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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