The Pathology of Round Cell Sarcomas

1
The Pathology of Round Cell Sarcomas

• Angelo P. Dei Tos M.D.
• Departments of Pathology Oncology
• Treviso, Italy

2
Round cell neoplasms

• Round cell sarcomas
• ES/PNET
• Alveolar rhabdomyosarcoma
• Desmoplastic round cell tumor
• Mesenchymal chondrosarcoma
• Poorly differentiated synovial sarcoma
• Lymphomas
• Neuroendocrine carcinoma
• Neuroblastoma and variants

3
Tumor type Cytogenetic changes Gene
rearrangt Ewings sarcoma/PNET t(1122)(q24q12) F
LI-1-EWS t(2122)(q22q12) ERG-EWS t(722)(p22q
12) ETV1-EWS t(1722)(q12q12) EIAF-EWS t(222)(
q33q12) FEV-EWS Alveolar rhabdomyosarcoma t(213)
(q35q14) PAX3-FKHR t(113)(p36q14) PAX7-FKHR My
xoid/round cell liposarcoma t(1216)(q13q11) CHOP
-TLS t(1222)(q13q11-12) CHOP-EWS DSRCT t(1122)
(p13q12) WT1-EWS Synovial sarcoma t(X18)(p11.2q
11.2) SSX1-SYT SSX2-SYT Clear cell
sarcoma t(1222)(q13q12) ATF-1-EWS Extraskeletal
myxoid CHS t(922)(q22q12) TEC-EWS DFSP/GCF t(17
22)(q22q13) PDGFB-COL1A1 Infantile
fibrosarcoma t(1215)(p13q25) ETV6-NTRK3 Alveolar
soft part sarcoma t(X17)(p11q25) ASPL-TFE3 Low
grade fibromyxoid sarcoma t(716)(q33p11) FUS-BBF
2H7
4
EES/PNET

• 1 of all sarcomas
• Peak incidence between 1st and 3rd decades
• Paravertebral region/limbs
• Visceral locations
• 30 involves a major peripheral nerve
• Askins Tumor

5
(No Transcript)
6
ES/PNET
Homer-Wright
7
EES/PNETimmunohistochemistry

• CD99 positive 95
• LMW cytokeratins 20
• Neuroectodermal markers
• Synaptophysin 20
• FLI1 70

8
CD99 (MIC2 antigen)

• Glycoprotein/30-32 kD
• Limited homology with
  collagen-like proteins
• Expression ubiquitous
• Adhesion mechanisms
• MIC2 gene
• short arm of X and Y
• The ES/PNET marker (?)
• Low specificity

9
CD99 (MIC2 antigen)

• ES/PNET
• up to 100
• Poorly differentiated synovial sarcoma
• up to 100
• Merkel cell carcinoma
• up to 40
• Alveolar rhabdomyosarcoma
• up to 15
• Mesenchymal chondrosarcoma
• 80
• T Lymphoblastic Lymphoma/Leukemia
• 90
• Solitary fibrous tumor
• gt 80
• DSRCT
• 10/cytoplasmic

10
EES/PNET at unusual sites

• Skin
• DD Merkel cell carcinoma
• Uterus
• Pancreas
• Urinary bladder
• Kidney
• DD. Wilms tumor (blastemal variant)
• Meninges
• DD. Central PNET
• Heart

11
Cutaneous ES/PNET

• Polypoid
• Round cell tumors
• Good prognosis
• DD Neuroendocrine carcinoma (Merkel cell tumor)

12
CD99
13
CK20
14
(No Transcript)
15
(No Transcript)
16
(No Transcript)
17
(No Transcript)
18
Fli-1
CD99
S-100
EWS
Fli-1
19
EES/PNET and prognosis

• Multimodal therapy
• Long term survival 40 (was 10)
• EES better response
• Controversial
• Type-1 EWS-FLI1 fusion
• Independent positive prognostic factor (?)
• p53 expression/INK4A deletion
• Poor prognosis

20
CD99
21
Synovial Sarcoma

• 10 of ST sarcomas
• Young adults
• Lower Limbs/head neck/mediastinum
• Males gt females
• Biphasic/Monophasic spindle cell/epithelial
• SSX1/SSX2/SSX4-SYT chimera

22
Synovial Sarcoma
23
Biphasic
Monophasic
24
Poorly Differentiated Synovial Sarcoma

• 20 of cases of synovial sarcoma
• Round cell
• DD ES/PNET, DSRCT, ARMS and MCC
• Large cell
• DD Epithelioid sarcoma, ERT, PD carcinoma
• Spindle cell
• MPNST and fibrosarcoma

25
(No Transcript)
26
Synovial Sarcomaimmunohistochemistry

• Expression of epithelial markers
• EMA gt cytokeratins
• CK negative in 50 of PDSS
• CD99 (MIC2) positive
• 30 S-100 positive

27
Synovial Sarcoma at Unusual Sites

• Abdominal Cavity
• Visceral sites
• Mediastinum
• Larynx and Hypopharynx
• Lungs

28
EMA
bcl2
29
EMA
30
Synovial Sarcoma and Prognosis

• Adverse clinical outcome
• Tumor size gt 5 cm
• Neurovascular invasion
• p53 overexpression
• High Ki67 proliferation index
• Poorly differentiated areas
• SSX2 vs SSX1 ?

31
Desmoplastic small round cell tumor

• Peritoneal cavity
• Gerald Rosai, 1991
• Pleura and tunica vaginalis
• Meninges, maxillary sinus, somatic STT
• Peak incidence in 2nd decade
• Polyphenotypic expression
• Neuronal, epithelial, myoid markers
• EWS/WT1 Chimera
• Clinically aggressive

32
DSRCT
33
(No Transcript)
34
DSRCT
35
DSRCTImmunohistochemistry

• Cytokeratins
• CK20 and CK5/6 negative
• Ema
• Desmin - dot like
• Vimentin
• WT1

36
WT1
37
Take Home Messages

• Heterogeneous category
• Biologically aggressive
• Integrated diagnostic approach
• HE, IHC, FISH, Real Time PCR

38
Thanks to

• Treviso
• Sabrina Rossi
• Licia Laurino
• Luisa Toffolatti
• Giovanna Gallina
• Marta Campo DallOrto
• Chiara Sartor
• Lucia Zanatta
• Serena Chinellato

• Aviano
• Roberta Maestro
• Daniela Gasparotto
• Leiden
• Pancras Hogendoorn
• Karoli Shuzai
• Judith Bovee
• Boston
• Chris Fletcher
• Jason Hornick
• Massimo Loda

39
(No Transcript)