CONTRIBUTION OF CHROMOSOME BANDING AND MOLECULAR

CYTOGENETIC ANALYSES FOR THE DIAGNOSIS OF SOFT TISSUE AND BONE

TUMORS OVER A 6-YEAR-PERIOD

Manuel Teixeira, MD, PhD Head of Department of Genetics

Carlos Lopes, MD, PhDDepartment of Pathology

Portuguese Oncology Institute, Porto, Portugal

Differential diagnosis:Small round cell tumors

Tumor type Cytogenetics Genes

Ewing’s sarcoma/PNET t(11;22)(q24;q12)t(21;22)(q22;q12)

FLI1/EWSERG/EWS

Alveolar rhabdomyosarcoma t(2;13)(q35;q14)t(1;13)(p36;q14)

PAX3/FKHRPAX7/FKHR

Desmopl. small round cell t. t(11;22)(p13;q12) WT1/EWS

Neuroblastoma del(1p), hsr, dmin MYCN

Non-Hodgkin lymphoma Typical changes IG/V, TCR/V

Ewing’s sarcoma/PNET

3’EWS5’EWS

Alveolar rhabdomyosarcoma with PAX7-FKHR Bone marow; no primary tumor found

3’FKHR5’FKHR

Differential diagnosis: Lipomatous tumors

Tumor type Cytogenetics

Lipoma 12q13~15 changes6p changes13q deletions

Atypical lipoma/WD liposarcoma +r/mar

Lipoblastoma 8q11~13 changes

Fusocellular lipoma 16q13~qter deletions

 Hybernoma 11q13~21 changes

 Liposarcoma- myxoid/round cell t(12;16)(q13;p11)

- pleomorphic Complex changes

Atypical lipoma/Well-differentiated liposarcoma

5’CHOP3’CHOP

Ampl. MDM2/CDK4

Myxoid/round cell liposarcoma

5’CHOP3’CHOP

Differential diagnosis: Fusocellular sarcomas

Tumor type Cytogenetics

Synovial sarcoma t(X;18)(p11;q11)

Fibrosarcoma Complex karyotype

Malign. perypheral nerve sheath t. Complex karyotype

Synovial sarcoma

5’SYT3’SYT

6942%

4025%

5433%

Pathognomonic

Informative

Non-specific

Types of genetic findings and their relevance for differential diagnosis

N=163/614

Apr. 2001 - Mar. 2007

Patients with a pathognomonic genetic finding

1726%

1420%

1116%

46%

23%

23%

11%

11%

11%

11%

1522%

Well-differentiatedliposarcomaEwing's sarcoma/PNET

Synovial sarcoma

Myxoid/round cellliposarcomaAlveolarrhabdomyosarcomaLipoma

Benign schwanoma

Extraskeletal myxoidchondrosarcomaDermatofibrosarcomaprotuberansLung hamartoma

Clear cell sarcoma

2

1

5

2

1

11

1

1

1

2

1

2

2

10

12

12

14

58

0% 20% 40% 60% 80% 100%

Extraskeletal myxoid chondrosarcoma

Dermatofibrosarcoma protuberans

Lung hamartoma

Lipoma

Clear cell sarcoma

Benign schwanoma

Alveolar rhabdomyosarcoma

Myxoid/round cell liposarcoma

Well-differentiated liposarcoma

Synovial sarcoma

Ewing's sarcoma/PNET

Total

Desagreement rate in patients with a pathognomonic genetic finding

2 ERMS

Extraskel. myxoid chondrosarcoma

2 lipomas, 2 myxoidlipos; 1 MSFT

Small cell osteos.

1 myxoid lipos;1 sarcoma NOS

Patients with informative but not pathognomonic genetic findings

1128%

1333%

1639% Decisive

Compatible

Not compatible

Patients with informative genetic findingsdecisive for differential diagnosis

328%

218%

19%

19%

19%

19%

19%

19%

Lipoma

Melanoma metastasis

Fibrosarcoma

Carcinoma metastasis

Malignant schwanoma

Tendon sheathsarcomaSarcoma NOS

Malignant solitaryfibrous tumor

Patients with informative genetic findingscompatible with morphologic diagnosis

322%

214%

18%

18%

18%

18%

18%

18%

18%

18%

EmbryonalrhabdomyosarcomaCarcinoma

Renal cell carcinoma

Chondroma

GIST

Malignant fibroushystiocytomaLipoma

Ossifying myositis

PleomorphicrhabdomyosarcomaSmall cell sarcoma

Patients with informative genetic findingsnot compatible with morphologic diagnosis

424%

319%

319%

213%

213%

16%

16%

Malignant schwanoma

Extraskeletal myxoidchondrosarcoma

Ewing's sarcoma/PNET

Myxoid/round cellliposarcoma

Synovial sarcoma

Pleuropulmonar blastoma

Well-differentiatedliposarcoma

Conclusions

42% of the tumors with genetic changes presented a pathognomonic chromosome alteration

Additional 25% of the tumors with genetic changes had an informative result for differential diagnosis

In 16% of the tumors presenting a pathognomonic chromosome change, the initial morphologic diagnosis was changed as a result of the cytogenetic finding

The tumor types that benefited most from the cytogenetic data for their correct diagnosis were alveolar rhabdomyosarcoma, well differentiated liposarcoma, synovial sarcoma, Ewing’s sarcoma, and myxoid liposarcoma

Thanks!