Pleomorphic Liposarcoma Initially Presenting with Multiple Organ Involvement Including the Heart

Abstract

A 42-year-old man visited our hospital due to a gradually swelling subcutaneous mass on the back of the right shoulder. The biopsy specimen was diagnosed pathologically as pleomorphic liposarcoma. Systemic computed tomography and ¹⁸F-fluorodeoxyglucose positron emission tomography revealed multiple organ metastases, including involvement of the heart, skin, liver, bone, and lung. Six cycles of doxorubicin plus ifosfamide initially controlled the disease. However, newly developed lung metastases grew rapidly during subsequent cycles of chemotherapy, and the patient died 10 months after the initial diagnosis. The initial presentation of multiple organ involvement, including the heart, is a rare clinical manifestation of pleomorphic liposarcoma.

Introduction

Liposarcoma is one of the most common subtypes of soft tissue sarcoma, representing approximately 20% of all soft tissue sarcomas (1,2). Four major subtypes can be distinguished based on their morphological and genetic features: well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma (PLS) (2,3). These lesions arise from lipoblasts and can be located throughout the body but are most frequently seen in the extremities and retroperitoneum (2-6). In general, treatment of liposarcoma without distant metastasis usually consists of surgical resection, and distant metastasis at the initial diagnosis of liposarcoma is uncommon (3-6). The lung, liver, and bone are common metastatic sites, but multiorgan involvement of liposarcoma, including the heart at initial clinical manifestation, is extremely rare.

We encountered a case of PLS initially presenting with multiple involved organs, including the heart, skin, bone, liver, and lung. We herein report the clinical presentation and treatment outcomes along with a review of the relevant literature.

Case Report

A 42-year-old man was referred to our hospital with progressive enlargement of a soft mass on the back of his right shoulder for 2 months. He had a history of smoking (440 pack-years) and drinking alcohol (20 g ethanol/day) over 20 years. A physical examination revealed an elastic hard mass measuring 50 mm×40 mm on the back of the right shoulder and several small subcutaneous nodules on the abdomen. Routine laboratory tests on admission, including tumor markers, were within normal ranges.

Contrast-enhanced computed tomography (CT) revealed masses in the back of the right shoulder and upper lobe of the right lung, swelling of the hilar and subcarinal lymph nodes, interventricular septal thickening, and liver metastasis (Fig. 1). ¹⁸F-Fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET)/CT revealed a positive ¹⁸F-FDG uptake in these masses (Fig. 2B-D), bone, and abdominal skin (Fig. 2A). Echocardiography showed a large mass measuring 71 mm×46 mm at the center of the interventricular septum, which projected into the right atrium (Fig. 2E). Electrocardiography (ECG) showed a normal sinus rhythm, but inverted T waves were observed in leads II, III and aVF.

Figure 1.

Contrast-enhanced computed tomography (CT) revealed a mass in the back of the right shoulder, a tumor in the upper lobe of the right lung, interventricular septal thickening, and liver metastasis.

Figure 2.

¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) revealed a positive ¹⁸F-FDG uptake in the mass in the back of the right shoulder (B), upper lobe of the right lung (C), left lower lung and interventricular septum (D). The ¹⁸F-FDG uptake was also observed in the liver, rib, iliac femur (arrow), and abdominal skin mass (arrow) (A). Echocardiography showed a large mass measuring 71 mm×46 mm at the center of the interventricular septum (E).

Needle biopsy specimens from the subcutaneous mass on the back of the right shoulder revealed a pleomorphic lipomatous tumor (Fig. 3A, B). An immunohistochemical examination showed positivity for p16 (+++, diffuse) (Fig. 3C) and MDM2 (±, focal) and negativity for CD34, S-100, and Cdk4. The Ki-67 index was 40-50%. The DDX3 (CHOP) gene signal was negative on a fluorescence in situ hybridization analysis. Therefore, a diagnosis of PLS with multiple organ metastases was made.

Figure 3.

A histological examination showed that tumor cells had a bizarre and diffuse distribution and were composed of highly cellular and cytologically atypical spindled and epithelioid cells (A). High-power magnification showed a pleomorphic cell population with scattered lipoblastic features (B). An immunohistochemical examination showed positivity for p16 (C).

Chemotherapy was performed with a 21-day cycle of doxorubicin (30 mg/m², days 1 and 2) and ifosfamide (2 g/m², days 1-5). The intrathoracic lesions and tumor mass on the back of the right shoulder were reduced in size after six cycles of doxorubicin and ifosfamide chemotherapy, but a new metastatic lesion was observed in the upper left lung after eight cycles of doxorubicin and ifosfamide chemotherapy (Fig. 4E). Pulmonary metastasis rapidly progressed within one month (Fig. 4F), and the patient died due to respiratory failure 10 months after the initial diagnosis. During the clinical course, the interventricular septal mass (Fig. 5) and serial electrocardiogram findings were unchanged. There was no cardiac dysfunction or specific cardiotoxicity due to doxorubicin. In addition, there were no radiographic or clinical signs of pulmonary thromboembolism throughout the course.

Figure 4.

Radiographic changes before and after chemotherapy. The tumor mass in the back of the right shoulder (A) and intrathoracic lesions (C) before chemotherapy were reduced in size after six cycles of doxorubicin and ifosfamide chemotherapy (B and D, respectively). However, a new metastatic lesion in the upper left lung (E, arrow) was observed after eight cycles of doxorubicin and ifosfamide chemotherapy. The intrapulmonary metastasis rapidly progressed within one month (F).

Figure 5.

Discussion

PLS is the rarest subtype of liposarcoma and is uniformly high grade (1-6). Over 50% of patients with PLS develop metastatic disease after resection with curative intent, and the overall survival is relatively poor compared with other types of liposarcoma (3-8). Although distant metastasis should be considered in patients with PLS, multiorgan involvement at the initial clinical manifestation is extremely rare (3-8). In the Surveillance, Epidemiology, and Results (SEER) database, 22 of 257 cases (7.89%) of PLS were registered with distant metastatic disease, with only 2 cases showing multiple metastases at the diagnosis (5).

Cases initially presenting with multiple organ involvement, as in the present case, are extremely rare. In particular, metastasis of liposarcoma to the heart is very rare. Although a pathological diagnosis of the heart was not performed in the present case, radiographic findings, including ¹⁸F-FDG-PET/CT, were compatible with PLS involvement. Pino et al. (9) summarized 27 cases of metastatic liposarcoma of the heart, including the pericardium, that developed after the initial diagnosis. In addition, there have been several case reports of primary and/or metastatic cardiac liposarcoma (10-12). However, to our knowledge, there have been no previous reports of the initial clinical manifestation of cardiac metastasis of PLS at the diagnosis.

As the primary origin in the present case could not be identified, it was necessary to consider the possibility of primary cardiac PLS in our case. Indeed, the tumor size was largest in the heart at the diagnosis in our patient. Based on previous reports of cardiac liposarcoma, the prevalence rates of myxoid and/or PLS are high (9-11). However, surgical resection was performed in those cases, and none of the patients presented with disseminated disease. Although whether cardiac disease was the primary or metastatic lesion in the present case remains unclear, cardiac involvement should be considered in cases of liposarcoma, especially myxoid and PLS.

With regard to the efficacy of chemotherapy, no significant differences in the survival were reported between patients with soft tissue sarcomas treated with doxorubicin plus ifosfamide or with doxorubicin alone (13). However, a subgroup analysis performed in the European Organization for Research and Treatment of Cancer 62,012 study showed that patients with pleomorphic sarcoma had an improved tumor response and overall survival (OS) with doxorubicin and ifosfamide combined chemotherapy compared to single-agent doxorubicin therapy (objective response: 9.90, 95% confidence interval: 1.93-50.7; hazard ratio: 0.44, 95% confidence interval 0.26-0.79) (14). Therefore, combination therapy was recommended in patients with PLS. Although doxorubicin and ifosfamide chemotherapy was initially effective for the intrathoracic lesions and the lesion in the back of the right shoulder, our patient subsequently developed left lung metastasis, which was fatal.

PLS has a complex karyotype often causing loss of the tumor suppressors p53 and Rb (1). However, these genomic alterations are notoriously difficult to exploit for therapeutic benefit. Recently, broad-based genomic sequencing analyses have facilitated the detection of actionable molecular alterations potentially related to the prediction of benefits of specific therapies (15). We did not have a chance to test the comprehensive gene profile in the present case, but this may be warranted for determining novel treatment choices for PLS.

In conclusion, we encountered a case of PLS initially presenting with multiorgan involvement, including the heart. The disseminated form of PLS at the onset was a unique clinical manifestation. This case provides important insight into the clinical manifestations of PLS.

The authors state that they have no Conflict of Interest (COI).