Rom J Morphol Embryol 2015, 56(2):413417 [613855]

Rom J Morphol Embryol 2015, 56(2):413–417
ISSN (print) 1220–0522 ISSN (on-line) 2066–8279 OORRIIGGIINNAALL PPAAPPEERR
Proximal tibial osteosarcoma in young patients: early
diagnosis, modular reconstruction
RĂZVAN ENE1), RUXANDRA DIANA SINESCU2), PATRICIA ENE3), DAN POPESCU1),
MONICA MIHAELA CÎRSTOIU4), FLORIN CĂTĂLIN CÎRSTOIU1)
1)Department of Orthopedics and Traumatology, Emer gency University Hospital, Bucharest, Romania
2)Department of Plastic Surgery and Reconstructive Microsurgery , “Elias” Emergency University Hospital, Bucharest, Romania
3)Department of ENT, Emergency Univer sity Hospital, Bucharest, Romania
4)Department of Obstetrics and Gynecology, Emer gency University Hospit al, Bucharest, Romania
Abstract
Osteosarcoma is the most common bone tumor that occurs in children and young adults with prevalence of teenage. There can be id entified
many subtypes of osteosarcoma by how they look on X-rays and under the microscope. Osteosarcoma can be classified as high-grade ,
intermediate grade, or low-grade. This has a significant prognostic value of tumor development suggesting the growth rate and t he potential for
expansion. Between 2009–2013, in the Department of Orthopedics and Traumatology, University Emergency Hospital of Bucharest, Romania, were treated seven cases of osteosarcoma of the proximal third of the tibia in young, early-diagnosed cases without me tastasis.
The treatment involved resection of tumor formation and reconstruction with a modular prosthesis. Postoperative patients were m obilized
for a week without charging the operated limb under the protection of orthesis. During this period continued active and passive mobilization
of the ankle and foot to prevent stiffness and to reduce postoperative swelling. From the second postoperative week, patients a re mobilizing
with progressive charging but not being allowed to do any flexion in order to protect de insertion of medial gastrocnemius musc le rotation
flap used to cover the prosthesis and to protect the patellar tendon reinsertion. This extensive surgery does not improve survi val rate of
these patients compared to treatment by amputation of this pathology but greatly increases the comfort of life and in all cases ensure
socio-professional reintegration of these patients. To ensure optimal postoperative results perform a complete diagnosis and pr eoperative
oncological treatment before surgery, if applicable.
Keywords :
osteosarcoma, modular prosthesis, func tional recovery, oncological treatment.
 Introduction
The osteosarcoma is so-called, because it is a
cancerous tumor that is derived from a mesenchymal stem
cell precursor that after becoming malignant produce
immature woven bone, or osteoid, which is the reason
for this tumor to be named osteosarcoma. This tumor
may be starting from bone cells or can also rarely arise
from soft tissues of the extremities [1, 2].
In addition to classification of osteosarcoma by
aggressiveness and prognostic, there is another classifi-
cation regarding the origin of the tumor: intramedullary
(the most frequent), juxtacor tical, intracortical. Of all
types of osteosarcoma, the most commonly found in a
proportion of 75% is the primary osteosarcoma with high
grade of differentiation, intramedullary located [3].
This tumor has a high risk of metastasis, most often
disseminating locally, in the same extremity or systemi-
cally, most commonly involving the lung, when worsens
dramatically the prognosis and completely change the
therapeutic attitude. Metastases that develop in the same
extremity or exceed neighboring joints are called skip
metastases. Eighty percent of the tumors at the time of
diagnosis are metastases free [4].
Osteosarcoma develops radial, in an inside-outside
manner penetrating the cortex and infiltrating the sur-
rounding muscles, and creating a reactive tumoral area
that during the operation should be removed between
oncological limits. Many decades ago, the only treatment for this disease
was the amputation but, starting with the last years effective
induction (neoadjuvant/preoperative) and adjuvant (post-operative) chemotherapy protocols have improved the
ability to perform safe limb-sparing resections, and have
also improved the survival rates [5, 6].
The purpose of this study is to determine the optimal
attitude in front of a proximal tibial osteosarcoma case,
knowing the high incidence of this type of tumor in young patients, requiring orthopedic surgeons to use limb rescue
techniques avoiding amputation of the affected limb.
 Patients and Methods
Between 2009–2013, in the Department of Orthopedics
and Traumatology, University Emergency Hospital of
Bucharest, Romania, were treated seven cases of osteo-sarcoma of the proximal third of the tibia in young
patients. Mean age was 22 years, with a range between
17 and 29-year-old. Gender ratio: two males/five females. One of the patients was from rural areas and the other
six were from urban areas. No patient had risk factors or
family history.
Clinical symptoms of patients started with localized
pain in the proximal third of the tibia for weeks or
sometimes months, most often associated with a sports
or domestic injury. Pain gradually become more severe
and accompanied by swelling and limitation of motion.
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Răzvan Ene et al.
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In all cases, the pain was more pronounced at night
awaking from sleep sometimes.
Clinical examination reveal ed tenderness, a certain
degree of muscle atrophy, limitation of movement of adjacent joints and to palpation, swelling or deformity suggesting the presence of a mass. None of the patients had weight loss because there were no secondary deter-minations at the time of diagnosis. After clinical exam,
standard X-ray (using a Swissray machine) examination
was performed and in order to achieve better anatomical details, and the expansion of the tumor CT (Siemens single source CT scanner) and MRI was performed.
In order to exclude other secondary determinations,
or associated pathology and the presence of metastases,
chest, and abdomino-pelvic CT was taken in every case.
For the biological activity of the tumor, and to evaluate secondary determinations, whole body bone scintigraphy was performed with Tc-99m, and SPECT was performed. Angiography was routinely performed in order to describe and to evaluate the blood supply of the tumor.
In order the exclude other malignant pathology or the
presence of bone metastases the following tumor markers were examined: TNF- β, CA 125 and CA 19-9.
Diagnosis was made after imaging examinations,
biological and histopathological examination of tumor tissue harvested performed by incisional biopsy and for
tumor classification we used the Enneking system. After
incisional biopsy the tissue samples was examined using standard paraffin slices, with Hematoxylin and Eosin (HE)
staining, the following cellular aspects were highlighted: nuclear pleomorphism, number of atypical cell mitosis,
hematic invasion of the tumor cells; due to the histo-
logical results, osteosarcomas were classified in low- and
high-grade malignant osteosarcomas.
After the aforementioned examinations, the patients
underwent to surgical removal of the tumor and to limb sparing surgery, with special modular prosthetic repla-cement of the affected joint and bone segment.  Results
The clinical appearance of osteosarcoma consists in
palpable mass, with a fast growing aspect in last months.
This aspect of the tumor often leads to skin lesions, night
pain and in some cases diurnal pain (the pain occurred in the knee as well) and compressive vascular or nervous
symptoms (Figure 1). These sarcomas were generated
swelling in three cases, as they increased. One of the
patients with advanced malignancy showed lameness at
admission.
Routine laboratory examinations in tumoral pathology
showed an increase of al kaline phosphatase (N: 40–
136 U/L) and erythrocyte sedimentation rate – ESR (N:
5–10 mm/h). Other laboratory results and tumor markers like TNF- β, CA 125 and CA 19-9 were within normal
ranges, excluding other malignant pathology or bone
metastases.
For X-ray analysis, we used plain-film radiographs to
cover the entire affected limb. Typical image of osteolysis
was represented in some of the patients alternating with
areas of osteosclerosis and in cases where the tumor was
revealed as cortical exceeded there was revealed the formation of a soft tissue mass (Figure 2). In one case, a
pathologic fracture was also identified.
MRI was useful to identify local extension of the
tumor and the invasion in the surrounding soft parts.
This way it was detected the relationship of the tumor to
the neurovascular bundle, and resectability could be estimated. There was no neurovascular encasement. This
investigation established accurately the limit of osteotomy
3 cm away from the tumor in order to have tumoral-free resection edges.
CT is complementary to MRI; it is useful in assessing
extraosseous and intraosseous extension and in cases of necrosis and edema around the tumors, it was superior
to MRI (Figures 3 and 4). It was also useful evaluating
the response to preoperative chemotherapy and looking for pulmonary metastases.

Figure 1 – Clinical
deformity. Figure 2 – Cortical
exceed. Figure 3 – Peri-tumoral
edema. Figure 4 – Extraosseous
extension.

Whole body bone scintigraphy was performed in
order to detect bone metastases and skip metastases. All
of the affected regions have shown hypercaptation in
metabolic phase, without secondary determinations of the tumor in other anatomical regions (Figure 5). The angiographic exam show ed an increase vascula-
rization of the tumor tissue, in one case being necessary
a preoperative embolization.
Regarding the Enneking system international classi-
fication, in five cases the tumor was stage IIA (high-grade,

Proximal tibial osteosarcoma in young patients: early diagnosis, modular reconstruction
415
intracompartmental, non-metastatic) and in two cases,
it was stage IIB (high-grade, extra-compartmental, non-
metastatic). In all cases, incisional biopsy was the key step in the
diagnosis, the collected tissue being sent for histopatholo-
gical examination and immunohistochemistry (Figures 6–8).

Figure 5 – Bone scintigraphy w ith Tc-99m showing
hypercaptation in metabolic phase of the right distal
femur. Figure 6 – Osteoid osteosarcoma, vascular gaps, pleo-
morphic atypical cells. HE staining, ×100.

Figure 7 – Image detail of osteosarcoma, atypical
mitosis, atypical cells. HE staining, ×400. Figure 8 – High-grade malignant osteosarcoma, with
atypical mitosis, atypical polymorphic hyperchrome cells. HE staining, ×400.

Chemotherapy is very important in the treatment of
osteosarcoma. It showed a substantial increase in survival
after chemotherapy and also a decrease in the rate of
relapse and the risk of metastasis.
In only half of the cases, we performed preoperative
chemotherapy and in all of cases, postoperative chemo-
therapy. In patients in whom preoperative chemotherapy
was performed, after the remove of the tumor, we
worked the tumoral necrosis index, which had values between 70–90%, which means a very good response to
chemotherapy. The percentage of tumor cell necrosis (cell
death) seen in the tumor after surgery gave us an idea of
the prognosis and also let th e oncologist know if the
chemotherapy regime should be altered after surgery.
All the patients were treated with limb sparing surgery
and reconstruction of a viable, functional extremity. In
the seven patients included in the study, we used two
types of prostheses with different design but on the same principles (Figures 9–12). We performed a radical
resection of proximal tibia with control, for margin
clearance and reconstruction of the knee joint and upper tibia with modular titanium total knee hinge prostheses
and also medial gastrocnemius muscle rotation flap to
cover the prostheses and to protect the patellar tendon
fixed to the tibial system.
After chemotherapy has been completed postopera-
tively, the orthopedic surgeon and oncologist followed the patients closely every three months for local and
systemic recurrence.
Postoperative patients were mobilized for a week
without charging the operated limb under the protection
of orthosis. Two weeks after surgery, patients begin to
walk with progressive loading on the operated limb without doing any flexion in order to protect the muscle
flap that covers and protects the patellar tendon. Three
weeks postoperatively the patients begin active and passive mobilization of the knee without registering any rupture
or disinsertion of extensor apparatus in any patient. They
had good joint stability, with good to excellent function in all cases (Figure 13, a and b). Tumoral endoprostheses
were associated with only minimal early postoperative
complications.

Răzvan Ene et al.
416

Figure 9 – Muscle flap
preparation. Figure 10 – Tendon
attachment. Figure 11 – Modular
prosthesis. Figure 12 – Patellar tendon
reattachment.

Figure 13 – (a and b) Post-operative X-ray aspects:
two different types of prosth esis, antero-posterior and
lateral incidence; knee pros thesis after limb-sparing
surgery.
So far, there are no signs of local recurrence. Three
years after surgery one patient developed a septic com-plication of the prosthesis. After an attempt of rehabi-
litation trying to keep the prosthesis, we decided to remove
the prosthesis and replace it with an acrylic cement spacer
impregnated with antibiotics until getting local sanitation.
Patients showed a decrease in levels of physical
activity without affecting postoperative limb function
operated. Social and family reintegration was fast in all
cases, two of the patients was planned to change their work with a physically less demanding one.
 Discussion
The etiology of osteosarcoma is still unclear; several
theories have been described, which may lead to malignant
proliferation of bone cells. Fuchs and Pritchard underline
the presence of chemical agents like beryllium, viruses,
irradiation as potential factors in the etiology of osteo-sarcoma [6]. Recent studies show that hereditary diseases,
like retinoblastoma, Rothmund–Thomson syndrome,
Bloom syndrome, Li–Fraumen i syndrome increase the
risk of developing osteosarcoma [7]. In our study, none
of the aforementioned diseases were present. Viral
infection may be an important etiological factor of osteosarcoma due to the in tracellular growth, and DNA modification. The key investigation in our cases for
the diagnosis is the histological examination; however,
immunohistochemistry plays an important but limited role in primary bone tumors. Pringle, in a recent study,
showed that immunohistochemistry may be more confusing
than helpful; he also underlines the fact that the results should be carefully assesse d taking into account the
clinical and radiological features and the morphological
aspects of HE sections [8].
The development of imagistic examination, like 3D
CT, MRI, PET, whole body scintigraphy, and a good
interdisciplinary cooperation between different specialties improved the prognostics of osteosarcoma. However,
osteosarcoma is often diagnosed in late stages with
metastases, which worsens the prognosis in which only palliative treatment can be applied [9–12]. Recent studies
have proved that metastases can appear, with similar
mechanism to prostatic cancer metastases, via Batson
venous plexus. Hatori et al. , in a recent study, demons-
trated lymphatic spread to the lungs as possible routes for metastases [13]. None of our cases had metastases in
the time of investigations, and surgical treatment.
Thirty years ago, amputatio n was the sole treatment
for a high-grade osteosarcoma, and more than half of
patients died of metastatic disease, especially to the lungs
[14]. Due to the current attitude, the use of chemotherapy as a (neoadjuvant/preoperative) and adjuvant (postope-
rative) protocol have improved the ability to perform safe
limb-sparing resections seeing a significant increase in survival [15–18]. Today, over 90% of patients with osteo-
sarcoma can be treated with limb-sparing surgery, and
70% of patients with locali zed disease are long-term
survivors but this situation has accentuated the need for
durable methods of reconstruction of large musculoskeletal
defects [19].
Our study underlines the importance of early and
correct diagnosis. Surgical treatment with modular pros-
thesis reconstruction of ostesarcoma, allows limb salvage
and do not affect the quality of life. The surgical and
chemotherapeutic combination in therapy has proven its efficacy [20, 21].
 Conclusions
Due to the early diagnosis of osteosarcoma and the
absence of metastases surgical removal and so-called
limb-sparing treatment could be applied in every case

Proximal tibial osteosarcoma in young patients: early diagnosis, modular reconstruction
417
with modular prosthetic reconstruction. Surgical treatment
and adjuvant chemotherapy makes this pathology to
have a good prognostic index, without worsening the quality of life. We conclude that the function of the
operated limb never achieves the same functional level
as the opposite normal extremity, however the quality of life does not change significantly, allowing to the patient
daily normal activities. It must be emphasized that the
main goal of generally treatment of osteosarcoma is to provide a longer relapse-free survival and only the second
goal is to preserve the limb function.
Conflict of interests
The authors declare that they have no conflict of
interests.
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Corresponding author
Răzvan Ene, MD, PhD, Department of Orthopedics and Traumatology, Emergency University Hospital, 169
Independen ței Avenue, 050098 Bucharest, Romania; Phon e +40740–082 338, e-mail: razvan77ene@yahoo.com

Received: October 21, 2014
Accepted: February 13, 2015