\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[T2A]{fontenc}
\usepackage[polish,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Direct Epidural Metastasis of Breast Cancer Mimicking a Large Lumbar
Disc Sequestrum: A Case Report and Review of Literature}



\author[1]{Babak Mirzashahi}%
\author[2]{Mohammadreza Razzaghof}%
\author[3]{Pouya  Tabatabaei Irani}%
\affil[1]{Tehran University of Medical Sciences}%
\affil[2]{Imam Khomeini Hospital Complex}%
\affil[3]{Joint Reconstruction Research Center, Tehran University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Abstract We report a case of cauda equina syndrome (CES) caused by an
epidural metastasis of breast cancer, which oddly mimicked a large disc
sequestrum leading to misdiagnosis. To our knowledge, it is the first
report of the direct metastasis of breast cancer to epidural space.%
\end{abstract}%



\sloppy


\textbf{Introduction}

As the most common malignancy, breast cancer is the second leading cause
of mortality in women \textsuperscript{1}. Speaking of metastases, it
has a special affinity for spine with around 67\% of the diagnosed bone
metastases occurring in spine \textsuperscript{2}. It is the most common
cause of symptomatic spine metastases as one-third of them becomes
symptomatic showing a spectrum of manifestations from lumbar pain to
cord compression or cauda equina syndrome (CES) \textsuperscript{3-5}.

Disc sequestration, accounting for 28.6\% of disc herniations, happens
when a herniated disc migrates into the intracanal space with no link to
the parent disc \textsuperscript{6,7}. Sometimes, the shape and place of
a disc sequestrum (DS) can cause confusion in the radiologic
diagnosis\textsuperscript{8}. The differential diagnoses include tumors,
abscess, hematoma, synovial cysts, and vascular lesions
\textsuperscript{7,9,10}.

In this study, we have reported a case of CES caused by an epidural
metastasis of breast cancer, which oddly mimicked a large disc
sequestrum leading to misdiagnosis. To our knowledge, it is the first
report of the direct metastasis of breast cancer to epidural space. We
believe it is a cautionary case to remind in patients with known breast
cancer, who present with disc herniation symptoms and MRI findings
suggestive of a DS.

\textbf{Case Report}

In July 2020, a 49-year-old woman was referred to our orthopedic spine
clinic by an orthopedist colleague with diagnosis of lumbar disc
herniation causing cauda equina syndrome. She had low back pain from six
months ago, which was aggravated since the last week and was severe
enough to completely disable the patient from her job and daily life.
She described it as radicular to both lower extremities. It was
aggravated by a short walk, 10 steps, and relieved only partially by
lying decubitus and rest for at least 30 minutes. She described
nocturnal pain since the beginning, but had no fever, malaise, and
history of recent trauma, drug, or alcohol abuse. She mentioned no
perianal/perineal anesthesia but some paresthesia of dorsal aspect of
both feet.

On past medico-surgical history, she had invasive ductal carcinoma of
right breast (ER-, PR-, HER2-) and had undergone right lumpectomy
(2009). In 2017, she developed the same pathology in her left breast and
was treated by left lumpectomy. She underwent standard chemoradiotherapy
regimen after both surgeries and had no sign of recurrence in her
regular follow-up.

On examination, there was no sign of skin rash or palpable mass in
lumbar area. She had difficulty in walking. Mild tenderness was found
over the lower lumbar vertebrae. Straight leg raise (SLR) and Cross SLR
tests were positive bilaterally. The lower extremity muscle forces were
4/5 proximally and 3/5 distally. The dorsiflexion force of both ankles
was 2/5. No sensory deficit was elicited. Patellar and Achilles deep
tendon reflexes were decreased in both sides. There was no Babinski
sign.

The magnetic resonance imaging (MRI) was in favor of a severe L4-L5 disc
herniation with a large teardrop shaped sequestrum, which migrated
caudally and caused severe canal stenosis at L5-S1 level. Sagittal and
axial cuts showed compression of both L5 roots by the sequestrated disc
in the L5-S1 neural foramina (Figure 1). However, due to the history of
breast cancer and some MRI features, discussed in the `discussion'
section, we were suspicious of the diagnosis of DS. Her past follow-up
positron emission/ computed tomography (PET/CT) in November 2019 showed
increased FDG uptake in L5 and lower L3 endplate, which was interpreted
as degenerative changes with no sign of metastatic lesions. Her last
whole body bone scan (May 2020) also had shown only degenerative changes
in L5.

Considering the eminent CES, we scheduled the patient for urgent
decompressive laminectomy and discectomy. We performed the surgery
through posterior midline incision by bilateral partial laminectomy and
foraminotomy. However, after laminectomy, we found suspicious lobular
tissue at the level of L4-L5 intervertebral disc bulging posteriorly
into the spinal canal. As the patient had known history of breast
cancer, we considered the tissue as metastasis, and tried to decompress
the spinal canal and foramina by carefully removing the intra-canal
mass, first diagnosed as a disc sequestrum on MRI by radiologist. Mass
resection was performed with as minimal dissection as possible to avoid
probable local tumor contamination. The whole resected tissue was sent
for pathologic study (Figure 2). The intervertebral disc was completely
intact, and we did not perform any discectomy. After sufficient
decompression of canal and nerve roots, standard hemostasis and wound
closure was performed.

The patient started ambulation the evening after surgery according to
our postoperative protocol. Lumbar pain was significantly relieved. She
was discharged after two days.

The pathology report was positive for metastatic breast -invasive
ductal- carcinoma (Figure 3). We referred the patient to
radio-oncologist, and she underwent a course of radiotherapy. Now, we
have a seven-month follow-up of her, and she has had no recurrence so
far.

\textbf{Discussion}

Epidural metastasis affects 5-10\% of patients with systemic
cancers\textsuperscript{11}. Breast cancer accounts for 15-20\% of all
metastatic epidural spinal cord compressions \textsuperscript{12}. There
are three routes for a metastatic tumor to reach the epidural space:
indirectly through vertebral column (85\%), local invasion from
paravertebral tissues (15\%), and direct metastasis to epidural space
(rare) \textsuperscript{11,13}. The first is the most common route for
most tumors including breast cancer, in which the tumor grows in the
highly vascular vertebral bone and then invades the epidural space. The
second route is mostly seen with tumors like lymphoma and neuroblastoma.
However, the third route, which is the case in our patient, is extremely
rare. To the best of our knowledge, it is the first report of a direct
epidural metastasis of breast cancer. Although due to the higher
vasculature of thoracic spine, it is the most common site of epidural
metastasis (60\%), our case was in the lumbosacral region
(10\%)\textsuperscript{14}.

DS can be a diagnostic challenge based on its shape, size, and place
within the spinal canal \textsuperscript{8,10}. Our review of literature
showed such challenge can exist in either of patterns: a DS mimicking a
tumor, and a tumor simulating a DS. In both patterns, the clinical
manifestations of disc herniation and the morphologic similarity between
DS and tumor coexist. The former has been reported much more frequently
in the literature, as we found 31 reports of DS resembling tumoral
lesions in the extradural \textsuperscript{6,8,10,15-27},
intradural\textsuperscript{19,28-32}, intramedullary
\textsuperscript{33}, foraminal \textsuperscript{34-39}, and
extraforaminal\textsuperscript{40-42} sites. Almost all the cases were
in lower lumbar region with few cases in cervical and thoracic spine.

However, the second scenario, which is the case in our report, has been
rarely reported \textsuperscript{43,44}. One was a 65-year-old male with
chordoma presenting as DS in the epidural space posterior to L4 and
extending into L4-L5 foramina \textsuperscript{43}. The other was a
41-year-old patients with a solitary fibrous tumor in the extradural
space along L4 mimicking a DS \textsuperscript{44}. Both patients had
worsening lumbar pain and radiculopathy and underwent laminectomy,
discectomy, and lesion resection, which was proved to be a tumor after
pathologic study. To our knowledge, no case of metastatic breast cancer
mimicking a DS has been reported so far. In our case, the extradural
lesion seemed to originate from L4-L5 disc and moved caudally along the
posterior surface of L5 to cause stenosis at the level of L5 and L5-S1
foramina. Our case was a metastatic tumor, while the two former studies
reported primary tumors. It should be kept in mind that in such
settings, the history of a previous malignancy, although remote, can
help the diagnosis tremendously.

MRI is the gold standard for assessing spinal intracanal lesions, as it
is unparalleled in visualization of bone marrow, disco-ligamentous
structures, and tumors \textsuperscript{45,46}. Generally, DS shows low
intensity in T1- and high intensity (80\%) in T2-weighted MRI. Although,
in 20\% of cases, it is isointense relative to the parent
disc\textsuperscript{47}. In our case, the lesion was isointense,
peripherally extended around the disc, and occupied both foramina in
axial T2 cuts highly mimicking a DS. The intracanal part was
teardrop-shaped in the sagittal and polygonal in the axial cuts with
clear distinction from the dural sac, not in favor of malignancy.
Another misleading finding was the seemingly disrupted posterior annulus
fibrosus of L4-L5 disc and the apparent origin of teardrop from it in
sagittal T2 cuts (Figure 1a). However, what makes us suspect the nature
of lesion as a DS was the unchanged disc height. As it should have been
decreased, had such a large sequestrum have originated from it. In
addition, gadolinium-enhanced MRI can help in differentiating the spinal
tumors \textsuperscript{45}. However, we did not have time to do it, as
the patient had a full blown CES.

\textbf{Conclusion}

In conclusion, breast cancer can rarely invade the epidural space
directly and mimic the radiologic features of a disc sequestrum. The
history of previous malignancy, although remote, in a patient presenting
with manifestations of disc herniation or CES should alarm the clinician
not to miss the diagnosis, which can cause significant morbidity for the
patient.

\textbf{References}

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. \emph{CA: a
cancer journal for clinicians.} 2020;70(1):7-30.

2. Briasoulis E, Karavasilis V, Kostadima L, Ignatiadis M, Fountzilas G,
Pavlidis N. Metastatic breast carcinoma confined to bone: portrait of a
clinical entity. \emph{Cancer.} 2004;101(7):1524-1528.

3. Shehadi JA, Sciubba DM, Suk I, et al. Surgical treatment strategies
and outcome in patients with breast cancer metastatic to the spine: a
review of 87 patients. \emph{European spine journal : official
publication of the European Spine Society, the European Spinal Deformity
Society, and the European Section of the Cervical Spine Research
Society.} 2007;16(8):1179-1192.

4. Mercadante S. Malignant bone pain: pathophysiology and
treatment.\emph{Pain.} 1997;69(1-2):1-18.

5. Gokaslan ZL. Spine surgery for cancer. \emph{Curr Opin
Oncol.}1996;8(3):178-181.

6. Hoch B, Hermann G. Migrated herniated disc mimicking a
neoplasm.\emph{Skeletal radiology.} 2010;39(12):1245-1249.

7. Montalvo Afonso A, Mateo Sierra O, Gil de Sagredo del Corral OL, et
al. Misdiagnosis of posterior sequestered lumbar disc herniation: report
of three cases and review of the literature. \emph{Spinal Cord Series
and Cases.} 2018;4(1):61.

8. Jia J, Wei Q, Wu T, He D, Cheng X. Two cases in which 3D MRI was used
to differentiate between a disc mass that mimics a tumor and
neurinoma.\emph{BMC musculoskeletal disorders.} 2018;19(1):154.

9. Kapetanakis S, Chaniotakis C, Kazakos C, Papathanasiou JV. Cauda
Equina Syndrome Due to Lumbar Disc Herniation: a Review of
Literature.\emph{Folia medica.} 2017;59(4):377-386.

10. Ajayi O, Shoakazemi A, Tubbs RS, Moisi M, Rostad S, Newell DW.
Atypical Presentation of a Sequestered Posterolateral Disc
Fragment.\emph{Cureus.} 2016;8(2):e502. doi:10.7759/cureus.502. Accessed
2016/02//.

11. Grossman SA, Lossignol D. Diagnosis and treatment of epidural
metastases. \emph{Oncology (Williston Park).} 1990;4(4):47-58.

12. Cole JS, Patchell RA. Metastatic epidural spinal cord
compression.\emph{The Lancet Neurology.} 2008;7(5):459-466.

13. Chamberlain MC. Neoplastic meningitis and metastatic epidural spinal
cord compression. \emph{Hematology/oncology clinics of North
America.}2012;26(4):917-931.

14. Hill ME, Richards MA, Gregory WM, Smith P, Rubens RD. Spinal cord
compression in breast cancer: a review of 70 cases. \emph{British
journal of cancer.} 1993;68(5):969-973.

15. Saruhashi Y, Omura K, Miyamoto K, Katsuura A, Hukuda S. A migrated
lumbar disc herniation simulating a dumbbell tumor. \emph{Journal of
spinal disorders.} 1999;12(4):307-309.

16. Stavrinou LC, Stranjalis G, Maratheftis N, Bouras T, Sakas DE.
Cervical disc, mimicking nerve sheath tumor, with rapid spontaneous
recovery: a case report. \emph{European spine journal : official
publication of the European Spine Society, the European Spinal Deformity
Society, and the European Section of the Cervical Spine Research
Society.} 2009;18 Suppl 2:176-178.

17. Ek\selectlanguage{polish}ş\selectlanguage{english}i MS, Yener U, Akakin A, Akakin D, Konya D. Posterior epidural
disc herniation at L3-L4 mimicking a spinal tumor: a case
report.\emph{Journal of neurosurgical sciences.} 2010;54(2):71-76.

18. Li K, Li Z, Geng W, Wang C, Ma J. Postdural disc herniation at L5/S1
level mimicking an extradural spinal tumor. \emph{European spine journal
: official publication of the European Spine Society, the European
Spinal Deformity Society, and the European Section of the Cervical Spine
Research Society.} 2016;25 Suppl 1:80-83.

19. Nievas MNC, Hoellerhage H-G. Unusual sequestered disc fragments
simulating spinal tumors and other space-occupying lesions: Clinical
article. \emph{Journal of Neurosurgery: Spine SPI.} 2009;11(1):42-48.

20. Peng B, Pang X. Tumour-like lumbar disc herniation. \emph{BMJ Case
Reports.} 2013;2013:bcr2013009358.

21. Oh CH, Park HC, Park CO, Yoon SH. A Lumbar Disc Herniation
Misdiagnosed as A Neurofibromatosis Type I: A Case Report. \emph{Korean
J Spine.} 2008;5(3):215-218.

22. Joaquim AF, Ghizoni E, Cabral SR, Hamilton DK, Shaffrey CI. Unusual
presentation of sequestered cervical disc herniation. \emph{JBNC-JORNAL
BRASILEIRO DE NEUROCIRURGIA.} 2010;21(4):239-241.

23. Biasi PR, Mallmann AB, Crusius PS, et al. Sequestered lumbar disc
herniation mimicking spinal tumor. \emph{Arquivos Brasileiros de
Neurocirurgia: Brazilian Neurosurgery.} 2013;32(04):268-270.

24. Passanisi M, Scalia G, Palmisciano P, et al. Difficulty
differentiating between a posterior extradural lumbar tumor versus
sequestered disc even with gadolinum-enhanced MRI. \emph{Surgical
neurology international.} 2021;12:267.

25. Yang L-M, Chien Y-L. A long sequestered lumbar disc with tumor
appearance and another minor one migrated caudally in an aged patient: A
case report. \emph{Formosan Journal of Musculoskeletal
Disorders.}2016;7(2):108-111.

26. Babashahi A, Taheri M. The Cervical Sequestrated Disc Fragment
Presenting as Mass Lesion: Case Report and Review of the
Literature.\emph{Iranian Journal of Neurosurgery.} 2016;2(2):24-29.

27. Altunrende ME, Akcakaya MO. Posterior epidural lumbar disc fragment
mimicking epidural mass. \emph{The Spine Journal.} 2015;15(10):e47-e48.

28. Liu CC, Huang CT, Lin CM, Liu KN. Intradural disc herniation at L5
level mimicking an intradural spinal tumor. \emph{European spine journal
: official publication of the European Spine Society, the European
Spinal Deformity Society, and the European Section of the Cervical Spine
Research Society.} 2011;20 Suppl 2(Suppl 2):S326-329.

29. Aydin MV, Ozel S, Sen O, Erdogan B, Yildirim T. Intradural disc
mimicking: a spinal tumor lesion. \emph{Spinal Cord.} 2004;42(1):52-54.

30. Lee JS, Suh KT. Intradural disc herniation at L5-S1 mimicking an
intradural extramedullary spinal tumor: a case report. \emph{J Korean
Med Sci.} 2006;21(4):778-780.

31. Demirci A, Er U. A lumbar disc herniation mimicking spinal tumor
with intra- and extradural components. \emph{The spine journal :
official journal of the North American Spine Society.} 2011;11(1):90-91.

32. Sharifi G, Alimohammadi E, Ebrahimzadeh K, Moradian K, Rezaei O.
Huge Sequestered Spinal Disc Mimicking Spinal Intradural
Tumor.\emph{Iranian Journal of Neurosurgery.} 2016;2(3):26-28.

33. Solmaz I, Onal MB, Civelek E, Sirin S, Kahraman S. Intramedullary
lumbar lesion mimicking spinal cord tumor: a case of non-neoplastic
intramedullary spinal cord lesion. \emph{European spine journal :
official publication of the European Spine Society, the European Spinal
Deformity Society, and the European Section of the Cervical Spine
Research Society.} 2010;19 Suppl 2:S169-173.

34. Pillai SS. Intra-radicuar Disc Herniation mimicking a Nerve Root
Tumor. \emph{Journal of orthopaedic case reports.} 2012;2(1):7-10.

35. Song K-J, Kim KB, Lee K-B. Sequestrated thoracic disc herniation
mimicking a tumoral lesion in the spinal canal--a case
report.\emph{Clinical imaging.} 2012;36(4):416-419.

36. Kuo C-H, Chang P-Y, Wu J-C, Huang W-C, Tu T-H, Cheng H. Letter to
the Editor: Lumbar disc mimicking tumor. \emph{Journal of Neurosurgery:
Spine SPI.} 2014;20(6):767-768.

37. Ashkenazi E, Pomeranz S, Floman Y. Foraminal herniation of a lumbar
disc mimicking neurinoma on CT and MR imaging. \emph{Journal of spinal
disorders.} 1997;10(5):448-450.

38. Emamian SA, Skriver EB, Henriksen L, Cortsen ME. Lumbar herniated
disk mimicking neurinoma. Case report. \emph{Acta radiologica
(Stockholm, Sweden : 1987).} 1993;34(2):127-129.

39. Hakan A, VURAL S, CANBEK \selectlanguage{polish}İ. \selectlanguage{english}Sequestered Lumbar Disc Fragment
Mimicking Dumbbell-Shaped Spinal Tumor. \emph{Anatolian Journal of
Emergency Medicine.} 3(1):24-26.

40. Bakar B, Sumer MM, Cila A, Tekkok IH. An extreme lateral lumbar disc
herniation mimicking L4 schwannoma. \emph{Acta neurologica
Belgica.}2009;109(2):155-158.

41. Levene HB, Nimmagadda A, Levi AD. An unusual case of footdrop:
anterior disc herniation mimicking a nerve sheath
tumor.\emph{Neurosurgery.} 2010;66(2):E419-420; discussion E420.

42. Wang P, Chen C, Xin X, et al. Giant intrapelvic malignant peripheral
nerve sheath tumor mimicking disc herniation: A case report. \emph{Mol
Clin Oncol.} 2016;5(5):653-656.

43. Ch\selectlanguage{ngerman}ávez-López JA, García-Cisneros R, Félix-Espinoza I. Cordoma de la
columna lumbar simulando una hernia discal secuestrada. \emph{Archivos
de Neurociencias.} 2016;21(4).

44. Verla T, Simpson V, Ropper AE. Solitary Fibrous tumor of the lumbar
spine mimicking a sequestered disc fragment. \emph{Radiology Case
Reports.} 2021;16(3):472-475.

45. Shah LM, Salzman KL. Imaging of spinal metastatic
disease.\emph{International journal of surgical oncology.}
2011;2011:769753.

46. Keogh C, Bergin D, Brennan D, Eustace S. MR imaging of bone tumors
of the cervical spine. \emph{Magnetic resonance imaging clinics of North
America.} 2000;8(3):513-528.

47. Masaryk TJ, Ross JS, Modic MT, Boumphrey F, Bohlman H, Wilber G.
High-resolution MR imaging of sequestered lumbar intervertebral
disks.\emph{AJR American journal of roentgenology.}
1988;150(5):1155-1162.



\textbf{Figure Legends}

\textbf{Figure 1.} Sagittal T2-weighted MRI showing the teardrop lesion,
which is relatively isointense to intervertebral disc and obstruct the
canal (a); myelogram showing partial obstruction at L5 level (b); axial
T2-weighted cuts showing the polygonal shape of lesion, which is clearly
distinct from dural sac and occupies the neural foramina (c).

\textbf{Figure 2.} Intraoperative photograph showing the lesion in situ
(yellow circle), which became visible after partial laminectomy. The
dural sac (asterisk) is drawn laterally by a Love retractor.

\textbf{Figure 3.} The photomicrograph of lesion showing invasive ductal
carcinoma (Hematoxylin and Eosin; \textbf{×} 200 and \textbf{×} 400)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

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

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

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

