Malignant intraosseous peripheral nerve sheath tumour of the proximal femur: a case report.

Abstract

We report a rare case of an intraosseous malignant peripheral nerve sheath tumour of the femoral head and neck. The tumour presented as a well-defined radiolucent lesion on plain radiography. Computed tomography showed aggressive destruction of the bone with no involvement of the adjacent soft tissues. Magnetic resonance imaging revealed an isointense signal intensity on T1-weighted images, hyperintensity on T2-weighted images, and non-homogeneously increased signal intensity after administration of contrast media. The final diagnosis was based on pathohistologic analyses due to the non-specific nature of the lesion.

Full text

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Malignant intraosseous peripheral nerve
sheath tumour of the proximal femur:
a case report
A Lesic, M Bumbasirevic
Institute for Orthopaedic Surgery and Traumatology, Clinical Centre of Serbia, Belgrade, Serbia and Montenegro
HDE Atkinson
Department of Orthopaedic Surgery and Traumatology, Imperial College Medical School, Hammersmith Hospital, London,
United Kingdom
R Maksimovic, J Sopta
Institute for Radiology, Clinical Centre of Serbia, Belgrade, Serbia and Montenegro
M Atanackovic
Institute of Pathology, School of Medicine, University of Belgrade, Belgrade, Serbia and Montenegro
INTRODUCTION
Neurilemmomata are relatively rare benign tumours
that originate in the Schwann cells of neurilemmal
sheaths and comprise around 0.2% of all bone
tumours.1–3 T heir rarer malignant form—
the malignant peripheral nerve sheath tumour
(MPNST)—is usually associated with neuro-
fibromatosis.4–6 The intraosseous localisation of
MPNST is very rare in the literature: Dahlin and
Krishanan1 reported 10 cases, Wirth and Bray7 31
cases, Bullock at al.8 18 cases, and de la Monte et al.9
presented 60 histologically documented cases. To the
best of our knowledge, only one case of an intraosseal
neurilemmoma of the proximal femur has been
published.4 The present case is also the first
case involving both the proximal femur and the
femoral head in a patient with no concomitant
neurofibromatosis.
Address correspondence and reprint requests to: Dr Henry DE Atkinson, 9 Sutcliffe Close, London NW11 6NT, United Kingdom.
E-mail: duscha@hotmail.com
ABSTRACT
We report a rare case of an intraosseous malignant
peripheral nerve sheath tumour of the femoral head
and neck. The tumour presented as a well-defined
radiolucent lesion on plain radiography. Computed
tomography showed aggressive destruction of the
bone with no involvement of the adjacent soft tissues.
Magnetic resonance imaging revealed an isointense
signal intensity on T1-weighted images, hyperintensity
on T2-weighted images, and non-homogeneously
increased signal intensity after administration of
contrast media. The final diagnosis was based on
pathohistologic analyses due to the non-specific
nature of the lesion.
Key words: bone neoplasms; magnetic resonance imaging;
neurilemmoma; tomography, X-ray computed
Journal of Orthopaedic Surgery 2006;14(1):84-9

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Vol. 14 No. 1, April 2006 Malignant intraosseous peripheral nerve sheath tumour of the proximal femur85
CASE REPORT
In August 2000, a 48-year-old woman presented to
the Clinical Centre of Serbia in Serbia and Montenegro
with an 18-month history of increasing right groin
pain and an antalgic gait. The patient was in good
health, without any signs of systemic disease including
neurofibromatosis. Plain pelvic and hip radiographs
taken upon admission showed an osteolytic lesion
involving almost two-thirds of the right femoral
neck, with partially sclerotic borders. The lesion
extended proximally into the femoral head and distally
to the intertrochanteric line (Fig. 1). Computed
tomography (CT) confirmed a considerable zone of
destruction of the femoral neck and the anterolateral
portion of the head (Fig. 2). Magnetic resonance
imaging (MRI) revealed a clearly delineated tumour
that was hypointense on T1-weighted images,
hyperintense on T2-weighted images, and showed a
heterogeneous enhancement after administration of
contrast media (Fig. 3). There was no extraosseal
spread of the tumour mass; the other pelvic bones had
a normal signal intensity and local lymph nodes were
not enlarged. Whole-body bone scintigraphy with a
740 MBg dose of Technetium 99 dihydropyrimidine
dehydrogenase showed marked accumulation of the
radionuclide in the head of the right femur (Fig. 4).
A biopsy was taken through a drill hole for
pathohistological analyses. On hematoxylin and eosin
staining, the tumour had a nodular appearance typical
to MPNST. Two types of tissue were found: Antoni
type A –like (fascicular) areas with spindle cells
Figure 1
osteolytic lesion with a cortical breach in the superior aspect
of the femoral head and neck.
Anteroposterior radiograph of the hip showing anFigure 2
lesion in the anterolateral aspect of the right femoral head
with destruction of the cortex (arrow).
A computed tomographic scan showing a lytic
(a)(b)(c)
Figure 3
signal intensity to the surrounding muscles on axial T1-weighted image. Perforation of the cortex is also evident. (b) The mass
has a hyperintense signal on axial T2-weighted image. (c) Coronal T1-weighted image after Gd-DTPA administration shows
heterogeneous enhancement of the area affected by the tumour and a loss of cortical definition in the superolateral aspect of the
femoral head.
Magnetic resonance imaging showing (a) a mass in the anterolateral portion of the right femoral head with similar

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86A Lesic et al.Journal of Orthopaedic Surgery
arranged with palisading ovoid basophilic nuclei and
an acidophilic cytoplasm, and Antoni type B–like
(reticular) areas with myxoid changes. Verocay
bodies consisting of acellular eosinophilic processes
were arranged in a band-like pattern (Fig. 5).
Hypercellularity, slight anisocytosis, and nuclear
atypia were also noted. A low mitotic index was
observed (1–2 mitoses/ 10 high-power field), with
a few fields of haemorrhage and necrosis. The tumour
tissue was stained for reticular fibres and a diagnosis
of fibrosarcoma was excluded. Immunohistochemistry
found the 2 cellular areas strongly positive for
S-100 protein and vimentin (Fig. 6). There was a
focal positivity for CD68, and cytokeratin was negative.
The stains were positive for neurofilaments and glial
fibrillary acidic protein. Tests for HMB-45 were
negative. The levels of necrosis, nuclear atypia, and
elevated mitotic rate within the lesion led to a diagnosis
of a low-grade MPNST.
The patient underwent a radical tumour resection
and a cemented bipolar hip hemiarthroplasty (Fig. 7).
Pathohistological examination of the resected
specimen showed no extraosseous extension, with
clear surgical margins. At 4-year follow-up, the patient
remained in good health with no evidence of tumour
recurrence.
DISCUSSION
The incidence of MPNST is low.1–3 The most frequently
affected bones are the jaw (nearly 50% of the cases,
probably because of the presence of neural tissue in
mandible),1,8 the skull, and the bones of the upper
limb (humerus, ulna, metacarpal, and phalangeal
bones). Involvement of the lower extremity is
extremely rare,1 with few reports of MPNST in the
distal femur1 and only one in the proximal femur
(trochanteric region).4
Neurilemmomata can affect bone by 3 different
mechanisms: the tumour tissue can be localised
extraosseously, eroding into the bone secondarily; it
can develop within a nutrient canal primarily
involving the bone secondarily; or it can primarily
arise within the central medullary canal.10
Figure 5
nodular appearance of a tumour with Verocay bodies (H&E,
x400).
Photomicrograph of the tumour showing a typical
Figure 4
accumulation of the radionuclide in the right proximal femur.
Scintigraphy of the pelvic region showing an
Figure 6
histochemically stained with S-100 showing marked positivity,
tumour hypercellularity, and anisonucleosis.
Photomicrograph of the tumour immuno-

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Vol. 14 No. 1, April 2006Malignant intraosseous peripheral nerve sheath tumour of the proximal femur87
Figure 7
excision of the tumour and implantation of a cemented bipolar
hip hemiarthroplasty.
Anteroposterior radiograph of the hip following
Two different cell patterns can usually be
recognised on microscopy: an Antoni type A–like
pattern, with spindle cells in a palisade formation,
surrounded by an interstitial substance that forms
Verocay bodies; and an Antoni type B–like pattern,
with irregular cells and a myxoid component.3,10–13
A lthough A ntoni type A and B arrangements are
commonly described in benign schwannoma,14 the
long duration and slow growth of low-grade MPNSTs
can lead to similar histological characteristics. The
presence of Verocay bodies is pathognomonic of
neurilemomma.15 Immunohistochemically the
tumour cells show immunoreactivity to the S-100
protein and vimentin, with focal positivity to CD68
and negativity to keratin.11,12,16
Intraosseous neurilemmomata are well-
encapsulated tumours usually less than 5 cm in
diameter. Tumours larger than 5 cm are known as giant
schwannomas and may confer a risk of malignancy.
MPNSTs tend to occur in middle age, with a possible
higher prevalence in women.9 Patients are often
diagnosed late, with prediagnostic periods of up to
6 years.10,17 The presentation of our 48-year-old female
patient was thus not unusual.
MPNST is associated with neurofibromatosis in 2%
to 29% of cases,4,5 although this association is usually
with the soft-tissue MPNST6 and not commonly
with intraosseous MPNST.4 Our patient had no clinical
signs of neurofibromatosis.
Radiologically, MPNST is a well-delineated
tumour and presents as a lytic lesion with sharp
sclerotic or partially sclerotic margins, and occasionally
disruption of the osseous cortex.10,18,19 Perforation of
the thinned cortex with periosteal new bone
formation and soft-tissue involvement should not be
taken as sure evidence of malignancy.10,16 The tumour
can be multilocular without central calcification or
ossification.9 On CT, MPNSTs present as hypodense,
non-homogenous masses due to areas of degeneration
and areas of varying cellular density.20 MPNSTs have
a signal isointense with muscle on T1-weighted MRI
images, while the signal is more intense than the
subcutaneous cellular tissue on T2-weighted images.
Heterogeneous signal intensities have also been
reported on T2-weighted images indicating
pericellular and myxoid areas.21 Hypercellular nodules
can be recognised by a strong contrast enhancement
compared with the faint enhancement of the loose and
less cellular areas. Multinodular enhancement patterns
are rarely seen in bone tumours and can also be helpful
in the diagnosis of intraosseous MPNSTs.
Differential diagnoses for MPNST are: synovial
sarcoma, cellular schwannoma, metastatic malignant
melanoma, desmoplastic fibroma, fibrous dysplasia,
malignant fibrous histiocytoma, non-ossifying
fibroma, and well-differentiated fibrosarcoma.2,22
T he definitiv e diagnosis of MPN ST is
pathohistological. We prefer obtaining specimen for
analysis by open biopsy, although needle biopsy is
sufficient with a high sensitivity.23 We are aware of
the higher complication rates in open biopsy. Open/
surgical biopsy allows us to exclude the possibility of
false negative findings and to take sufficient tumour
tissue for both standard and specialist histological
analyses.
Through immunohistochemical staining, the
tumour in this case was found to be strongly positive
for S-100 protein, indicating a tumour of neural
differentiation. A lthough S-100 protein can be
positive in 10% to 20% of fibrosarcomas, the additional
presence of neurofilaments and glial fibrillary acidic
protein excluded such a diagnosis.24 Negativity
for cytokeratin with an additional absence of a
coexpression of vimentin and cytokeratin excluded
synovial sarcoma.25
Although CD68 is a marker of histiocytes and is
more typical of malignant fibrous histiocytoma, a focal
positivity for CD68 has been described in MPNST.12,16
Nonetheless, the absence of a storiform arrangement
of spindle cells on histology excluded malignant
fibrous histiocytoma.26 H MB-45, a marker for
melanotic pigment, was also negative, thus excluding
malignant melanoma.27 Fibrous dysplasia and non-

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88A Lesic et al. Journal of Orthopaedic Surgery
ossifying fibroma were excluded by their very
different histological appearances from MPNST.
Our patient had a low-grade malignant form of
neurilemmoma. The diagnosis was based on the main
histological criteria for malignancy: tumour larger
than 5 cm, high cellularity, presence of mitosis, necrotic
fields, and haemorrhage zones.7,11,12 Mitotic index is
the most important criterion for tumour grading
(1-2 mitosis/ 10 high-power field point).
The recommended treatment for benign neuri-
lemmomata is phenolisation and bone grafting,10,11,28,29
but in a low-grade MPNST such as in our case, with
large amounts of bony destruction near the joint, the
optimal treatment is wide resection and implantation
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ACKNOWLEDGEMENTS
The authors wish to thank Prof Gernot Jundt from
K nochentumor Referenzzentrum, Institute of
Pathology, University of Basel in Switzerland and Prof
Erwin W Morscher from the L aboratory of
Orthopaedic Biomechanics in Basel, Switzerland for
reviewing the manuscript and providing useful
suggestions.

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