Malignant Bone Tumours. PathoBasic, Daniel Baumhoer

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1 Malignant Bone Tumours PathoBasic, Daniel Baumhoer

2 FNCLCC Grading The differentiation score is defined as the extent to which a tumor resembles adult mesenchymal tissue (score 1), the extent to which the histologic type is known (score 2), or the observation that the tumor is undifferentiated (score 3). Has not been established on biopsies! Is not valid for bone tumours!

3 Bone (TNM) Extremities and facial bones T1 T2 T3 Tumour <8cm in largest diameter Tumour >8cm in largest diameter Discontinous growth in primary bone affected

4 Bone (TNM) Spine T1 T2 T3 T4a T4b Tumour limited to one or to adjacent vertebral segments Tumour limited to three vertebral segments Tumour limited to four vertebral segments Tumour with infiltration of the vertebral canal Tumour with infiltration of larger vessels or Tumour-related thrombosis in one of the larger vessels

5 The five vertebral segments include: right pedicle, right side of the vertebral body, left side of the vertebral body, left pedicle, posterior element

6 Bone (TNM) Pelvis T1a T1b T2a T2b Tumour <8cm in largest diameter, limited to one pelvic segment, no extraosseous growth Tumour >8cm in largest diameter, limited to one pelvic segment, no extraosseous growth Tumour <8cm in largest diameter, limited to one pelvic segment with extraosseous growth or two adjacent segments without extraosseous growth Tumour >8cm in largest diameter, limited to one pelvic segment with extraosseous growth or two adjacent segments without extraosseous growth

7 Bone (TNM) Pelvis T3a T3b T4a T4b Tumour <8cm in largest diameter, limited to two pelvic segments and with extraosseous growth Tumour >8cm in largest diameter, limited to two pelvic segments and with extraosseous growth Tumour affecting three pelvic segments or crossing the sacro-iliac joint into the sacral neuroforamen Tumour surrounds the external iliac vessels or macroscopically visible tumuor thrombosis in the great pelvic vessels

8 The four pelvic segments are: sacrum; pelvic fossae; acetabulum / periacetabulum and pelvic rami; symphysis and pubic bone

9 Im KWUB nicht verwendet!

10 10% vital tumour residues Osteosarcoma and Ewing sarcoma

11 good response poor response Osteosarcoma 10y-OS 73% 10y-OS 42%

12 Malignant bone tumours (BTRC) Osteosarcoma Chondrosarcoma Ewing sarcoma Lymphoma of bone Undiff. pleomorphic sarcoma Chordoma Adamantinoma Malignant GCT Angiosarcoma (36.4%) (25.8%)

13 Conventional osteosarcoma

14 Conventional osteosarcoma

15 Conventional osteosarcoma WHO 2013: A high-grade, intraosseous, malignant neoplasm, in which the neoplastic cells produce bone. The tumor is primary when the underlying bone is normal and secondary, when the bone is altered by conditions such as previous radiation, coexisting Paget disease, infarction, and rarely, other disorders.

16 Conventional osteosarcoma Most common primary malignant tumour of bone 2 nd decade (add. peak 6 th -7 th decade) Metaphyses of long bones 3-4 per per year Peripheral skeleton 90%, craniofacial bones 10% of cases

17 > 90% at initial diagnosis

18 Osteosarcoma (OS) subtypes Intramedullary osteosarcoma (~93%) Conventional OS and subtypes Telangiectatic OS Small cell OS Low-grade central OS Surface osteosarcoma (~7%) Parosteal OS (G1) Periosteal OS (G2) High-grade surface OS (G3)

19 Osteosarcoma (OS) subtypes Primary osteosarcoma (~95%) Secondary osteosarcoma (~5%) Paget-related Radiotherapy-related Syndrome related osteosarcoma Bloom syndrome Li-Fraumeni syndrome Familiar retinoblastoma Rothmund-Thomson syndrome Werner syndrome

20 Osteosarcoma (OS) subtypes High-grade osteosarcoma (~92%) Conventional intramedullary (~93%) Telangiectatic (~4%) Small cell (~1.5%) Surface (~1%) Low-grade osteosarcoma (~8%) Central (~1%) Parosteal (~5%) Periosteal (~2%)

21 Conventional osteosarcoma Classification according to predominant matrix type osteoblastic (50%) fibroblastic (25%) chondroblastic (25%) Always at least focal production of osteoid directly by the tumour cells

22 Osteoblastic (sclerosing) OS

23 Osteoblastic OS

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26 Conventional osteosarcoma WHO 2013: A high-grade, intraosseous, malignant neoplasm, in which the neoplastic cells produce bone. The tumor is primary when the underlying bone is normal and secondary, when the bone is altered by conditions such as previous radiation, coexisting Paget disease, infarction, and rarely, other disorders.

27 Telangiectatic osteosarcoma WHO 2013: A high-grade malignant bone-forming neoplasm, characterized by large spaces filled with blood, often with septations

28 Telangietatic OS

29 Telangietatic OS T2-w

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31 Telangiectatic OS ABC: 70% with USP6 rearrangement

32 NUMA1 ATRX PTEN FANCA WRN RECQL4 ATM RB1 BRCA2 BAP1 RET TP53 MDC1 MUTYH

33 BRCA complex consists of at least 69 genes! 95% of tumours showed a mutation in at least on of those genes On average, 17 mutations in those genes were detected per tumour

34 BRCA1/2 mutation HRR deficiency

35 RB1 TP53 PTEN RAD50 PALB2 FANCA BRCA1/2 mutation HRR deficiency ATR ATM BARD1 MYC RAD51 CHEK2

36 Chondrosarcoma

37 Chondrosarcoma

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39 Chondrosarcoma (CS) subtypes Conventional chondrosarcoma (~85%) Atypical cartilaginous tumour / CS grade I (ICD-O 1) Chondrosarcoma grade II-III (ICD-O 3) Secondary central CS (arising in pre-existing Enchondroma) Secondary peripheral CS (arising in pre-existing Osteochondroma) Periosteal chondrosarcoma Dedifferentiated chondrosarcoma Mesenchymal chondrosarcoma Clear cell chondrosarcoma (Extraskeletal myxoid chondrosarcoma)

40 Conventional Chondrosarcoma Second most common primary malignant tumour of bone in adults Most patients > 50 years of age Any bone derived from enchondral ossification can be affected Pelvis > femur prox > humerus prox > femur dist > ribs Enchondroma and ACT are both treated by curretage, differentiation can be difficult histologically and requires Rx correlation IDH1/2 mutations in roughly 50% of cases

41 Enchondroma: bone encases cartilage

42 Chondrosarcoma: cartilage encases bone

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44 Conventional Chondrosarcoma - grading Grade 1 Grade 2 Grade 3

45 Clear cell chondrosarcoma

46 Mesenchymal chondrosarcoma

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