A case of alveolar rhabdomyosarcoma of the ethmoid sinus invading the orbit in an adult.

Abstract

A case study and literature review of alveolar rhabdomyosarcoma (RMS) in an adult.
A 48-year-old male patient presented at our clinic complaining of proptosis that had persisted for 2 weeks in his left eye. A computed tomography (CT) scan revealed a destructive soft-tissue mass in the left ethmoid sinus with invasion of the left orbit and compression of the medial rectus muscle. Endoscopic intranasal biopsy revealed alveolar RMS. Conservative debulking and orbital wall decompression were performed.
Immunohistochemical testing was positive for desmin, S-100, and smooth muscle actin (SMA), supporting the diagnosis of RMS. Since ipsilateral cervical and spinal metastasis was detected, systemic treatment was administered simultaneously.
Although rarely found in adults, RMS should be considered in the differential diagnosis of orbital tumors. Immunohistochemical analysis plays an important role in the definitive diagnosis of RMS.

Full text

Page 1

70
A Case of Alveolar Rhabdomyosarcoma of the Ethmoid
Sinus Invading the Orbit in an Adult
Hyun Seung Moon, MD, Sang Won Kwon, MD, Jong Hyeok Lee, MD
Department of Ophthalmology, Gachon Medical School, Gil Medical Center, Incheon, Korea
Purpose: A case study and literature review of alveolar rhabdomyosarcoma (RMS) in an adult.
Methods: A 48-year-old male patient presented at our clinic complaining of proptosis that had persisted for
2 weeks in his left eye. A computed tomography (CT) scan revealed a destructive soft-tissue mass in the
left ethmoid sinus with invasion of the left orbit and compression of the medial rectus muscle. Endoscopic
intranasal biopsy revealed alveolar RMS. Conservative debulking and orbital wall decompression were
performed.
Results: Immunohistochemical testing was positive for desmin, S-100, and smooth muscle actin (SMA),
supporting the diagnosis of RMS. Since ipsilateral cervical and spinal metastasis was detected, systemic
treatment was administered simultaneously.
Conclusions: Although rarely found in adults, RMS should be considered in the differential diagnosis of
orbital tumors. Immunohistochemical analysis plays an important role in the definitive diagnosis of RMS.
Korean Journal of Ophthalmology 20(1):70-75, 2006
Key Words: Adult rhabdomyosarcoma, Ethmoid, Orbital tumor
Received: September 15, 2005 Accepted: December 30, 2005
Reprint requests to Jong Hyeok Lee, MD. Department of Ophthal-
mology, Gachon Medical School, Gil Medical Center，#1198,
Guwol-dong, Namdong-gu, Incheon 405-760, Korea. Tel: 82-32-460-
3750, Fax: 82-32-460-3358, E-mail: ljhcyj@lycos.co.kr
＊None of the authors has a financial or proprietary interest in any
material or method mentioned
＊This study was presented at the 93rd annual meeting of the Korean
Ophthalmologic Society, April, 2005.
Rhabdomyosarcoma (RMS) is the most common soft
tissue sarcoma in the pediatric population, accounting for
approximately 5% of all childhood cancers and about 20%
of all malignant soft tissue tumors.1,2 The primary sites of
RMS are: head and neck (40%), genitourinary system (20%),
extremities (20%), trunk (10%), and other (10%).3 Although
RMS can occur at any age, it is primarily a disease of young
children with a mean age at diagnosis of 8 years. Only a very
small percentage of reported RMS cases have occurred in
people over the age of 20 years.1,4 The present study
describes a case of alveolar RMS of the ethmoid sinus
invading the orbit in an adult and reviews related literature.
Case ReportCase Report
A 48 year old male patient presented at our clinic
complaining of proptosis and lid swelling in his left eye that
had persisted for 2 weeks. The patient had no significant past
history or family history associated with ocular disease,
trauma, or tumors. Although no palpable mass was noted,
exophthalmometry measurements were 20 mm on the left,
and 18 mm on the right with a base of 104 mm. Motility
was slightly limited in adduction. Results of ocular examina-
tion including visual acuity, color vision, and funduscopy
were normal. The thyroid function test was also normal. A
computed tomography (CT) scan revealed a destructive
soft-tissue mass in the left ethmoid sinus with adjacent
invasion of the left orbit and compression of the left medial
rectus muscle (Fig. 1). Magnetic resonance imaging (MRI)
showed that the signal intensity of the mass was low on a
T1-weighted image with contrast enhancement and isointense
to muscles on a T2-weighted image. The lesion extended into
the left orbit with compression of the left medial rectus
muscle, and there was also intracranial extension with
compression of left side frontal lobe (Fig. 2).
A fiberoptic endoscopic biopsy of the nasal cavity revealed
alveolar RMS. Metastatic work-up revealed cervical lymph
node involvement, indicating a stage IV RMS based on the
Intergroup Rhabdomyosarcoma Study (IRS) TNM Pretreat-
ment Staging System.5 Since distant metastasis was detected,
radiation therapy and chemotherapy were scheduled; how-
ever, approximately one week later the visual acuity of the
left eye had decreased to 20/40, and there was increased
proptosis (5.5 mm) and severe limitation of ocular movement
(Fig. 3). Surgery was considered necessary to preserve vision
and ameliorate the symptoms, therefore conservative

Page 2

HS Moon, et al. ADULT RHABDOMYOSARCOMA OF THE ETHMOID SINUS
71
Fig. 2. Orbital magnetic resonance imaging (MRI) scans show rhabdomyosarcoma in left ethmoid sinus with low signal intensity on
T1-weighted image (A,B) and moderate enhancement on enhanced scan (C). On a T2-weighted image, the lesion is isointense to
extraocular muscles and hypointense to orbital fat (D). The lesion extends into the left orbit with compression of the left medial rectus
muscle, and has intracranial extension with compression of the left side frontal lobe.
Fig. 1. Coronal (A) and axial (B,C) CT scans show a well-circumscribed, homogeneous mass in the left ethmoid sinus with extension into
the left orbit and compression of the left medial rectus muscle. The tumor shows marked enhancement with contrast agents.
debulking and orbital wall decompression were performed
through a transconjunctival incision in the inferior fornix
under general anesthesia.
Gross examination revealed a well-circumscribed, ovoid,
reddish tumor, which measured 1.5×1.2×1.0 cm (Fig. 4).
Microscopic examination revealed diffuse small spindle-
shaped to round cells with abundant eosinophilic cytoplasm
and eccentric nuclei. There was no evidence of cross-
striation. Immunohistochemical analysis was positive for
desmin, S-100, smooth muscle actin (SMA), and CD56,
consistent with a diagnosis of alveolar RMS (Fig. 5). After
surgery, the patient experienced some return of visual
function and ocular motility (Fig. 6). The patient was treated
with chemotherapy including adriamycin, combined with
irradiation of the orbit and ethmoid sinus of 5800 cGy over
a period of 6 weeks. The chemotherapy was discontinued
because the patient developed pancytopenia. A bone scan
indicated progressive metastasis to the spine and the patient

Page 3

Kor J Ophthalmol Vol.20, No.1, 2006
72
Fig. 3. Preoperative photography of a 48-year-old man suffering diplopia, with marked limitation of ocular movement, chemosis, proptosis
in the left eye.
Fig. 4. Gross examination showed a circumscribed reddish tumor
measuring 1.5×1.2×1.0 cm.
died 7 months after the initial diagnosis.
DiscussionDiscussion
Although RMS is the most common sarcoma in the
pediatric population, it is very uncommon in adults.1
Microscopically, the four major histopathologic types of
RMS are: pleomorphic, embryonal, alveolar, and botryoid.6
In the Intergroup Rhabdomyosarcoma Study-IV, the overall
distribution of the subtypes was 70% embryonal, 20%
alveolar, and 10% others;5 however, Little et al7 reported
subtype proportions in adults to be 43% pleomorphic, 34%
embryonal, and 23% alveolar. The relative paucity of
embryonal tumors and increase in alveolar and pleomorphic
types are characteristic of adult RMS.8,9 Embryonal RMS is
the most common variant found in the head and neck region
while the alveolar and pleomorphic types are rare in the
orbit.1,6 The prognostic significance of this classification is
undecided, but it is generally accepted that pleomorphic,
better differentiated tumors have a better prognosis, while the
alveolar subtype has the worst prognosis.10 Alveolar RMS
occurs primarily in adults between the age of 10 and 25
years, and involves tumor cells that are mostly undif-
ferentiated in nature, and therefore readily develop distant
metastasis resulting in poor prognosis.11 Indeed, in the case
presented here distant metastasis was already present at the
time of diagnosis.
RMS shows a strong tendency for local invasion, local
recurrence, and hematogenous and lymphatic metastasis.12
Alveolar RMS appears to be more aggressive that other
subtypes and often shows lymph node involvement; therefore

Page 4

HS Moon, et al. ADULT RHABDOMYOSARCOMA OF THE ETHMOID SINUS
73
Fig. 5. Photomicrograph of isolated rhabdomyosarcoma. (A) Low magnification reveals diffuse small round cells (Hematoxylin-eosin, original
magnification ×40). (B) High magnification reveals round cells (rhabdomyoblast) with eosinophilic cytoplasm and eccentric nuclei (arrow)
(Hematoxylin-eosin, original magnification ×400). (C) Immunohistochemistry gave positive results with desmin, confirming the diagnosis of
rhabdomyosarcoma (original magnification ×400). (D) Immunohistochemistry with smooth muscle actin (original magnification ×400).
combined treatment protocols involving chemotherapy and
radiotherapy have typically been used. The most common
pathway of distant spread of RMS is by hematogenous
dissemination, particularly to the lung, cervical lymph nodes,
and bone.6,13-15
Orbital RMS can present insidiously, clinically and
radiologically mimicking other space-occupying lesions. The
most characteristic presentations are rapid onset and progres-
sion of proptosis, and displacement of the globe.4 Intracranial
extension and invasion of the paranasal sinuses are
uncommon at presentation, while changes in the adjacent
bone frequently occur.16 In the case presented here, the
epicenter of the tumor was identified within the left ethmoid
by CT, and the medial rectus muscle was intact. It seems
unlikely that the tumor originated in the orbit and then
invaded and filled the ethmoid sinus since the presenting
symptoms included proptosis that had been present for only
2 weeks. Therefore, our case was considered to have
originated within the ethmoid sinus and subsequently invaded
the orbit.
It is important that RMS tumors are distinguished from the
more common tumors of the head and neck occurring in
adults, including nasopharyngeal carcinoma, lymphoma,
neuroendocrine carcinoma, melanoma, poorly differentiated
carcinoma, and metastatic tumor.10,17 Differential diagnosis
depends on imaging techniques in combination with
histological and immunohistological analysis.
Various imaging methods have proved useful in the
diagnosis and determination of the extent of RMS. CT and
MRI are fundamental techniques for preoperative evaluation
to determine tumor location and size, and are also important
in evaluating residual or recurrent disease.4 In RMS, CT
shows a moderately well-circumscribed, homogeneous, round
to ovoid mass that is isodense to the extraocular muscle,
which shows moderate to marked enhancement with contrast
agents. On T1-weighted MR images, the tumor is usually
isointense to the extraocular muscles and hypointense with
respect to the orbital fat. On T2-weighted MR images,
hypointensity, isointensity, and even hyperintensity may be
appreciable with respect to both extraocular muscles and
orbital fat.1,4
As differential diagnosis can be difficult when based solely
on radiologic analysis, histologic evaluation is also required.
Grossly, RMS is a well-circumscribed tumor while in the
early stages. Larger, more aggressive tumors have an
irregular border as a result of tumor invasion though the

Page 5

Kor J Ophthalmol Vol.20, No.1, 2006
74
Fig. 6. 5-month postoperative photograph showing improvement of ocular movement and enophthalmos in the left eye.
pseudocapsule. The tumor has a light gray to pink color and
may show areas of hemorrhage and cyst formation. Micro-
scopically, RMS consists of small spindle-shaped to round
rhabdoblasts with abundant eosinophilic cytoplasm and
eccentric nuclei. The alveolar type appears as loosely
arranged, malignant cells with septae that are reminiscent of
the alveoli of the lung.1 Since these lesions exhibit morpho-
logical features in common with other spindle cell neoplasms
further immunohistochemical analysis is necessary for
definitive diagnosis1,9 RMS is characteristically positive for
desmin, smooth muscle actin, and myoglobin.1,13,14
Survival of patients with RMS generally depends on
several factors, including histopathologic and cytologic tumor
type, extent of disease at diagnosis, tumor burden at
diagnosis, primary tumor site, patient age, cellular ploidy, and
therapeutic response.12 The favorable prognostic charac-
teristics for disease specific survival are: age ≤20 years,
tumor size ≤5 cm, absence of regional or distant disease,
surgical resection with negative margins, and pleomorphic
type.9,18
Treatment of RMS involves a combination of chemo-
therapy, radiation therapy, and surgery depending on the
primary tumor site, pathologic findings, and the clinical stage
of the tumor.4 For tumors that develop in the vicinity of the
orbit a diagnostic biopsy is performed, and chemotherapy and
radiation therapy are administered. In contrast, for sarcomas
in the trunk, the extremities, and in the tissues adjacent to
the testis, the tumor is surgically resected as aggressively as
possible while avoiding local damage and preserving
function, and chemotherapy and radiation therapy are admini-
stered. In cases where the tumor is too large for resection,
surgery may be performed after the tumor size has been
reduced by chemotherapy and radiation therapy.12
In summary, adult RMS is an extremely rare malignant
tumor that is difficult to manage. A treatment plan should be
made on an individual basis, taking into consideration the age
of the patient, the disease stage, and the size of the tumor.
Although it is rarely found in an adult, RMS should be
considered in the differential diagnosis of orbital tumors
irrespective of age. Immunohistochemisty should be
performed in addition to radiologic imaging techniques and
histology for a definitive diagnosis of RMS. Following
diagnosis of RMS, systemic evaluation for distant metastasis
is necessary.
Reference Reference
1. Shields JA, Shields CL. Rhabdomyosarcoma: review for the
ophthalmologist. Surv Ophthalmol 2003;48:39-57.
2. Crist W, Gehan EA, Ragab AH, et al. The Third Intergroup
Rhabdomyosarcoma Study. J Clin Oncol 1995;13:610-30.
3. Lanzkowsky P. Rhabdomyosarcoma and other soft tissue
sarcomas. In : Manual of Pediatric Hematology and
Oncology, 3rd ed. New York: Academic Press, 2000; v. 1.
chap. 20
4. Karcioglu ZA, Hadjistilianou D, Rozans M, DeFrancesco S.
Orbital rhabdomyosarcoma. Cancer Control 2004;11:328-