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AAOOP Companion MeetingBone and Orbital Wall Lesions

Tatyana Milman, MD

ACCME/DisclosuresThe USCAP requires that anyone in a position to influence or control the content of CME disclose

any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their

spouse/partner have, or have had, within the past 12 months, which relates to the content of

this educational activity and creates a conflict of interest.

Dr. TATYANA MILMAN declares she has no conflicts of interest to disclose.

The Bony OrbitThe Bony OrbitThe Bony Orbit

7 Bones7 Bones

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The Roof Frontal Bone

The Medial Wall

The Inferior Wall

And

Palatine Bone(not shown here)

The Lateral Wall

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https://embryology.med.unsw.edu.au

Primary lesions of the bony orbit

0.6%-2%

of all orbital tumors

Primary lesions of the bony orbit0.6%-2% of all orbital tumors

Selva D et al. Primary bone tumors of the orbit. Surv Ophthalmol 2004;49:328-42.

Primary osseous and fibro-osseous lesions: ~40%

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Primary osseous and fibro-osseous orbital lesions

Benign orbital fibro-osseous lesions• Fibrous dysplasia• Ossifying fibroma• Osteoma• Osteoid osteoma and osteoblastoma

Interesting cases

Fibrous dysplasia

Definition• Dysplastic skeletal anomaly• Distortion of normal medullary bone and

replacement with immature woven bone

Fibrous dysplasia Clinical presentation

• First 2 decades (most patients <30)• M = F

http://www.waent.org/archives/2009/vol2-2/fibrous-dysplasia/

Monostotic fibrous dysplasia

Fibrous dysplasia Clinical presentation

• First 2 decades (most patients <30)• M = F

Polyostotic fibrous dysplasia in McCune Albright Syndrome

http://tumorlibrary.com/

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Fibrous dysplasia Clinical presentation

• First 2 decades (most patients <30)• M = F

Craniofacial dysplasiahttp://maayafoundation.org/http://radiopaedia.org/images/

Fibrous dysplasia Clinical presentation

www.ijri.orghttp://radiopaedia.org/images/

Orbital wall involvement

http://eyewiki.aao.org/

Fibrous dysplasia Pathophysiology / Genetics

Fibrous dysplasia Pathophysiology / Genetics

GTPase mutations

Codon 201 Exon 8 ~60%

GTPase

CREB pathway

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GNAS and fibrous dysplasia Fibrous dysplasia Imaging

http://radiopaedia.org/images/ http://reference.medscape.com/

Fibrous dysplasia Pathology

Ossifying fibroma - like

Low-grade central osteosarcoma

Morita R et al. Low-grade central osteosarcoma of the orbit. J Craniofac Surg. 2012;23(3):e178-80.

Amplification of 12q13-15(MDM2 and CDK4 genes)

MDM2 and CDK4 protein overexpression

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Positive rate of GNAS mutation

Overall: 23% - 100%Long bones: 80%Flat bones: 43%

Craniofacial bones: ~50%

Fibrous dysplasia Diagnosis

• Clinical – radiographic – pathologic correlation

Fibrous dysplasia Prognosis

• Typically quiescent after puberty• Occasionally persistent growth • Malignant transformation

• Osteosarcoma > chondrosarcoma / fibrosarcoma

Management • Observation• Bone contouring• Curettage / resection• Optic nerve decompression / radical resection• Bisphosphonates• Radiation contraindicated

Ossifying fibroma Definition• Benign bone producing neoplasm,

composed of fibrocellular tissue and mineralized material of varying appearances

• Craniofacial skeleton – 2 variants:

1) Ossifying fibroma of odontogenic origin (cemento-ossifying fibroma, ossifying fibroma NOS)

2) Juvenile ossifying fibroma- Psammomatoid variant- Trabecular variant

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Ossifying fibroma Pathophysiology / Genetics

No GNAS1 mutations

Orbital ossifying fibroma:• Non-random chromosome break points at Xq26 and 2q33 - t(X;2)

Psammomatoid ossifying fibroma• MDM2 gene amplifications WITHOUT protein overexpression

Sawyer JR. Nonrandom Chromosome Breakpoints at Xq26 and 2q33 Characterize Cemento-Ossifying Fibromas of the Orbit. Cancer 1995;1853-9.

Clinical presentation• Average at presentation 16-33 years (range 3 mo-72 yrs)• F > M

Ossifying fibroma

Selva D et al. Primary bone tumors of the orbit. Surv Ophthalmol 2004;49:328-42.

http://www.entusa.com/

Ossifying fibroma Imaging

www.jaypeejournals.com http://www.jaypeejournals.com/

Ossifying fibroma Pathology

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Diagnosis• Clinical – radiographic – pathologic correlation

Ossifying fibroma

Ossifying fibroma

Management and Prognosis

• Progressive growth

• Multiple recurrences following incomplete excision

• Complete excision recommended

• Malignant transformation not reported

Definition• Benign lesion composed of mature bone

with predominantly lamellar structure• Almost exclusively identified in craniofacial skeleton

Osteoma

Pathophysiology / Genetics• Traumatic, infectious and developmental theories• No well-characterized genetic alterations

Association with Gardner syndrome

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OsteomaClinical presentation

• 4th – 5th decades (10 - 82 yrs)• M = F vs. M:F = 2:1• Most are asymptomatic and incidental

http://www.sarawakeyecare.com/

OsteomaImaging

OsteomaPathology

http://www.archivesofpathology.org/ Ivory osteoma

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Trabecular osteoma Osteoblastoma-like osteoma

Osteoma

Management and Prognosis

• Observation if asymptomatic

• Complete surgical resection (curative):• Symptomatic• Sphenoid sinus lesions

Osteoid osteoma and osteoblastoma

Definition• Benign osteoblastic tumors with overlapping

clinical, radiographic and histologic findings

Osteoid osteoma: • <1.5 cm in greatest dimension• Extremely rare in the head and neck region

Osteoblastoma: • >1.5 cm in greatest dimensions

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Pathophysiology / Genetics

• Not well understood

• Potential genetic overlap (clonal chromosomal abnormalities)

• Osteoid osteoma• Distinct structural chromosomal alterations (22q13)

• Osteoblastoma• Three-way translocations involving Chr 1, 2, 14• Rearrangement of 1q42

Osteoid osteoma and osteoblastoma

Clinical presentation• Distinct predilection for males, 10 – 20 years• Nocturnal pain in extraorbital lesions

Osteoid osteoma and osteoblastoma

Osteoid osteoma and osteoblastomaImaging

Nidus

Sclerotic rim

Pathology

Osteoid osteoma and osteoblastoma

Rim of sclerotic reactive lamellar bone

Central nidus

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Epithelioid (aggressive) osteoblastoma Osteoblastoma-like osteosarcoma

MDM2, CDK4, TOP2A, MACC1 amplification

Complex chromosomal alterationsLOH for Chr 3q, 13q, 17p, 18q

TP53 and RB1 mutations

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Management and Prognosis

Osteoid osteoma• Conservative surgical resection curative

Osteoblastoma • Can be locally aggressive (epithelioid osteoblastoma)• Recurrences following incomplete resection

or piecemeal removal• Complete excision recommended

• Risk of malignant transformation into osteosarcoma?? • Debated

Osteoid osteoma and osteoblastoma Selected cases

Osseous Tumor of the Orbital Bone

Osseous Tumor of the Orbital Bone

Nasreen A. Syed, M.D.F.C. Blodi Eye Pathology Laboratory

University of Iowa

Fibro-osseous orbital lesion

Michele M. Bloomer, MD Department of Ophthalmology UCSF

MIDFACIAL MASSSander R. Dubovy, MD

Florida Lions Ocular Pathology LaboratoryBascom Palmer Eye Institute

Sander R. Dubovy, MDFlorida Lions Ocular Pathology Laboratory

Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine

Midfacial MassEastern Ophthalmic Pathology Society

Boston, MA September 2005

15 y.o.Haitian girl with 3 year history of growing right mid-facial mass

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Ossifying fibroma

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Treatment Goals• En-block resection of tumor

• Reconstruction:• Floor of orbit• Right maxilla• Function• Cosmesis

Osseous Tumor of the Orbital Bone

Nasreen A. Syed, M.D.F.C. Blodi Eye Pathology Laboratory

University of Iowa

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8 year old boy, previously healthy

Progressive right proptosis x 6 weeks

2.7 x 1.8 x 1.6 cm mass

2.7 x 1.8 x 1.6 cm mass

Anterior orbitotomy with piece-meal removal of the lesion

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Osseous Tumor of the Orbital BonePathology

Diagnosis?

Diagnosis rendered in consultation with bone pathologist:

“Benign osseous neoplasm most consistent with osteoid osteoma”

Recurrent proptosis 1 month post-operatively

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Osseous Tumor of the Orbital BonePathology

Osseous Tumor of the Orbital BonePathology

Diagnosis

Diagnosis rendered in consultation with outside bone pathologist:

“Osteoblastic variant of osteosarcoma”

Initial clinical presentation, radiology and pathology re-review

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Fibro-osseous orbital lesion

Michele M. Bloomer, MDDepartment of OphthalmologyUniversity of California, San Francisco

Verhoeff Zimmerman Society MeetingApril 29 – May 2, 2010Hyatt Regency, Sarasota

65 year old, otherwise healthy Asian man with right eye swelling and diplopia x 6 weeks

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Lamellar bone

Woven bone

Disease Course

Immediate post-operative image revealed near gross total resection

No alteration in the residual mass >1 year after resection

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Paget’s Disease

Most patients >55 years

Skull frequently affected

Presents with diplopia and globe displacement

Polyostotic and monostotic forms

Radiographically similar to fibrous dysplasia

Can be self-limited

Rare in Asians

Paget’s Disease

Disordered bony remodeling – Early: osteoblastic and osteoclastic rimming

– Late: burnt out phase

Classic histologic feature “jigsaw puzzle”

Occasional transformation into osteosarcoma

Primary osseous and fibro-osseous orbital lesions

• Benign tumors• Fibrous dysplasia• Ossifying fibroma• Osteoma• Osteoblastoma

• Challenges in pathologic diagnosis• Fragmented nature of the specimens• Significant clinical, histologic, and radiographic

overlap

• Need for careful clinical-radiographic-pathologic correlation

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