 12 months, although the case report authors point out that multimodal­ity treatment may be associated with improved survival compared with surgery alone.

Complete resection of the cardiac sarcoma is considered the treatment of choice, notwithstanding barriers to operability such as the anatomic location, degree of heart fail­ure, the patient's performance status, and other patient comorbidities.

Adjuvant chemotherapy can help manage local residu­al disease, prevent local recurrence, and control distant me­tastasis. In selected patients, neoadjuvant treatment to decrease the tumor burden has been observed to improve the rate of complete resection and survival, although the role has not been clarified.

The rarity of cardiac sarcomas precludes clinical trials to identify the most effective approach to treatment.

Auto-transplantation is a rarely employed surgical approach to left-sided cardiac tumors, which has reportedly improved survival in two small series of 11 and 26 patients, the case report authors note. The technique involves excising the heart, resecting the tumor ex vivo, and re-im­planting the heart.

The approach was reported in 2014 to be associated with 1- and 2-year survival rates of 46% and 28%, respectively, in the 26-patient study. However, the balance of risks versus benefits has yet to be determined, and for patients with disease progression or lack of re­sponse, phase I clinical trials remain a viable option.

The case authors note that even with the general overall survival of 6 to 12 months, this patient survived more than 4 years after diagnosis, with clinicians using different lines of treatment, close monitoring, and immediate treatment adjustments on detection of disease progression.

Conclusions

A multidisciplinary team is required to diagnose and manage cardiac sarcomas, including sarcoma oncology specialists, specialized pathologists, cardiac radiologists, and cardiothoracic surgeons, the authors note, emphasizing that treatment plans should be determined on a case-by-case basis.

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