Disease |
Diagnostic Morphology or Immunohistochemistry |
Cytogenetic Event |
Molecular Abnormality |
Molecular Diagnostica |
Myxoid/round cell liposarcoma |
Lipoblasts, plexiform vasculature, myxoid atrix |
t(12;16)(q13;p11)t(12;22)(q13;q12) |
FUS-DDIT3 (>90%)EWSR1-DDIT3 (<5%) |
DDIT3 breaks (FISH)16,187 |
Ewing sarcoma family tumor |
Small, blue, round cells; CD99 and FLI1 expression; lack of lymphoid biomarker expression |
t(11;22)(q24;q12)t(21;22)(q22;q12)Alternative events: fusions of 22q12 with 7p22, 17q22, 2q33; inv 22q12; t(16;21) (p11;q22) |
EWSR1-FLI1 (>80%)EWSR1-ERG (10-15%)Other ETS family partners: ETV1, ETV4, FEV, PATZ1 (˜5%) FUS-ERG (<1%) |
EWSR1 breaks (FISH)36 or RT-PCR |
Desmoplastic small, round cell tumor |
Small, blue, round cell islands in dense stroma; positive for keratin, desmin, vimentin, and WT1 |
t(11;22)(p13;q12) |
EWSR1-WT1 (>75%) |
EWSR1 breaks (FISH)36 |
Synovial sarcoma |
Biphasic histology, positive for TLE164 |
t(X;18)(p11;q11) (>90%) |
SYT-SSX1 (66%), SYT-SSX2 (33%), SYT-SSX4 (<1%) |
SYT breaks (FISH)188 |
Alveolar rhabdomyosarcoma |
Small, blue cells expressing desmin, myogenin, myoD1 |
t(2;13)(q35;q14)t(1;13)(p36;q14) |
PAX3-FOXO1 (˜80%)PAX7-FOXO1 (˜20%)PAX3-NCOA1 (<1%) PAX3-NCOA2 (<1%) |
PAX3/7 typespecific FISH or RT-PCR189 |
Alveolar soft-part sarcoma |
Nested polygonal cells in vascular network; positive for TFE378 |
t(X;17)(p11;q25) |
ASPSCR1-TFE3 (>90%) |
ASPSCR1-TFE3 RT-PCR190 |
Dermatofibrosarcoma protuberans |
Bland spindle cells, storiform and honeycomb growth in subcutis, positive for CD34 |
Rings derived from t(17;22) (>75%)t(17;22)(q22; q13.1)86,87,191 (10%) |
COL1A1-PDGFB |
Embryonal rhabdomyosarcoma |
Spindle cells and rhabdomyoblasts, positive for desmin and myogenin |
Trisomies 2q, 8 and 20 (>75%) |
LOH at 11p15 (>75%) |
Extraskeletal myxoid chondrosarcoma |
Bland epithelioid cells arranged in reticular pattern in myxoid stroma |
t(9;22)(q22;q12) |
EWSR1-NR4A3 (75%) |
EWSR1 breaks (FISH); RT-PCR95-97 RT-PCR95-97 |
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t(9;17)(q22;q11)t(9;15)(q22;q21)t(3;9)(q12;q22) |
TAF15-NR4A3 (<10%)TCF12-NR4A3 (<10%) TFG-NR4A3 (<5%) |
Endometrial stromal tumor |
Bland spindle cells, positive for CD10 and ER |
t(7;17)(p15;q21) |
JAZF1-SUZ12 (30%) |
Clear cell sarcoma |
Nested epithelioid cells with clear or amphophilic cytoplasm, positive for S100 and HMB-45 |
t(12;22)(q13;q12)t(2;22)(q34;q12) |
EWSR1-ATF1 (>75%)EWSR1-CREB1 (<5%) |
EWSR1 breaks (FISH)36,192 |
Infantile fibrosarcoma |
Monomorphic spindle cells, herringbone pattern |
t(12;15)(p13;q25) |
ETV6-NTRK3 (>75%) |
FISH, RT-PCR |
Inflammatory myofibroblastic tumor |
Myofibroblastic cells with lymphoplasmacytic infíltrate, positive for ALK |
t(1;2)(q25;p23)t(2;19)(p23;p13)t(2;17)(p23;q23) |
ALK-TPM34 ALK-TPM ALK-CLTC |
ALK breaks (FISH) |
Gastrointestinal stromal tumor |
Spindle (70%), epithelioid (20%) or mixed (10%) morphology, positive for CD117 (KIT), DOG1, and CD34 |
Monosomies 14 and 22 (>75%)Deletion of 1p (>25) |
KIT or PDGFRA mutation (>90%)193,194 |
PCR mutation analysis |
Desmoid fibromatosis |
Bland myofibroblastictype cells, fascicular growth, nuclear positivity for β-catenin |
Trisomies 8 and 20 (30%) |
APC inactivation by mutation/deletion (10%)CTNNB1 (β-catenin) mutations (85%) |
IHC for β-catenin expression |
Well-differentiated/dedifferentiated liposarcoma |
Atypical multinucleated stromal cells, lipoblasts, positive for MDM2, CDK4 |
12q13-15 rings and giant markers |
MDM2 and CDK4amplification (>85%) |
MDM2 amplification (FISH) |
Pleomorphic liposarcoma |
Pleomorphic spindle and giant cells, pleomorphic lipoblasts |
Complexb (>90%) |
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None |
Myxofibrosarcoma and pleomorphic MFH |
Pleomorphic spindle and giant cells, storiform growth, variable myxoid stroma |
Complexb (>90%) |
SKP2 amplification |
None |
Leiomyosarcoma |
Elongated fusiform cells with eosinophilic cytoplasm, in intersecting fascicles, positive for desmin and smooth muscle actin |
Complexb (>50%) Deletions of 1p |
RB1 point mutations/deletions |
None |
Malignant peripheral nerve sheath tumor |
Monomorphic spindle cells, high mitotic count, geographic necrosis |
Complexb (90%) |
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None |
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NF1 mutation, loss or deletion (>50%) |
None |
FISH, fluorescence in situ hybridization; RT-PCR, reverse transcription polymerase chain reaction; LOH, loss of heterozygosity; IHC, immunohistochemistry; MFH, malignant fibrous histiocytoma. |
a Refers to molecular tests that can be run on formalin-fixed paraffin-embedded material for molecular confirmation of diagnosis: quantitative RT-PCR of transcripts,189 or FISH to interphase genomic DNA.195b Complex karyotypes containing multiple numerical and structural chromosomal aberrations. |