Pediatric Soft Tissue Tumors - PDF Free Download

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 4 - - From Barocca and Bom Sucesso - 2014 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

Vascular tumours Germ cell tumours Retinoblastoma Langerhans histiocytosis Ewing-family tumours Non-small cell sarcoma Synovial sarcoma Neuroblastoma, not otherwise specified Pleuropulmonary blastoma Rhabdoid tumour Hepatoblastoma Mesoblastic nephroma Congenital fibrosarcoma Nephroblastoma Clear cell sarcoma Hodgkin lymphoma Epithelioid tumour Rhabdomyosarcoma Carcinoma Embryonal sarcoma Anaplastic large cell lymphoma Burkitt lymphoma Osteosarcoma Lymphoblastic /Diffuse large B-cell lymphoma Hodgkin 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 oncologists surgeons radiologists anaesthesiologists pathologists

Procedure 8 - -

Which procedure? Enough material FNA +/- cell-block Percutaneous CNB Surgical biopsy +/- to +++ +/- to +++ ++ to +++ Safe +++ +++ +/- to ++ Easy +++ +/- to +++ +/- to + Low cost +++ ++ -

Diagnostic samples distribution CNB CB FNA Diagnosis Cryopreservation Pool Karyotyping Molecular Diagnosis Flow Cytometry 10 - -

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Palpable lesions 12 - -

13 - - Calinox Emla

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Pool Cryopreservation CNB CB 15 - - FNA

Non-palpable lesions Ultrasound-guided 16 - -

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Morphologic and molecular diagnoses 20 - -

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CNB or Cell bloc Diagnosis Immunohistochemistry 22 - -

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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 Fibromatoses / desmoids Chromosome abnormality Beta Catenin Gene fusions 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 - -

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Clinical and Fine Needle Aspiration Key Features In favor Difficulties Against - Poorly cellular material comprising spindle-shaped regular cells - Hyalinized tissue fragments - Characteristic clinical and radiological presentations - Some smears may be rich with a mixture of fibroblasts/myofibroblasts - Atypical cells, numerous mitotic figures 37 - -

Low-grade spindle cell tumors 1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma 38 - -

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Clinical and Fine Needle Aspiration Key Features In favor Difficulties Against - Hypercellular smears showing mononuclear cells with eccentric, regular nuclei - Multinucleated giant cells - Macrophages or inflammatory background - Mitotic figures or Myxoid background - 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 - -

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Storiform 47 - -

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Clinical and Fine Needle Aspiration Key Features In favor Difficulties - Smears rich in spindle cells isolated or clustered - Discrete cytonuclear atypia. - 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 - -

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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 - -

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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 - -

64 - - Round cell tumors

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 dualcolor 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 - -

RMS 78 - - 0102823

0105779 RMS 79 - -

Why FNA? To diagnose RMS To provide material for karyotyping or molecular biology techniques Atypical sites 80 - -

RMS 81 - -

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RMS-desmin 83 - -

Cellular components Rhabdomyoblasts Excentric nuclei Binucleated cells Spindle-shaped cells Abundant cytoplasms 84 - -

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RMS-alv 86 - -

RMS-alv 87 - -

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RMS-alv 89 - -

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Gluteal 91 - -

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Clinical and Fine Needle Aspiration Key Features (RMS) Yes Maybe No -Roundish cells, rhabdomyoblastic cells, alveolar structures, positivity of muscular markers -Specific fusion transcript PAX FKHR (alveolar) - Polymorphous morphology, spindle-shaped cells - Double round cell population - Rosettes - Perinuclear inclusions - Papillary structures - Epithelial cells 94 - -

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97 - - PNET 9906270

Why FNA? To diagnose Ewing/PNET To provide material for karyotype or molecular biology techniques 98 - -

99 - - PNET/EWING

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Cellular components Round, irregular cells «neuroendocrine» pattern Rosette-like structures 101 - -

102 - - PNET/EWING

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PNET/EWING 104 - -

105 - - PNET/EWING-cell bloc

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Clinical and Fine Needle Aspiration Key Features (ES/PNET) Yes Maybe No -Young adult - Double population of large and small cells - Rosette formation - CD99 + - Specific fusion transcript EWS FLI and karyotypic translocation (85%) - Spindle cells, necrosis - Extraskeletal localizations - No specific genomic abnormality or absence of abnormality (15%) - Fibrillary stroma - Osteoid 109 - -

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113 - - Desmin

Clinical and Fine Needle Aspiration Key Features (DSRCT) Yes Maybe No - Age - Intraabdominal site - Poorly differentiated round cells with inconspitious cytoplasm - Paranuclear cytoplasmic densities (Inter fil +) - Specific molecular transcript (EWS/WT1) - Sarcomateous polymorphous cells - Extensive necrosis - Rhabdomyoblasts, fibrillary stroma, rosettes. 114 - -

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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 No - Lack of malignant chondroid component - Rosettes, physaliphorous cells 118 - -

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 - -

A B C 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 - -

129 - - RhT

Clinical and Fine Needle Aspiration Key Features (RT) Yes Maybe No - Young age, kidney localization - Round-to-oval rhabdomyoblastic cells - Perinuclear inclusions that are keratin (+) - SMARB1/INI1 negativity - Lack of perinuclear densities. - Epithelioid pattern with clusters - 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 - -

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Clinical and Fine Needle Aspiration Key Features (SS) Yes Maybe No - Highly cellular smears with oval-to-spindleshaped cytoplasm - Branching tumor tissue fragmentsand vessel stalks -Cohesive epithelial cells in biphasic subtype -SYT/SSX1 or 2 or 4 abnormality - Secretory mucin - Rosette-like structures - Mitotic figures and connective stromal components are usually scarce - True rosettes - Double population of roundish cells 136 - -

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Clinical and Fine Needle Aspiration Key Features (MLipoSa) Yes Maybe No - Abundant myxoid background - Isolated and regular small spindle-shaped and stellated cells - Extremities dermal and subcutaneous localization - FUS, EWSR1/DDIT3 abnormality - Round cells - Giant multinucleated cells - Lack of cytonuclear atypia - High-grade atypical cells and mitotic figures - Deep localization 140 - -

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 - -

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151 - - Thank you!!!!