Pediatric Soft Tissue Tumors
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1 Pediatric Soft Tissue Tumors Jerzy Klijanienko MD PhD MIAC Institut Curie Paris, France 1 - -
2 General 2 - -
3 Cancer incidence in children Type of malignancy % Hematology 38.6 CNS 19 Neuroblastoma 9.2 Kidney 8.7 Soft tissue % Bone 4 Retinoblastoma 3.7 Germ cell tumors 3.4 Liver 1.2 Others
4 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 From Barocca and Bom Sucesso 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
5 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 From Barocca and Bom Sucesso 2014
6 Technical aspects Surgical biopsy Core needle biopsy Fine needle biopsy (aspiration) Molecular diagnosis 6 - -
7 Tumor board meeting before biopsy is mandatory oncologists surgeons radiologists anaesthesiologists pathologists
8 Procedure 8 - -
9 Which procedure? Enough material FNA +/- cell-block Percutaneous CNB Surgical biopsy +/- to +++ +/- to to +++ Safe /- to ++ Easy +++ +/- to +++ +/- to + Low cost
10 Diagnostic samples distribution CNB CB FNA Diagnosis Cryopreservation Pool Karyotyping Molecular Diagnosis Flow Cytometry
11 11 - -
12 Palpable lesions
13 Calinox Emla
14 14 - -
15 Pool Cryopreservation CNB CB FNA
16 Non-palpable lesions Ultrasound-guided
17 17 - -
18 18 - -
19 19 - -
20 Morphologic and molecular diagnoses
21 21 - -
22 CNB or Cell bloc Diagnosis Immunohistochemistry
23 23 - -
24 Two main groups of STT
25 Spindle cell tumors (mainly superficial in children)
26 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
27 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
28 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
29 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)
30 Low-grade spindle cell tumors 1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma
31 31 - -
32 32 - -
33 33 - -
34 34 - -
35 35 - -
36 36 - -
37 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
38 Low-grade spindle cell tumors 1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma
39 39 - -
40 40 - -
41 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
42 Low-grade spindle cell tumors 1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Fibrosarcoma
43 43 - -
44 44 - -
45 45 - -
46 46 - -
47 Storiform
48 48 - -
49 49 - -
50 50 - -
51 51 - -
52 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
53 Low-grade spindle cell tumors 1. Fibromatoses or desmoids 2. Nodular fasciitis 3. Dermatofibrosarcoma protuberans 4. Cong Inf Fibrosarcoma
54 54 - -
55 55 - -
56 56 - -
57 57 - -
58 58 - -
59 59 - -
60 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
61 61 - -
62 62 - -
63 Content 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
64 Round cell tumors
65 Round cell tumors Round cell sarcomas Diagnosis by definition Round cell tumors Diagnosis by round cell component
66 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
67 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
68 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
69 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
70 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
71 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
72 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
73 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/AE
74 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
75 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
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 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
78 RMS
79 RMS
80 Why FNA? To diagnose RMS To provide material for karyotyping or molecular biology techniques Atypical sites
81 RMS
82 82 - RMS -
83 RMS-desmin
84 Cellular components Rhabdomyoblasts Excentric nuclei Binucleated cells Spindle-shaped cells Abundant cytoplasms
85 85 RMS - -
86 RMS-alv
87 RMS-alv
88 88 - -
89 RMS-alv
90 90 - -
91 Gluteal
92 92 - -
93 93 - -
94 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
95 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
96 96 - -
97 PNET
98 Why FNA? To diagnose Ewing/PNET To provide material for karyotype or molecular biology techniques
99 PNET/EWING
100 PNET/EWING
101 Cellular components Round, irregular cells «neuroendocrine» pattern Rosette-like structures
102 PNET/EWING
103
104 PNET/EWING
105 PNET/EWING-cell bloc
106
107
108
109 Clinical and Fine Needle Aspiration Key Features (ES/PNET) Yes Maybe No -Young adult - Double population of large and small cells - Rosette formation - CD 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
110 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
111
112
113 Desmin
114 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
115 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
116
117
118 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
119 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
120 Rhabdoid tumor 1978 RMS-like morphology Kidney and extra-kidney localizations Homozygous deletion of 22q % in the first year, 85% in 2 yrs Aggressive behaviour
121 Rhabdoid tumor Monomorphous appearance RMS-like proliferation Dispersed cells Epithelioid cords Cytoplasmic inclusions
122 Why FNA? To diagnose Rhabdoid tumor To provide material for karyotyping or molecular biology techniques
123 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).
124 RbT
125 EMA
126 Cellular components Rhabdomyoblasts-like Perinuclear bodies Nucleoli
127 RbT
128 RbT
129 RhT
130 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
131 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
132 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
133
134
135
136 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
137 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
138
139
140 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
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 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
144 Histiocytosis X
145 Why FNA? To confirm diagnosis Clinics + Radiology + FNA = Diagnosis
146 Cellular components Eosinophilic leukocytes Macrophages Mono-, bi-, multinucleated cells
147 H-X
148
149 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
150
151 Thank you!!!!
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