Uterine leiomyosarcoma (LMS) is a rare malignancy of mesenchymal tissues and in advanced stages its prognosis is very poor. Surgery followed by radiotherapy and/or chemotherapy is the treatment of choice for advanced disease. Cardiac metastases are very uncommon and only a few cases have been described to date.
A 55-year-old woman was referred to our center for a uterine LMS with lung metastases at diagnosis. After 3 lines of chemotherapy for persistent lung disease, CT scan showed suspected thrombosis in the right pulmonary vein, along with disease progression in the lungs. The patient started treatment with low-molecular-weight heparin and a fourth line of chemotherapy. After 3 months of therapy, a new CT scan showed a larger thrombus and she underwent a cardiology visit that revealed an intracardiac mass. Submitting the patient to palliative surgery or radiation therapy was not possible because of the aggressiveness of the lung metastases, so she continued chemotherapy, resulting in disease stabilization.
Surgery is the best option for intracardiac dissemination of uterine LMS, but when this is not possible based on the performance status of the patient and spread of the disease, the combination of chemotherapy and radiotherapy seems to be the best option according to the literature. In our case we treated the patient only with chemotherapy.
Tumori 2016; 102(Suppl. 2): e90 - e92
Article Type: CASE REPORT
AuthorsGrazia Artioli, Lucia Borgato, Sara Calamelli, Giuseppe Azzarello
- • Accepted on 08/02/2016
- • Available online on 09/04/2016
- • Published online on 11/11/2016
This article is available as full text PDF.
Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation. A significant proportion of tumors originate in the uterus; the remainder arise in various soft tissue sites where they are often thought to derive from smooth muscle cells in vessel walls.
Uterine LMS accounts for 25%-36% of uterine sarcomas and 1% of uterine malignancies (1, 2). The disease may spread locally, regionally or by hematogenous dissemination to lung (67.7%), cranial/intracranial (16.2%), skin/soft tissues (15.3%), and bone (13.8%). Lung metastasis is known to occur both as single and multiple nodular lesions.
The treatment of this tumor is very heterogeneous. Surgery for the primary site and, when possible, metastatic lesions is the cornestone. Pelvic external beam radiation therapy with or without brachytherapy is suggested for localized resected tumors, in particular for high-risk disease. Chemotherapy is an option in early stages of disease and is indicated in advanced and metastatic disease. Little is known about its molecular heterogeneity and no targeted therapy currently exists for the treatment of LMS. Recently, Guo et al (3) showed that consensus clustering identified 3 molecular subtypes of LMS based on gene expression data. These findings indicate distinct biological subclasses in LMS that may respond differently to novel therapeutic agents.
Cardiac dissemination of uterine LMS is very uncommon but its incidence seems to be increasing, possibly in relation to the prolonged survival of cancer patients (4). These metastases may originate from the connective tissues of the blood vessel walls or from the myocardial smooth cells. Onset symptoms are usually arrhythmia, tachycardia or dyspnea (4-5-6). To date, only sporadic case reports about cardiac metastases of uterine LMS have been published, hence the lack of consensus about the treatment.
In May 2013, a 55-year-old postmenopausal woman was admitted to our hospital because she presented metrorrhagia. Abdominal MRI revealed a pelvic mass of 10 cm in greatest diameter. Chest and abdomen CT scan confirmed the presence of the pelvic mass but also showed multiple bilateral lung metastases with a greatest diameter of 2 cm.
In June 2013, the patient underwent a hysterectomy with bilateral oophorectomy. The pathology report confirmed the diagnosis of LMS of the uterus, characterized by pleomorphic, often epithelioid and multinucleated cells, with high mitotic activity, areas of necrosis and signs of angioinvasion of the myometrium. Immunohistochemical analysis showed neoplastic elements intensely and diffusely positive for smooth muscle actin and focally for EMA and desmin but negative for CD45, CK MNF116, CD10 and alpha-inhibin. Weak and diffuse positivity for estrogen and progesterone receptors was also reported.
After 1 month, our patient received the first administration of epirubicin 45 mg/m2 intravenously (iv) on days 2-3 and ifosfamide 2.5 mg/m2 continued infusion in 24 hours (IC) with mesna on days 1-5 every 21 days. Unfortunately, a CT scan revealed an increase in the lung metastases after 3 cycles, so second-line chemotherapy consisting of gemcitabine 900 mg/m2 iv on days 1 and 8 and docetaxel 75 mg/m2 iv on day 8 every 21 days was started in November 2013. Initial disease control was observed after 3 cycles, but pulmonary progression (greatest lesion diameter 3 cm) was confirmed by the CT scan performed after 6 cycles.
In May 2014, the patient underwent chemotherapy with trabectedin 1.5 mg/m2 conitinued infusion/24 hours (IC) on day 1 every 21 days, repeated for only 2 cycles because of a further increase in the number of lung metastases. Oral therapy with pazopanib 800 mg/day was started in August 2014. One month later, the treatment was complicated by grade 2 neutropenia, which required a dose adjustment to 400 mg/day after 2 weeks’ rest for restoration of the white cell count.
The restaging CT scan performed in November 2014 showed stable disease with a probable thrombotic area in the right superior pulmonary vein (
In February 2015, a chest CT scan showed not only progression of disease in the lungs with an increased number of lesions (greatest diameter 5 cm) but also enlargement of the pulmonary vein thrombus invading the left cardiac atrium (
The consulting cardiologist performed an echocardiography and clarified that the thrombotic lesion found by CT scan was an intracardiac tumor lesion. The patient underwent a cardiac MRI that showed an ovalar mass of 55 × 25 mm in the left atrium. The mass started from the smooth muscle of the right pulmunary vein and reached the mitralic valve during the systole (
Cardiac MRI showing the left atrial mass.
The only symptom the patient reported was tachycardia, which was confirmed by ECG. Continued growth of the mass inside the heart could result in complete invasion of the atrium and fatal pulmonary edema.
A multidisciplinary discussion with the cardiologist, oncologist and heart surgeon was conducted to evaluate the option of surgical removal of the intracardiac lesion, as the literature suggests. At that moment, surgery was excluded for our patient because of the rapid progression of her disease and the high surgical risk, but this approach was postponed to a possible moment in future for symptom palliation or to revert an emergent life-threatening situation.
She was not eligible for local irradiation either, and started having tachycardia. At cardiac auscultation grinding noises of the heart walls were heard, so the patient was started on palliative chemotherapy with gemcitabine 1,000 mg/m2 iv on day 1 and dacarbazine 500 mg/m2 iv on days 1-14, which at the time of writing is still ongoing. After 3 cycles of chemotherapy, chest CT scan shows stable disease and no symptoms are present.
LMS is a malignant soft tissue neoplasm with complex genetic abnormalities. This tumor presents varying degrees of smooth muscle differentiation and often appears to be derived from smooth muscle cells also in the myometrium. It may also arise from the walls of blood vessels or connective tissues throughout the body. In clinical practice, LMS is treated differently depending on whether the tumor originates from the uterus or extrauterine sites.
We present an original case report of the unusual cardiac localization of a metastatic uterine LMS. Review of the literature shows that cardiac metastasis is a very rare event. Cases were treated in different ways because of its rarity.
A recent case was reported of a 57-year-old woman with an interventricular septum mass as well as extensive systemic metastases and a recurrent pelvic mass. The patient’s symptoms responded to palliative radiotherapy followed by chemotherapy (7). Nguyen et al (8) described a patient who underwent cardiac surgery for debulking of a metastatic lesion in the tricuspid valve, resulting in long survival. With 11 cases collected, a Japanese study is the largest report of cardiac metastases of uterine LMS (9). The authors observed that the median survival of patients who received radiation therapy was better than that of patients who did not, 10.5 vs. 3.5 months, respectively as reported in
Review of the literature
|Author and year (ref.)||No. pts.||Time to cardiac mts.||Treatment||Survival from cardiac mts.|
|ref = reference; No = number; pts = patients; mts = metastasis; CT = chemotherapy; RT = radiotherapy.|
|Moreno 2006 (4)||1||6 years||Surgery||30 months|
|Hoy 1988 (5)||1||Surgery||24 months|
|Calleja 2009 (6)||1||4 years||Surgery/CT/RT||12 months|
|Tunio 2014 (7)||1||10 years||CT/RT||-|
|Nguyen 2012 (8)||1||2 months||Surgery/RT/CT||-|
|Takenaka 2011 (9)||5||65/36/108/30/52 months||No treatment (1), RT (4)||0/24/13/7/18 months|
|Peng 2004 (10)||1||9 years||Surgery/CT||-|
Surgery, radiation therapy and chemotherapy, alone or in combination, seem to be effective, but the choice of treatment should be based on the performance status of the patient and the extent of systemic spread (4, 5).
In conclusion, the limited literature on the subject suggests that a surgical approach, when possible, is the best option; when this is not possible, the combination of chemotherapy and radiotherapy seems to be better than chemotherapy alone.
We thank Dr. Martina Boscaro for assistance in medical writing revision.
- Artioli, Grazia [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Borgato, Lucia [PubMed] [Google Scholar] 1
- Calamelli, Sara [PubMed] [Google Scholar] 2
- Azzarello, Giuseppe [PubMed] [Google Scholar] 1
Oncohematology Unit, Medical Science Department, ULSS 13, Mirano (Venice) - Italy
Cardiology Department, ULSS 13, Mirano (Venice) - Italy