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\begin{document}

\title{Pulmonary valve sarcoma in patient with coronavirus disease of 2019
(COVID-19), mimicking pulmonary thromboembolism, a very rare case}



\author[1]{Rozita Jalalian}%
\author[1]{Javad Sadraei}%
\author[1]{soheil azizi}%
\author[1]{Babak Bagheri}%
\author[2]{Mohammadreza Iranian}%
\affil[1]{Mazandaran University of Medical Sciences}%
\affil[2]{Iran University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 16, 2024}


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\selectlanguage{english}
\begin{abstract}
Pulmonary artery and pulmonary valve sarcoma are malignant and very rare
vascular tumors with aggressive clinical course and very poor outcomes.
Patients affected by coronavirus disease of 2019 (COVID-19) are at
higher risk for thromboembolism complication. we describe young woman
with history of corona virus pneumonia and progressive dyspnea,
hemodynamic disturbance, edema with initial evaluation and clinical
diagnosis of pulmonary thromboembolism. But further imaging study and
pathology demonstrated, Giant sarcoma of pulmonary valve, obstructing
pulmonary valve and extending to right ventricular outflow tract and
main of pulmonary artery.%
\end{abstract}%



\sloppy


\textbf{Introduction:}

Pulmonary artery sarcomas (PASs) are the most common primary tumors of
the pulmonary artery (PA), but the incidence of this diagnosis is
extremely rare. PASs is predominantly presented among patients from
their third to seventh decade, with an average age of 49 years. PASs are
always highly malignant, women are involved twice as often as men. The
most common clinical manifestation of PASs is dyspnea (72\%) followed by
chest pain (45\%), cough (42\%), and hemoptysis (24\%). Systematic
symptoms of PASs are less rare and they include weight loss (21\%),
syncope (9\%), and fever (8\%). The presence of these symptoms often
causes misdiagnosis of pulmonary thromboembolism (PTE) (1-3).

\textbf{Case report:}

A 40 years old woman presented at the emergency department because of
progressive dyspnea, orthopnea, edema, weakness. She has involved with
COVID-19 about 2 months ago according to polymerase chain reaction (PCR)
and chest computed tomography (CT), But she didn't recover from
respiratory symptoms in spite of adequate treatment. In admission time,
she has respiratory distress, tachycardia, tachypnea, edema, cyanosis
and coldness of extremely and systemic hypotension (Blood Pressure:
90/65 mmHg). O2 saturation in air room was 86\% and with noninvasive O2
therapy increased to 89\%.

Electrocardiogram (ECG) showed sinus tachycardia, right axes deviation
and right ventricle (RV) strain pattern in precordial leads (Figure 1).
Chest X ray showed significant cardiomegaly, RV enlargement and
prominent main of PA and left PA without evidence of pulmonary venous
congestion (Figure 2). Spiral chest CT demonstrated evidence of previous
COVID-19 involvement with ground glass appearance and air trapping in
both lungs and also cardiomegaly and large size pericardial effusion
(Figure 3).

Transthoracic echocardiography (TTE) showed severe RV enlargement with
severe RV systolic dysfunction, right atrial (RA) enlargement and
abnormal interventricular septal motion. D shaped appearance of
Interventricular septum in parasternal short axis (PSAX) view with mid
systolic flattening, representing severe RV pressure overload and signs
of severely increased RV afterload pattern. In PSAX view, very large
size nonhomogeneous solid mobile mass is seen in distal right
ventricular outflow tract (RVOT) extended to main PA and has attachment
to pulmonary valve (PV). The PV obstruction was severe and blood flow to
main PA was reduced. Left and right PA and pulmonary bifurcation were
evaluated, that were spared without any mass. Color doppler study of
tricuspid valve (TV) inflow showed severe tricuspid regurgitation (TR)
and hemodynamic study with continuous doppler wave in apical 4 chamber
view demonstrated TR peak velocity of 4.4 m/s (TR peak gradient: 77
mmHg). Evaluation of inferior vena cava (IVC) in subcostal view was
done. IVC was severely enlarged (2/75 cm diameter) without respiratory
collapse. Therefore, hemodynamic study estimated RA pressure about 20
mmHg, more compatible with chronic course of disease and indicating of
more gradual increasing of RV pressure rather than acute event. Massive
pericardial effusion was seen more localized in posterolateral of left
ventricle (LV) (maximum diameter: more than 3 cm). There was significant
respiratory variation in Doppler study of mitral valve (MV) and TV
diastolic inflow velocity more than 30\% (Figure 4).

Laboratory data containing hematologic, inflammatory and biomarkers were
measured. D dimer was increased about 4000 \selectlanguage{greek}μ\selectlanguage{english}g/l and pro-brain
natriuretic peptide (pro-BNP) 12500 ng/d.

According to previous history of the COVID-19, ECG manifestation,
echocardiography, chest X ray, spiral chest CT, laboratory data and
abnormal hemodynamic condition, massive sub-acute PTE was highly
suggested. Due to our patient hemodynamic disturbance, massive
pericardial effusion and giant mass, emergent cardiac consultation with
cardiovascular surgical team for surgical resection was done and the
patient was taken to operating room.

Thoracotomy and median sternotomy was done and then cardiopulmonary
bypass was established. Main PA was incised. Unexpectedly, out of
previous suspicious, our surgeon encountered with large size tumoral
solid mass with firm texture that was attached to right leaflet of PV
and protruded to main PA and RVOT, which appearance was highly
suggestive for sarcoma rather thrombosis. Therefore, mass completely was
resected and because of tumoral involvement, right leaflet of PV removed
(Figure 5). Reevaluation for residual masses in other parts was done
with intraoperative echocardiography. TEE confirmed there was not any
other masses in PA. Severe pulmonary insufficiency (PI) was seen after
removal of right leaflet of PV. Staged operation for reconstruction of
RVOT with conduit PV was postponed after preparing the result of tumor
pathology and probably need for adjuvant chemotherapy. Patient had
stable hemodynamic in ICU, intubated easily and discharged after 7 days
without any cardiac event.

Pre-discharge TTE was done. RV and RA were severely enlarged. RV
systolic function was severely impaired and severe TR and severe PI was
seen. No residual mass was seen in RVOT, PV, PA and main of PA.
Continuous doppler wave study showed peak TR velocity 4 m/s and short
pressure half time (PHT:24 ms) and in 2D study evidence of increased RV
after load pattern was permanent. IVC plethora and engorgement without
respiratory collapse was seen (Figure 6).

Pre-discharge pulmonary CT angiography was done that any mass or
thrombus in pulmonary vasculature wasn't seen. In addition,
abdominopelvic and brain CT for further evaluation were performed which
were not abnormal.

\textbf{Pathology:}

Histopathological examination of resected mass showed malignant
mesenchymal neoplasm composed of sheets and individual tumoral cells
embedded in a desmoplastic and collagenized stroma. These cells are
charactherized by enlarged, pleomorphic hyperchromatic and vesicular
nuclei with frequent mitotic figures and visible nucleoli. Necrosis and
hemorrhage are also present. Immunohistochemistry staining were negative
for S100 and CD34 but positive for vimentin, desmin, smooth muscle actin
(SMA), MNF116. In addition, about 15-20\% with Ki67 also positive in
osteoclast like giant cells with CD68. (Figure 7) All this data shows
malignant mesenchymal neoplasm compatible with undifferentiated
pleomorphic sarcoma.

The patient referred to oncologist for chemotherapy. Just the day before
initiation of chemotherapy, TTE was done and recurrence of tumoral mass
(1.5*1.5 cm) was seen in distal part of RVOT just beneath PV. Patient
admitted in hospital for receiving Chemotherapy protocol with
carboplatin and taxotere (docetaxel) with close monitoring of cardiac
condition and hemodynamic. Unfortunately, after one course of
chemotherapy patient was died in hospital with cardiogenic shock because
of severe right sided heart failure.

\textbf{Discussion:}

Primary cardiac sarcoma are rare tumors and sarcoma of PV are very rare
(4). Initial manifestation of these tumors are usually consist
nonspecific symptoms of cardiopulmonary disease such as cough, dyspnea,
chest pain, infrequently hemoptysis, pneumothorax and tamponade in cases
with invasion to pericardium, mediastina or lung parenchyma (2-5). PA
sarcoma can mimicking clinical and paraclinical findings of PTE and
caused difficulties in early diagnosis and management. Some case reports
representing misdiagnosis of PA sarcoma with PTE in early evaluating and
for this reason the patients underwent thrombolytic therapies without
any improvement and subsequent evaluations demonstrated malignant tumor
of pulmonary artery (1,6,7).

Chest CT scan can help differentiate PA sarcoma from PTE by
low-attenuation filling defect occupying the entire luminal diameter of
the main or the proximal PA, expansion of any segment of the PA, and
extraluminal extension of the tumor. These image features to be
suggestive of PA sarcoma (8).

Magnetic resonance imaging (MRI) is also useful diagnostic method for
distinguishing PASs and PTE. On MRI, low-intensity heterogeneous
features on T1-weighted images and peripheral enhancement of the
thickened pulmonary artery wall on T2-weighted images and after
gadolinium injection have classically been thought to support a
diagnosis of PA tumor (9).

Fluorodeoxyglucose / positron emission tomography (FDG/PET) CT can
distinguish PASs from PTE based on the FDG uptake with maximum
standardized uptake value (SUVmax) (SUVmax of PA sarcoma is higher than
of PTE) (10).

Other characteristics, such as the absence of risk factors for deep vein
thrombosis and high erythrocytes sedimentation rate should raise the
suspicion of a process other than PTE (1).

The only method to definitely differentiate diagnosis between PASs and
PTE is histopathology (3).

Surgery is the most effective treatment of PA sarcoma (1,7).
Chemotherapy and radiotherapy are used and may provide longer survival,
especially in patient with metastasis and incomplete resection.
Endovascular stenting remains as palliative therapy for inoperable
patient with obstructing tumors. Most cases of pulmonary sarcomas were
diagnosed late in coarse of diseases and these made difficulties in
surgical resection. Some reports shown that early diagnosis and surgical
resection may provide longer survival (4-7).

Overall, PA sarcoma are very poor prognosis tumor because of late
diagnosis and average of survival among reported case series were
between 1.5 month to 12 months (5,11). Among patients reported have
longer survival, RV function were preserved and didn't mention
significant increased PA pressure (5). Our patients had severe RV
dysfunction in presentation and remaining of PA pressure severely high
even after total resection of giant tumoral mass and in absence of any
other mass or thrombosis in pulmonary arteries in pulmonary CT
angiography after operation.

Patients with COVID-19 pneumonia and high D dimer value has higher
prevalence PTE and myocarditis (12-15). Prior infection with COVID-19
pneumonia in our case maybe the other causes of RV failure and also
masquerading sarcoma.

On the other hand, RV dysfunction due to cardiotoxicity of chemotherapy
may considered as the other mechanism for progression of RV failure in
our patient. Chemotherapy could induce impairment of RV structure,
function and mechanistic (16,17).

Our case report emphasizes that PASs should always be included in the
differential diagnosis of PTE especially if symptoms progress despite
anticoagulation therapy (or any risk factor for deep vein thrombosis is
not present). However, our patient underwent surgery immediately due to
impaired hemodynamic and was diagnosed early compared to the time of
hospitalization.\selectlanguage{english}
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\textbf{Figure 1.} Electrocardiogram\selectlanguage{english}
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\textbf{Figure 2.} Chest X ray\selectlanguage{english}
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\textbf{Figure 3.} Spiral chest computed tomography (CT)\selectlanguage{english}
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\textbf{Figure 4.} Transthoracic echocardiography (TTE) before surgery\selectlanguage{english}
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\textbf{Figure 5.} A: Incision of pulmonary artery with tumoral mass, B:
Surgical specimen from total resection of pulmonary tumoral mass\selectlanguage{english}
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\textbf{Figure 6.} TTE after surgery\selectlanguage{english}
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\textbf{Figure 7.} Histopathological examination of tissue resected

\textbf{Figure legends}

\textbf{Figure 1. Electrocardiogram.} Electrocardiogram showed sinus
tachycardia, right axis deviation and right ventricle strain pattern (qR
in V1 and T inversion V1-V6).

\textbf{Figure 2. Chest X ray.} Chest X ray showed significant
cardiomegaly, RV enlargement and prominent main of PA and left PA
without evidence of pulmonary venous congestion.

\textbf{Figure 3. Spiral chest computed tomography (CT).} Chest CT
showed evidence of previous COVID-19 involvement with ground glass
appearance and air trapping in both lungs and also cardiomegaly and
large size pericardial effusion.

\textbf{Figure 4. Transthoracic echocardiography (TTE) before
surgery.}TTE showed severe RV enlargement with severe RV systolic
dysfunction, right atrial (RA) enlargement, abnormal interventricular
septal motion, severe TR, enlargement of IVC size, massive pericardial
effusion and mobile mass in distal right ventricular outflow tract
(RVOT) extended to main PA and has attachment to pulmonary valve (PV).

\textbf{Figure 5. A: Incision of pulmonary artery with tumoral mass, B:
Surgical specimen from total resection of pulmonary tumoral mass}

\textbf{Figure 6. TTE after surgery.} A and B: TTE parasternal short
axis (PSAX) view showed no residual mass in PA after surgical resection
of right leaflet of pulmonary valve and color doppler study of pulmonary
valve showed severe pulmonary insufficiency (PI). C: Continuous doppler
wave study of pulmonary valve after surgical resection showed severe PI
and short pressure half time (PHT:24 ms).

\textbf{Figure 7. Histopathological examination of tissue resected.} A:
Pleomorphic undifferentiated sarcoma with areas of necrosis and packed
cellular areas surrounding vessels. B: In same area tumor has a vascular
pattern with anastomosing irregular sinusoid channels and erythrocytes
extravasation. C: In this area, there are cellular atypia, variation in
cell size and shapes which consist of round cells, spindle cells,
epithelioid, endothelial like and multi nuclear giant cells.

\textbf{References}

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