Accepted Manuscript
Primary intracranial leiomyosarcoma with intra-tumoral hemorrhage: Case report and
review of literature
Koichi Torihashi, Chin Masaki, Kazumichi Yoshida, Osamu Narumi, Sen Yamagata
PII:

S1878-8750(18)30949-5

DOI:

10.1016/j.wneu.2018.05.004

Reference:

WNEU 8065

To appear in:

World Neurosurgery

Received Date: 19 March 2018
Revised Date:

1 May 2018

Accepted Date: 2 May 2018

Please cite this article as: Torihashi K, Masaki C, Yoshida K, Narumi O, Yamagata S, Primary
intracranial leiomyosarcoma with intra-tumoral hemorrhage: Case report and review of literature, World
Neurosurgery (2018), doi: 10.1016/j.wneu.2018.05.004.
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Torihashi

ACCEPTED MANUSCRIPT
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Abstract

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prim ary i ntracrani al l ei om yos arcom a wit h int ra-t umoral hemorrhage.
Case Description
A 41- yr ol d fem al e pres ent ed with ri ght hemi paresis and gait di sturbance.
And she has the brain tumor on frontal lobe. And the tumor was

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i n c r e a s i n g r a p i d l y. I n t r a - t u m o r a l h e m o r r h a g e w a s s u d d e n l y o c c u r r e d . We
removed the tumor after hemorrhage. After operation, postoperative
chemotherapy and radiotherapy were not performed, but recurrence did
n o t o c c u r.
Conclusions

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Background
P ri mar y i nt racranial l ei om yos arcom a is a very rare occurrence. And
prim ary l ei om yos arcom a wit h i nt ra-tumoral hemorrhage has not been
p u b l i s h e d . We f i r s t l y p r e s e n t a c a s e r e p o r t o f a r a p i d l y e n l a r g i n g

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intra-tumoral hemorrhage.

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To t h e b e s t o u r k n o w l e d g e , t h i s p r e s e n t s t h e f i r s t r e p o r t o f p r i m a r y
i n t r a c r a n i a l l e i o m y o s a r c o m a w i t h i n t r a - t u m o r a l h e m o r r h a g e . We f i r s t l y
describe the clinical and radiological findings and the histological
ex amination of t his prim ary i ntracrani al l ei om yos arcom a wi th

Background

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Int racrani al neopl as ms of m es enchym al ori gi n are ex cept ionall y rare.
The majority of these tumors are metastatic lesions that originated from

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the
gastrointestinal
tract
or
female
reproductive
s ys t em1 2
Lei om yos arcom a i s an aggressi ve cancer that exhi bit s sm ooth m us cle
di fferenti at ion. Although prim ary i nt racrani al l eiom yos arcom a is ver y
rare, these tumors are seen in both adult and pediatric patients 3 4 5 6.
They often present as a mass lesion in the dura, but occasionally involve
t he parench ym a of the cent ral nervous s ys t em (C NS ). Res ect ion i s t he
most effective treatment for leiomyosarcoma. A high rate of local

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recurrence of these cancers is seen despite gross total resection.
We d e s c r i b e a p a t i e n t w h o u n d e r w e n t g r o s s t o t a l r e s e c t i o n w i t h o u t
postoperative radiotherapy and chemotherapy and in whom recurrence
d i d n o t o c c u r. We d e s c r i b e t h e c o u r s e o f t h i s p a t i e n t w i t h i n t r a - t u m o r a l
hemorrhage of a pri mar y i nt racrani al lei om yos arcom a.

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Case Report

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A 41- year-ol d fem al e pres ent ed wi th ri ght hemi pares is and gait
disturbance.
Magnetic resonance imaging (MRI) on admission showed a lobulated
cortical and subcortical lesion in the left frontal region. Most of the

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t h e m a s s . N i n e d a y s l a t e r, s h e n o t e d t h a t t h e h e m i p a r e s i s h a d a p p e a r e d .
At that time, mass effect and edema had developed as observed with MRI
(Fig. 1). She experienced a sudden onset of consciousness disturbance
and aphasia. She developed multiple seizure. Significant intra-tumoral
hemorrhage with ventricular hemorrhage and uncal herniation was

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mass was isointense compared with gray matter on T1-weighted images
and sli ghtl y h yp erint ense on T2-wei ght ed i mages wi th mi nim al
associated vasogenic edema. Gadolinium-enhanced MRI was performed
6 days l at er and showed homogeneous enhancem ent and rapid growth of

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observed with computed tomography (CT) (Fig. 2). She underwent
e m e r g e n c y s u r g e r y t h a t i n v o l v e d a l e f t f r o n t o - p a r i e t a l c r a n i o t o m y. T h e
presum pti ve di agnos is was m ali gnant l ym phom a. Foll owing t he
f r o n t o - p a r i e t a l c r a n i o t o m y, a r e d d i s h w e l l - d e m a r c a t e d f i b r o u s t u m o r w a s
identified that showed acute hemorrhage. The frontal hematoma was
e v a c u a t e d . Wi t h d i s s e c t i o n o f t h e a p p a r e n t c a p s u l e f r o m s u r r o u n d i n g
tissues, gross total removal of the tumor was accomplished (Fig. 3). The
size of the round tumor that was removed was 4 × 4 × 5 cm. After the

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r e m o v a l o f t h e t u m o r, t h e e d e m a a n d m a s s e f f e c t o f t h e b r a i n i s w o r s e n e d .
And we thought the bone flap should not be replaced after the removal of

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t h e t u m o r.
Hem at ox yl i n and eosi n st aini ng of s ecti ons of the t um or demonst rat ed
interlacing fascicles of pleomorphic spindle cells with a moderate
am ount of eosi nophi li c c yt opl asm.
M oderat e at ypi a and occasi onal mitoti c fi gures were i dent i fi ed, and
necrosis was absent. Immunoperoxidase staining showed that the tumor
was positive for α-smooth muscle actin, but not glial fibrillary acidic

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prot ei n or S -100 protein (Fi g. 4). The di agnosi s of a l ei om yos arcoma
was
made,
and
the
histological
diagnosis
was
intracranial
l e i o m y o s a r c o m a . A n i n t e n s i v e s e a r c h f o r a n e x t r a c r a n i a l p r i m a r y t u m o r,
which included plain radiographs of the abdomen and chest,
u l t r a s o n o g r a p h y, C T, M R I , w h o l e - b o d y p o s i t r o n e m i s s i o n t o m o g r a p h y,
and clinical follow-up, proved negative. The final diagnosis of a primary
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intracranial leiomyosarcoma was then established.
After the operation, she became totally bedridden. Although we
e x p l a i n e d h e r f a m i l y a b o u t t h e c h e m o t h e r a p y a n d r a d i o t h e r a p y, h e r
family refused those treatments. And we didn’t treat the radiotherap y
a n d c h e m o t h e r a p y. O n e m o n t h a f t e r s u r g e r y, h y d r o c e p h a l u s d e v e l o p e d ,
and she underwent surgery to insert a ventriculo-peritoneal shunt and for
p l a c e m e n t o f a n O m m a y a r e s e r v o i r. S h e s t a r t e d r e h a b i l i t a t i o n , a n d s h e
c o u l d c o m m u n i c a t e b e t t e r g r a d u a l l y. S i x m o n t h s l a t e r t h e t u m o r h a d n o t
e n l a r g e d a s s e e n o n M R I ( F i g . 5 ) . H o w e v e r, 7 m o n t h s l a t e r, t h e p a t i e n t
died suddenly due to a pulmonary embolism.

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gastrointestinal tract, skin, and blood vessels. Most intracranial soft
tissue sarcomas represent metastatic disease. Metastases from these
sites are unique, but may be directed to bone, lung, and liver 7 1 8 2. Even
more uncommon is metastasis to the CNS9. Primary intracranial
s arcom as are extrem el y rare. Three previ ous cas es of l ei om yos arcom as
were reported from a series of 25000 brain biopsies 10, for a 0.012%
p r e v a l e n c e . We f o u n d n o c a s e s o f i n t r a - t u m o r a l h e m o r r h a g e a s s o c i a t e d
wit h a pri mar y i nt racrani al l ei om yos arcom a.

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smooth
uterus,

The prognosis of lei om yos arcom a depends on it s locat ion, siz e, and
m itoti c rat e. Int raut eri ne leiom yos arcom as have a much bett er prognosis

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Discussion
Lei om yos arcom as are m al i gnant neopl asms dem onst rati ng
m u s c l e d i ff e r e n t i a t i o n t h a t a r i s e p r i m a r i l y f r o m t h e

t h a n d e e p - s e a t e d s o f t - t i s s u e l e i o m y o s a r c o m a s , a n d t h i s p a t i e n t ’s l e s i o n
i s p r o b a b l y b e t t e r c l a s s i f i e d a s t h e l a t t e r.
The local recurrence rate is 25.9% after treatment of the initial lesion
with postoperative radiotherap y 11. This particular tumor appeared to
h a v e g r o w n e x t r e m e l y r a p i d l y, a s t h e n o n - c o n t r a s t C T s c a n d e m o n s t r a t e d
o n l y m o d e r a t e a s y m m e t r y w i t h a m i n i m a l m a s s e ff e c t , b u t a n M R I 6 d a y s
later demonstrated edema and a moderate mass effect.

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No treatment protocol exists for this extremely rare primary CNS
neopl asm . Al though the num ber of cas es of l ei om yos arcom a is
increasing, too few patients have been identified to formulate effective
treatment regimens.
The prognosis for primary intracranial
l e i o m y o s a r c o m a r e m a i n s p o o r. A f t e r a c o m p r e h e n s i v e l i t e r a t u r e r e v i e w,
w e f o u n d o n l y 11 r e p o r t e d c a s e s o f p r i m a r y i n t r a c r a n i a l l e i o m y o s a r c o m a
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reports, there is no established standard treatment regimen for primary
intracranial leiomyosarcoma. But the main treatment seems to be the
c o m p l e t e r e s e c t i o n o f t h e t u m o r. S u rg i c a l r e s e c t i o n i s p e r f o r m e d i n 1 2
c a s e s , a n d 3 c a s e s w e r e o n l y p a r t i a l r e s e c t i o n a n d 1 c a s e w a s b i o p s y. I n 4
partial removal cases, 3 patients died (75%) and one patient was lost in
f o l l o w u p o n e y e a r. C h e m o t h e r a p y w a s u s e d i n 4 / 1 2 ( 3 0 % ) o f c a s e s
reviewed. But 2 cases died (50%). Radiotherapy was used in 9/12
(75%) of cases. 5 cases died. (55.6%)

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Complete surgical removal together with radiotherap y are the mainstay
for other non-CNS sarcomas. Gross total resection, depending on the site
and age of the patient, is the treatment goal. Postoperative regimens of
doxorubi ci n, vi ncri sti ne, dactinomyci n, c ycl ophosphami de, and/or
i n t e r f e r o n - α a r e c o n s i d e r e d p a l l i a t i v e t r e a t m e n t 2 1 2 2 2 3 . We p e r f o r m e d

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without any association with immune-suppression, infection, prior
r a d i a t i o n , o r p l a n t h i s t o r y 3 , 5 , 1 2 - 2 0 ( Ta b l e 1 ) .
Due to very few cases

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a d e q u a t e r e m o v a l o f t h e t u m o r, a n d t h u s , r a d i o t h e r a p y a n d c h e m o t h e r a p y
were not required. This patient did not develop the recurrence more than
6 m o n t h s a f t e r s u r g e r y.

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Conclusions
To t h e b e s t o f o u r k n o w l e d g e , t h i s i s t h e f i r s t c a s e o f a t u m o r a l
hemorrhage due to a primary intracranial leiomyosarcoma. The

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r a d i o t h e r a p y a n d c h e m o t h e r a p y.

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F I G. 1 A x i a l T 1 - w e i g h t e d M R i m a g e s a n d T 2 - w e i g h t e d M R i m a g e s o n

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admis si on (A, B), enhanced T1-wei ght ed MR im ages s ix da ys l at er (C ),
T2-wei ght ed M R im ages ni ne days l ater (D)

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F I G. 2 C o m p u t e d t o m o g r a p h y s c a n s w i t h t u m o r a l h e m o r r h a g e ( A ) ,
intraventricular hemorrhage (B).

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Fig. 3 En bloc resection is performed. The tumor is reddish and solid.

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Fig.

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eosin–stained sections revealing spindled (A). Immunoperoxidase stains
showed positively for smooth muscle antigen (B).

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Photomicrographs

of

tumor

sections.

Hem at ox yl i n

and

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F I G. 5 E n h a n c e d T 1 - w e i g h t e d M R i m a g e s a f t e r s i x m o n t h s o f s u r g e r y ( A ) ,

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computed tomograph y scans after surgical removal (B),.

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Reported cases of primary intracranial leiomyosarcoma

Author

Age

Sex

Tumor size

years
Louis et al.,

72

Resection

F

5×4×4

lt. lateral

None

6

Alive

CR

RT + CT (Adriamycin,

20

Alive

ventricle
8

M

ND

lt. parietal

procarbazine)
13

M

8×7×4

lt. parietal

CR

RT + CT

21

Dead

26

M

ND

rt.

CR

RT (61.8Gy 34fr) + CT

7

Dead

18

Alive

parieto-occipital
5

M

ND

subdural

al., 2009

CR

collection, rt.

SC

al., 2006
Mathieson et

Outcome

CR

al., 2004
Hussain et

Follow up
(months)

1997
Eckhardt et

Adjuvant therapy

(cm)

1989
Lee TT et al.,

Tumor lesion

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RT (40.25Gy 23fr), CT

(Vincristine,

Ifosfamide, Doxorubicin,

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frontal

Etoposide)

Fujimoto et

45

F

ND

lt. CP angle

PR

RT

10

Dead

58

M

1.6×1.4

lt. anteromedial

CR

None

3 weeks

Dead

PR

Gamma knife

3

Dead

CR

RT

30

Alive

biopsy

Stereotactic

44

Dead

al., 2010
Aeddula et
al., 2011
26

F

ND

19

M

5cm

2012
Alijani et
al., 2013
Saito et al.,

75

F

ND

M

lt. cavernous sinus

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5.9×4.4×

radiosurgery 15Gy 5fr

lt. temporoparietal

PR

RT

12

NA dropout

lt. frontal

CR

None

7

Dead

5.2

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2017
present case

subcutaneous, rt.

parieto-occipital

2014
Gautam et al.,

corpus callosum

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Zhang et al.,

temporal lobe

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F

4×4×5

ND, not described; F, female; M, male; lt., left; rt., right; CR, complete resection; PR, partial
resection; RT, radiotherapy; CT, chemotherapy; NA, not avilable

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Highlight for review
・To the best of our knowledge, our report is the first documented case of a tumoral
hemorrhage due to a primary intracranial leiomyosarcoma.

agree with all these comments and incorporated them.

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・I’m very pleased to see the favorable comments of reviewers. I fundamentally

・I added one figure about the removal of the tumor (Fig 3) and the review of the

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literature (table 1).

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Abbreviation list

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CT computed tomography
MRI magnetic resonance imaging
C NS cent ral nervous s ys t em

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