101
ORIGINAL SCIENTIFIC ARTICLE
Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the peripheral skeleton
Copyright (c) 2023 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
Prognostic factors of recurrence after an intralesional 
excision of benign bone tumour in the peripheral 
skeleton
Napovedni dejavniki za recidiv po intralezijski izpraznitvi benignega kostnega  
tumorja perifernega skeleta
Luka Pilič Turk,1 Blaž Mavčič1,2
Abstract
Background: Most aggressive benign bone tumours are treated surgically by an intralesional excision and bone defect 
filling. The primary aim of our study was to evaluate prognostic factors of recurrence after an intralesional excision of a 
benign bone tumour in the peripheral skeleton. We asked whether patient age and gender, maximal tumour diameter, 
histological diagnosis, and the tumour’s location statistically significantly impact postoperative tumour recurrences. The 
secondary aim was to evaluate preoperative differences between different histopathological groups of benign bone tu-
mours and the impact of age and gender, maximal tumour diameter, histological diagnosis, and the tumour location on 
the number of diagnostic biopsies and curative surgical procedures.
Methods: Retrospective analysis of prospectively collected data included a cohort of patients operated on at a single ter-
tiary tumour centre between 2010 and 2020 with at least one-year follow-up. Ordinal logistic regression was used to assess 
the influence of input variables on the number of diagnostic/curative surgical procedures and postoperative recurrences.
Results: The cohort analysis included 261 patients with 61 local recurrences. The risk of tumour recurrence was signifi-
cantly lower with higher patient age (p = 0.001) and tumour location in the distal femur (p = 0.033). Higher number of 
diagnostical procedures correlated with higher patient age (p = 0.028), larger maximal tumour diameter (p = 0.035) and 
connective tissue tumour diagnosis (p = 0.027). Higher number of curative procedures correlated with larger maximal tu-
mour diameter (p = 0.008) and lower patient age (p = 0.001).
1 Chair of Orthopaedics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
2 Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Slovenia
Correspondence / Korespondenca: Blaž Mavčič, e: blaz.mavcic@kclj.si
Key words: bone neoplasms; neoplasm recurrence, local; prognosis; intralesional excision
Ključne besede: kostni tumorji; recidiv tumorja, lokalni; napoved izida; intralezijska izpraznitev
Received / Prispelo: 11. 5. 2022 | Accepted / Sprejeto: 13. 9. 2022
Cite as / Citirajte kot: Pilič Turk L, Mavčič B. Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the 
peripheral skeleton. Zdrav Vestn. 2023;92(3–4):101–13. DOI: https://doi.org/10.6016/ZdravVestn.3361
eng slo element
en article-lang
10.6016/ZdravVestn.3361 doi
11.5.2022 date-received
13.9.2022 date-accepted
Surgery, orthopaedics, traumatology Kirurgija, ortopedija, travmatologija discipline
Original scientific article Izvirni znanstveni članek article-type
Prognostic factors of recurrence after an intral-
esional excision of benign bone tumour in the 
peripheral skeleton
Napovedni dejavniki za recidiv po intralezijski 
izpraznitvi benignega kostnega tumorja periferne-
ga skeleta
article-title
Prognostic factors of recurrence after an intral-
esional excision of benign bone tumour in the 
peripheral skeleton
Napovedni dejavniki za recidiv po intralezijski 
izpraznitvi benignega kostnega tumorja periferne-
ga skeleta
alt-title
bone neoplasms, neoplasm recurrence, local, 
prognosis, intralesional excision
kostni tumorji, recidiv tumorja, lokalni, napoved 
izida, intralezijska izpraznitev kwd-group
The authors declare that there are no conflicts 
of interest present.
Avtorji so izjavili, da ne obstajajo nobeni 
konkurenčni interesi. conflict
year volume first month last month first page last page
2023 92 3 4 101 113
name surname aff email
Blaž Mavčič 1,2 blaz.mavcic@kclj.si
name surname aff
Luka Pilič Turk 1
eng slo aff-id
Chair of Orthopaedics, Faculty 
of Medicine, University of 
Ljubljana, Ljubljana, Slovenia
Katedra za ortopedijo, 
Medicinska fakulteta, Univerza v 
Ljubljani, Ljubljana, Slovenija
1
Department of Orthopaedic 
Surgery, University Medical 
Centre Ljubljana, Slovenia
Ortopedska klinika, Univerzitetni 
klinični center Ljubljana, 
Slovenija
2
Slovenian Medical Journallovenian Medical Journal
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1 Introduction
1.1 Benign bone tumours
The Latin meaning of the word tumour, in its broad-
er sense, is used to designate every macroscopically vis-
ible increase in the tissue or organ volume. In the past, 
tumour marked one of the five cardinal signs of inflam-
mation; however, today, it is used in a stricter sense and 
designates a neoplasm (1). In terms of the invasive or 
disseminative potential of tumours, they are divided in-
to benign or malignant tumours (2). Benign neoplasms 
are collections of well-differentiated cells that are very 
similar or the same as the cells from which they origi-
nated (1,2). The processes in these cells resemble those 
performed by normal original cells; mitoses are also ra-
re, particularly in well-differentiated tumours (2). Their 
growth is mostly slow and they all remain localized in 
their site of origin. They usually grow expansively and 
only push the surrounding tissue away (1), as they do 
not possess the ability to infiltrate, invade or metasta-
size into surrounding tissue or organs – this is the main 
Conclusions: Preoperative features of benign bone tumours significant impact the number of surgical procedures needed 
to treat the tumour and the risk of postoperative recurrence. Although most of these factors are nonmodifiable, they rep-
resent an incentive to create evidence-based guidelines for biopsy indications, surgical techniques and consistent postop-
erative follow-up.
Izvleček
Izhodišča: Večina agresivnih benignih kostnih tumorjev se zdravi kirurško s t.i. intralezijsko izpraznitvijo in zapolnitvijo 
kostnega defekta. Glavni cilj naše študije je oceniti napredne dejavnike ponovitve po intralezijski izpraznitvi benignega 
kostnega tumorja v perifernem skeletu. Preučili smo vprašanje, ali starost in spol bolnika, največji premer tumorja, histolo-
ška diagnoza in umestitev tumorja statistično pomembno vplivajo na tveganje za recidiv tumorja po operaciji. Sekundarni 
cilj je bil oceniti razlike med različnimi histopatološkimi skupinami benignih kostnih tumorjev, ocenjenimi pred operacijo, 
ter vpliv starosti in spola, največjega premera tumorja, histološke diagnoze in umestitve tumorja na število diagnostičnih 
biopsij in kurativnih kirurških posegov.
Metode: Retrospektivna analiza prospektivno zbranih podatkov je vključevala kohorto bolnikov, operiranih v enem sa-
mem terciarnem tumorskem centru med letoma 2010 in 2020 z vsaj enoletnim spremljanjem. Za oceno vpliva vhodnih 
spremenljivk na število diagnostičnih in kurativnih kirurških posegov in recidivov po posegu smo uporabili statistično me-
todo ordinalne logistične regresije.
Rezultati: Kohortna analiza je vključevala 261 bolnikov z 61 lokalnimi recidivi. Tveganje za recidiv tumorja je bilo po-
membno manjše ob višji starosti bolnika (p = 0,001) in umeščenosti tumorja v distalnem delu stegnenice (p = 0,033). Večje 
število diagnostičnih posegov je bilo v soodvisnosti z višjo starostjo bolnika (p = 0,028), večjim maksimalnim premerom 
tumorja (p = 0,035) in diagnozo vezivnega tumorja (p = 0,027). Večje število kurativnih posegov je bilo v soodvisnosti z ve-
čjim maksimalnim premerom tumorja (p = 0,008) in nižjo starostjo bolnika (p = 0,001). 
Zaključek: Značilnosti benignih kostnih tumorjev, ugotovljenih pred operacijo, pomembno vplivajo na število kirurških 
posegov, potrebnih za zdravljenje tumorja in za tveganje recidiva. Čeprav večine teh dejavnikov ni mogoče spremeniti, so 
osnova za sprejemanje z dokazi podprtih smernic glede indikacij za biopsijo, izbiro kirurške tehnike in oblikovanje enotnih 
načel spremljanja po operaciji.
differentiating feature from malignant tumours (2).
Primary benign bone tumours substantially out-
number their malignant counterparts and are 100 times 
more frequent (3), especially in patients up to 40 years 
of age (2). The most often discovered benign bone tu-
mours include fibrous tumours and matrix forming tu-
mours, out of which non-ossifying fibroma is the most 
common (4). The 5th edition WHO Classification of 
Soft Tissue and Bone Tumours includes 27 different 
benign bone tumours (4), but for the purposes of our 
research, we sorted them into nine different groups of 
related diagnoses.
Modern orthopaedic surgery offers multiple ways of 
treating benign bone tumours. Some neoplasms require 
only regular radiological follow-up, while others require 
surgical treatment after a previous thorough diagnostic 
evaluation (5,6).
Fundamentally, the extent of the surgical intervention 
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ORIGINAL SCIENTIFIC ARTICLE
Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the peripheral skeleton
into the bone can be divided into four groups, according 
to the attained surgical margins (7):
• intralesional excision: the plane of dissection runs 
directly through the tumourous tissue,
• marginal excision: the plane of dissection runs tight-
ly around the lesion but not through it,
• wide excision: the plane of dissection runs through 
the surrounding healthy tissue close to the tumour,
• radical excision: the entire bone or tumour compart-
ment is removed.
When performing an intralesional excision, the le-
sion is accessed through a surgically made bone win-
dow. The pathologically altered tissue is removed using 
different surgical instruments; most often, the tissue is 
removed by scraping it with a curette. The hence-made 
bone defect may then be filled with polymethylmethac-
rylate (PMMA, i.e., the bone cement), bone substitutes 
of different origin (e.g., calcium triphosphate) or bone 
transplants, either from the patient himself (autologous 
graft) or from a bone graft bank (homologous graft of 
another human individual). Different methods of osteo-
synthesis are sometimes needed to strengthen the bone 
if it was weakened with surgical excision (5,8).
1.2 The exploratory research questions
The presented study’s primary aim was to determine 
the prognostic factors for recurrence after an intrale-
sional excision of benign bone tumours in the periph-
eral skeleton. The study protocol included 261 consec-
utive patients diagnosed with a benign bone tumour in 
the peripheral skeleton and surgically treated with an 
intralesional excision between 1 January 2010 and 31 
December 2021 at the Department of Orthopaedic Sur-
gery, University Medical Centre Ljubljana, Slovenia. For 
each patient, the following data were collected prospec-
tively: date of birth, gender, histopathological diagno-
sis, tumour location, tumour dimensions and estimated 
tumour volume, number of preoperative pathological 
fractures, dates and content of diagnostic and curative 
procedures, number of postoperative tumour recur-
rences and the name of the operating surgeon who per-
formed the surgical treatment.
The following exploratory research questions were 
analysed:
1. Do patients’ age, gender, maximal tumour dimen-
sion, tumour localization, and histopathological di-
agnosis correlate with the number of postoperative 
recurrences after an intralesional excision of a be-
nign bone tumour?
2. Do preoperative features of benign bone tumours, 
such as patients’ age at the first surgery, maximal tu-
mour dimension, estimated tumour volume, and the 
number of preoperative pathological fractures, differ 
between groups of histopathological diagnoses?
3. Do patients’ age, gender, maximal tumour dimen-
sion, tumour localization, and histopathological 
diagnosis correlate with the number of diagnostic 
surgical procedures and curative surgical procedures 
performed in a patient with a benign bone tumour?
2 Methods
2.1 Patients
Our retrospective analysis of prospectively collect-
ed data included all patients surgically treated with an 
intralesional excision of a benign bone tumour in the 
peripheral skeleton between January 1, 2010 and De-
cember 31, 2021 at the only tertiary orthopaedic hos-
pital in the Republic of Slovenia to treat bone tumours 
(University Medical Centre Ljubljana, Department of 
Orthopaedic Surgery). The presented cohort, therefore, 
includes the vast nationwide majority of all patients in 
Slovenia who have undergone such procedures in the 
designated period. All data were collected from the dig-
ital medical archives of treatment records and the radio-
logical imaging database.
2.2 Inclusion and exclusion criteria
The main inclusion criterion was the surgical treat-
ment of the patient between 1 January 2010 and 31 De-
cember 2021 with an intralesional excision of a benign 
bone tumour in the peripheral skeleton, with or without 
subsequent filling of the bone defect. This period was 
chosen because of the wide availability of digital medi-
cal records and radiographic images since 2010.
The exclusion criteria were: no clear histological di-
agnosis after excision (four patients excluded) and un-
availability of required medical documentation because 
the patient was or later became a resident of a foreign 
country (five patients excluded).
2.3 Gathered data
For each patient, the following data were gathered: 
date of birth, gender (male, female), histopathological 
diagnosis (the diagnoses were combined into 9 groups 
as follows: aneurismal bone cysts, enchondromas and 
chondromas, unicameral bone cysts, connective tissue 
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tumours, giant cell tumours of bone, vascular tumours, 
chondroblastomas, nonossifying fibromas, other diag-
noses), tumour location (pelvis, proximal femur, distal 
femur, proximal tibia, distal tibia, fibula, small bones 
of hand/foot, humerus), tumour dimensions (length/
width/height) and estimated tumour volume, number 
of preoperative pathological fractures, dates of diagnos-
tical procedures, dates of curative procedures, number 
of postoperative tumour relapses and number of other 
postoperative complications.
2.4 Statistical analysis
The statistical analysis of the gathered data was per-
formed with Microsoft Excel 2019 (Microsoft Corpora-
tion, Redmond, ZDA) and IBM SPSS 23.0 for Windows 
(IBM Corporation, Armonk, USA). The differences be-
tween mean parameter values of histopathological diag-
noses groups were evaluated by the chi-square test for 
categorical variables (number of males/females, num-
ber of preoperative pathological fractures) and one-way 
ANOVA for numerical variables (mean age at first sur-
gery, mean maximal tumour diameter, mean estimated 
tumour volume).
The impact of independent variables (patient age 
and gender, maximal tumour dimension, histopatho-
logical diagnosis, localization) on the number of pro-
cedures and the number of recurrences was evaluated 
with ordinal regression. The key assumption in ordinal 
regression is that the effects of any explanatory vari-
ables are consistent or proportional across the different 
thresholds (i.e., the proportionality of odds). Therefore, 
they are assumed to have the same effect on the odds 
regardless of the threshold. A separate statistical model 
of ordinal regression was designed for each dependent 
variable: the number of diagnostical procedures, the 
number of curative procedures and the outcome with at 
least one recurrence.
2.5 Ethical approval
The presented non-interventional observation-
al retrospective study of medical archive data was ap-
proved by the National Medical Ethics Committee of 
the Republic of Slovenia on 20 October 2020, case No. 
0120-456/2020-3). The data for this study were collect-
ed prospectively during regular clinical work and then 
analysed retrospectively without any direct or indirect 
contact with the participants. No medical interventions, 
examinations, diagnostic or therapeutic procedures 
were performed during the research. Participation in 
the study was not financially compensated, nor did any 
expenses emerge. No recognizable patient data were 
disclosed or relevant for this purpose.
3 Results
3.1 Preoperative results
After all the required data were gathered, 261 pa-
tients were included in the study based on the aforemen-
tioned inclusion criteria, four patients were excluded 
due to unclear postoperative histological diagnosis and 
five due to the unavailability of required medical doc-
umentation. Table 1 shows the numerical distribution 
of patients into nine histopathological diagnosis groups 
based on four preoperative features (mean patients’ 
age at first surgery, mean maximal tumour dimension, 
mean estimated tumour volume, and the number of 
preoperative pathological fractures). A p-value is given 
for each preoperative feature, indicating whether the 
features statistically significantly differ in average values 
among different histopathological diagnosis groups.
Out of 261 patients in the study, 138 were female 
(52%), and 123 were male (48%). The gender ratio 
was fairly equal throughout the entire study; the on-
ly noticeable deviation occurred in the enchondroma 
or chondroma diagnosis group (1.6 times more often 
in male patients) and in the unicameral bone cyst di-
agnosis group (2.5 times more prevalent in female pa-
tients). The most frequent diagnosis was a unicameral 
bone cyst, followed by enchondroma/chondroma and 
aneurismal bone cyst. The mean age of the entire pa-
tient cohort was 24.4. years, with the highest age in the 
other diagnoses group, followed by the enchondroma/
chondroma diagnosis group and the giant-cell tumour 
of the bone group, respectively. The lowest age was pres-
ent in the non-ossifying fibroma group, followed by the 
chondroblastoma group, while the aneurismal bone 
cyst group had the third lowest average age, and these 
differences were statistically significant (p < 0.01).
The largest average maximal tumour dimensions 
were measured in the giant cell tumour of the bone 
group (59 mm) and were almost the same as in the uni-
cameral bone cyst group (58 mm). The smallest aver-
age maximal tumour dimensions were recorded in the 
chondroblastoma (29 mm) and enchondroma/chon-
droma (31 mm) groups of diagnoses. Once again, the 
differences in the average maximal tumour dimensions 
were statistically significant (p < 0.01).
Among the calculated average tumour volumes, 
the giant cell tumour of the bone group had the largest 
105
ORIGINAL SCIENTIFIC ARTICLE
Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the peripheral skeleton
average volume (74.4 cm3), while the enchondroma 
group of diagnoses had the smallest average volume 
(8.5 cm3). The difference between the average calculated 
tumour volumes was statistically significant (p < 0.01).
The highest number of preoperative pathological 
fractures, almost 80 % of all cases, was observed in the 
unicameral bone cyst group. The mean number of frac-
tures per patient amounted to 1.5, which means that 
most patients in the unicameral bone cyst group en-
dured more than one preoperative fracture.
Analysis of collected data was then performed with 
three separate statistical models of ordinal regression 
in order to evaluate the impact of a set of independent 
variables on three separate dependent variables: the 
number of diagnostic procedures per patient, number 
of curative procedures per patient and the outcome with 
at least one postoperative recurrence.
3.2 Postoperative recurrences
In the entire cohort of the analysed 261 study pa-
tients, we observed 78 postoperative recurrences of a 
benign bone tumour in 68 patients (23% of the entire 
cohort). The highest percentage of patients with at least 
one postoperative recurrence was present in unicameral 
bone cysts (38% of patients with this diagnosis), while 
0% recurrence risk was observed in the non-ossifying 
fibroma and vascular tumour group (Figure 1).
Table 1: Preoperative features of different histopathological diagnosis groups.
Histopathological 
diagnosis groups
Number of 
patients
[female / male]
Mean patient age 
at first surgery 
[years]
Mean maximal 
tumour 
dimension
[mm]
Mean 
estimated 
tumour volume
[cm3]
Number of pre-operative 
pathological fractures 
[no. of patients]
Aneurismal bone 
cysts
38
[19 / 19]
20.5
± 16.5
44
± 24
20.1
± 30.0
4
[4]
Enchondromas and 
chondromas
71
[27/44]
40.4
± 15.2
31
± 24
8.5
± 13.5
3
[3]
Unicameral bone 
cysts
76
[54/22]
19.6
± 18.5
58
± 30
24.5
± 26.8
44
[29]
Connective tissue 
tumours
11
[7/4]
33.3
± 17.9
47
± 17
14.6
± 10.5
1
[1]
Giant cell tumours 
of the bone
23
[11/12]
36.9
± 16.4
59
± 23
74.4
± 74.5
2
[2]
Vascular tumours 6
[2/4]
35.3
± 20.6
37
± 25
13.5
± 18.8
0
[0]
Chondroblastomas 9
[6/3]
18.5
± 7.9
29
± 13
10.1
± 12.1
0
[0]
Nonossifying 
fibromas
10
[5/5]
16.4
± 9.5
48
± 16
15.7
± 14.2
2
[2]
Other diagnoses 17
[7/10]
43.2
± 18.3
45
± 27
12.1
± 11.5
0
[0]
p-value / < 0.01 < 0.01 < 0.01 < 0.01
0
5
10
15
20
25
30
35
40
26
14
38
9
26
0
33
0
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Percentage of patients with at least one postoperative relapse [%]
Figure 1: Percentage of patients with at least one 
postoperative recurrence.
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SURGERY, ORTHOPAEDICS, TRAUMATOLOGY
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The ordinal regression analysis (Table 2) showed 
a statistically significant impact of patients’ age on 
postoperative recurrences (p = 0.001): the odds of re-
currence decreased with higher age (exp(B) = 0.952). 
Along with patient age, the localization of a tumour 
on the distal part of the femur was also shown to have 
an influence on recurrences (p =0.033). Patients who 
had a tumour in the distal part of the femur had a 
lower number of recurrences than other localizations 
(exp(B) = 0.871). Patient gender (p = 0.429), histo-
pathological diagnosis (p (for all diagnoses) > 0.05) 
and maximal tumour dimension (p = 0.050) had no 
statistically significant impact in this regard.
Table 2: Ordinal regression analysis of the impact of independent variables on the outcome of postoperative tumour 
recurrence.
B SE 95% CI of B 
(lower limit)
95% CI of B 
(upper limit)
Sig.
Age -0.049 0.014 -0.077 -0.021 0.001
Maximal tumour 
dimension
0.014 0.007 0.000 0.027 0.050
Gender
• female -0.310 0.392 -1.078 0.458 0.429
• male 0 / / / /
Diagnosis
• aneurismal bone cyst 0.823 0.953 -1.045 2.691 0.388
• enchondroma/
chondroma
0.712 0.979 -1.207 2.631 0.467
• unicameral bone cyst 0.488 0.965 -1.403 2.379 0.613
• connective tissue 
tumour 
1.341 1.025 -0.669 3.350 0.191
• giant cell tumour of 
bone
-0.282 1.399 -3.024 2.460 0.840
• vascular tumour -18.9 8534.0 -16745.2 16707.4 0.998
• chondroblastoma 0.597 1.157 -1.671 2.866 0.606
• nonossifying fibroma -17.7 0.000 -17.7 -17.7 /
• other 0 / / / /
Localization
• small bone hand/foot -0.514 0.642 -1.772 0.744 0.424
• pelvis -19.401 0.000 -19.401 -19.401 /
• proximal femur -0.547 0.486 -1.499 0.405 0.260
• distal femur -1.380 0.648 -2.650 -0.110 0.033
• proximal tibia 0.612 0.631 -0.625 1.848 0.332
• distal tibia -1.681 1.129 -3.894 0.531 0.136
• fibula -1.595 1.202 -3.951 0.761 0.185
• humerus 0 / / / /
Legend: B − ordinal regression coefficient; SE − standard error; CI − confidence interval; Sig. − significance (p-value).
107
ORIGINAL SCIENTIFIC ARTICLE
Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the peripheral skeleton
3.3 Diagnostic procedures
Altogether 90 diagnostic procedures were per-
formed on 261 patients, which amounts to an average 
of 0.34 diagnostic procedures per patient. As shown 
in Figure 2, the highest mean number of diagnostic 
procedures was performed in the giant cell tumours 
of bone (0.83) and the lowest in the unicameral bone 
cyst (0.09). The overall mean of diagnostic procedures 
is lower than 1 because not all surgeons decided on a 
separate diagnostic procedure before a curative one. A 
separate diagnostic procedure is medically indicated 
in tumours with an aggressive radiological appearance 
and in tumours of large volume.
The ordinal regression analysis (Table 3) showed a 
statistically significant impact of patients’ age on the 
number of diagnostic procedures per patient (p = 
0.028), i.e., the higher the age, the higher the number 
of diagnostic procedures (exp(B) = 1.022). Likewise, 
the maximal tumour dimension was significantly re-
lated (p = 0.028) to higher number of diagnostic pro-
cedures (exp(B) = 1.015). Two histological diagnosis 
groups statistically significantly influenced the num-
ber of diagnostic procedures per patient: aneurismal 
bone cyst (p = 0.017) and connective tissue tumour (p 
= 0.027). An aneurismal bone cyst had a lower num-
ber (exp(B) = 0.167), and connective tissue tumours 
had a higher number (exp(B) = 5.275) of diagnostic 
procedures per patient in comparison to other diag-
noses. The influence of patient gender (p = 0.234) and 
tumour localization p (for all localizations) > 0.05) 
was not statistically significant.
3.4 Curative procedures
A total of 368 curative procedures were performed 
on 261 patients in the cohort of the presented study, 
i.e., a mean of 1.41 curative procedures per patient. 
The mean number of curative surgical procedures 
was more than one procedure per patient in all but 
one group of diagnoses. In this context, the curative 
procedures included possible revision surgery due to 
the residual tumour tissue (the postoperative imaging 
showed the tumour was not excochleated in its entire-
ty), possible postoperative complications (e.g., infec-
tion), removal of osteosynthesis material (e.g., remov-
al of drainage screw in case of a simple bone cyst) or 
revision surgery due to tumour recurrence (total mac-
roscopic removal at the primary operation, recurrence 
occurred later).
Curative procedures were performed most often 
on unicameral bone cysts (1.68) and least often on 
non-ossifying fibroma (1.00) (Figure 3). The ordinal 
regression analysis (Table 4) showed a statistically sig-
nificant impact of patient age (p = 0.001) and maximal 
tumour dimension (p = 0.008) on the number of cura-
tive procedures. Contrary to the observed correlation 
between young age and a higher number of diagnostic 
procedures, the number of curative procedures de-
creased with higher patient age (exp(B) = 0.942). An 
increase in the number of curative procedures was al-
so related to the maximal tumour dimension (exp(B) 
= 1.017). Histopathologic diagnosis (p for all diagno-
ses > 0.05), tumour localization (p for all localizations 
> 0.05) or patient gender (p = 0.774) did not exhibit 
any statistically significant influence in this regard.
Figure 2: Mean number of diagnostic procedures per 
patient.
0
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0.6
0.7
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AN
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Mean number of diagnostic procedures per patient
Figure 3: Mean number of curative procedures per patient.
0
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0.8
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1.6
1.8
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1.33 1.33
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1.18
Mean number of curative procedures per patient
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4 Discussion
4.1 Key findings
In our study, we asked three main exploratory re-
search questions. The primary aim was to find out if 
the preoperative characteristics of different benign 
bone tumours (patient age, patient gender, maximal 
tumour diameter, histopathological diagnosis and tu-
mour localization) correlate with the number of post-
operative recurrences after an intralesional exchoche-
lation of such a tumour. Multivariate analysis showed 
a correlation between higher patient age and tumour 
localization on the distal part of the femur with a low-
er number of postoperative recurrences, while other 
characteristics had no statistically significant impact 
Table 3: Ordinal regression analysis of the impact of independent variables on the number of diagnostic procedures.
B SE 95% CI of B 
(lower limit)
95% CI of B 
(upper limit)
Sig.
Age 0.022 0.010 0.002 0.042 0.028
Maximal tumour 
dimension
0.015 0.007 0.001 0.029 0.035
Gender
• female 0.405 0.340 -0.262 1.072 0.234
• male 0 / / / /
Diagnosis
• aneurismal bone cyst -1.787 0.751 -3.259 -0.316 0.017
• enchondroma/
chondroma
-0.340 0.652 -1.618 0.938 0.602
• unicameral bone cyst 0.274 0.691 -1.079 1.628 0.691
• connective tissue 
tumour 
1.663 0.752 0.188 3.138 0.027
• giant cell tumour of 
bone
0.748 0.824 -0.867 2.362 0.364
• vascular tumour 1.291 0.960 -0.592 3.173 0.179
• chondroblastoma 0.139 0.996 -1.813 2.090 0.889
• nonossifying fibroma 1.220 1.040 -0.818 3.258 0.241
• other 0 / / / /
Localization
• small bone hand/foot -1.047 0.627 -2.275 0.181 0.095
• pelvis 0.808 0.978 -1.110 2.726 0.409
• proximal femur -0.008 0.564 -1.113 1.098 0.989
• distal femur 0.160 0.538 -0.896 1.215 0.767
• proximal tibia -0.058 0.571 -1.177 1.061 0.920
• distal tibia -0.113 0.691 -1.467 1.240 0.870
• fibula -0.820 0.879 -2.544 0.904 0.351
• humerus 0 / / / /
Legend: B − ordinal regression coefficient; SE − standard error; CI − confidence interval; Sig. − significance (p-value).
109
ORIGINAL SCIENTIFIC ARTICLE
Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the peripheral skeleton
on the recurrence risk. The secondary aim was to find 
out whether the preoperative characteristics of benign 
bone tumours differ significantly between different 
histopathological diagnoses. All four analysed pre-
operative parameters showed statistically significant 
differences between nine groups of histopathological 
diagnoses: the mean patient age at first surgery, the 
mean maximal tumour diameter, the mean estimat-
ed tumour volume, and the number of preoperative 
pathological fractures. Finally, we wanted to evaluate 
the impact of prognostic factors (patient age, patient 
gender, maximal tumour diameter, histopathological 
diagnosis, and tumour localization) on the number of 
performed diagnostic and curative surgical procedures. 
Table 4: Ordinal regression analysis of the impact of independent variables on the number of curative procedures.
B SE 95% CI of B 
(lower limit)
95% CI of B 
(upper limit)
Sig.
Age -0.060 0.013 -0.087 -0.034 0.001
Maximal tumour 
dimension
0.017 0.007 0.005 0.030 0.008
Gender
• female -0.103 0.358 -0.806 0.599 0.774
• male 0 / / / /
Diagnosis
• aneurismal bone cyst 0.375 0.873 -1.337 2.087 0.668
• enchondroma/
chondroma
0.461 0.898 -1.299 2.221 0.608
• unicameral bone cyst 0.021 0.884 -1.712 1.753 0.981
• connective tissue 
tumour 
1.462 0.926 -0.353 3.278 0.114
• giant cell tumour of 
bone
0.865 1.054 -1.201 2.931 0.412
• vascular tumour -20.366 0.000 -20.366 -20.366 /
• chondroblastoma 0.016 1.085 -2.110 2.143 0.988
• nonossifying fibroma 1.208 1.253 -1.247 3.664 0.335
• other 0 / / / /
Localization
• small bone hand/foot -0.659 0.629 -1.891 0.574 0.295
• pelvis -20.617 0.000 -20.617 -20.617 /
• proximal femur -0.255 0.447 -1.132 0.621 0.568
• distal femur -0.598 0.538 -1.652 0.456 0.266
• proximal tibia 0.494 0.607 -0.695 1.683 0.415
• distal tibia -1.327 0.872 -3.037 0.382 0.128
• fibula -2.012 1.233 -4.429 0.405 0.103
• humerus 0 / / / /
Legend: B − ordinal regression coefficient; SE − standard error; CI − confidence interval; Sig. − significance (p-value).
110
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Higher patient age, larger maximal tumour diameter, 
and connective tissue tumour diagnosis correlated 
with a higher mean number of diagnostic procedures 
per patient, while the diagnosis of an aneurismal bone 
cyst was linked to a lower number of procedures. Fur-
thermore, larger maximal tumour diameter correlated 
with a higher mean number of curative procedures 
per patient, and higher age was linked to a lower mean 
number of procedures.
4.2 Study limitations
The first limitation of our study was the fact that five 
different orthopaedic surgeons of the Department of 
Orthopaedic Surgery, University Medical Centre Lju-
bljana, performed the analysed surgical procedures. 
This circumstance had no impact on the preoperative 
(prognostic) factors; however, it might have affected 
postoperative results. The decisions of performing an 
exclusively diagnostic procedure before a curative one, 
whether a curative procedure is not needed after a di-
agnostic one or whether a diagnostic and curative pro-
cedure can be combined into one procedure depend-
ed on each individual orthopaedic surgeon. Extensive 
professional guidelines on treating benign bone tu-
mours exist, but a subjective influence cannot be en-
tirely excluded. Moreover, the surgeon’s experience or 
the thoroughness of his surgical technique may have 
affected the postoperative recurrence risk, and some of 
the surgeons were prone to take over more demanding 
cases by choice. The impact of this confounding vari-
able (i.e., different surgeons) was reduced by selecting 
a cohort of patients treated at the University Medical 
Centre Ljubljana, Department of Orthopaedic Surgery, 
in a uniform environment with uniform clinical guide-
lines and conditions of surgical work.
The second limitation of our study was the retro-
spective nature of the study. Only retrospective cohort 
studies provide a sufficiently large number of partic-
ipants when the researched events are rare, which is 
the case in certain histopathological diagnoses, patho-
logical fractures, or tumour recurrences. Other prog-
nostic factors may also exist which were not taken into 
account and would require too much time to search for 
in archives or were not recorded when the study was 
being designed (e.g., patient height and weight). Fur-
thermore, the archival image data was in part incom-
plete; for example, no 3-dimensional radiological im-
aging was available in some older cases, or mismatched 
data from different archival sources was present.
4.3 Literature review
The analysis of patient gender distribution in differ-
ent diagnosis groups showed considerable asymmetry 
in a relatively large group of patients with enchondro-
mas/chondromas and unicameral bone cysts. Contrary 
to our findings, the literature review suggests a male 
gender predilection of unicameral bone cysts (4,5,6). 
Enchondromas and chondromas are supposed to have 
no gender predilection (4,5). The most frequent his-
topathological diagnosis in our study was unicameral 
bone cyst, followed by enchondroma/chondroma. The 
frequency of unicameral bone cysts (9) and enchon-
dromas (10) is very low in comparison to non-ossify-
ing fibroma, as both diagnoses contribute 3% and 2% 
(respectively) to the entire prevalence of benign bone 
tumours. Nonetheless, most nonossifying fibromas do 
not require surgical treatment, while bone cysts are 
much more likely to require an operation. The preva-
lence of unicameral bone cyst is not known with cer-
tainty because some of them are never discovered due 
to their frequent asymptomatic nature (11). The same 
applies to nonossifying fibromas (10).
The highest patient age in our cohort was marked in 
the other diagnoses group, followed by the enchondro-
ma/chondroma group and the giant cell bone tumour 
group. Most enchondromas are diagnosed between ag-
es 20 to 40 (12,13), which places our average on the 
upper limit of the age interval. Giant cell bone tumours 
are most commonly discovered in patients aged 20 to 
40 years (14,15), which corresponds well to the mean 
patient age of our cohort. The diagnosis group with the 
lowest average patient age was the non-ossifying fibro-
ma group, followed by the chondroblastoma group and 
the unicameral bone cyst group. Non-ossifying fibro-
ma is one of the most common benign bone lesions in 
children (16,17), which matches our results, and the 
majority of chondroblastomas are diagnosed in the 
second or third decade of life, on average between 19 
and 23 years of age (18), which is close to the average 
age of our study group. According to our results, uni-
cameral bone cysts occur most commonly in children 
or adolescents (19,20).
The largest mean maximal tumour diameter was 
recorded in the giant cell tumour of the bone group, 
closely followed by the unicameral bone cyst group. 
Our mean maximal tumour diameter of the giant cell 
tumour of bone closely matches the one measured by 
the Tianjin Hospital researchers by less than 10 mm - 
in a cohort of 250 patients, the mean was 58 mm or 69 
mm, depending on the localization (21). The smallest 
111
ORIGINAL SCIENTIFIC ARTICLE
Prognostic factors of recurrence after an intralesional excision of benign bone tumour in the peripheral skeleton
mean maximal diameter was observed in the chond-
roblastoma group and the enchondroma group. On 
average, chondroblastomas measure from 30 - 60 mm 
(22,23), which places our average close to the bottom 
limit of the interval. Enchondromas are typically le-
sions measuring less than 30 mm (24); in the study, 
conducted by M.J Walden et al., including 449 patients, 
the average diameter was 19 mm (25), 12 mm more 
than our average.
The largest average calculated volume was found in 
the giant cell tumour of the bone group and the small-
est in the enchondroma group. The latter finding is 
supported by enchondromas often being discovered in 
small carpal and tarsal bones with comparatively small 
diameters (4,13). Furthermore, the shape of these tu-
mours is often ellipsoid, which explains why this group 
was the smallest in volume – one of the diameters could 
have been relatively larger, but the remaining two were 
very small. Most preoperative pathological fractures 
occurred in the unicameral bone cyst group. This find-
ing corresponds well with the literature, which sug-
gests that the unicameral bone cyst is one of the most 
frequent (26) causes of a pathological fracture caused 
by a benign bone lesion.
To date, no study has been published to include 
more than 250 patients from the same hospital, who 
were all surgically treated with intralesional excision 
due to different benign bone tumours and would con-
tain an analysis of predictive factors for the number of 
diagnostic procedures, curative procedures and post-
operative recurrences.
The only study with a similar basic design was pub-
lished in 1985 by A. Kreicbergs et al., Karolinska Hos-
pital, Sweden (27). The study included a cohort of 155 
patients surgically treated by intralesional curettage 
due to different benign bone tumours. A subsequent 
analysis of possible predictive factors for recurrence 
was performed. A recurrence occurred in 23% of pa-
tients, which is an astonishingly similar result to our 
study. Patient gender and histological diagnosis were 
also found to be statistically significant predictive fac-
tors of recurrence. Furthermore, the diagnoses of an 
aneurismal bone cyst and a giant cell tumour of bone 
were found to be predictive factors of recurrence for 
the female study participants, whereas the diagnosis 
of a unicameral bone cyst was the predictive factor for 
participants up to 9 years of age. A correlation between 
an individual histological diagnosis and the occurrence 
of a recurrence was not proven in our study; however, 
there was a correlation between tumour localization 
and patient age with tumour recurrence.
Other similar studies are mostly based on a single 
histological diagnosis, most frequently the diagnosis of 
a giant cell tumour of bone (28-39). Predictive factors 
of recurrence after intralesional excision were some-
times only identified, and other times also statistically 
evaluated. For example, patient gender and age were 
the researched predictive factors in a study conduct-
ed by Mohaidat et al. (28): male gender and lower age 
were linked to a higher number of recurrences. On the 
contrary, C. Errani et al. concluded that none of the 
predictive factors were statistically insignificant (29); 
the same conclusion was stated by Teixera et al. (30).
Predictive factors, researched in other studies, in-
clude tumour localization (31), the occurrence of an-
other bone tumour simultaneously with a giant cell 
tumour of bone (32), usage of different surgical adju-
vants (bone cement (33,34), phenol (35)), occurrence 
of pathological fractures (36) and microscopic char-
acteristics of surrounding tissue (37). Other histolog-
ical diagnoses to be more frequently found in similar 
studies are chondroblastoma (38-41), aneurismal bone 
cyst (42), osteoblastoma (43), and enchondroma (44). 
Predictive factors of recurrence included biological ag-
gressiveness of a tumour (39), patient gender (40,41), 
tumour size (42), and the usage of phenol as a surgical 
adjuvant (43), to name a few.
Ours is the first clinical study to research the field 
of active and aggressive benign bone tumours in the 
Republic of Slovenia. Its findings and conclusions 
have direct clinical applicability in forming guidelines 
for surgical treatment and postoperative follow-up of 
benign bone tumours. The study was also the first to 
analyse the predictive factors of recurrence among dif-
ferent diagnosis groups in a cohort greater than 250 
patients. It was shown that higher patient age and the 
localization of a tumour on the distal femur correlate 
with a lower number of postoperative recurrences.
5 Conclusion
The preoperative features of benign bone tumours 
(patient age at first surgery, maximal tumour diameter, 
estimated tumour volume, and the number of preop-
erative pathological fractures) statistically significant-
ly differ among different histopathological diagnosis 
groups. A higher number of diagnostic procedures in 
the treatment of benign bone tumours is statistically 
significantly linked to patient age, maximal tumour 
diameter, and the diagnosis of a connective tissue tu-
mour. A lower number is linked to a diagnosis of an 
aneurysmal bone cyst. Other variables (patient gender, 
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other diagnosis groups, and tumour localization) have 
no statistically significant impact.
A higher number of curative procedures in the 
treatment of benign bone tumours is statistically sig-
nificantly linked to maximal tumour diameter and a 
lower number to patient age. Other variables (patient 
gender, histopathological diagnosis and tumour lo-
calization) have no statistically significant impact on 
the number of curative surgical procedures. A lower 
risk of postoperative recurrences after an intralesional 
excision of a benign bone tumour is statistically sig-
nificantly linked to a higher patient age and a higher 
number of recurrences to the tumour localization on 
the distal femur.
Therefore, the characteristics of benign bone 
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Conflict of interest
None declared.
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