Discussant: Jonathan Kim, MD & Sandy Zhang-Nunes, MD
A 27-year-old woman with no significant past ocular or medical history presents with:
Left eye proptosis and pain
Decreased Vision to Light Perception for three weeks
Also endorses two months of worsening left eye “swelling” and intermittent epistaxis with nasal congestion and dysphonia
ROS otherwise negative
Eye meds: None
OS: LP with projection
IOP: OD 16 || OS 24
OD: Round and Reactive
OS: Round, slightly dilated, with sluggish response to light, +rAPD
OS: -4 in all directions of gaze
CVF: Full OD. Unable to assess OS
Brightness sense diminished OS
Slit lamp examination:
Left Lower Lid:
OD: proptosis to 19 mm on Hertel
OS: significant proptosis to 30 mm on Hertel, with periorbital edema, ptosis, lagophthalmos of 3 mm
OD: white & quiet
OS: mild chemosis
OS diffuse PEE’s, areas of epithelial thinning, mildly diffuse corneal edema
Iris: flat without NVI OU
Anterior Chamber: deep & quiet OU
Lens: clear OU
Anterior vitreous: clear OU
Dilated Fundus Exam:
OD sharp and pink, CDR 0.3
OS hyperemia, blurring of disc margins and obscuration of vessels, CDR 0.3
Macula: flat OU
Vessels: within normal limits OU
Vitreous: clear OU
Periphery: 360 attached OU
nasopharyngeal carcinoma/squamous cell carcinoma
poorly differentiated carcinoma
Thyroid eye disease
CT orbits, MRI Face w/ w/o contrast: large aggressive mass (7.1 x 8.2 x 5.7 cm) centered in the region of the left nasal cavity and left maxillary sinus with extensive bony destruction and extension into the anterior cranial fossa, bilateral orbits, left pterygopalatine fossa, as well as the left cavernous sinus through the left superior orbital fissure.
Biopsy: Undifferentiated malignant neoplasm that stained positive for desmin and Myo D1, leading to the diagnosis of rhabdomyosarcoma.
MRA head: possible encasement of left ophthalmic artery, which remained patent.
MRI brain: confirms extension into anterior cranial fossa; mass appears separate from brain parenchyma.
Rhabdomyosarcoma, subtype unknown, originating from the left nasal cavity and left maxillary sinus
Arises from immature mesenchymal cells
Embryonal (70 percent): generally associated with a more favorable prognosis
Botryoid (with pleomorphic, makes up remaining 10 percent)
Alveolar subtype more common in adults, especially for sinonasal malignancies
For the alveolar subtype, PCR can show a t(2;13) translocation with subsequent expression of an encoded oncogene, PAX3-FKHR
Due to rarity in adults, pediatric treatment protocol is extrapolated to adults
Chemotherapy with adjuvant radiation +/- surgery is mainstay of therapy for head and neck rhabdomyosarcoma
Vincristine, dactinomycin, ifosfamide, doxorubicin, cyclophosphamide, and/or vinorelbine are chemotherapeutic agents of choice
Prognosis and Future Directions
Rhabdomyosarcoma (RMS) arising primarily from the sinuses or nasal cavity is an aggressive disease that can invade both orbits and is associated with a poor prognosis; studies have estimated a five-year overall survival in adults of 28 percent.
Paranasal sinus RMS most commonly metastasizes to cervical lymph nodes, lungs, bones. Strong tendency for local invasion, recurrence and hematogenous and lymphatic metastasis.
Recently, gene therapy targeting tumor suppression has been studied.
Most common primary orbital malignancy in children
Most common childhood soft tissue sarcoma, 10 to 20 percent occur in the orbit
Male to female ratio, 5:3
70 percent occur in the first decade, average age 6 to 8 years old (range, birth to 78 years)
Clinical Presentation: Rhabdomyosarcoma
Acute or subacute exophthalmos (weeks)
2/3 are superonasal, may also arise from sinuses, nasopharynx
Edema, ptosis, strabismus
May mimic inflammatory syndrome
History of trauma may be present
Alveolar Rhabdomyosarcoma: translocation creates a fusion protein
Alveolar subtype 20 percent
FKHR Translocation (Recombination of 13 to 1 or 2)
FKHR locus 13:PAX3 gene on 2
Encode chimeric protein FKHR-PAX3
FKHR locus 13:PAX7 gene on 1
Encode chimeric protein FKHT-PAX7
FKHR gene fusions present in 80 percent of alveolar rhabdomyosarcoma (PAX3>PAX7)
For patients with metastatic disease, PAX3 patients have significantly worse survival
Translocation negative alveolar subtype has similar prognosis to embryonal subtype
Rhabdomyosarcoma: Group classification
I Localized disease, completely resected (clear margins)
II Residual microscopic disease
III Macroscopic residual disease
IV Distant metastases
2 drug VA protocol
Vincristine (vinca alkaloid)
Actinomycin D (RNA synthesis)
3 drug VAC protocol
Cyclophosphamide (alkylating agent) added
Radiotherapy to prevent local failure
Utilized for Groups II, III, IV
Typically given after initiation of chemotherapy
Total dose 36-45 Gy
Consideration with any orbital mass lesion in young patients
Biopsy to establish diagnosis
Biopsy and debulking of gross disease if anterior and circumscribed
Factors which worsen prognosis:
Alveolar subtype with translocation
Extending outside the orbit
Group III or IV
Rhabdomyosarcoma in adults:
Primary orbital involvement is extremely rare
Less likely to be embryonal
Worse 5 year survival (80 percent vs 50 percent)
Crist WM, Anderson JR, Meza JL et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091–102.
Amato MM, Esmaeli B, Shore JW. Orbital rhabdomyosarcoma metastatic to the contralateral orbit. Ophthalmol. 2002;109:753–6.
Liu W, Jiang L, Jin Y et al. Alveolar rhabdomyosarcoma of the sphenoid sinus mimicking optic neuritis presenting with intermittent visual loss in an adult. J Onco Targets Ther. 2016 Oct;9:6333–6.
Stepan K, Konuthula N, Khan M et al. Outcomes in Adult Sinonasal Rhabdomyosarcoma. Otolaryngol Head Neck Surg. 2017 Jul;157(1):135–41.
Shields CL, Shields JA, Honavar SG et al. Clinical Spectrum of Primary Ophthalmic Rhabdomyosarcoma. Ophthalmology. 2001 Dec;108(12):2284–92.
Moon HS, Kwon SW, Lee JH. A case of alveolar rhabdomyosarcoma of the ethmoid sinus invading the orbit in an adult. Korean J of Ophthalmol. 2006 Mar;20(1):70–5.
Parikh D, Spindle J, Linden C et al. Adult rhabdomyosarcoma of the maxillary sinus with orbital extension. Orbit. 2014 Aug;33(4):302–4.
Torres-Peña J, Castrillo A, Mencía-Gutiérrez E et al. Nasal Cavity or Alveolar Paranasal Sinus Rhabdomyosarcoma with Orbital Extension in Adults: 2 Cases. Plast Reconstr Surg Glob Open. 2015 Jun;3(6):e414.
Chu Y, Liu HG, Yu ZK. Patterns and incidence of sinonasal malignancy with orbital invasion. Chin Med J (Engl). 2012 May;125(9):1638–42.