Full text of DOI:10.1080/13577140020008093

Sarcoma (2000) , 125±128
4
CASE REPORT
Cerebral metastases from malignant ®brous histiocytoma of bone
SUSANNE J. ROGERS & JEREMY S.WHELAN
London Bone and Soft Tissue Tumour Service, Middlesex Hospital, London, UK
Abstract
Four patients with malignant ®brous histiocytoma of bone (MFH-B) metastasizing to brain are reported. In two cases, signs
of cerebral involvement developed between 4 and 28 months after diagnosis. Both patients had known pulmonary or bony
metastases. As a consequence of this experience, two further patients were subsequently identi®ed, one with a de®nite
cerebral metastasis and one who had an asymptomatic supratentorial lesion, possibly metastatic. It is suggested that patients
with MFH-B and widespread metastatic disease at presentation or developing within a short interval should undergo
cerebral imaging.
Key words: malignant ®brous histiocytoma of bone, brain, cerebral, metastases
chemotherapy were administered, with endopros-
thetic replacement of the proximal humerus after the
second. Radiotherapy (60 Gy in 30 fractions)
completed the treatment. The patient remained well
for 11 months before developing pain in the right leg.
An isotope bone scan was consistent with metastases
in the ®bula and also in the 9th rib. Local radiotherapy
was given but further metastases were evident on a
bone scan 2 months later, and renal and adrenal
tumour deposits were seen on abdominal CT.
Three months later, she became agitated and
disorientated and demonstrated inappropriate
behaviour. Contrast-enhanced CT showed multiple
enhancing lesions in both cerebral hemispheres.
Further palliative radiotherapy was given, but the
patient died 8 weeks later, 30 months after diagnosis.
Introduction
Malignant ®brous histiocytoma arising in bone
(MFH-B) is an uncommon but well de®ned primary
spindle cell tumour, predominantly affecting adults.1
The tendency to affect long bones and metastasize to
the lung encourages comparison with osteosarcoma
(OS). Similarly, neoadjuvant chemotherapy with the
agents active in OS appears to improve survival in
MFH-B.2,3 In this report we describe a previously
unreported metastatic site of MFH-B and discuss
the implications for the clinical management of this
disease.
Case histories
Patient 1
A 48-year-old female presented with a 5-month
history of pain in the left arm. Plain radiographs
revealed a predominantly lytic lesion and a
pathological fracture of the metaphysis of the proximal
humerus.No other abnormalities were demonstrated
on staging scans which included isotope bone scan,
computed tomography (CT) of the thorax, mammog-
raphy and abdominal ultrasound.Core needle biopsy
diagnosed a tumour with bundles of spindle-shaped
®broblastic cells in a storiform pattern with a high
mitotic rate, consistent with MFH-B. Neoadjuvant
chemotherapy with doxorubicin and cisplatin was
Patient 2
A 45-year-old male presented with a pathological
fracture of the left distal femur, sustained whilst
exercising. Lytic areas in the cortex, with subperio-
steal new bone formation, were seen adjacent to the
fracture site on plain radiography. Magnetic resonance
imaging (MRI) revealed a large lesion in the distal
metaphysis and core needle biopsy was diagnostic of
MFH-B. Isotope bone scan showed this to be unifocal
bone disease. However, bilateral pulmonary metas-
tases were evident on CT thorax. Prior to surgery, he
received two cycles of ifosfamide (9 g/m2). He failed
to attend for post-operative chemotherapy but
presented 1 month later with three
3
commenced. The ®rst cycle was complicated by
febrile neutropenia and acute renal failure, so carbo-
platin was substituted for cisplatin. Six cycles of
Correspondence to: J. Whelan, London Bone and Soft Tissue Tumour Service, Meyerstein Institute of Oncology, Middlesex Hospital,
Mortimer Street, London W1N 8AA, UK.Tel: +44 (0) 171380 9092; Fax: +44 (0) 171 436 0160; E-mail: jeremy.whelan@uclh.org
½
1357-714Xprint/1369-1643online/00/030125-04 2000Taylor & Francis Ltd
DOI: 10.1080/13577140020008093

126
S. J. Rogers & J. S.Whelan
grand mal seizures. CT of the head showed multiple
metastases with considerable oedema (Fig. 1A,B).
The ®ts were controlled pharmacologically and pallia-
tive whole-brain radiotherapy was given (30 Gy in 10
fractions). He died 7 months after diagnosis.
Patient 3
A 54-year-old female described an 18-month history
of pain around the right knee, exacerbated by weight
bearing. CT showed a lesion near the medial condyle
of the right femur and histological review of the bone
biopsy con®rmed MFH-B. Staging CT of the chest
and isotope bone scan were negative for metastases.
Two cycles of chemotherapy were given
pre-operatively (methotrexate 4 g/m2 day 1, ifosfa-
mide 3 g/m2 and doxorubicin 60 mg/m2 day 10) and
2 further cycles were administered after endopros-
thetic replacement.
Ten years later, metastases were detected in the left
lung on routine chest X-ray and, at thoracotomy,
four nodules consistent with MFH-B were resected.
She received six cycles of chemotherapy with ifosfa-
mide, doxorubicin and dacarbazine post-operatively.
However, a 6 cm skin recurrence overlying the
prosthesis was detected 1 year later.This was excised
and followed by local radiotherapy (60 Gy in 30 frac-
tions). A CT of the thorax 4 months later revealed
progressive disease in the right lung with possible
new metastases in the left lung.
In view of the protracted disease course and
multiple recurrences, before proceeding to further
chemotherapy or surgery, further assessment included
a CT scan of the brain. This detected a large
asymptomatic supratentorial lesion, of which the
differential diagnosis was a meningioma or a
metastasis. Biopsy was considered but rejected as
unjusti®ably dangerous in the presence of no
symptoms and disease elsewhere. An MRI scan was
performed 3 months later which showed no change
in the cerebral lesion (Fig. 2). The patient remains
asymptomatic and thoracotomy has been recom-
mended.
Patient 4
A 40-year-old man had experienced pain in the right
¯ ank for 6 years. The severity had increased in the
Fig.1A,B. CT head scan of patient 2, showing multiple cerebral
metastases.
Fig. 2. MRI head scan of patient 3, showing supratentorial
mass.

Cerebral metastases
127
preceding 6 months, presumed secondary to a groin
strain, but had failed to respond to rest and analgesia.
A plain X-ray of the pelvis showed a large osteolytic
lesion destroying the right acetabulum and ischial
spine with a large associated soft-tissue mass. MRI of
the pelvis con®rmed these ®ndings and bone biopsy
revealed MFH-B. Staging CT thorax and abdomen
showed multiple bilateral lung metastases, para-
aortic lymphadenopathy and a left adrenal metastasis.
With consideration given to experience of patients
1±3, a CT head scan was performed and was normal.
Palliative chemotherapy was initiated with doxoru-
bicin and cisplatin.3 Symptomatic improvement
following chemotherapy lasted only days and, after
the third cycle, palliative radiotherapy (8 Gy in a
single fraction) was given to the right hemipelvis. He
then noticed frequent twitching around the left corner
of the mouth consistent with focal ®ts. A left upper
motor neurone VIIth nerve palsy rapidly developed
and he started to vomit. CT head showed a right
frontal lesion with associated oedema (Fig. 3). Steroids
and anti-convulsants were commenced with resolu-
tion of the symptoms. In view of his poor response to
chemotherapy and deteriorating condition, he was
transferred to a hospice for palliative care and died 3
weeks later, 4 months after diagnosis.
Patient details are summarized in Table 1.
Discussion
MFH-B represents approximately 5% of primary
bone tumours and occurs predominantly in the long
bones of patients aged 10±60 years, with a predilec-
tion for the distal femur and proximal tibia in 50%.1
Twenty per cent of MFH-B arises in abnormal bone,
e.g. bone infarcts, Paget’s disease and enchon-
droma,4 or after radiotherapy.5 MFH-B is differenti-
ated histologically from osteosarcoma by characteristic
features which include spindle-shaped ®broblastic
cells in a storiform pattern and an absence of osteoid
formation.
Fig. 3. CT head scan of patient 4, showing cerebral metastasis.

128
S. J. Rogers & J. S.Whelan
Historically, treatment with surgery or radiotherapy
alone resulted in disease recurrencein 70% of patients
within 5 years.6 The two main sites of early metas-
tases are lung and bone.A series of 76 cases reported
the development of metastases in 52 patients. Forty-
four had pulmonary involvement, 6 had bony spread
and 1 had positive lymph nodes.6 Renal, hepatic,
adrenal, cardiac, peritoneal, cutaneous and pleural
interval is short. It remains to be seen whether early
detection of cerebral metastases from MFH-B
improves survival.
Acknowledgements
We would like to thank Mr J. Cobb for granting us
permissionto report patient 1, and Mr S. Cannon for
patients 2, 3 and 4.
4,7
lesions have also been described. The brain is
recognized as an unusual site of metastasis in patients
with osteosarcoma (1.5% incidence at autopsy).8
Craniotomy is a treatment option, although the
diagnosis of cerebral metastases is often a terminal
event. There is a single case report of 8-year disease-
free survival in a child treated with chemotherapy
alone for bilateral cerebral metastases from an oste-
osarcoma.9 Retrospective analysis of 254 cases of
osteosarcoma yielded 13 who had disease recurrence
(median 3 months after diagnosis) and subsequently
developed cerebral metastases (median 10 months
after relapse).9 The patients mostly had pulmonary
or bony involvement at presentation and particularly
aggressive disease behaviour. It has been suggested
that patients with osteosarcoma with metastatic
disease at or within 12 months of diagnosis should
have CT or MRI of the brain.9
References
1 Mirra JM. Bone tumours. Philadelphia: Lea & Felbiger,
1989;771±80.
2 Earl H, Pringle J, Kemp H, Morittu L, Miles D,
Souhami R. Chemotherapy of malignant ®brous histio-
cytoma of bone. Ann Oncol 1993;4:409±15.
3 Bramwell V, Steward W, Nooij M, Whelan J, Craft A,
Grimer R et al. Neoadjuvant chemotherapy with doxo-
rubicin and cisplatin in malignant ®brous histiocytoma
of bone: a European Osteosarcoma Intergroup Study. J
Clin Oncol 1999;17:3260±9.
4 Spanier S. Malignant ®brous histiocytoma of bone.
Orthop Clin N Am 1997;8:947±61.
5 Dahlin D, Unni K, MatsunoT. Malignant ®brous histio-
cytoma of
1977;39:1508±16.
6 Capanna R, Bertoni F, Bacchini P, Bacci G, Guerra A,
Campanacci M. Malignant ®brous histiocytoma of
bone: the experience at the Rizzoli Institute: report of
90 cases. Cancer 1984;54:177±87.
boneÐfact or fancy? Cancer
We have now reported cerebral metastases in
MFH-B. Imaging of the brain is required for all
patients with symptoms or signs suggesting cerebral
involvement.The similarities in the disease behaviour
between osteosarcoma and MFH-B lead us to recom-
mend that brain imaging should be considered in
patients with widespread pulmonary and/or bone
metastases at relapse, particularly if the disease-free
7 Spanier S, EnnekingW, Enriquez P. Primary malignant
®brous histiocytoma of bone. Cancer 1975;36:2084±98.
8 Danziger J, Wallace S, Handel S, Alonso de Santos L.
Metastatic osteogenic sarcoma to the brain. Cancer
1979;79:707±10.
9 Marina N, Pratt C, Shema S, Brooks T, Rao B, Meyer
W. Brain metastases in osteosarcoma. Report of a long
term survivor and review of the St Jude’s Children’s
Hospital experience. Cancer 1993;71:3656±60.

Copyright of Sarcoma is the property of Hindawi Publishing Corporation and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.