Degenerazione maligna nella malattia delle esostosi ... · Ollier disease and Maffucci syndrome...
Transcript of Degenerazione maligna nella malattia delle esostosi ... · Ollier disease and Maffucci syndrome...
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Degenerazione malignanella malattia delle esostosi multiple
e m. di Ollier e Maffucci
Prof Domenico Andrea Campanacci
Direttore
SOD ORTOPEDIA ONCOLOGICA E RICOSTRUTTIVA
AZIENDA OSPEDALIERA UNIVERSITARIA CAREGGI, FIRENZE
Azienda Ospedaliero
Universitaria
Careggi
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Multiple Hereditary ExostosesAutosomal dominant disorder
Almost complete penetrance (95%) 1 /50.000
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MHEslightly short stature, growth deformities of bones, and multiple
cartilage-capped bony exostoses that develop on the metaphyses of long bones and other sites including ribs and vertebrae
K. B. Jones et al, Connect Tissue Res 2014
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Hereditary Multiple Exostoses (MHE)
2013
Mild
Intermediate
Severe
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143 patients (65 HME families)
EXT1 genotype > number of exostoses EXT2 genotype
(p 0.006)
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Male patients EXT1 > exostosis upper limb than female & EXT2
Clement ND et al, Scottish Medical Journal, 2014
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Donna 35 aa, claudicatio vascolare
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Angio RMN
Ostruzione cronica
dell’art. poplitea
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Rixx A et al, Acta Orthopædica Belgica, 2013
Deformities
Knee 33%
Hip 25%
Ankle 50%
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Rixx A et al, Acta Orthopædica Belgica, 2013
Shortening of the ulna, higher curved radius & disturbed proximal pronation, subluxation or dislocation of the radial
head & Madelung deformity
25% pts
40-74% pts
7%
30-70%
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Hereditary Multiple Exostoses (MHE)
Secondary Peripheral
Chondrosarcoma
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> 1.5 cm
Peripheral CHS
MRI recommended
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90% grade 1 CHS(OS > 90% 5 yrs)
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10% dedifferentiated chondrosarcomas
(OS 24% 5 yrs)
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No consensus in the
literature
From < 1% to 25%
Hereditary Multiple Exostoses (MHE)Secondary peripheral chondrosarcoma
Czajka and Dicaprio, 2014
Sonne-Holm et al., 2014
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529 pts from two different European MHE referral centers
• Not significantly linked to EXT mutations, sex, severity of disease (mild, intermediate, severe) or numbers of skeletalsites with exostoses
• More frequently in pelvis, scapula, proximal femur• Principally in individuals with a positive family history
Malignant trasformation in 5%
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F>M in Class I and M>F in Class III; p
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2.7%
757 pts, 41 countries
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283 pts
Malignant trasformation in 184 adults pts
7%
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88% adults and 48% children
required at least one surgical procedure
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StirT2
Pre-operative MR
Hereditary Multiple Exostoses (MHE)
Secondary G1 Peripheral
Chondrosarcoma in paediatric age
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Pre-operative TC
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Post-operative MR, stir
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Hereditary Multiple Exostoses (MHE)
Secondary G1 Peripheral
Chondrosarcoma in paediatric age
Female 9 yrs, histology
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Segni istologici di malignità:- Ipercellularità- Nuclei rigonfi- Pleiomorfismo- Doppi nuclei
Situazioni cliniche dove questi segni sono compatibili con la benignità:- Età pediatrica- Lesioni della mano e del piede- Condromi periostei- M Ollier- M Maffucci- Condromatosi sinoviale
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Patologie benigne che possono esprimere aspetti istologici di malignità
- Tumori cartilaginei di mani e piedi
- Tumori cartilaginei in età infantile
- Condromi periostei
- Sindrome di Ollier
- Sindrome di Maffucci
- Condromatosi sinoviale
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Hereditary Multiple Exostoses (MHE)Multiple Osteochondromas & Intraosseous Atypical
Chondroid Tumor or Chondrosarcoma Grade 1
• From 195 adults patients from the nationwide Ducth tertiary referral center for MHE
• Not metachondromatosis (genetic testing positive for MHE)
• Clinically, radiografically and pathologically consistent with atypical cartilaginous tumor
or Chondrosarcoma WHO grade 1 (WHO guidelines of 2013 for diagnosis)
• Seven patients identified (3.6%)
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Multiple Osteochondromas & Intraosseous Atypical
Chondroid Tumor or Chondrosarcoma Grade 1
Treatment• Extended curettage (high-speed burr and
phenolization) 5 pts• Wide en-bloc resection 1 pts• Scheduled for surgery 1 pts
- No complications occurred- No local recurrence (mean FU 48 months, range12-144 months)- Five pts (71%) also had a total of 7 secondaryperipheral chondrosarcomas during follow-up
Incidence of 3.6% (7/195)
“However, on the basis of the study
design, the true incidence of
central cartilagineous tumor in
patients with MHE is unknown,
and only the incidence of what the
authors believed were malignant
central chondroid tumors is
included in this study.”
Temple T., 2015 Commentary on
the article by Goud et al.
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grade 1 CHSin MHE
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EnchondromatosisPansuriya et al.
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EnchondromatosisOllier disease and Maffucci syndrome
Malignant degeneration
Secondary central chondrosarcoma
Incidence highly variable, estimated to occur in
5-50% of cases (literature)
Others non-skeletal malignancies reported:
• Ollier disease: gliomas, juvenile granulosa cell tumors, non-small cell lung cancer;
• Maffucci syndrome: pancreatic and hepatic adenocarcinoma, mesenchymal
ovarian tumors, brain tumors (glioma and astrocytoma), acute myeloid leukemia,
and various kinds of sarcomas.
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21 yrs old girlAsymptomatic
Bone scan +scapula and humerus
Sled runner track
Diagnosis:Ollier disease
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Sled runner track
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Male, 46 y.o., humeral
pathological fxt, Ollier Disease...
HG sarcoma
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Herget et al. Neoplasma 61, 4, 2014
Secondary central chondrosarcoma
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Herget et al. Neoplasma 61, 4, 2014
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161 pts from 13 European centers 144 Ollier and 17 Maffucci pts
• Group I (enchondromas in the hand and feet only) 18%• Group II (long bones including scapula and pelvis only) 39%• Group III (Both small and long/flat bones) 43%
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Secondary central chondrosarcomas
Only 50% of the patients had their first event before the
age of 35 yrs
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Secondary central chondrosarcomas
Cumulative probability of secondary transformation over a lifetime is
different according to distribution patterns of enchondroma
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TOTAL 87 CHS
48 pts (72%) one CHS
18 pts (27%) two to four CHS
(33% synchronous, 56%
metachronous, 11% unknown)
Histological grade:
• Grade I 52%
• Grade II 32%
• Grade III 6%
• Unknow grade 10%
Secondary central chondrosarcomasSite and histological grade
Higher risk site:
PELVIS
The odds ratio associated with enchondroma of the pelvis was
3.8, with a 95% CI of 1.8–8.0 (p.001)
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Secondary central chondrosarcomasType of surgery
• Intralesional curettage +/- adjuvants 24 (29%)
• Resection 46 (55%)
• Amputation 13 (16%)
• No surgery 5 (6%)
• + post-operative radiation therapy in 2 pts
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EnchondromatosisDisease-related mortality
Chondrosarcomas-relateddeaths:• Polmonary METS• 8 pts/161• 8 pts / 66CS (12%)• 57 months (mean time to death
from first surgery for CHS)• Mean age 44.5 yrs (range 29.2-
58.9)
Non chondrosarcoma-relateddeaths:• Hepatic carcinoma (1), glioma (2)• 3 pts/161
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Conclusioni
Rischio di degenerazione maligna:
- Malattia delle esostosi multiple: Età adulta: da 2.7 a 7%
Età pediatrica: eccezionale
- Malattia di Ollier: 40-46%
- Malattia di Maffucci: 53-55%
Età pediatrica nel 7% dei casi di condrosarcomi su Ollier e Maffucci
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Grazie