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\begin{document}

\title{Diaphragmatic Extraskeletal Ewing's Sarcoma Masquerading as Hydatid
Disease: A Case Report}



\author[1]{Ali Raza}%
\author[2]{Hritvik Jain}%
\author[1]{Ahmad Munib}%
\author[3]{Juhi Pujara}%
\author[4]{MOHAMMED QUADER Naseer}%
\author[2]{Ankit Singh}%
\author[2]{Jyoti Jain}%
\author[5]{Prakriti Pokhrel}%
\affil[1]{Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College}%
\affil[2]{All India Institute of Medical Sciences - Jodhpur}%
\affil[3]{The Maharaja Sayajirao University of Baroda}%
\affil[4]{Kaloji Narayana Rao University of Health Sciences}%
\affil[5]{Kathmandu Medical College and Teaching Hospital}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\textbf{Title: Diaphragmatic Extraskeletal Ewing's Sarcoma Masquerading
as Hydatid Disease: A Case Report}

\textbf{Key Clinical Message:}

This paper highlights a very rare diaphragmatic origin of EES that
initially presented with features of sub-acute intestinal obstruction.
Clinicians should suspect EES as a differential in such varied
presentations.

\textbf{Keywords} :

Ewing sarcoma; sarcoma; neoplasms; laparotomy

\textbf{Introduction} :

Ewing sarcoma (ES) is a malignant bone tumour that typically affects
adolescents and has a rather aggressive course with 85-90\% mortality
due to metastasis despite treatment (1,2).

ES affects soft tissues and bones with a peaking incidence between the
ages 15-20 years (1,3). The most common anatomical sites of ES include
the pelvis, axial skeleton, femur and ribs (1,4). Extraskeletal Ewing's
sarcoma (EES) most commonly involves the upper thigh, hips, and
shoulders, and has a reported incidence of 0.4 per million (5,6). EES
presents as a rapidly growing mass and follows a bi-modal age
distribution, peaking in ages \textless{}5 and \textgreater{}35 years
(5,7). Very few cases of EES arising from the diaphragm have been
reported, and primary diaphragmatic ES diagnosis is considered to be
extremely rare (8,9). Here, we report a case of diaphragmatic EES in a
17-year-old male.

\textbf{Case History/Examination} :

We describe the case of a 17-year-old South Asian male presenting to the
emergency department with complaints of abdominal pain and distension
for the past 2 weeks and relative constipation for the past 2 days. He
had a history of approximately 8 kg weight loss in the past 3-4 months
and a chronic dry cough on and off. He had no history of fever, nausea,
vomiting, loose stools, anorexia, dyspnea, palpitations, headache,
seizures, vertigo, altered sensorium, burning micturition, jaundice, and
rash. He had passed flatus 1 hour ago, but the stool was not passed.

On general physical examination, he had pallor, but no icterus,
clubbing, cyanosis, lymphadenopathy, koilonychia or edema. On
inspection, abdominal distension was noted with normal umbilicus. On
palpation, the liver was enlarged with the lower border of the liver
palpated 6 finger breadths below the right costal margin. On percussion,
shifting dullness was elicited in the abdomen. The bowel sounds were
exaggerated and the digital rectal examination was unremarkable. A
working clinical diagnosis of ``subacute intestinal obstruction'' was
made.

\textbf{Differential Diagnosis, Investigation, and Treatment} :

Ultrasound abdomen showed the liver span to be 14.5 cm, with dilation of
gut loops, and a bulky echotexture of the pancreas. A large hypoechoic
area with internal septations was found in the epigastrium (15x11x13 cm)
with moderate-to-gross ascites with a fluid collection of
\textasciitilde{}1200 ml was also noted.

Contrast-enhanced computed tomography (CECT) scan of the thorax, abdomen
and pelvis revealed a solid cystic area of 32 x 11 cm along the upper
abdomen anteriorly with effacement of the anterior surface of the liver,
stomach, and pancreas (Figure 1). Multiple loculations were seen on the
superior aspect of this area with its lower limit reaching the iliac
fossa inferiorly (Figure 2 and Figure 3). Mild-to-moderate right-sided
pleural effusion causing basal atelectasis was also noted but no
significant mediastinal lymphadenopathy was seen (Figure 4). CECT scan
confirmed the presence of ascites. CECT scan was suggestive of a large
hydatid disease and/or complicated abscess collection.

Differential diagnoses at this point were:

\begin{enumerate}
\tightlist
\item
  Hydatid disease
\item
  Complicated abscess collection
\item
  Liver hemangioma adherent to diaphragm
\item
  Abdominal tuberculosis (TB)
\end{enumerate}

Due to the suspicion of hydatid disease, a hemagglutination test for
Echinococcus was done which was negative (6.73 IU/ml). Due to the high
prevalence of TB in South Asia, sputum samples were sent which were
negative for the presence of tuberculosis.

Owing to the inconclusive serology and imaging, exploratory laparotomy
was performed. Intraoperatively, an incident finding of a large
irregular, highly vascular mass attached to segment VII of the liver and
right hemidiaphragm, encroaching sub-diaphragmatic space was noted and
was excised. Intraoperatively, anterolateral thoracotomy was also done
to delineate the mass attached to the right hemidiaphragm. Along with
this, approximately 1500 ml of malignant ascitic fluid was also drained.
Metastatic lesions (seedlings) were observed on the lung surfaces and
chest wall. The large tumour was also seen on the superior surface of
the right hemi-diaphragm. Intraoperatively, the liver transplant unit
was consulted to rule out the hepatic origin of the mass. The mass was
concluded to be arising from the diaphragm or the right lateral
abdominal wall.

\textbf{Outcome and Follow-up} :

Histopathology samples of the mass and cell cytology samples of the
ascitic fluid were sent. A microscopic section of the mass revealed a
malignant tumour made up of sheets and nests of round-to-oval cells with
moderate-to-marked atypia, frequent mitosis, and a higher
nuclear-to-cytoplasmic ratio, with extensive necrosis.
Immunohistochemistry was positive for CD99 and NKX2.2 while it was
negative for Desmin and Myo D1. A definitive diagnosis of ``Ewing's
Sarcoma'' was made.

\textbf{Discussion} :

ES is a malignant tumor that belongs to the ES family of tumours
(ESFTs), which can be divided into skeletal-ES, EES, peripheral
primitive neuroectodermal tumor (pNET) and Askin tumor of the chest wall
(10). The most common sites of primary EES include intracranial,
para-vertebral, thoracopulmonary, the extremities, kidneys, adrenals,
pancreas, gastrointestinal, intraperitoneal, ovaries and urinary bladder
(11). Some studies suggest a higher prevalence of EES in males, but
controversies exist in the sex distribution of EES (7,11). Presenting
symptoms of EES vary widely depending on the location of the primary
tumor and the extent of local as well as distant invasion (11).

The absence of conclusive clinical symptoms often delays the management
of EES. This case is particularly interesting since the patient
presented with symptoms of subacute intestinal obstruction which later
turned out to be diaphragmatic EES. Though small bowel EES has been
described, it is also extremely rare (11). Raney et al studied 15 cases
of diaphragmatic sarcomas and reported alveolar rhabdomyosarcoma to be
the most common subtype of diaphragmatic sarcoma (8). EES was reported
only in 3 of the studied 15 cases, emphasizing the rarity of the tumor
(8). Studies indicate that patients with EES are more likely to have
axial tumors (12).

On comparison of prognostic factors for ES and EES, no major differences
have been reported (12). For EES, elevated baseline ESR has been
demonstrated to have inferior event-free survival (12). EES patients
with a primary tumor in the pelvis have shown improved survival
characteristics (12). Imaging plays an important role in the diagnosis
of EES. As EES is a malignant tumor, positron emission
tomography/computed tomography (PET/CT) should be utilized as it has
demonstrated appreciable sensitivity in detecting EES metastasis (13).

Surgery with complete excision of the tumor mass is the mainstay of
treatment for localized EES. For more advanced EES, radiotherapy and
chemotherapy are added to the treatment protocol to improve the
progression-free survival period, prognostic outcomes, and clinical
improvement. EES patients are more likely to receive surgery along with
radiation than surgery alone, which can be explained by the fact that
more EES patients have an axial location of the primary tumor that is
not amenable to complete surgical resection with tumour-negative margins
(12). The addition of chemotherapy to the management protocol has
significantly improved survival rates of EES patients from 10\%
five-year survival for patients without chemotherapy to 70-80\%
five-year survival for patients who received chemotherapy (11).

\textbf{Conclusion} :

ES is a malignant and aggressive tumor which can also be found
extraskeletally, called EES. The most common locations of EES are
intracranial, para-vertebral, thoracopulmonary, and the extremities. The
presenting features of EES depend on the location of the primary tumor,
hence EES has a very varied presentation and is difficult to diagnose.
Imaging should be used extensively to aid in the timely diagnosis of
EES, as EES often presents at an advanced stage. For more advanced
cases, PET/CT has proven to aid in the diagnosis of EES. The management
protocol of EES includes extensive surgery with/without radiotherapy or
chemotherapy, depending on the extent of invasion and metastasis. EES,
albeit rare, should be kept as a differential diagnosis for ill-defined
and atypical masses.

\textbf{Author Contributions} :

\textbf{Ali Raza} : Conceptualization; writing -- original
draft.\textbf{Hritvik Jain} : Methodology; writing -- original draft;
writing -- review \& editing. \textbf{Ahmad Munib} : Conceptualization;
writing -- original draft. \textbf{Juhi Prashant Pujara} : Writing --
original draft. \textbf{Mohammed Quader Naseer} : Writing -- original
draft.\textbf{Ankit Singh} : Writing -- original draft, writing --
review \& editing. \textbf{Jyoti Jain} : Writing -- original
draft.\textbf{Prakriti Pokhrel} : Writing -- original draft.

\textbf{References} : 1. Durer S, Shaikh H. Ewing Sarcoma. In:
StatPearls {[}Internet{]}. Treasure Island (FL): StatPearls Publishing;
2023 {[}cited 2023 Oct 12{]}. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK559183/

2. Ewing Sarcoma - an overview \textbar{} ScienceDirect Topics
{[}Internet{]}. {[}cited 2023 Oct 12{]}. Available from:
https://www.sciencedirect.com/topics/medicine-and-dentistry/ewing-sarcoma

3. Khan S, Abid Z, Haider G, Bukhari N, Zehra D, Hashmi M, et al.
Incidence of Ewing's Sarcoma in Different Age Groups, Their Associated
Features, and Its Correlation With Primary Care Interval. Cureus. 2021
Mar 18;13(3):e13986.

4. Burchill SA. Ewing's sarcoma: diagnostic, prognostic, and therapeutic
implications of molecular abnormalities. J Clin Pathol. 2003
Feb;56(2):96--102.

5. Abboud A, Masrouha K, Saliba M, Haidar R, Saab R, Khoury N, et al.
Extraskeletal Ewing sarcoma: Diagnosis, management and prognosis. Oncol
Lett. 2021 May;21(5):354.

6. van den Berg H, Heinen RC, van der Pal HJ, Merks JHM. Extra-osseous
Ewing sarcoma. Pediatr Hematol Oncol. 2009 Jun;26(4):175--85.

7. Applebaum MA, Goldsby R, Neuhaus J, DuBois SG. Clinical features and
outcomes in patients with Ewing sarcoma and regional lymph node
involvement. Pediatr Blood Cancer. 2012 Oct;59(4):617--20.

8. Raney RB, Anderson JR, Andrassy RJ, Crist WM, Donaldson SS, Maurer
HM, et al. Soft-tissue sarcomas of the diaphragm: a report from the
Intergroup Rhabdomyosarcoma Study Group from 1972 to 1997. J Pediatr
Hematol Oncol. 2000;22(6):510--4.

9. Ero\selectlanguage{polish}ğ\selectlanguage{english}lu A, K\selectlanguage{ngerman}ürkçüo\selectlanguage{polish}ğ\selectlanguage{english}lu IC, Karao\selectlanguage{polish}ğ\selectlanguage{english}lano\selectlanguage{polish}ğ\selectlanguage{english}lu N, Alper F, G\selectlanguage{ngerman}ündo\selectlanguage{polish}ğ\selectlanguage{english}du C.
Extraskeletal Ewing sarcoma of the diaphragm presenting with hemothorax.
Ann Thorac Surg. 2004 Aug;78(2):715--7.

10. Y I. Diagnosis and treatment of Ewing's sarcoma. Japanese journal of
clinical oncology {[}Internet{]}. 2007 Feb {[}cited 2023 Oct
26{]};37(2). Available from: https://pubmed.ncbi.nlm.nih.gov/17272319/

11. Wright A, Desai M, Bolan CW, Badawy M, Guccione J, Rao Korivi B, et
al. Extraskeletal Ewing Sarcoma from Head to Toe: Multimodality Imaging
Review. Radiographics. 2022;42(4):1145--60.

12. Cash T, McIlvaine E, Krailo MD, Lessnick SL, Lawlor ER, Laack N, et
al. Comparison of clinical features and outcomes in patients with
extraskeletal versus skeletal localized Ewing sarcoma: A report from the
Children's Oncology Group. Pediatr Blood Cancer. 2016
Oct;63(10):1771--9.

13. Javery O, Krajewski K, O'Regan K, Kis B, Giardino A, Jagannathan J,
et al. A to Z of extraskeletal Ewing sarcoma family of tumors in adults:
imaging features of primary disease, metastatic patterns, and treatment
responses. AJR Am J Roentgenol. 2011 Dec;197(6):W1015-1022.

\textbf{Figure Legends} :

Figure 1: Axial section of CECT image showing a large solid cystic mass
along the upper abdomen border anteriorly (white doughnut and white star
representing the solid and cystic areas respectively). The lesion is
also seen effacing the anterior surface of the liver (black arrow) and
the stomach (white arrow).

Figure 2: Coronal section of CECT image showing multiple loculations at
the superior aspect of the lesion (open block white arrow).

Figure 3: Coronal section of CECT image showing inferior extension of
the lesion till right iliac fossa (doughnut and star representing solid
and cystic areas of the lesion respectively).

Figure 4: Axial CECT image showing mild to moderate right-sided pleural
effusion (open block white arrow).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Pokhrel-Figure-1-EES/Pokhrel-Figure-1-EES}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Pokhrel-Figure-2-EES/Pokhrel-Figure-2-EES}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Pokhrel-Figure-3-EES/Pokhrel-Figure-3-EES}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Pokhrel-Figure-4-EES/Pokhrel-Figure-4-EES}

\end{center}
\end{figure}

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