Jpn. J. Clin. Oncol.-2014-Xue-926-31.pdf

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Post-operative Radiotherapy for the Treatment of Malignant Solitary

Fibrous Tumor of the Nasal and Paranasal AreaYing Xue, Guangjin Chai, Feng Xiao, Ning Wang, Yunfeng Mu, Yujie Wang and Mei Shi *

Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, Xian, China

*For reprints and all correspondence. Department of Radiation Oncology, Xijing Hospital, The Fourth Military MedicalUniversity, Chang Le West Street, No. 17, 710032 Shaanxi, Xian, China. E-mail: [email protected] author: Ying Xue, (1971.08.29), doctor, doctor-in-charge, mainly engaged in the comprehensive treatment ofchest tumor.

Received December 31, 2013; accepted July 8, 2014

Objective: Solitary fibrous tumor is a rare tumor occurring in almost every anatomic location ofhuman body; however, reports of malignant solitary fibrous tumor in the nasal and paranasalarea are especially rare. In this report, we describe a case of non-recurrent malignant solitaryfibrous tumor of the nasal and paranasal area.Methods: The patient was initially treated with nasal and paranasal tumor cytoreductive

surgery, followed by post-operative three-dimensional conformal intensity modulated radiationtherapy (dynamic MLC Varian 600CD Linac, inversely optimized by the Eclipse system) andstereotactic body radiation therapy to provide a radical cure for residual tumor.Results: The tumor of the nasal and paranasal area was effectively treated and the integrity of theright eye kept. There were no signs of recurrence after four and a half years of further follow-up.Conclusions:This is the first attempt to successfully combine cytoreductive surgery with inten-sity modulated radiation therapy and stereotactic body radiation therapy together to treat solitary

fibrous tumor of the nasal and paranasal area, which may provide a potential strategy for thetreatment of similar cases.

Key words: solitary fibrous tumor radiotherapy

INTRODUCTION

Solitary fibrous tumor (SFT) is an uncommon spindle cell tumor

that was first recognized and fully characterized in 1994 by

Westra et al. (1). SFT often originates from the pleura, and occa-

sionally from other parts of the body, including the extremities,mediastinum, peritoneum, parotid gland and orbit (16). Radical

surgical resection is the preferred treatment for SFT. Here, we

present a case of malignant SFT of the nasal and paranasal area

that was treated by cytoreductive surgery combined with intensity

modulated radiation therapy (IMRT) and solitary fibrous tumor

(SBRT). No recurrence was seen in long-term follow-up.

CASE REPORT

An 18-year-old female was admitted to the Xijing Hospital of

Shaanxi Province, China in April due to painless proptosis,

decreased visual acuity and epiphora in the right eye. Prior to

the onset of symptoms, the uncorrected visual acuity was 4.3

and 4.8 in the right and left eyes, respectively. The patient had

no family history of similar symptoms.

An orbital computed tomography (CT) scan showed that

a large mass fully occupied the right nasal cavity, sinusesand frontal sinuses (Fig.1A and B). The mass impinged on

the right eye and the right maxillary sinus, and caused nasal

septum perforation with oppressing on the left ethmoidal

cellules (Fig.1 A and B). In order to keep the integrity of

the right eye, nasal and paranasal tumor cytoreductive

surgery was performed to partially resect the paranasal

sinus tumor inside the right nasal cavity with image

navigation. During the operation, a wider range of tumor in-

vasion was observed, showing invasion of the ethmoid

bone roof, the sphenoid sinus anterior wall , nostrils and the

laminapapyrace.

# The Author 2014. Published by Oxford University Press. All rights reserved.For Permissions, please email: [email protected]

Jpn J Clin Oncol 2014;44(10)926 931

doi:10.1093/jjco/hyu100

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The tumor tissue was grayish-white, like fish with brittle

textures, covered with a fibrous bone shell. The post-operative

specimen was a dark brown nodular mass (9 6.5 5 cm)

with incomplete envelope. On the cut section, the tumor

was grayish-white, lobulated, firm and well-demarcated, with

a whorled and fasciculated surface. Light microscopic

examination of the resected tumor showed large numbers oftumor cells that are oval and fusiform, distributed in patches

with significant atypia by Hematoxylin and eosin staining.

The branched blood vessels, abnormal cells, mitotic

figures and nuclear polymorphisms were frequently noted

(Fig.2A and B).

Due to the low incidence and histologic similarity to other

spindle cell tumors, early diagnosis of nasal and paranasal

SFT is difficult. The main clinical manifestation is pain-

less proptosis. The diagnosis is mainly dependent on

immunohistochemical studies. It has been documented that

SFT exhibits strong positivity with CD99 (70%), vimentin

(95%) and Bcl-2 (35%) antibodies, and is negative for S-100

(7). In addition, Ki-67 proteins are excellent markers for deter-

mining the so-called growth fraction of a given cell popula-

tion. In the present case, immunohistochemical staining

revealed that cells were positive for CD99 (Fig. 3 A), Vim(Fig. 3B) and Bcl-2 (Fig. 3C), and contained scattered

CD34-positive cells (Fig.3D). Ki67-positive cells accounted

for almost 28% of all cells (Fig.3E). All cells were negative

for S-100 (Fig. 3F). On the basis of the aforementioned

results, pathological evaluation ascertained the presence of a

malignant SFT with bone invasion.

Three weeks after surgery, magnetic resonance imaging

(MRI) imaging of the nasopharynx revealed an irregular, in-

homogeneous mass in the right nasal cavity and ethmoid sinus

(4.1 2.8 cm) (Fig. 4). A radiation treatment plan, three-

dimensional conformal IMRT was developed for the patient

after CT-guided tumor localization. VRIAN 600CD was usedas the treatment machine. The Eclipse planning system was

LUNA TM 260. The gross tumor volume (GTV), including re-

sidual tumor, was visualized on CT and MRI. The clinical

tumor volume (CTV) was calculated including the right nasal

cavity, part of the left nasal cavity, right maxillary sinus, an-

terior and posterior ethmoid sinus, sphenoid sinus and part of

the nasopharyngeal mucosa. The planning target volume

(PTV) was 0.3 cm outside of the CTV. The total GTV irradi-

ation received was 60 Gy/24F, 2.5 Gy/F, one session/day and

five sessions/week. The total PTV irradiation was 55.2 Gy/

24F, 2.3 Gy/F, one session/day, and five sessions/week.

During the second treatment course, SBRT therapy was deliv-

ered targeting the GTV, with a total irradiation dose of 12 Gy/

3F, 4 Gy/F, one session/every other day. A 50% isodose line

surrounded the targeted region. Dose constraint for each organ

Figure 1. Orbital computed topographies scan of right orbit solitary fibrous

tumor (SFT). (A) The image shows a 5 cm-sized, well-demarcated nodule

with an eccentric nodular enhancement. (B) A coronal image shows a mass

lying in the orbit.

Figure 2. Hematoxylin and eosin-stained slide. (A) Microscopic examination of the orbit lesion shows proliferation of relatively uniform spindle cells that are

either patternless or have a focally storiform pattern. (B) Focal vascular dilatation with collagenized stroma, dense collagen nodules and perivascular hyalinization

is also observed.

Jpn J Clin Oncol 2014;44(10) 927


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at risk were as follows: brainstem,Dmax 54 GyD1 60 Gy;

optic chiasma,Dmax

54 GyD1 60 Gy; bilateral crystal,

Dmax 5 Gy D33 8 Gy; bilateral eye,Dmax 50 Gy; and

the left optic nerve,Dmax 54 GyD1 60 Gy. Besides, the

DVH for each organ were as follows: brainstem (Dmax

44.1 Gy;

D1 45.6 Gy), optic chiasma (Dmax

43.2 Gy;D1 44.1 Gy), bilat-

eral crystal (Dmax

5.1 Gy; D33 5.4 Gy), bilateral eye (Dmax

41.2 Gy) and the left optic nerve (Dmax

45.4 Gy; D1 46.5 Gy).

After radiation therapy, the patient complained of xerostomia,

ageusia and anosmia. Furthermore, there was no significant

relief of right nasal cavity obstruction and binocular visual

acuity after treatment.

With reexamination for primary tumor 5 months after radio-therapy, nasal congestion symptoms were abated in the right

nasal cavity, but still accompanied with the xerostomia,

ageusia and anosmia. The visual acuity of the right eye was

4.3, indicating no change compared with levels before radi-

ation therapy. MRI analysis showed an absence of the right

turbinate and the medial wall of the right maxillary sinus. The

lesions on the right nasal cavity and ethmoid sinus showed

hyper signals (2.9 3.4 2.1 cm) with defined border using

enhanced MRI (Fig.5A1 and A2).

Eighteen months after radiation therapy, reexamination

showed that the xerostomia was significantly ameliorated.

Symptoms of stuffy nose and headache had disappeared. The

Figure 3. Immunohistochemical test of the SFT. Immunohistochemical tests showed that the tumor was positive for CD99 (A), Vim (B) and Bcl-2 (C), and

contains scattered CD34-positive cells (D). Ki67-positive cells accounted for28% of all cells (E). All cells are negative for S-100 (F).

Figure 4. Tumor image of MRI at 3 weeks after surgery.

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Figure 5. Follow-up reviews. The follow-up reviews after 5 months (A1, A2) and eighteen months (B1, B2) showed a reduction in the size of the mass, and four

and a half years after therapy, no change was seen in the size of the mass in the right nasal cavity (C1, C2).



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sense of taste and smell had almost returned to normal levels.

Visual acuity of the right eye was 4.3. MRI showed a reduc-

tion in size of the mass (2.5 3.1 1.6 cm) in the right nasal

cavity and ethmoid sinus (Fig.5B1 and B2).

Four and a half years after radiation therapy, the symptoms

of xerostomia had completely disappeared. The left eye visual

acuity was stable (4.6) and the right eye visual acuitydecreased slightly (4.1). The senses of taste and smell were

normal. MRI showed no change in the size of the mass in the

right nasal cavity and ethmoid sinus (2.0 3.1 1.5 cm). No

local recurrences were observed (Fig.5C1 and C2).

DISCUSSION

SFT is a rare soft tissue spindle cell tumor. It can occur in

every site of the body, including the mediastinum, lung,

pleura, liver, kidney, orbit and meninges (3,8,9). The age of

onset is mainly between 40 and 70 years. There was no signifi-cant difference between males and females (9,10). Most SFT

cases are benign neoplasms; however, 10 15% are malig-

nant neoplasms, especially those in mediastinal, abdominal,

pelvic and retroperitoneal locations (6,11). Metastases may

occur in the lungs, bones and liver. Malignancy is defined as a

significantly increased tumor cell density, clear cell atypia,

more than four mitotic figures in every 10 HPF, and the pres-

ence of necrosis (6,1113).

SFT of the nasal and paranasal area was first reported in

1994 (14) and most SFT are benign (15, 16). Infiltrating

growth is not a common feature of pathology, and only a few

cases reveal malignant transformation. SFT displays high

CD34 reactivity in 79100% of cases (14). On the contrary,

malignant SFT may show high mitotic counts and loss of

CD34 immunoreactivity (17,18). Therefore, CD34 is used to

distinguish benign and malignant SFT. Most samples in this

case report showed immunohistochemistry results that were

negative for CD34, resulting in the diagnosis of a possible ma-

lignant entity according to the benignmalignant system.

Combined with the appearance of branched blood vessels,

abnormity cells, mitotic figures and nuclear polymorphisms

under the light microscope, it is reasonable to judge this case

to be a malignant lesion.

SFT of the nasal and paranasal area is a rare neoplasm, and

there are no standard clinical treatment guidelines. Completesurgical removal is the main treatment strategy, but some

drawbacks still exist in the clinical application in SFT of the

nasal and paranasal area. Complete resection is often restricted

due to the small volume of the nasal and paranasal tissue, the

presence of vital organs, large tumor volumes, a lack of com-

ple te enc apsulation and invasi ve growth. Rece ntly, tumor

cytoreduction combined with post-operative adjuvant therapy

has been considered more advantageous in SFT from nasal

and paranasal area. Stereotactic radiation therapy is often used

as post-operative therapy, and has been reported to effectively

control residual tumors (19,20). However, radiation therapy

can damage the optic nerve, optic chiasm, cornea and lens,

resulting in decreased visual acuity or visual field defects.

Consequently, post-operative radiation therapy may need to be

improved for the treatment of SFT in the head.

IMRT is known to enable the delivery of lower doses of ra-

diation to normal tissue, while increasing or maintaining the

tumor dose, which exhibits more advantages than two-

dimensional radiotherapy (2DRT) or three-dimensional con-formational radiotherapy (3DCRT). The potential of IMRT

for sparing organs has been demonstrated in patients with

mixed head and neck tumors (21) and nasopharyngeal cancers

(22). In this study, the patient had a large localized nasal and

paranasal tumor with diffuse local extension. To preserve the

right eye, as required by the patient, the tumor was partially

resected. In order to better control the primary tumor and

avoid recurrence and metastases, a post-operative IMRT was

used to eliminate residual tumors. In this patient, IMRT was

well used and the healthy tissues of the left side received non-

toxic doses of radiation, which preserved the visual acuity and

visual field of the patients left eye. In the subsequent follow-up, the vision of the patient was maintained at a stable level

after treatment, confirming that our strategy was effective and

can be referenced. However, the eye, lens and optic nerve of

the right eye were closely related to the tumor, so IMRT could

not be strictly targeted.

SBRT is a relatively new type of radiosurgery that is

capable of the precise delivery of converging beams of radi-

ation on a small target in almost any location in the body (23,

24). Studies have shown that SBRT after external irradiation

improves the local control and survival rates in nasopharyn-

geal cancer. SBRT could effectively enhance the protection

of healthy tissues, which is important in the treatment of

head and neck cancers (25,26). In this case, SBRT was used

in combination with IMRT in the residual tumor to remedy

the deficiency of IMRT and protect contralateral healthy

organs and reduce the acute and late-stage side effects of

radiation. In the subsequent follow-up, the right nasal cavity

and paranasal sinus tumors progressively decreased in size.

The patient experienced no obvious decline in visual acuity

or visual field defects, even though the maximum dose deliv-

ered to the right optic nerve and right eye were up to 64 and

62 Gy, respectively. The symptoms of nasal obstruction, xer-

ostomia, ageusia and anosmia disappeared gradually during

follow-up.

CONCLUSION

In this report, we described a case of malignant SFT originat-

ing from the nasal and paranasal area. Following cytoreduc-

tive surgery, two post-operative radiation therapies of IMRT

and SBRT were performed; no recurrences or metastases oc-

curred during long-term follow-up. Therefore, this report indi-

cates an effective strategy for the treatment of malignant SFT

of the nasal and paranasal area. More research and longer

follow-up should be explored in the future based on the

recommended strategy.

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Conflict of interest statement

None declared.

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