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\begin{document}

\title{One-stage combined approach en bloc vertebrectomy for primary Ewing's
sarcoma of mobile spine in an adult patient: 3 years following agressive
surgery for a rare entity}



\author[1]{Mohamed Amine Gharbi}%
\author[1]{Houssem Eddine Chahed}%
\author[1]{Sana Ben Slama}%
\author[1]{Anis Teborbi}%
\author[1]{Ramzi Bouzidi}%
\author[1]{Mouadh Nefiss}%
\affil[1]{University Hospital Center Mongi Slim}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Primary Ewing's sarcoma (EWS) of non-sacral spine is extremely rare,
especially in middle-age. Therapeutic strategy aims: to large tumor
resection, to provide spine stability and to avoid recurrence through
chemo and radiotherapy. We report a case of thoracic spine EWS in an
adult treated by combined approach en bloc vertebrectomy.%
\end{abstract}%



\sloppy


\emph{Title}

One-stage combined approach en bloc vertebrectomy for primary Ewing's
sarcoma of mobile spine in an adult patient: 3 years following agressive
surgery for a rare entity

\emph{Authors and Affiliations}

Mohamed Amine GHARBI \selectlanguage{ngerman}¹ ³, Houssem Eddine CHAHED ¹ ³, Sana BEN SLAMA ² ³,
Anis TEBORBI ¹ ³, Ramzi BOUZIDI ¹ ³, Mouadh NEFISS ¹ ³

¹ Department of Orthopedic and Trauma Surgery, Mongi Slim Marsa
University Hospital Center, Tunis, Tunisia

² Department of Anatomical Pathology, Mongi Slim Marsa University
Hospital Center, Tunis, Tunisia.

³ University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia.

\emph{Corresponding Author}

Mohamed Amine GHARBI

University of Tunis El Manar, Faculty of Medicine of Tunis, Department
of Orthopedic and Trauma Surgery, Mongi Slim Marsa University Hospital
Center, Tunis, Tunisia.

Email: gharbi.m.a@gmail.com

\emph{Abstract}

Primary Ewing's sarcoma (EWS) of non-sacral spine is extremely rare,
especially in middle-age. Therapeutic strategy aims: to large tumor
resection, to provide spine stability and to avoid recurrence through
chemo and radiotherapy. We report a case of thoracic spine EWS in an
adult treated by combined approach en bloc vertebrectomy.

\emph{Keywords} \textbf{}

Ewing's sarcoma, thoracic spine, surgery, en bloc vertebrectomy

\emph{Key Clinical Message}

Currently, there is no consensus on the optimal management of
non-metastatic Ewing's sarcoma of the mobile spine. However, associated
to chemotherapy, aggressive surgery with en bloc wide resection seems to
improve local control and survival.

\emph{Introduction}

Primary Ewing's Sarcoma (EWS) of the spine is extremely rare. It
accounts for only 3.5\% to 14.9\% of all primary bone sarcomas
{[}1,2{]}. It is characterized by a high proliferative and invasive
potential and a confusing variety of imaging manifestations in adult
patients {[}3{]}. Non-specific signs are often in the first place and
the delay from the onset of symptoms to the diagnosis can take months
which can worsen the prognosis {[}4{]}. Because of the rarity of the
spinal localization of primary EWS in adults there is not a well-coded
management protocol and a multitude of therapeutic strategies that mimic
the management of EWS of the appendicular skeleton have been employed.
The therapeutic goal is a complete tumor removal and spinal column
stability restoration {[}1{]}. The publications of Weinstein, Boriani
and Biagini and their surgical staging system (WBB) have been of great
interest in this field {[}5-6{]}. We report a rare localization of
solitary thoracic EWS in an adult patient that was treated with en bloc
vertebrectomy.

\emph{Case report}

A 30-year-old man presented with a one-year history of a progressive,
worsening back pain associated to a right intercostal neuralgia, no
motor weakness or sphincter disturbance were found. There was no history
of fever or trauma. Blood tests were normal and the X-ray rechecks after
making the diagnosis showed an unobvious suspect image at the level of
the right pedicle of the 12th thoracic vertebra (T12) with disappearance
of its normal contours (Figure 1A). Magnetic resonance imaging (MRI)
revealed a vascularized mass affecting the right hemivertebral body and
posterior arch of T12 with paravertebral soft tissue extension. The
spinal cord was mildly compressed (Figure 1B). An extension assessment
concluded that it is a primary localization. We performed a computerized
tomography (CT) guided biopsy and the diagnosis of EWS was confirmed by
histopathology and immunohistochemistry showing uniformly small round
cells which were strongly positive to CD99 (Figure 2).

After receiving neo-adjuvant chemotherapy, a new MRI showed vertebral
and paravertebral soft tissue mass regression (Figure 1C). According to
the WBB surgical staging system, sectors included in the axial T12
imaging were 1 to 6 (part of the body and part of the left posterior
arch) and layers of tissue penetration were A to D.

We performed an en bloc vertebrectomy through a double approach surgery:
firstly a posterior approach with pedicle screw insertion (2 levels
above and 2 levels below), remove of the healthy part of the posterior
arch which allow to release the spinal cord from the tumor pseudocapsule
, ligation and section of T12 roots (Figure 3A). Secondly a
thoraco-phreno-lombotomy to separate the anterior part of the tumor and
control the segmental artery. The separation was made by a Gigli saw and
the extraction of the vertebra released from all its attachments was
possible through a simple rotation of the specimen (Figure 3B and 3C).
Reconstruction was performed with interbody free non-vascularized
fibular bone grafting stabilized by the posterior instrumentation.

Postoperative course was uneventful. After six weeks of the surgery, the
patient started adjuvant chemotherapy and completed treatment with no
evidence of disease on re-evaluation at the end of therapy. Three years
after surgery, the patient is surviving without neurologic deficit,
X-rays revealed consolidation (Figure 4) and with no evidence of
recurrence.

\emph{Discussion}

Ewing's sarcoma remains an enigmatic and particular malignant tumor 100
years after its discovery. Spinal involvement most commonly results from
metastasis in advanced stages of the disease, while EWS originating from
the spine is rare and extremely rare if the sacrum is excluded
{[}2,3{]}. Diagnosis could be quite difficult due to an insidious onset,
non-specific symptoms and misinterpreted images. Thus, symptoms may not
be present until neurological deficits occur and diagnosis suspicion may
be after several consultations which increase doubts {[}7,8{]}. The
average delay from the onset of symptoms to the diagnosis has been
reported to be 34 weeks all locations combined {[}9{]}. In our case the
delay was 48 weeks. That's why approximately 25\% of patients present
with metastatic disease at diagnosis; fortunately this was not the case
of our patient {[}3{]}.

Definitive diagnosis requires cytological, immunohistochemical (CD99)
and cytogenetic analysis of a pathologic specimen. The translocation
involving chromosome 22 is identified in more than 90\% of cases, and it
is the landmark to differentiate EWS from other small, round blue cell
tumors {[}3,10{]}.

Currently, early diagnosis and multimodal treatment combining surgery,
chemotherapy, and local radiation therapy increases the chance of a
successful outcome {[}11{]}. Indelicato et al {[}12{]}, in a review have
reported a five-year overall survival rate of 71\% and local control
rate of 89\% for non-metastatic spinal and paraspinal EWS. However, when
compared to other sites of occurrence, prognosis of EWS of the spine
remains worse {[}13{]}.

Initial chemotherapy and local radiotherapy might be administered before
surgery with the aim to shrink bulky and unresectable tumors, to
eradicate micrometastases and for acute relief of epidural compression,
but it should be noted that there is a variable sensitivity to radiation
and chemotherapy due to biological heterogenecity {[}1{]}.

During the last two decades, the outcome in patients with localized
disease has improved through an aggressive surgery known as en bloc
vertebrectomy by combining anterior and posterior approach or from a
single posterior approach as described by Tomita and al {[}14{]}.

Boriani et al {[}6{]} described three major methods of performing en
bloc excisions in the thoracolumbar spine: vertebrectomy if the tumor is
confined to zones 4 to 8 or 5 to 9; sagittal resection when the tumor
occupies zones 3 to 5 or 8 to 10 and resection of the posterior arch
when it is located between the zones 10 and 3 according to their
surgical staging system.

However, en bloc resection is a highly demanding procedure that must be
carefully planned and the greater surgical risk can be accepted only if
it offers a safer result and is performed by specialized surgical and
anesthesiology teams {[}5{]}.

Among the difficulties to be considered is the release of the spinal
cord if the tumor is expanding to layer D according to WBB staging
system. In this case theoretical safe margin should include the dura in
the resection specimen but the cost-to-benefit ratio of such procedure
should be carefully evaluated. Boriani and his collaborators have shown
that a simple release of the dura without resection can be accepted and
without proven consequence on the risk of recurrence {[}6,13{]}.

Compared to cases where only decompression or lesionectomy was done,
patients who underwent en bloc spondylectomy had a lower recurrence rate
{[}8,15{]}. This is why, whenever possible, surgical en bloc wide
resection with an anterior column reconstruction is preferable in order
to obtain a better oncological control and a better preservation of the
spine biomechanics {[}3{]}.

\emph{Conclusion}

Primary Ewing's sarcoma of the thoracic spine is an extremely rare
tumor. It is a challenging disease not only to treat but also to
diagnosis. A high index of suspicion is needed in patients who present
with few or non-specific symptoms. Early diagnosis is essential to
obtain better results and improve prognosis. In localized forms of the
tumor multi modal treatment involving neo-adjuvant chemotherapy, en bloc
vertebrectomy and adjuvant radiotherapy and chemotherapy is required for
patient outcome and satisfactory quality of life.

\emph{AUTHOR CONTRIBUTION}

Mohamed Amine Gharbi and Mouadh Nefiss: wrote the manuscript and
performed bibliographic research. Houssem Eddine Chahed and Sana Ben
Slama: contributed to the data analysis and collected iconographic
elements. Anis Teborbi and Ramzi Bouzidi: critically revised the
manuscript and gave final approval.

\emph{Acknowledgements}

None.

\emph{CONFLICT OF INTEREST}

The authors declare having no conflicts of interest regarding this
manuscript.

\emph{DATA AVAILABILITY STATEMENT}

None.

\emph{CONSENT}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.

\emph{References}

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spine: case report.~Arq Neuropsiquiatr. 2006; 64: 654\selectlanguage{english}-659.

{[}2{]} Goktepe AS, Alaca R, Mohur H, Coskun U. Paraplegia: an unusual
presentation of Ewing's sarcoma.~Spinal Cord. 2002; 40: 367\selectlanguage{english}-369.

{[}3{]} Iacoangeli M, Dobran M, Di Rienzo A, Di Somma LGM, Moriconi LAE,
Nocchi N et al. Nonmetastatic Ewing's Sarcoma of the Lumbar Spine in an
Adult Patient.~Case Rep Oncol Med. 2012; 2012: 165289.

{[}4{]} Nair M, Sukumaran Nair R, Raghavan R, Parukkutty K, Sukumaran R.
Primary Ewing's Sarcoma of the Spine in Pediatric Patients: A Case
Series Analysis and Literature Review. Middle East Journal of Cancer.
2015; 6: 115-120.

{[}5{]} Boriani S, Biagini R, De Iure F, Andreoli I, Campanacci L, De
Fiore M et al. Primary bone tumors of the spine: a survey of the
evaluation and treatment at the Istituto Ortopedico Rizzoli.
Orthopedics. 1995; 18: 993\selectlanguage{english}-1000.

{[}6{]} Boriani S, Weinstein JN, Biagini R. Primary bone tumors of the
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{[}7{]} Ilaslan H, Sundaram M, Unni KK, Dekutoski MB. Primary Ewing's
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{[}8{]} Weinstein JB, Siegel MJ, Griffith RC. Spinal Ewing sarcoma:
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{[}9{]} Widhe B, Widhe T. Initial symptoms and clinical features in
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{[}10{]} Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM.
Chromosome study of Ewing's sarcoma (ES) cell lines. Consistency of a
reciprocal translocation t(11;22)(q24;q12).~Cancer Genet Cytogenet.
1984; 12: 1\selectlanguage{english}-19.

{[}11{]} Sharafuddin MJ, Haddad FS, Hitchon PW, Haddad SF, el-Khoury GY.
Treatment options in primary Ewing's sarcoma of the spine: report of
seven cases and review of the literature.~Neurosurgery. 1992; 30:
610\selectlanguage{english}-619.

{[}12{]} Indelicato DJ, Keole SR, Shahlaee AH, Morris CG, Gibbs CP,
Scarborough MT et al. Spinal and paraspinal Ewing tumors.~Int J Radiat
Oncol Biol Phys. 2010; 76: 1463\selectlanguage{english}-1471.

{[}13{]} Boriani S, Amendola L, Corghi A, Cappuccio M, Bandiera S,
Ferrari S et al. Ewing's sarcoma of the mobile spine.~Eur Rev Med
Pharmacol Sci. 2011; 15: 831\selectlanguage{english}-839.

{[}14{]} Tomita K, Kawahara N, Baba H, Tsuchiya H, Fujita T, Toribatake
Y. Total en bloc spondylectomy. A new surgical technique for primary
malignant vertebral tumors.~Spine (Phila Pa 1976). 1997; 22: 324\selectlanguage{english}-333.

{[}15{]} Samartzis D, Marco RA, Benjamin R, Vaporciyan A, Rhines LD.
Multilevel en bloc spondylectomy and chest wall excision via a
simultaneous anterior and posterior approach for Ewing sarcoma.~Spine
(Phila Pa 1976). 2005; 30: 831\selectlanguage{english}-837.

\emph{Figures}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1:}

(A) Standard x-ray (antero-posterior and lateral view) showing a
disappearance of normal contours of the right pedicle of T12

(B) MRI (sagittal and axial view) revealing a vascularized mass
affecting the right hemivertebral body and posterior arch of T12 with
paravertebral soft tissue extension and spinal cord compression

(C) Axial MRI view showing tumor regression after neo-adjuvant
chemotherapy\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 2:} Microscopic examination

Classical Ewing's Sarcoma: Sheets of monotonous small round blue cells
with minimal amounts of stroma. Presence of Peripheral bone at the top
(hematoxylin-eosin: HEx100).

Cartridge: Cellular details with round nuclei and minimal cytoplasm
(hematoxylin-eosin: HEx200).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 3:}

(A) Posterior approach with pedicle screw insertion and release of the
spinal cord

(B) En bloc vertebrectomy of T12 through the combined approach

(C) Photo and x-ray of T12 after extraction\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{Figure 4:}

Reconstruction of the anterior column by interbody free non-vascularized
fibular bone grafting stabilized by the posterior instrumentation: X-ray
at 3 years fellow-up showing consolidation without kyphosis

\selectlanguage{english}
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\end{document}

