Case Study: Too Nosey

Han Kim
Presenter: Andy Han, MD, PGY-2 Discussant: Jonathan Kim, MD & Sandy Zhang-Nunes, MD
 

History

  • A 27-year-old woman with no significant past ocular or medical history presents with:
    • Left eye proptosis and pain
    • Binocular diplopia
    • 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
  • Allergies: None

Figure 1
Figure 1: Photographs taken three weeks prior to initial presentation. Patient’s external exam was essentially normal, with slight proptosis of the left eye, and no obvious ophthalmoplegia

 

Exam Findings

  • VA (sC):
    • OD: 20/30
    • OS: LP with projection
  • IOP: OD 16 || OS 24
  • Pupils:
    • OD: Round and Reactive
    • OS: Round, slightly dilated, with sluggish response to light, +rAPD
  • EOM:
    • OD: full
    • 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
    • Sclera/Conjunctiva:
      • OD: white & quiet
      • OS: mild chemosis
    • Cornea
      • OD clear
      • 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:
    • Optic Nerves
      • 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

 

Figure 2
Figure 2: Patient had a much more noticeable proptosis than at initial presentation. You can also see signs of a reddish mass in her left nares.

Figure 3
Figure 3: MRI T2 Axial image obtained at initial presentation showed relatively homogeneous multilobulated extensive mass involving the sphenoid and ethmoid sinus, and nasal passages with extension in the left orbit, displacing the medial rectus and optic nerve laterally. Mass does not appear to have invaded the dura or intracranial cavity.
Figure 4
Figure 4: Two weeks after initial presentation, proptosis had dramatically worsened. At this point patient had no light perception.

 

Differential Diagnosis

  • Sinonasal malignancies
    • nasopharyngeal carcinoma/squamous cell carcinoma
    • lymphoma
    • neuroendocrine carcinoma
    • melanoma
    • poorly differentiated carcinoma
    • metastatic tumor
    • rhabdomyosarcoma
  • Intracranial mass
  • Thyroid eye disease

Additional Investigations

  • 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.
Figure 5
Figure 5: CT brain and orbits with contrast (axial and coronal views). Significant increase in the size of the mass, with increased bony destruction and rapid growth in the left intraorbital soft tissue component.

 

Diagnosis

  • Rhabdomyosarcoma, subtype unknown, originating from the left nasal cavity and left maxillary sinus

Pathophysiology

  • Arises from immature mesenchymal cells
  • Four subtypes:
    • Embryonal (70 percent): generally associated with a more favorable prognosis
    • Alveolar (20 percent): poorly differentiated, worst prognosis, rapidly develops distant metastasis
    • Pleomorphic
    • 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

Treatment

  • 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.

Clinical Summary

  • 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
  • Rhabdomyosarcoma: Pathology
  • 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
      • Rhabdomyosarcoma: Treatment
    • Chemotherapy
      • 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
    • Rhabdomyosarcoma Summary
    • 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)

References

  • 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.

Contact

  • Jonathan Kim, MD, Associate Professor of Clinical Ophthalmology, jonkim@chla.usc.edu
  • Sandy Zhang-Nunes, MD, Assistant Professor of Clinical Ophthalmology, Director, Oculofacial Plastic Surgery Service, zhangnun@med.usc.edu
  • Andy Han, MD, PGY-2, Ophthalmology resident, han8025@gmail.com

Section Editors

 

Produced by: Monica Chavez, John Daniel, Mellissa Linton and Dr. Vivek Patel