Case No 4 A 23yearold woman presented with a 3month history of - - PowerPoint PPT Presentation

Case No 4

A 23‐year‐old woman presented with a 3‐month history of progressive pain in her left knee. A well‐ circumscribed lytic lesion in the metaphyseal region

• f the fibula was detected. CT scan did not reveal

distant disease. Core biopsy was performed with a diagnosis of SRCT‐NOS due to scant material. Subsequently a resection of the tumor with clear margins was performed.

XXXII International Academy of Pathology Congress

PAS

CD99 CD99 NKX2.2 ETV4

Immunohistochemical negative results

• EMA, CK (AE1/AE3), CK18, CK5
• S100, p63, GFAP, CD10
• Melan‐A, HMB‐45, MITF1, SOX10, SOX9
• FLI‐1, CD34,ERG, CD31
• SMA, desmin, myogenin
• Chromogranin, Synaptophysin, CD56, TTF‐1
• WT1, BCOR, CCNB3

EWSR1

EWSR1 GENE AMPLIFICATION OF THE 5´

EWSR1/NFATC2

Molecular Biology negative results

• EWSR1/Fli1, EWSR1/ERG, EWSR1/ETV4, EWSR1/FEV
• EWSR1/ATF1, EWSR1/CREB1
• EWSR1/NR4A3
• EWSR1/PBX1, EWSR1/ZNF444, EWSR1/POU5F1

EWSR1/NFATC2 sarcoma: Molecular Biology

Charville GL et al, Modern Pathol, 2018

(nuclear factor of activated T‐cells, cytoplasmic, calcineurin‐dependent 2 also known as NFAT1 or NFATp ),

EWSR1/NFATC2 sarcomas

• Bone (8 cases) or soft tissue sarcoma (2 cases)
• Long bones of young men in the second/third decades
• Resemble a myoepithelial tumor, but immunophenotype

does not fit within this category.

• The clinical course is more indolent than that of Ewing

sarcoma (ES)

• Chemoresistant to the ES regimen. This lack of treatment

response suggests a biological difference between EWSR1‐ NFATC2 tumors and Ewing sarcoma.

Szuhai et al, Clin Cancer Res 2009. Cohen JN et al, Human Pathol, 2018 Charville GL et al, Modern Pathol, 2018 Baldauf MC, Modern Pathol, 2018

Srct tumor in young patients (bone or soft tissue) What are the most probable diagnoses?

‐Ewing sarcoma with Conventional EWSR1 gene fusion ‐Ewing with EWSR1/ETV4 and EWSR1/NFATC2 gene fusion ‐BCOR sarcomas ‐CIC‐DUX4 sarcomas ‐Myoepithelioma ‐Myxoid chondrosarcoma ‐Clear cell sarcoma. ‐Other undifferentiated srct (NOS)

EWSR1/NFATC2 sarcomas Diagnostic pitfalls

• Bone or soft tissue tumor
• Myoepithelioma‐like pattern
• EWSR1 translocation and EWSR1 amplification
• Lack of BCOR, NR4A3 and CIC rearrangement
• Frequent lack of myoepithelial markers
• Poor response to conventional Ewing treatment.

EWSR1 22q12 FUS/TLS 16p11

CHOP/DDIT3 12q13

myxoid liposarcoma

POU5F1; 6p21 PBX1; 1q23 ZNF444; 19q13

Myoepithelial carcinoma

NR4A3(TEC) 9q22

Myxoid chondrosarcoma

TAF15‐NR4A3 TCF12‐NR4A3 TFG‐NR4A3 WT1 11p13

Desmoplastic small round cell tumor

ETS family FLI‐1; 11q24 ERG; 21q22 FEV; 2q35 ETV1; 7p22 ETV4; 17q12 NFATC2; 20q13 SP3; 2q31 PATZ1; 1q36.1 SMARCA5; 4q31 ZSG; 22q12

ESFT ESFT‐LIKE

AML (FUS/ERG)

ESFT

FUS/ERG FUS/FEV

ATF1; 12q13 CREB3L1; 2q321

Pulmonary myxoid sarcoma (EWSR1/CREB1) Angiomatoid fibrous histiocytoma EWSR1/CREB1 FUS/ATF1 Classic clear cell sarcoma (EWSR1/ATF1) (EWSR1/CREB1) Clear cell sarcoma salivary gland (EWSR1/ATF1) Clear Cell Sarcoma–like Tumor of GIT (EWSR1/ATF1) (EWSR1/CREB1)

CREB3L2; 7q33 CREB3L1; 11p11

Low‐grade fibromyxoid sarcoma and subset of sclerosing epitheliod fibrosarcoma

SUMMARY OF FUSIONS IN CLASSICAL EWING SARCOMA AND EWING‐LIKE TUMORS

Renzi et al. J Cell Physiol.2018.1‐9

EWSR1/NFATC2 sarcoma

• Should it be excluded from the category of

Ewing‐like sarcomas and similar tumors ?

XXXII International Academy of Pathology Congress

Ewing‐like sarcoma with myoepithelioma‐like pattern and EWSR1/NFATC2 gene fusion

Antonio Llombart‐Bosch1, Isidro Machado2, Akihiko Yoshida3 ,Antonina Parafioriti4

1‐Pathology Department, University of Valencia, Spain 2‐Pathology Department, Instituto Valenciano de Oncología, Valencia, Spain. 3‐Pathology Department, National Cancer Center, Tokyo , Japan. 4‐Pathology Department, Centro Specialistico Ortopedico Traumatologico Gaetano Pini, , Milan, Italy

FOTO DE VALENCIA

VALENCIA: CITY OF ARTS AND SCIENCE

THANKS FOR YOUR ATTENTION