Sarcoma Andrew E Rosenberg, MD - PowerPoint Presentation

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Sarcoma

Andrew E Rosenberg, MD

Department of Pathology

University of Miami

Miami, Florida

Arosenberg@miami.edu

Address basic questions about its biologyProvide foundation of information – greater understanding

Cure

Sylvester Comprehensive Cancer Center

PATHOLOGY

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Derivation: New Latin, from Greek

sarkōma

,

sarkōmat

-, fleshy excrescence, from sarkoun, to produce flesh, from

sarx, sark-, flesh. Definition: Malignant tumor of connective tissue/muscleSar·co·ma (sär-kō'mə )

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Sarcoma Epidemiology

Approximately 15,000 new cases in U.S.

1 per 20,000 individuals

(625,000 breast, lung, and prostate – 1 per 480 individuals)

Account for 1% of cancers in adults and 15-20% of cancers in children

Approximately 6,200 sarcoma patients die each year – 17/day

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50%

9%

30%

20%

10%

Soft Tissue

Sarcomas

Thigh

Abdomen

Arm

Bone Sarcomas

Knee

Pelvis

Spine

Arm

10%

13%

Sarcoma Location

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Sarcoma Age Distribution

Develop in all age groups

Soft Tissue

Bone

Age (decades)

%

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Sarcoma Symptoms

Presence of a mass

Pain, swelling, progressive enlargement

Restriction of motion, bleeding

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Causes of Sarcoma

? Trauma

Underlying diseases - Paget

’

s disease,

bone infarction, radiation, syndromes - von Recklinghausens disease, Maffucci’s syndrome, Li Fraumani syndrome, bilateral retinoblastoma, Werner syndrome

Toxic exposuresAlterations of genetic material

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Mesenchymal Stem Cells

Expression of genes that determine phenotype (recapitulate normal tissue) and alter biologic traits

Mutations leading to

sequential and well-

orchestrated genetic changes

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Classification of Sarcoma

Phenotype - normal tissue counterpart

fibrous tissue, fat, skeletal muscle, endothelium, smooth muscle, skeletal muscle, cartilage, bone, notochord, peripheral nerve, …..

Fibrosarcoma, liposarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, leiomyosarcoma, etc.

70 types and subtypes90% sarcoma have normal counterpart, 8% no counterpart, but consistent findings, 2% unique.

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Sarcomas Genetics

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Genetics of Soft Tissue Sarcoma

approx. 1/3 of all sarcomas

15 different sarcoma types

with over 25 different

translocations

• fusion genes: aberrant chimeric transcription factors (most) or aberrant kinases (some)

approx. 2/3 of all sarcomas• biology: genetic gains &

losses, chromosomal instability,

telomere dysfunction

KEY CONCEPTS

• sarcomas contain their fusion gene from earliest presentation• sarcomas with fusion genes do not show benign or premalignant phase

• fusion gene in all tumor cells

• fusion gene expressed throughout clinical course

• biology: transcriptional deregulation or aberrant signaling

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Sarcoma Genetics

Competitive advantage to cancer cells

Induces phenotype

Stimulates cell proliferation

Evade cell growth inhibitors

Avoids apoptosis Fuels angiogenesis Facilitates invasion and metastasis

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Sarcoma Genetics

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Sarcoma Diagnosis

Review clinical information

Review imaging studies

Obtain tissue

Classify and grade sarcoma

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Types of Specimens

Plan tissue retrieval

Fine needle aspiration

Needle biopsy

Open biopsy

En block resectionFrozen section laboratory

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Sarcoma Diagnosis

Needle Biopsy

Identify sarcoma type and aggressiveness

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Desmoid Tumor High grade Spindle Cell Sarcoma

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Sarcoma Grade

Grade 1 Grade 2 Grade 3

Well differentiated Fibrosarcoma Osteosarcoma

Liposarcoma

Low risk Intermediate risk High risk

Risk of developing metastases

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Grading Sarcomas

Pathologic Grade- is single most important prognostic factor

Grade 1 (low grade, 2 (intermediate grade), and 3 (high grade)

mitotic activity, % necrosis, and degree of differentiation

Clinical Grade Low grade (pathologic grade 1)

High grade (pathologic grade 2 and 3)

Normal Low grade High grade

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Grading Sarcomas

Low Grade

High Grade

Grade 1

Grade 3

Grade 2

Well Differentiated Osteosarcoma Grade 2 Osteosarcoma Grade 3 Osteosarcoma

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Arch Pathol Lab Med

2006;130:1448.

FNCLCC Grading and Outcome

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Sarcoma Resection

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What does the patient need to know about the disease?

Histologic diagnosis (what is it?)

Prognosis (how bad is it?). size, grade, Adverse features

for localized: is it all gone? (margins)

What is the best treatment?

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Picasso at work

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