European Spine Journal

https://doi.org/10.1007/s00586-018-5589-x

IDEAS AND TECHNICAL INNOVATIONS

Spondylolisthesis and tumors: a treatment algorithm

Riccardo Cecchinato1   · Stefano Boriani1

Received: 5 March 2018 / Accepted: 7 April 2018

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Abstract
Background  Pars defect and spondylolisthesis are frequent conditions, while bone tumors—particularly the primaries—are
rare. The contemporary occurrence can delay the diagnosis of the tumor, if symptoms are considered related to spondylolis-
thesis, or can make reconstruction more demanding. To our knowledge, only two case reports of this contemporary occur-
rence have been published in the literature. Being such rare, guidelines on surgical treatment have not been proposed yet.
Materials and methods  A retrospective review of patients treated for spine bone tumors by the senior author from 1990
to 2017 was performed to find cases of contemporary occurrence of spondylolisthesis and/or pars defect and spine bone
tumors. General health data, radiological imaging, histological tumor diagnosis, treatment, and follow-up were analyzed
and discussed.
Results  Among the 1870 patients treated for spinal tumors between 1990 and 2017 by the senior author, 14 cases of associa-
tion between tumors and spondylolysis/spondylolisthesis were observed. The cohort includes five males (35.7%) and nine
females (64.3%), aged 14–72. Mean age of patients at surgery time was 47.
Conclusions  Interactions between spondylolisthesis and bone tumors of the spine are episodic. These two conditions rarely
occur in the same patient. No treatment strategy has been described until now. The target of this paper is to propose an
algorithm to surgically treat patients with concomitant bone tumor and spondylolisthesis. This classification identifies a
treatment-oriented algorithm based on two major categories: type A, bone tumor arising on the same vertebra or to an adja-
cent level; type B, bone tumor arising at least one unit far from the spondylolisthesis. This algorithm can help the surgeon
facing this rare combination of diseases in the appropriate preoperative planning.
Graphical abstract  These slides can be retrieved under Electronic Supplementary Material.

Spondylolisthesis and Tumors. Key points and figures Spondylolisthesis and Tumors. Key points and figures Spondylolisthesis and Tumors. Classificaon and take home message

L5

Type A.3 - Tumor adjacent to Spondylolisthesis or lythic vertebra (1 level) - oncological

Type A.1 - Tumor in Spondylolisthesis or lythic vertebra - spondylolisthesis/lysis is
criteria in tumor treatment, spondylolisthesis/lysis affects fusion extension
treated with tumor, or removed if radical treatment

Type A.2 - Tumor in Spondylolisthesis or lythic vertebra - local tumor treatment, Type B - Tumor distant from Spondylolisthesis or lythic vertebra -
spondylolisthesis/lysis is left untreated spondylolisthesis/lysis can be left untreated or treated subsequently

Keywords  Spondylolisthesis · Spondylolysis · Spinal tumors

Introduction
Electronic supplementary material  The online version of this
article (https​://doi.org/10.1007/s0058​6-018-5589-x) contains Spondylolisthesis (S) can be defined as loss of alignment
supplementary material, which is available to authorized users. between vertebral bodies related to disk failure associ-
ated or not associated with developmental or congenital
Extended author information available on the last page of the article

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 European Spine Journal

condition (pars defect). Conversely bone tumors are neo-
plastic diseases, primary or secondary to distant carcino-
mas or less frequently to distal sarcomas. Primary bone
tumors in the spine represent about 10% of all the skeletal
tumors, which are calculated to range about 0.1% of all
human tumors [1]. The expected occurrence of spine bone
tumors is about five individuals per million population per
year. Spine metastases are 80–100 times more frequent [2].
Spondylolisthesis is the mechanical consequence of
a degenerative and/or a developmental condition, while
bone tumors are a wide constellation of diseases. There
is no apparent correlation between these two conditions,
unless we consider that it is theoretically possible that the
lytic effect of tumoral bone erosion can create instabil-
ity by destroying the anatomical elements responsible of
segmental stability. From a clinical point of view, the pain
reported by a patient already known as affected by S can
delay the diagnosis of a spine tumor.
This is particularly relevant, also considering the much
higher incidence of pars defect (PD) and S compared to
spine bone tumors.
The literature has not considered till now the possible
combination of these different diseases and the relative
consequences on diagnosis and treatment. Guidelines of
surgical treatment are missing, leading to heterogeneity in
indications and surgery. To our knowledge, only two case
reports have been published. A case report on Ewing’s
sarcoma presenting as S was published in 1986 [3]. An
isolated metastasis of a listhetic vertebra was described
in 2013 [4].
The aim of this study is to retrospectively review all the
tumor cases observed by the senior author proposing a new
treatment-oriented algorithm for the combination of spine
bone tumor and PD/S.
Materials and methods
A revision of the archives of the senior author’s personal
experience over the years (1990–2017) was performed. All
the patients contemporarily affected by bone tumor and by
pars defect or spondylolisthesis were identified. For each
patient, demographic features, histological diagnosis,
affected levels and treatment option (surgical and conserva-
tive management) were recorded. Preoperative and postoper-
ative radiological examinations were collected and analyzed.
Treatment options were categorized to allow the identifica-
tion of similar features in the different disease presentations,
considering mainly the localization of the tumor and PD/S.
PD/S’s eventual influence on surgical treatment as fusion/
non-fusion or fusion extension was identified. Based on this,
a treatment algorithm is designed to suggest the appropriate
treatment for the different clinical scenarios.
Results
The revision of the database allowed the identification of
14 patients out of 1870 (0.75%) observed and treated from
1990 to 2017. Demographic features of the patients are
reported in Table 1. The cohort includes five males (35.7%)
and nine females (64.3%), aged 14–72. Most of the cases
were observed in the fifth and seventh decades. Mean age
of patients at surgery time was 47.

Table 1  Demographic features of included patients

Patient # Age at surgery Sex Type of tumor Histological diagnosis T vertebra PD/S vertebra

1 40 F Primary, benign Osteoid osteoma L5 L5

2 14 M Primary, benign Osteoid osteoma S1 L5
3 16 F Primary, benign Osteochondroma C7 L5
4 43 F Primary, benign Langerhans cell histiocytosis L5 L5
5 27 F Primary, benign Giant cell tumor L3 L5
6 47 M Primary, benign Pheochromocytoma L3 L4
7 45 F Primary, malignant Fibrosarcoma L5 L5
8 72 F Primary, malignant Chordoma T11 L5
9 62 M Secondary or systemic Myeloma L4 L5
10 65 M Secondary or systemic Myeloma L4 L5
11 46 F Secondary or systemic Metastasis, breast L2 L5
12 77 F Secondary or systemic Metastasis, breast L1 L5
13 42 F Secondary or systemic Metastasis, breast T11 L5
14 52 F Secondary or systemic Metastasis, breast T10 L5

14 out of 1870 patients observed and treated by the senior author for spinal bone tumor from 1990 to 2017
T vertebra tumor vertebra, PD/S vertebra pars defect/spondylolisthesis vertebra

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European Spine Journal

The histological diagnosis was available for all the cases
and is reported in Table 1: six benign tumors (43%: two
osteoid osteomas, one osteochondroma, one eosinophilic
granuloma, one giant cell tumor, one pheochromocytoma),
two primary malignant tumors (14%: one fibrosarcoma, one
chordoma), and six secondary or systemic tumors (43%: four
metastases and two myelomas) were observed. The treat-
ment adopted is described in Table 2. En bloc resection,
vertebroplasty, local corticoid injection, and intralesional
excision were the treatment of choice depending on onco-
logical [5–8] and spinal surgical criteria [9–11].
In eight cases (57%) the tumor arose in the same unit
affected by PD/S or adjacent to it. In six cases (43%) the
tumor arose more than one spine unit far from PD/S.
Discussion
Pars defect and spondylolisthesis (isthmic and degenerative)
on one side and bone tumors on the other are usually distinct
and unrelated conditions. Exceptionally, the erosive effect of
a lytic neoplasm occurring in the postero-lateral vertebral
elements (pedicle, facet joints, and isthmus) can provoke a
pathologic spondylolisthesis. In the literature we can find
only two case reports on the association between these two
entities [3, 4]. In the considered database, we observed 14
cases of associated spine tumors and PD/S. The treatment
of the different cases was planned according to oncological
and spinal criteria. An L5-fibrosarcoma on a pre-existing
isthmic defect was submitted to en bloc resection, which
included the removal of all the anatomical elements, ending
in a fusion of L3-ileum with posterior titanium construct and
anterior expandable cage replacing L5 vertebral body. In one
case, osteoid osteoma arose exactly in the pars. The lesion
recurred after intralesional excision, and a circumferential
fusion was considered necessary after an extensive excision
was performed. Spinal fixation with pedicle screw implants
was performed in ten cases. Four more cases required ver-
tebroplasty, corticoid injection, or intralesional excision
without reconstruction.
It is obvious how the presence of PD/S can influence the
treatment of spinal neoplasm, especially in the selection of
fusion levels and in those cases where the tumor arises in the
PD/S vertebra or adjacent to it. To our knowledge no other
papers were published and a guideline on surgical treatment
is missing.
Observing the features of the examined cases, we can
highlight two main categories of PD/S and tumor associa-
tion. The first is when the tumor arises in the lytic/listhetic
vertebra, or on the immediate adjacent spine unit (type A).
The other category is when the tumor occurs at a different
level (more than one unit far) in respect to spondylolisthesis/
lysis (type B). When the tumor occurs in the same spine unit
or in the adjacent one, we can recognize three conditions:
– Type A.1: the tumor provokes the PD/S. Oncological cri-
teria should be followed first. If an en bloc resection is
needed, the pathologic vertebra is completely removed
and a circumferential fusion is mandatory. When a less-
aggressive oncological treatment such as intralesional
excision is indicated, circumferential fusion is a reason-
able choice.
– Type A.2: the tumor occurs on pre-existing PD/S, but
oncological treatment is not influenced by the presence
of the lysis/listhesis. This is the case of benign tumors
or metastases where local therapies can be delivered

Table 2  Treatment options
Patient # Histological diagnosis T vertebra PD/S vertebra Oncological treatment Fusion area

1 Osteoid osteoma L5 L5 Intralesional excision L4–S1

2 Osteoid osteoma S1 L5 Intralesional excision None
3 Osteochondroma C7 L5 Observation None
4 Langerhans cell histiocytosis L5 L5 Corticoid injection None
5 Giant cell tumor L3 L5 Denosumab + en bloc L1–L4
6 Pheochromocytoma L3 L4 Intralesional excision L1–L5
7 Fibrosarcoma L5 L5 En bloc L2–pelvis
8 Chordoma T11 L5 En bloc T7–L2
9 Myeloma L4 L5 Fixation and RT L3–S1
10 Myeloma L4 L5 Vertebroplasty None
11 Metastasis, breast L2 L5 Intralesional excision L1–L3
12 Metastasis, breast L1 L5 Fixation and RT T12–L2
13 Metastasis, breast T11 L5 Decompression and fixation T8–L2
14 Metastasis, breast T10 L5 En bloc T6–L1

T vertebra tumor vertebra, PD/S vertebra pars defect/spondylolisthesis vertebra, RT radiotherapy

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(radiotherapy, limited intralesional excision, and local
corticosteroid injection). The treatment of PD/S depends
on eventual patient symptoms and local stability, but can
be delivered in a second time.
– Type A.3: the tumor arises in a vertebra adjacent to
PD/S. If the oncological principles bring to the need of
posterior fusion, the listhetic vertebra will be included,
and usually an extension of the fusion area is required.
The need of reduction of the spondylolisthesis can be
assessed using appropriate methods, already published
in the literature [9–11].
When the bone tumor occurs in more than one spine unit
far from the spondylolisthesis or pars defect (type B), we
can consider that not only the oncological criteria for tumor
surgical treatment must be applied (Enneking grading sys-
tem [12], Weinstein–Boriani–Biagini classification [13], and
scoring systems or flowchart for metastases) [7, 8]), but also
the biomechanical criteria for a correct sagittal balance must
be observed [9–11]. If the tumor rises distant enough from
the listhetic vertebra and the posterior fusion area does not
involve PD/S, this can be left untreated if asymptomatic.
The most remarkable effect of the occurrence of a bone
tumor in a spine affected by a developmental or degenerative
spondylolisthesis is related to the problems of reconstruction
connected to the sagittal alignment. Based on the reported
experience, the fixation after tumor excision should be per-
formed as short as possible with more careful respect of sag-
ittal alignment when the tumor occurs far from spondylolis-
thesis, while the fusion of the spondylolisthesis should be
performed during the surgical session of tumor excision if
the tumor is in the same or in the adjacent spine unit. In the
reported cohort, short fusions did not worsen the sagittal
balance in patients already affected by spondylolisthesis,
Table 3  Association between bone tumors and spondylolisthesis
Type of association Description S influences
tumor treat-
ment
Type A.1 Tumor causes S or develops on a Yes
pre-existing S
Type A.2 Tumor develops on a pre-existing S No
Type A.3 Tumor in vertebra adjacent to S Yes
Type B Tumor in a vertebra far from S No
Proposed Algorithm
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European Spine Journal
while long fusions (more than seven levels) performed irre-
spective of sagittal balance rules ended in poor functional
results, deteriorating the excellent oncological results. In the
three cases in which gross total or en bloc resection was
required and longer fixation was performed (7, 8, 9 levels),
the sagittal alignment was heavily influenced. In two cases,
a proximal kyphosis impaired only partially the function, in
the third case the reconstruction after en bloc resection of a
single breast carcinoma metastasis arisen in T9 required the
fixation of nine vertebrae (T5–L1), which further decompen-
sated the imbalance due to L5 spondylolisthesis. Distal junc-
tional kyphosis became soon clinically and radiographically
evident by loosening of distal screws with kyphotic instabil-
ity. Two revision surgeries and an intense program of muscle
rehabilitation ended in acceptable functional performances
(no pain, good functional ability), coexisting with persistent
sagittal imbalance. The patient is still under follow-up pro-
gram 8 years after the en bloc resection.
Conclusions
Interactions between spondylolisthesis and bone tumors
of the spine are episodic. These two conditions are rarely
occurring in the same patient. No treatment strategy has been
described until now. Symptoms attributed to an already well-
known spondylolisthesis can delay the diagnosis of spine
bone tumor. The misunderstanding of the biomechanical
effect of spondylolisthesis can negatively affect the validity
of the reconstruction after bone tumor treatment. The target
of this paper is to propose an algorithm to surgically treat
patients with concomitant bone tumor and spondylolisthesis.
This classification identifies an algorithm (Table 3) based
on two major categories: type A, bone tumor arising on the
Criteria followed Notes
Oncological If tumor excision provides instability, a
Spinal balance circumferential fusion is mandatory.
If an en bloc excision is indicated, S
is removed
Oncological Tumor treatment does not influence
segmental stability (i.e. Langerhans
cells histiocytosis)
Oncological S may change the extension of poste-
Spinal balance rior fusion
Oncological Tumor treatment is independent from
Spinal balance S. Spinal reconstruction must follow
spinal balance rules
European Spine Journal
same vertebra or to an adjacent level; type B, bone tumor
arising at least one unit far from the spondylolisthesis.
Type A
A tumor erodes anatomical stability elements causing
spondylolisthesis, or the tumor develops over a pre-exist-
ing spondylolisthesis (type A.1—Fig. 1). The treatment
of the tumor has the priority and must follow the criteria
of oncological appropriateness (Enneking staging system
indications for primary tumors and multidisciplinary deci-
sion making process for metastases). If the oncologic indi-
cation is simple intralesional excision, this procedure will
also include restoration of the stability by fixation aiming
a full-circumferential reconstruction. If en bloc resection
or gross total excision is indicated, the spondylolisthesis
will not affect the treatment in any way, as the whole-spine
unit will be resected and reconstructed.
In case a tumor arises in a PD/S vertebra and its treat-
ment does not affect the vertebral stability (type A.2—
Fig. 2), the treatment of the lysis or listhesis can be consid-
ered only in symptomatic or unstable cases. Radiotherapy
or local therapies like corticoid injections (eosinophilic
granuloma, solitary cyst, and so on) are examples of this
category. If symptomatic instability persists after the
tumor treatment, fusion will then be considered.
When a spine tumor arises in a vertebra adjacent to a
PD/S (type A.3—Fig. 3), if a posterior fixation is needed
after the oncological treatment, the PD/S is necessarily
included in the fusion area. In this case, according to bio-
mechanical and surgical criteria, the length of posterior
Fig. 1  a–d Type A.1 association between spine tumor and spondylol-
ysis/spondylolisthesis. Preoperative MRI (a) and CT scan (b) that
demonstrate a L5 lysis associated with a neoplasm affecting L5 ver-
fusion can be influenced by the presence of PD/S. The
need of spondylolisthesis reduction can be assessed based
on appropriate literature.
Type B
If the bone tumor arises at least two functional units far
from the PD/S, the oncologic criteria must be first ful-
filled (Fig. 4). If the resection must be followed by a long
fusion, the biomechanical requirements to restore a proper
sagittal balance must be fulfilled (Severity Index, Lamar-
tina square—ref.). If no fixation is required, or if PD/S
are asymptomatic and does not affect the sagittal profile
reconstruction, pars defect or spondylolisthesis can be left
untreated or postponed to a subsequent surgery.
This article is a speculative analysis of a rare combina-
tion of unrelated conditions which can create diagnostic and
therapeutic problems if undiscovered.
The study has several limits. First, it is a retrospective
study, solicited by the problems of sagittal malalignment
arising after bone resection and reconstruction in a case of
previously asymptomatic pars defect and spondylolisthesis.
Second, it is the real incidence. The number of 14 cases out
of 1840 is without any doubt underestimated, as only the
cases of clinically evident spondylolisthesis and the asymp-
tomatic pars defect or spondylolisthesis incidentally discov-
ered on imaging studies were reported. Probably many more
cases of tumor/spondylolisthesis/pars defect combinations
remain undiscovered.
However, some conclusions can be reached. Multicentric
prospective studies on primary and metastatic bone tumors
tebral body extending to L4. A biopsy revealed a high grade fibrosar-
coma. A L4–5 vertebrectomy was performed with a L2-pelvis fusion
(c, d)
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 European Spine Journal

Fig. 4  a, b Type B association between spine tumor and spondylol-

ysis/spondylolisthesis. Preoperative CT scan (a) of a 77-year-old
female affected by L1 breast cancer metastasis and L5 spondylolis-
thesis. The oncological treatment for the metastasis included a short
T12–L2 fixation and postoperative radiotherapy, so the L5 spon-
dylolisthesis was left untreated (b)

should include a full-spine sagittal radiogram to discover the

real incidence of this combination. In daily practice, a sim-
ple full-spine standing radiogram including at least femoral
heads and shafts is recommended for a better planning of
spine reconstruction.
Fig. 2  a, b Type A.2 association between spine tumor and spon-
dylolysis/spondylolisthesis. Preoperative CT scan (a) of a 43-year-old
female affected by a concomitant L5 spondylolysis and Langerhans
cell histiocytiosis. Since the treatment of the diseases consists of local
corticoid injection (b), the lysis does not affect the treatment

Fig. 3  a–d Type A.3 association between spine tumor and spon- lysis of L5. The posterior fusion area has been extended from L3–5 to
dylolysis/spondylolisthesis. MRI (a) and CT scan (b) of a 65-year-old L3–S1 (c) considering the risk of instability due to the long-lever arm
male affected by a L4 myeloma. The preoperative CT scan revealed

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Compliance with ethical standards  6. Boriani S, Fisher CG (2014) Evaluation and decision-making.
In: Vialle LR, Gokaslan ZL, Fisher CG, Boriani S. AOSpine
master series: primary spinal tumors thieme; 2014, p 1–14
Conflict of interest  None of the authors has any potential conflict
7. Tomita K, Kawahara N, Kobayashi T, Yoshida A, Murakami H,
of interest.
Akamaru T (2001) Surgical strategy for spinal metastases. Spine
(Phila Pa 1976) 26:298–306
8. Boriani S, Gasbarrini A (2005) Point of view. Spine (Phila Pa
References 1976) 30:2227–2229
9. Labelle H, Mac-Thiong JM, Roussouly P (2011) Spino-pelvic
sagittal balance of spondylolisthesis: a review and classification.
1. Sundaresan N, Boriani S, Okuno S (2009) State of the Art
Eur Spine J 20(Suppl 5):S641–S646
Management in Spine Oncology. Spine (Phila Pa 1976)
10. Lamartina C (2001) A square to indicate the unstable zone in
34(Supplement):S7–S20
severe spondylolisthesis. Eur Spine J 10(5):444–448
2. Chi JH, Bydon A, Hsieh P, Witham T, Wolinsky JP, Gokaslan
11. Lamartina C, Berjano P, Petruzzi M, Sinigaglia A, Casero G,
ZL (2008) Epidemiology and demographics for primary verte-
Cecchinato R, Damilano M, Bassani R (2012) Criteria to restore
bral tumors. Neurosurg Clin N Am 19(1):1–4
the sagittal balance in deformity and degenerative spondylolis-
3. Klaassen MA, Hoffman G (1987) Ewing sarcoma presenting
thesis. Eur Spine J 21(Suppl. 1):S27–S31
as spondylolisthesis. Report of a case. J Bone Joint Surg Am
12. Enneking WF, Spanier SS, Goodmann M (1980) A system
69(7):1089–1092
for surgical staging of musculoskeletal sarcoma. Clin Orthop
4. Galasso O, Gasparini G, Mariconda M, Signorelli F (2013)
153:106–120
Isolate metastasis of listhetic vertebra. J Back Musculoskelet
13. Boriani S, Weinstein JN, Biagini R (1997) Primary bone
Rehabil 26(3):255–259
tumors of the spine. Terminology and surgical staging. Spine
5. Fisher CG, Vaccaro AR, Whang PG, Patel AA, Thomas KC,
22(9):1036–1044
Mulpuri K et al (2013) Evidence-based recommendations for
spine surgery. Spine (Phila Pa 1976) 38:E30–E37

Affiliations

Riccardo Cecchinato1   · Stefano Boriani1

* Riccardo Cecchinato
dott.cecchinato@gmail.com
1
IRCCS Galeazzi Orthopedic Institute, Milan, Italy

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