Part 1. Slides 1-38, Rita Alaggio Soft tissue tumors Trondheim 14. mars 2013
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1 Part 1 Slides 1-38, Rita Alaggio Soft tissue tumors Trondheim 14. mars 2013
2 Pediatric Pathology Soft Tissue Tumors AN UPDATE Rita Alaggio Azienda Ospedaliera Università di Padova
3 Soft Tissue Tumors More than 200 histotypes and subtypes
4 Focus on the most frequent the most difficult
5 RHABDOMYOSARCOMA
6 RHABDOMYOSARCOMA 5th most frequent pediatric tumor Most frequent pediatric sarcoma 5-10% of pediatric solid tumors
7 RHABDOMYOSARCOMA Malignant mesenchymal tumor with morphologic and/or immunophenotypic features of embryonal skeletal muscle
8 Rhabdomyosarcoma Subtypes RMS ERMS ARMS
9 RHABDOMYOSARCOMA Clinical and Molecular Features Age (yr) Site Prognosis Molecular Features ERMS 0-5 (18% >10) Head/neck GUtract. orbit, bile ducts, retroperitoneum ARMS extremities, paraspinal, perineal, breast Favourable Unfavorable t(2;13) (q35;q14) t(1;13)(p36;q14)
10 Rhabdomyosarcomas in WHO 2013 Main Issues Re-definition of ARMS lacking the translocation Introduction of recently described entities, ie. Sclerosing RMS
11 EMBRYONAL RMS A primitive, malignant soft tissue sarcoma that recapitulates the phenotypic and biological features of embryonic skeletal muscle.
12 EMBRYONAL RMS
13 EMBRYONAL RMS
14 EMBRYONAL RMS
15 RHABDOMYOSARCOMA Histologic Classification (WHO 2002) Embryonal RMS Botryoid Classic Anaplastic Spindle cell
16 RHABDOMYOSARCOMA Histologic Classification (WHO 2002) Embryonal RMS Spindle cell /Sclerosing RMS Botryoid Classic Anaplastic
17 Alternting cellular and myxoid areas EMBRYONAL RMS A:Variable cellularity: alternance of highly cellular and myxoid areas B: Stellate and elongated cells loosely arranged in a myxoid background
18 EMBRYONAL RMS, BOTRYOID
19 ERMS WITH ANAPLASIA The presence of enlarged, atypical cells with hyperchromatic nuclei defines the anaplastic variant of rhabdomyosarcoma. WHO 2013
20 RHABDOMYOSARCOMA Histologic Classification (WHO 2002) Embryonal RMS Spindle cell /Sclerosing RMS Botryoid Classic Anaplastic
21 SPINDLE CELL/SCLEROSING RMS Densely arrayed whorls or fascicles of spindle cells constitute the spindle cell variant of embryonal rhabdomyosarcoma. These spindle cells often resemble smooth muscle cells, with blunted central nuclei and tapered ends, but cytoplasmic cross striations, if present, and/or bright eosinophilia indicate striated muscle differentiation WHO 2002
22 SPINDLE CELL/SCLEROSING RMS Densely arrayed whorls or fascicles of spindle cells constitute the spindle cell variant of embryonal rhabdomyosarcoma. These spindle cells often resemble smooth muscle cells, with blunted central nuclei and tapered ends, but cytoplasmic cross striations, if present, and/or bright eosinophilia indicate striated muscle differentiation WHO 2002
23 SPINDLE CELL/SCLEROSING RMS Densely arrayed whorls or fascicles of spindle cells constitute the spindle cell variant of embryonal rhabdomyosarcoma. These spindle cells often resemble smooth muscle cells, with blunted central nuclei and tapered ends, but cytoplasmic cross striations, if present, and/or bright eosinophilia indicate striated muscle differentiation WHO 2002
24 SPINDLE CELL/SCLEROSING RMS Spindle cell/sclerosing RMS is an uncommon variant of RMS that has spindle cells morphology. Affecting both adult and children composed of a predominant population of spindled neoplastic cells with ovoid or elongated vescicular chromatin, inconspicuous nucleoli and scan, palely eosinophilic cytoplasm. Rare to scattered eospinophilic rhabdomyoblasts with eccentrically placed, hypercromatic nuclei are usually present throughout the tumor. cross striations may sometimes be apparent. Nuclear atypia, hypercromasia mitotic figures are common WHO 2013
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28 SPINDLE CELL/SCLEROSING RMS The nosological status of this subgroup remains somewhat uncertain WHO 2013 In fact
29 Recurrent NCOA2 Gene Rearrangements in Congenital/Infantile Spindle Cell Rhabdomyosarcoma SRF-NCOA2 gene fusion in 3/21 Spindle cell RMS 3 children (7 month, 3 month and 4 week-old) Site : 1 neck, 2 chest wall. Favourable clinical course Conclusions: Despite similar histomorphology in adults and young children, these results suggest that spindle cell RMS is a heterogeneous disease genetically as well as clinically. Mosquera M et al. Genes Chromosomes & Cancer published online MAR 2013
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31 Rabdomyofibrosarcoma Lundgreen L. et al Hum Pathol 1993;24: A tumor resembling infantile fibrosarcoma, containing neoplastic cells with properties of fibroblasts, myofibroblasts and rhabdomyoblasts
32 IRMFS: the Italian Series Clinico-pathologic features Case (yr diagnosis) Age Site Initial Diagnosis 1 28 m Forearm (5 cm) 2 1d Shoulder (6 cm) Treatment Follow-up CIFS Surgery IV Local relapses, LN mts DOD (2yrs) IRMFS IVADO/Surge ry CR (4a) 3 1d Shoulder (7 cm) IRMFS EpSSG-RMS CR (14 m) R. Alaggio et al. PPS-SPPJoint Meeting, Philadelphia 2009
33 MNR at diagnosis (case 3)
34 Spindle cells in a fascicular pattern dissecting muscle fibers
35 eosinophilic cytoplasms, nuclei with finely disersed chromatine and small nucleoli
36
37 Immunohistochemical Findings Marker Vimentin 3/3 Smooth muscle actin 3/3 Muscle specific actin 3/3 Desmin 3/3 Myogenin 3/3 S100 protein 0/3 Cytokeratin 0/3 Epithelial membrane antigen Positive 0/3 CD34 and/or CD31 0/3 CD99 0/3 Desm
38 Immunohistochemical Findings Marker Vimentin 3/3 Smooth muscle actin 3/3 Muscle specific actin 3/3 Desmin 3/3 Myogenin 3/3 S100 protein 0/3 Cytokeratin 0/3 Epithelial membrane antigen Positive 0/3 CD34 and/or CD31 0/3 CD99 0/3 Myf4
39 Immunohistochemical Findings Marker Vimentin 3/3 Smooth muscle actin 3/3 Positive Muscle specific actin 3/3* Desmin 3/3* Myogenin 3/3* S100 protein 0/3 Cytokeratin 0/3 Epithelial membrane antigen 0/3 CD34 1/3 CD99 0/3 CD34
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