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\begin{document}

\title{Management of primary cardiac leiomyosarcoma in a young lady}



\author[1]{Mehmet Onalan}%
\author[1]{Ahmet Demirkaya}%
\author[1]{Kemal Behzatoglu}%
\author[1]{Ersin Erek}%
\affil[1]{Acibadem University}%


\vspace{-1em}



  
  \date{May 08, 2024}


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\selectlanguage{english}
\begin{abstract}
Cardiac leiomyosarcoma is an extremely rare tumor with a poor prognosis.
We reported an 18- year-old girl with a left atrial leiomyosarcoma
extending to right lower pulmonary veins. We performed complete tumor
excision by the right anterolateral mini-thoracotomy approach using
minimally invasive techniques. After pathological confirmation of the
tumor, right lower lobectomy was performed with the same incision one
week later to prevent a recurrence. Although no tumor remnant was found
in the lobectomy specimen, adjuvant chemotherapy was started. No
recurrence was detected during the 12-month follow-up.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Cardiac tumors are a very rare condition with a frequency of 0.02\%. The
prevalence ranges from 0.001\% to 0.3\%, and only 25\% is malignant (1).
The most common histological types are angiosarcomas, followed by
rhabdomyosarcomas, mesotheliomas, and fibrosarcomas.

Leiomyosarcoma appears for less than 1\% of cases (1). Despite
aggressive multidisciplinary treatment including surgery, chemotherapy,
and radiotherapy, the prognosis is poor, with median survival about 12
months (2,3,4). Metastasis is familiar, and up to 60\% of cases have
metastasis at the time of diagnosis (3). Adequate surgical resection,
which may require lung resection ranging from lobectomy to
pneumonectomy, is the mainstay of the treatment.

Clinical presentation is nonspecific; this makes early diagnosis
difficult, and most cases are diagnosed on histology specimens and at
autopsy. It is twice as common in females; the average age of occurrence
is 45 years (range, 6 weeks to 77 years) (5).

In this case report, we present a successful management of
leiomyosarcoma in a young lady.

\textbf{Case report}

An 18-year-old young lady with mild dyspnea and a 15-day history of
treatment with a preliminary diagnosis of respiratory infection was
admitted to our hospital. The diagnosis of pneumonia was suspected. In
this context, a computerized tomographic (CT) scan revealed a 4 x 2,5 cm
mass, involving the left atrium and the right inferior pulmonary vein,
suggesting an intracardiac neoplasm. The patient was referred to us with
a suspected diagnosis of a left atrial tumor. This was confirmed by a
cardiac magnetic resonance imaging (MRI) that also showed a 4.4 x 3 x
2.2 cm mass in the left atrium extending to the right inferior pulmonary
vein with gadolinium enhancement. A transthoracic and transesophageal
echocardiogram showed a mass with little mobility in the left atrium
extending to the right inferior pulmonary vein (Figure 1). The tumor was
not obstructive, and both ventricular functions were preserved. We
performed positron emission tomography (PET) CT to exclude malignancy
and metastasis. PET CT revealed high fludeoxyglucose (FDG) uptake, and
surgery was planned.

Because of the possible necessity for lung resection, the right
submammarian thoracotomy approach was chosen. A double-lumen
endotracheal tube was placed for unilateral ventilation during surgery.
A right sub-mammary skin incision was performed to avoid damaging the
mammary gland, after that subcutaneous fat and mammary gland were
dissected from the fascia to expose the 4\textsuperscript{th} rib. After
unilateral lung ventilation was initiated, the pericardium was opened
vertically 1.5-2 cm anterior to the right phrenic nerve and suspended to
ensure adequate exposure. After heparin was administered, aorta cannula
was placed in the ascending aorta, and bicaval venous cannulas were
inserted via the same thoracic incision. The cardioplegia needle was
placed into the aortic root from the thoracic incision, and
cardiopulmonary bypass (CPB) was started with mild hypothermia. A
Chitwood clamp was used through the 4th intercostal space to clamp the
ascending aorta, and cold blood cardioplegia was given. After the heart
was arrested, the right atriotomy incision was performed, the
interatrial septum was opened and the mass in the left atrium was
reached. The tumor had a stable consistency, there was no necrosis or
ulceration on its surface, and it was gently attached to the left atrial
wall with a thin capsule. The tumor extended to the bifurcation of the
right lower pulmonary vein branches, and it could be excised entirely
with its stalk (Figure 2). Cold saline was used to rinse the heart
chambers, and careful examination was performed to ensure complete
resection. After the de-airing procedure, the interatrial septum and the
right atriotomy was closed primarily. The aortic cross-clamp was
removed, and the heart was reperfused.

The tumor was evaluated with the frozen section examination but couldn't
be classified as benign or malignant neoplasm during the operation.
Therefore, we didn't perform lymph node dissection and right lower
lobectomy. Cessation of CPB was uneventful, and the thoracotomy was
closed. The patient recovered smoothly, she was transferred to ward on
postoperative day 1, and discharged from the hospital on postoperative
day 6. On the histopathologic evaluation, multiple sections
revealed~pleomorphic spindle tumor cell fascicles~with nuclear
hyperchromasia. Atypical mitosis was seen (14 mitotic activity/10 HPF)
with coagulation necrosis. Actin and Desmin were positive for reaction,
but CD34 and S100 were negative (Figure 3). A total of 30\% positivity
was shown by tumor cells for Ki-67, and these morphological features
were consistent with a diagnosis of leiomyosarcoma.

After histopathologic confirmation of leiomyosarcoma, we planned right
lower lobectomy to be sure complete resection of the tumor and to
prevent a recurrence. The same incision was used. Right lower lobectomy
with right inferior pulmonary vein excision, mediastinal lymph node
dissection and partial left atrial resection was performed without CPB.
The samples of tissues were taken from the surgical margin. The
thoracotomy was closed, and the patient was transferred to the
cardiovascular intensive care unit. The postoperative period was
uneventful, and the chest tube was removed on postoperative day 5. The
patient discharged from the hospital on a postoperative day 7.
Histopathological examination revealed that the resected pulmonary vein
and left atrial specimen borders were histologically clear.

Thorax and abdomen MR scans revealed no metastases in the postoperative
early period. According to a multidisciplinary staff, adjuvant
chemotherapy consisting of four cycles of Doxorubicin and Ifosfamide was
prescribed by the medical oncology department. Moreover, she had
adjuvant cardiac radiotherapy (54 Gy in 27 fractions) at postoperative
5\textsuperscript{th} month. The patient is regularly followed, no
metastasis was detected in PET CT and thoracic MR scans, after 4 and 6
months follow up, respectively. After a follow-up of 12 months, she
still has no clinical or radiological evidence of recurrence.

\textbf{Discussion}

We present a rare case of cardiac leiomyosarcoma in a young lady who
treated surgically, followed by adjuvant chemotherapy. The patient is
still alive without metastasis after 9 months of follow-up.

There are few reports of limited cases in the literature about primary
cardiac leiomyosarcoma. Wang et al. reviewed all the literature and
identified 79 instances derived from 72 unique reports with primary
cardiac leiomyosarcoma (4). In this study, the median age at diagnosis
was 48 with a female predominance, and the symptom of obstruction was
the most common complaint at diagnosis. The recurrence-free survival and
the 5-year overall survival rates were 14.7\% and 25.4\%, respectively.
They showed that overall survival was affected by age, surgery, and
adjunct chemotherapy or radiotherapy in this study. In our case, the
patient had mild dyspnea and a history of treatment with a respiratory
infection. The diagnosis was suspected on the findings of a CT performed
for pneumonia.

Echocardiography is usually the initial imaging modality for cardiac
masses. It may show its extent, location, and hemodynamic effects
(Figure 1). CT scan and cardiac MRI supply additional instructions about
morphology, location, and extent of the mass (Figure 2) (6). CT scan is
helpful to evaluate extracardiac extent or metastasis, and cardiac MRI
has been shown to differentiate the tumor from a thrombus by contrast
enhancement (3). Moreover, MRI is more useful to assess myocardial
involvement. For the differential diagnosis of a mass lesion, PET CT
helps differentiate the results of CT and MRI (7). In our case, we used
PET CT and MRI for the definitive diagnosis of the cardiac tumor and for
the follow-up.

The most common cardiac chamber of cardiac leiomyosarcomas in the left
atrium (51\%), like our case. A biopsy is the gold standard for
histological confirmation, but this step can sometimes be overcome,
especially in cardiac masses, and then diagnosed by histopathological
examination of the resected mass (6).

The best treatment strategy is not certain; but, early diagnosis and
adequate surgical resection remain the mainstay for the treatment of
this tumor in the literature (3). Adjuvant radiotherapy and chemotherapy
have been shown to prolong survival and improve disease control in some
cases (7). Frozen section guided excision border of 1cm for all left
atrial tumors was suggested by Marin and colleagues for better survival
(7). Adequate excision of a pulmonary vein tumor may require lung
resection ranging from lobectomy to pneumonectomy (3). In our case, the
left atrial tumor was extending to the branches of the pulmonary veins,
so the right inferior lobectomy with right inferior pulmonary vein
excision was performed to reach the clean surgical margin. Adjuvant
radiotherapy and chemotherapy was given to our patient by
multidisciplinary staff decision.

The conventional median sternotomy approach is widely used in cardiac
tumors operations. This approach has great exposure; on the other hand,
it also coexists with some troubles, such as poor cosmetic effect,
sternal dehiscence and risk of postoperative mediastinitis (8). Since Ko
et al. reported the cardiac myxoma excision via the right anterolateral
mini-thoracotomy approach two decades ago (9), minimally invasive
approaches have been progressively performed to the treatment of cardiac
tumors. However, because of the rareness of primary cardiac tumors,
there are only limited reports in the literature. In addition, there are
some concerns about incomplete tumor resection with minimally invasive
surgery due to insufficient minimally invasive experience, and the
clinical benefit of this approach is still controversial, especially for
cardiac masses. Luo et al. conducted a study on 50 patients with primary
benign cardiac tumors who underwent either conventional or minimally
invasive surgery from 2008 to 2018 (10). In this study, there was no
significant difference in aortic cross-clamp time and cardiopulmonary
bypass time between the two groups and the duration of postoperative
intubation time, intensive care unit stay, and hospital stay were
shorter in the minimally invasive group, but the differences were not
statistically significant.

The necessity of lung resection is high for this type of tumor, and it
may difficult to perform from median sternotomy. Additional right
thoracotomy may be needed. We suggest that the right submammarian
thoracotomy approach is feasible and effective for both cardiac tumor
resection and right lower lobectomy.

The recurrence rate is high in cardiac leiomyosarcomas despite optimal
surgical resection of the primary tumor. According to the literature of
cardiac leiomyosarcomas, the mean survival time of patients who
underwent surgery and chemotherapy was about 12 months (2,3,4).

In our case above, she is still alive, and there is no evidence of local
or distant recurrence or metastasis after a follow-up of 12 months.

\textbf{Conclusion}

Cardiac leiomyosarcoma is an extremely rare tumor with a poor prognosis,
and frozen section guided complete resection is the key to the
treatment. Adjuvant chemoradiotherapy may further prolong survival and
regular echocardiography should be followed up after the operation. The
right submammarian thoracotomy approach has the advantages of its less
invasive nature and suitability for complete tumor resection with
lobectomy.

\textbf{References}

1. Patel J, Sheppard MN. Pathological study of primary cardiac and
pericardial tumors in a specialist UK Centre: surgical and autopsy
series. Cardiovasc Pathol. 2010;19(6):343--52.

2. Lv Y, Pang X, Zhang Q, Jia D. Cardial leiomyosarcoma with multiple
lesions

involved: a case report. Int J Clin Exp Pathol. 2015;8(11):15412--6.

3. Gukop P, Frassetto G, Karapanagiotidis G, et al.: Leiomyosarcoma of
pulmonary vein presenting as left atrial mass: An outline of management
principles. Case Rep Cardiol 2012:396319, 2012.

4. Wang J-G, Cui L, Jiang T, Li Y-J, Wei Z-M. Primary cardiac
leiomyosarcoma: an analysis of clinical characteristics and outcome
patterns. Asian Cardiovasc Thorac Ann. 2015;23(5): 623--30.

5.Y. Hattori, T. Iriyama, K. Watanabe, K. Negi, I. Takeda, and S.
Sugimura, ``Primary cardiac sarcoma---two case reports,'' Japanese
Circulation Journal, 2000; 64(3) 222--224.

6. Behi K, Ayadi M, Mezni E, Meddeb K, Mokrani A, Yahyaoui Y, et al. Two
years survival of primary cardiac leiomyosarcoma managed by surgical and
adjuvant therapy. Clin Sarcoma Res. 2017 7:5.

7. Morin JE, Rahal DP, Huttner I. Myxoid leiomyosarcoma of the left
atrium: a rare malignancy of the heart and its comparison with atrial
myxoma. Canadian Journal of Cardiology. 2001;17(3): 331--6.

8. Lee HP, Cho WC, Kim JB, Jung SH, Choo SJ, Chung CH, et al. Surgical
outcomes of cardiac Myxoma: right Minithoracotomy approach versus median
sternotomy approach. The Korean journal of thoracic and cardiovascular
surgery. 2016;49(5):356--60.

9. Ko PJ, Chang CH, Lin PJ, Chu JJ, Tsai FC, Hsueh C, et al.
Video-assisted minimal access in excision of left atrial myxoma. Ann
Thorac Surg. 1998;66(4):1301--5.

10. Luo C, Zhu J, Bao C, Ding F, Mei J. Minimally invasive and
conventional surgical treatment of primary benign cardiac tumors.
Journal of Cardiothoracic Surgery. 2019;14:76.

\textbf{Figure Legends}

\begin{enumerate}
\tightlist
\item
  Transesophageal echocardiography is showing a hyperechoic mass lesion,
  measuring 2,8 \selectlanguage{ngerman}×2.6 cm, in the left atrium (A). Cardiac MRI is showing
  the left atrial mass extending into the pulmonary vein (B, C).
\item
  The view of cardiac tumor in the left atrium after interatrial septal
  incision (A). The complete excision of the tumor via the right
  anterolateral mini-thoracotomy approach (B). Resected left atrial
  tumor showed a smooth white surface without any necrosis or ulceration
  (C).
\item
  Hematoxylin \& eosin stains showed a sarcomatous lesion with prominent
  inflammatory reaction and epithelioid neoplastic cells (orig. x400)
  (A). Immunohistochemical stains showed strong and diffuse cytoplasmic
  immunoreactivity with smooth-muscle actin (orig. x100) (B).
\end{enumerate}\selectlanguage{english}
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