Case Presentations 17-20
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1 Case Presentations 17-20
2 Case Presentations 17
3 Case 17 2 year old boy with history of urinary retention and prostate biopsy. After biopsy and chemotherapy, child regains urine flow but the mass does not shrink on imaging. A total prostatectomy was performed. 3
4 Geographic necrosis Viable neoplasm Case 17: Prostatic neoplasm: capsule 4
5 Case 17. Undifferentiated neoplasm 5
6 Case 17. Moderately pleomorphic primitive cells Lymphs, mits, karyo 6
7 Case 17. Anaplasia 7
8 Case 17. Anaplasia 8
9 Case 17. Anaplasia 9
10 10
11 IHC Desmin: strongly positive MyoD1: strongly positive SOX-9: strongly positive [by report] Myogenin: focally positive 11
12 Cytogenetics FISH for FOXO1 (13q14.1) gene rearrangement: negative (performed at two institutions) 12
13 Case 17 Diagnosis: Treated embryonal rhabdomyosarcoma, with diffuse anaplasia, fusion-negative 13
14 Anaplastic rhabdomyosarcoma (RMS) Original concepts Seen in both forms of RMS, embryonal and alveolar Builds on concepts of anaplastic Wilms tumor Nucleomegaly (>3X size of adjacent cells) Hyperchromasia Atypical multipolar mitoses Diffuse and focal forms Diffuse = clonal Focal = occasional isolated cell 14
15 Anaplastic RMS: prognosis Persists with chemotherapy (marker of chemoresistance) Proven marker of bad outcome in embryonal RMS in prospective and retrospectic studies No effect on alveolar RMS outcome Did not make level of significance in multivariate analysis Has not been used to make protocol-based treatment decisions 15
16 Qualman et al: IRSG/COG studies Nine per cent of embryonal RMS (23/223 cases) Eight per cell of alveolar RMS (12/139 cases) Two of 17 spindle cell RMS cases One of 36 botryoid RMS cases Total 7% of RMS cases (39/463) 16
17 Qualman et al: Outcome analysis of embryonal RMS No difference between diffuse and focal anaplasia Univariate analysis: 5 year survivals With anaplasia: 68% Without anaplasia: 82% Only predictive with intermediate risk disease Multivariate analysis Demonstrated a statistical trend (p = 0.08) Was not a significant factor compared to proven factors like metastasis, age, stage, site, group, etc. 17
18 Anaplastic RMS: Genetics Qualman: Double minutes (gene amplification) found in 6 of 9 karyotypes Bridge: Genomic amplication frequent on comparative genomic hydridization All but one of 6 ERMS with amplicons showed anaplasia These 6 Involved 15q, 18q, 11q, and 12 q. 18
19 Case Presentations 18
20 Case month-old male infant with large buttock mass Pulmonary metastasis found on imaging. Wide excision of soft tissue mass was performed. Slides courtesy of Dr. Denise Malicki, Rady Children s Hospital, San Diego. 20
21 Case 18. Fibrosarcoma-like spindle cell tumor 21
22 Case 18: Permeation of adjacent fat 22
23 Case 18: Permeation of adjacent fat 23
24 Focal myxoid change 24
25 Focal myxoid change 25
26 Herring bone pattern 26
27 CD34 27
28 CD34 28
29 BCL2 29
30 CD99 30
31 Glut 1: negative CD31: negative D2-40: negative Factor XIIIa: negative Other IHC 31
32 ETV6-PDGFB RT-PCR: negative for fusion SS18 FISH: Cytogenetics negative for 18q11.2 rearrangement NTRKC FISH: negative for rearrangement 32
33 Diagnosis: CD34 positive fibrosarcoma, most consistent with fibrosarcoma ex dermatofibrosarcoma protuberans 33
34 Comment: Cannot absolutely exclude extrapleural solitary fibrous tumor. STAT6 testing may be helpful. 34
35 Differential diagnosis of pediatric fibrosarcoma Infantile fibrosarcoma: t(12;15), ETV6-NTRK3 fusion Low grade fibromyxoid sarcoma: MUC4, alternating pattern, large collagenous rosettes, FUS-CREB3L1/FUS-CREBL2 fusions Synovial sarcoma: EMA/CK/TLE1 positivity, SSX-SS18 fusions MPNST: involvement of nerve or neurofibroma, NF1 history, S100 positivity Fibroma-like epithelioid sarcoma: EMA/CK positivity, INI1 negativity 35
36 Differential diagnosis of pediatric fibrosarcoma Dermatofibrosarcoma protuberans Solitary fibrous tumor 36
37 Dermatofibrosarcoma protuberans (DFSP) in children Relatively uncommon in children but being increasingly recognized Congenital lesions may appear innocuous Slowly progressive lesion most often in trunk May be associated with immunodeficiency May be multifocal 37
38 DFSP: pathology Classic, giant cell, myxoid, fibrosarcomatous, and pigmented forms Permeation of fat CD34 positive, Factor XIIIa negative (beware intermediate lesions in spectrum of dermatofibroma) CD34 expression often lost in fibrosarcomatous areas Has t(17;22) translocation, COL1A1-PDGFB fusion Two of seven RT-PCR negative in one study 38
39 DFSP: Differential diagnosis Nodular fasciitis (positive for USP6 fusions) Infantile myofibroma (actin positive) Deep dermatofibroma/intermediate lesions (may be Factor XIIIa and CD34 positive) Spindle cell melanoma (check epidermis, melanocytic markers) 39
40 Solitary fibrous tumor in children Extremely rare, limited to isolated case reports Pleural or extrapleural Patternless and hemangiopericytomatous patterns CD34, CD99, BCL2 positive (may be actin positive) A new marker: STAT6 (has gene fusion and overexpression) 40
41 Case 19 41
42 Case year old girl with tumor involving metaphysis of distal radius. Periosteal elevation and soft tissue extension found on radiographs. The patient was treated with chemotherapy. An en bloc resection was performed afterwards. 42
43 Case 18. malignant cartilage 43
44 Case 19. Cartilage with osteoid 44
45 Case 19. Lacy osteoid, no cartilage 45
46 Case 19. Small cell pattern 46
47 Diagnosis: Conventional osteosarcoma, high grade, chondroblastic variant 47
48 Differential diagnosis: malignant chondroblastic neoplasms in children Primary chondrosarcoma Rare but may occur in spine and head and neck Usually mesenchymal variant High grade chondroblastic osteosarcoma (more common in kids) Differentiate from osteoid producing mesenchymal chondrosarcoma Intermediate grade chondroblastic periosteal osteosarcoma Teratomatous lesions (look for other elements) Heterologous differentiation in dedifferentiated liposarcoma, Sertoli-Leydig tumor, PNET, RMS (other elements) Chordoma (location and cytokeratin/brachyury expression) 48
49 Primary pediatric chondrosarcoma Age range of 16 months-81 years in one large metaanalysis, with mean of years and peak between years Includes mesenchymal chondrosarcoma (covered in another lecture) Genetic predisposition Ollier's disease Maffucci's disease Hereditary exostosis (EXT1, EXT2, EXT3 mutations) Even rarer osteodysplasias (PTPN11, ACP5 mutations) Acquired mutations in IDH1, IDH2 frequent overall Isocitrate dehydrogenase genes in Kreb cycle 49
50 Chondroblastic osteosarcoma One of multiple other variants Osteoblastic/sclerosing Fibroblastic Anaplastic Fibrohisticytic or epithelioid (beware cytokeratin positivity) Telangiectatic Round cell (covered in another lecture) 50
51 51
52 Case 20 52
53 Case year old male who develops swelling and increasing pain of lower jaw Follows wisdom teeth extraction. CT shows a destructive lytic and sclerotic lesion of mandible. A biopsy was performed. 53
54 Case 20: irregular bony trabeculae 54
55 Case 20. Collagenous intertrabecular region 55
56 Case 20: Sparse lymphocytes 56
57 Variable osteoid seam 57
58 Variable osteoid seam 58
59 Case 20. dense cortical bone 59
60 60
61 61
62 62
63 Case 20. Dense collagneous zones, with osteoid transition 63
64 Dense collagen 64
65 65
66 Diagnosis: Chronic sclerosing osteomyelitis 66
67 Differential diagnosis: non-neoplastic bony lesions Fracture callus (hemorrhage, organization, chondroid matrix) Osteomyelitis (inflammation, osteonecrosis, reactive bone) Fibrous dysplasia of bone (woven bone, non-osteoblastic) Osteofibrous dysplasia (tibia, cytokeratin) Osteitis fibrosa cystica (hyperparathyroidism, high serum Ca) In soft tissue, consider myositis ossificans, dermatomyositis, heterotopic bone, trauma, periostitis ossificans 67
68 Garré's sclerosing osteomyelitis First described by Carl Garré in 1893 Non-suppurative chronic osteomyelitis form of periostitis ossificans Proliferative periosteum Peripheral subperiosteal bone formation Mild but prolonged infection or irritation, without necrosis or exudate Particularly common in tibia, jaws 68
69 Garré's sclerosing osteomyelitis Clinical features Facial assymetry, bony assymetry Progressive swelling Variable pain, malaise, trismus Unilateral induration with normal overlying skin or mucosa 69
70 Garré's sclerosing osteomyelitis May or may not respond to antibiotics Resolution of pain, bony changes May require multiple CT scans, with relatively high dose of irradiation Rarely progresses to secondary osteosarcoma May occur with multifocal recurrent osteomyelitis, an autoimmune disease with a genetic basis 70
71 Garré's sclerosing osteomyelitis: histology Fibrous dysplasia-like pattern ("ground glass" appearance on imaging) Retiform pattern (lace-like) Paralled (lamellated) pattern - do not confuse with parosteal osteosarcoma Overlapping features with Caffey's disease (cortical hyperostosis), seen in infants 71
72 Other diseases to consider Low grade, osteoblastic-like osteosarcoma Parosteal osteosarcoma Hypertrophic osteoarthopathy History of heart or lung disease Congenital syphilis Cherubism (bilateral, extensive) 72
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