Pediatric Soft Tissue Tumors Jerzy Klijanienko MD PhD MIAC Institut Curie Paris, France
1 - - General
2 - - Cancer incidence in children
Type of malignancy % Hematology 38.6 CNS 19 Neuroblastoma 9.2 Kidney 8.7 Soft tissue 6.8 42.4% Bone 4 Retinoblastoma 3.7 Germ cell tumors 3.4 Liver 1.2 Others 5.4
3 - - Anterior: Lymphoma, germ cell tumours
Mediastinum: Midlle: Lymphoma, germ cell tumours
Posterior: Ganglioneuroblastoma, neuroblastoma
Lung: Pleuropulmonary blastoma, Ewing-family tumours
Thorax: Ewing-family tumours, synovial sarcoma
Limbs: Congenital fibrosarcoma Rabdomyosarcoma Synovial sarcoma Ewing-family tumours Osteosarcoma Vascular tumours
Retroperitoneum and abdominal cavity: Lymphoma Germ cell tumours Ewing-family tumours Neuroblastoma Rhabdomyosarcoma Desmoplastic small round cell tumour Synovial sarcoma Kidney: Nephroblastoma, rhabdoid tumour, clear cell sarcoma, mesoblastic nephroma Liver: Hepatoblastoma, mesenchymal hamarthoma, adenoma 4 - - From Barocca and Bom Sucesso - 2014 Vascular tumours Germ cell tumours
Retinoblastoma Ewing-family tumours
‘Non-small cell’ sarcoma Langerhans histiocytosis Synovial sarcoma
Neuroblastoma, not otherwise specified
Pleuropulmonary blastoma Epithelioid tumour Rhabdomyosarcoma
Nephroblastoma Carcinoma Embryonal sarcoma Rhabdoid tumour Anaplastic large cell lymphoma
Clear cell sarcoma Burkitt lymphoma Osteosarcoma Hepatoblastoma Lymphoblastic /Diffuse large B-cell lymphoma Mesoblastic nephroma Congenital fibrosarcoma Hodgkin Hodgkin lymphoma lymphoma
0 2 10 18 5 - - From Barocca and Bom Sucesso 2014 Technical aspects
Surgical biopsy
Core needle biopsy
Fine needle biopsy (aspiration)
Molecular diagnosis
6 - - Tumor board meeting before biopsy is mandatory surgeons oncologists
radiologists
anaesthesiologists
pathologists Procedure
8 - - Which procedure ?
FNA Percutaneous Surgical +/- CNB biopsy cell-block Enough +/- to +++ +/- to +++ ++ to +++ material
Safe +++ +++ +/- to ++
Easy +++ +/- to +++ +/- to +
Low cost +++ ++ - Diagnostic samples distribution
CNB FNA CB
Diagnosis Cryopreservation Pool
Karyotyping Molecular Diagnosis Flow Cytometry
10 - - 11 - - Palpable lesions
12 - - Calinox ® 13 - - Emla ® 14 - - Pool Cryopreservation CNB
CB
FNA 15 - - Non-palpable lesions
Ultrasound-guided
16 - - 17 - - 18 - - 19 - - Morphologic and molecular diagnoses
20 - - 21 - - CNB or Cell bloc
Diagnosis Immunohistochemistry
22 - - 23 - - Two main groups of STT
24 - - Spindle cell tumors (mainly superficial in children)
25 - - Proposed cytological classification
Low-grade spindle cell tumors Tumors with fibrillary stroma Malignant spindle-cell tumors Myxoid tumors Atypical lipomateous tumors Pleomorphic sarcomas Epithelioid tumors Round cell sarcomas
26 - - Morphological approach in FNA to differentiate STT
Low-grade spindle cell tumors
Spindle and oval cells without prominent cytonuclear atypia Mitotic figures are scant or absent Connective debris Naked nuclei No necrosis Inflammatory cells Variable cellularity
27 - - Morphological approach in FNA to differentiate STT (in pediatrics)
Low-grade spindle cell tumors Possibility of diagnosis:
1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Congenital enfantile fibrosarcoma
28 - - Spindle cell tumors – molecular
Entity Chromosome Gene fusions
abnormality
Fibromatoses / desmoids Beta Catenin
Nodular fasciitis t(17;22)(p13;q12.3) USP6-MYH9
DFSP t(17;22)(q21.33;q13.1) COLIA1/PDGFB
Cong. Enf. Fibrosarcoma t(p12;q15)(p13.2;q25.3) ETV6/NTRK3
+ STAT6 antibody (SFT)
29 - - Low-grade spindle cell tumors
1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma
30 - - 31 - - 32 - - 33 - - 34 - - 35 - - 36 - - Clinical and Fine Needle Aspiration Key Features
In favor - Poorly cellular material comprising spindle-shaped regular cells - Hyalinized tissue fragments - Characteristic clinical and radiological presentations Difficulties - Some smears may be rich with a mixture of fibroblasts/myofibroblasts
Against - Atypical cells, numerous mitotic figures
37 - - Low-grade spindle cell tumors
1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma
38 - - 39 - - 40 - - Clinical and Fine Needle Aspiration Key Features
In favor - Hypercellular smears showing mononuclear cells with eccentric, regular nuclei - Multinucleated giant cells - Macrophages or inflammatory background Difficulties - Mitotic figures or Myxoid background
Against - Necrosis, important cytonuclear atypia, atypical mitoses
41 - - Low-grade spindle cell tumors
1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma
42 - - 43 - - 44 - - 45 - - 46 - - Storiform
47 - - 48 - - 49 - - 50 - - 51 - - Clinical and Fine Needle Aspiration Key Features
In favor - Smears rich in spindle cells isolated or clustered - Discrete cytonuclear atypia.
Difficulties - Rare mitotic figures
Against -Numerous mitotic figures -Giant multinucleated cells, histiocytic cells - Fibrillary stroma
52 - - Low-grade spindle cell tumors
1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Cong Inf Fibrosarcoma
53 - - 54 - - 55 - - 56 - - 57 - - 58 - - 59 - - Clinical and Fine Needle Aspiration Key Features In favor - Spindle and polymorphous cells - Aggregates of connective tissue - Wavy fascicles - No mitotic activity - Deep soft tissue mass - Exclusion of other spindle-shaped tumor Difficulties - Some smears may be paucicellular - Roundish/epithelioid cells Against - Giant cells - Fibrillary stroma - Epithelial cells - High cellularity - Lipoblasts 60 - - 61 - - 62 - - Content
- 161 children and adolescents in last 20 yrs
- malignant 44%, benign 32% and pseudotumors in 24%.
- The diagnosis of benign was made in 50% using clinico-radiologic data, - The diagnosis of benign was made in 79% in benign and in 86% in pseudotumors using FNA.
- The diagnosis of malignant was made in 39% using clinico-radiologic data, - The diagnosis of malignant was made in 89% using FNA.
63 - - Round cell tumors
64 - - Round cell tumors
Round cell sarcomas Diagnosis by definition
Round cell tumors Diagnosis by round cell component
65 - - Proposed cytological classification 2011
Low-grade spindle cell tumors Tumors with fibrillary stroma Malignant spindle-cell tumors Myxoid tumors Atypical lipomateous tumors Pleomorphic sarcomas Epithelioid tumors Round cell sarcomas
66 - - Morphological approach to differentiate STT
Round cell sarcomas Roundish, clearly malignant cells Moderate cytonuclear atypia Numerous mitotic figures Necrosis may be present Usually extremely high cellularity
67 - - Morphological approach to differentiate STT
Round cell sarcomas Diagnosis by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
68 - - Morphological approach to differentiate STT
Round cell tumors Diagnosis by round cell component
1. Poorly diff synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
69 - - Morphological approach to differentiate STT Round cell sarcomas How to diagnose ?
- Clinical and radiological informations are important - Round cell pattern (RCP) * Specific RCP for diagnosis (NB, Ewing, ….) ** Not specific RCP for diagnosis - Immuno(histo/cyto)chemistry - Specific molecular alterations in many entities
70 - - Morphological approach to differentiate STT Round cell sarcomas Strong points of FNA
- Round cell pattern (RCP) well seen - Hypercellular material * Cell pooling for molecular techniques ** Cell blocs for IHC - Rapidity - On situ diagnosis for CNB indication etc….
71 - - Morphological approach to differentiate STT Round cell sarcomas What to do on morphology ?
- Search for rhabdomyoblasts, binucleation, rosettes, and double cell population - Chondroid is usually well detected - Poorly differentiated synovial sarcoma may mimick Ewing sarcoma, search for rosettes and double cell population
72 - - Morphological approach to differentiate STT Round cell sarcomas What to do on ICH ?
NB84 INI1/SMARB1 Chromogranin Synaptophisin CD45-RB-LCA Desmin MyoD1 CD99-Mic2 AE1/AE3
73 - - Morphological approach to differentiate STT Round cell sarcomas What to do in molecular diagnosis ?
-PCR -FISH -Karyotyping -CGH
FISH with a EWSR1 dual- color breakapart probe on a Ewing tumor
74 - - Molecular specific diagnosis in RCT
PNET/Ewing: fusion transcript EWS FLI (85%) Alveolar RMS: fusion transcript PAX FKHR Allelic loss of 1p36 in neuroblastoma Desmoplastic small round cell tumor: EWS/WT1 Synovial sarcoma: SYT/SSX1 or 2 or 4
75 - - Round cell sarcomas by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
76 - - Round cell sarcomas by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
77 - - RMS
0102823 78 - - 0105779
RMS
79 - - Why FNA?
To diagnose RMS To provide material for karyotyping or molecular biology techniques Atypical sites
80 - - RMS 81 - - 82 -RMS - RMS83 - - -desmin Cellular components
Rhabdomyoblasts Excentric nuclei Binucleated cells Spindle-shaped cells Abundant cytoplasms
84 - - 85RMS - - RMS-alv 86 - - RMS-alv 87 - - 88 - - RMS-alv 89 - - 90 - - Gluteal 91 - - 92 - - 93 - - Clinical and Fine Needle Aspiration Key Features (RMS)
Yes -Roundish cells, rhabdomyoblastic cells, alveolar structures, positivity of muscular markers -Specific fusion transcript PAX FKHR (alveolar) Maybe - Polymorphous morphology, spindle-shaped cells
No - Double round cell population - Rosettes - Perinuclear inclusions - Papillary structures - Epithelial cells
94 - - Round cell sarcomas by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
95 - - 96 - - PNET 97 - - 9906270 Why FNA?
To diagnose Ewing/PNET To provide material for karyotype or molecular biology techniques
98 - - PNET/EWING 99 - - PNET/EWING 100 - - Cellular components
Round, irregular cells « neuroendocrine » pattern Rosette-like structures
101 - - PNET/EWING 102 - - 103 - - 104PNET/EWING - - 105 - - PNET/EWING-cell bloc 106 - - 107 - - 108 - - Clinical and Fine Needle Aspiration Key Features (ES/PNET) Yes -Young adult - Double population of large and small cells - Rosette formation - CD99 + - Specific fusion transcript EWS FLI and karyotypic translocation (85%) Maybe - Spindle cells, necrosis - Extraskeletal localizations - No specific genomic abnormality or absence of abnormality (15%) No - Fibrillary stroma - Osteoid
109 - - Round cell sarcomas by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
110 - - 111 - - 112 - - Desmin113 - - Clinical and Fine Needle Aspiration Key Features (DSRCT)
Yes - Age - Intraabdominal site - Poorly differentiated round cells with inconspitious cytoplasm - Paranuclear cytoplasmic densities (Inter fil +) - Specific molecular transcript (EWS/WT1) Maybe - Sarcomateous polymorphous cells - Extensive necrosis
No - Rhabdomyoblasts, fibrillary stroma, rosettes.
114 - - Round cell sarcomas by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
115 - - 116 - - 117 - - Clinical and Fine Needle Aspiration Key Features (EMCS)
Yes -Double component of small round cells and malignant chondroid -Specific molecular transcript (EWSR1, TAF15, TCF12/NR4A3)
Maybe - Lack of malignant chondroid component
No - Rosettes, physaliphorous cells
118 - - Round cell sarcomas by definition
1. Embryonnal and alveolar rhabdomyosarcoma 2. Ewing sarcoma/pPNET 3. Desmoplastic small round cell tumor 4. Extraskeletal mesenchymal chondrosarcoma 5. Rhabdoid tumor
119 - - Rhabdoid tumor
1978 RMS-like morphology Kidney and extra-kidney localizations Homozygous deletion of 22q11-12 60% in the first year, 85% in 2 yrs Aggressive behaviour
120 - - Rhabdoid tumor
Monomorphous appearance RMS-like proliferation Dispersed cells Epithelioid cords Cytoplasmic inclusions
121 - - Why FNA?
To diagnose Rhabdoid tumor To provide material for karyotyping or molecular biology techniques
122 - - C A B
Enfant de 14 mois présentant une masse cervicale droite isolée, prise initialement pour une malformation artérioveineuse et surveillée. Progression clinique rapide en 3 mois (figure A) faisant redresser le diagnostic en tumeur rhabdoïde des parties molles. Aspect IRM coronal T2 (figure B) et axial T2 Fat Sat (figure C). RbT 124 - - EMA 125 - - Cellular components
Rhabdomyoblasts-like Perinuclear bodies Nucleoli
126 - - RbT 127 - - RbT
128 - - RhT 129 - - Clinical and Fine Needle Aspiration Key Features (RT)
Yes - Young age, kidney localization - Round-to-oval rhabdomyoblastic cells - Perinuclear inclusions that are keratin (+) - SMARB1/INI1 negativity Maybe - Lack of perinuclear densities. - Epithelioid pattern with clusters
No - True rhabdomyoblasts, alveolar structures
130 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
131 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma (spindle?) 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
132 - - 133 - - 134 - - 135 - - Clinical and Fine Needle Aspiration Key Features (SS)
Yes - Highly cellular smears with oval-to-spindle- shaped cytoplasm - Branching tumor tissue fragmentsand vessel stalks -Cohesive epithelial cells in biphasic subtype -SYT/SSX1 or 2 or 4 abnormality Maybe - Secretory mucin - Rosette-like structures - Mitotic figures and connective stromal components are usually scarce No - True rosettes - Double population of roundish cells
136 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
137 - - 138 - - 139 - - Clinical and Fine Needle Aspiration Key Features (MLipoSa) Yes - Abundant myxoid background - Isolated and regular small spindle-shaped and stellated cells - Extremities dermal and subcutaneous localization - FUS, EWSR1/DDIT3 abnormality Maybe - Round cells - Giant multinucleated cells - Lack of cytonuclear atypia No - High-grade atypical cells and mitotic figures - Deep localization
140 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
141 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
142 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
143 - - 0002524
Histiocytosis X
144 - - Why FNA?
To confirm diagnosis Clinics + Radiology + FNA = Diagnosis
145 - - Cellular components
Eosinophilic leukocytes Macrophages Mono-, bi-, multinucleated cells
146 - - H-X 147 - - 148 - - Tumors with RC component
1. Poorly differentiated synovial sarcoma 2. Round cell myxoid liposarcoma 3. Neuroblastic tumors 4. Nephroblastoma 5. Langerhans cell histiocytosis 6. Round cell osteosarcoma
149 - - 150 - - Thank you !!!!
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