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

Multiple Hereditary ExostosesAutosomal dominant disorder

Almost complete penetrance (95%) 1 /50.000

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

Hereditary Multiple Exostoses (MHE)

2013

Mild

Intermediate

Severe

143 patients (65 HME families)

EXT1 genotype > number of exostoses EXT2 genotype

(p 0.006)

Male patients EXT1 > exostosis upper limb than female & EXT2

Clement ND et al, Scottish Medical Journal, 2014

Donna 35 aa, claudicatio vascolare

Angio RMN

Ostruzione cronica

dell’art. poplitea

Rixx A et al, Acta Orthopædica Belgica, 2013

Deformities

Knee 33%

Hip 25%

Ankle 50%

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%

Hereditary Multiple Exostoses (MHE)

Secondary Peripheral

Chondrosarcoma

> 1.5 cm

Peripheral CHS

MRI recommended

90% grade 1 CHS(OS > 90% 5 yrs)

10% dedifferentiated chondrosarcomas

(OS 24% 5 yrs)

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

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%

F>M in Class I and M>F in Class III; p

2.7%

757 pts, 41 countries

283 pts

Malignant trasformation in 184 adults pts

7%

88% adults and 48% children

required at least one surgical procedure

StirT2

Pre-operative MR

Hereditary Multiple Exostoses (MHE)

Secondary G1 Peripheral

Chondrosarcoma in paediatric age

Pre-operative TC

Post-operative MR, stir

Hereditary Multiple Exostoses (MHE)

Secondary G1 Peripheral

Chondrosarcoma in paediatric age

Female 9 yrs, histology

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

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

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%)

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.

grade 1 CHSin MHE

EnchondromatosisPansuriya et al.

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.

21 yrs old girlAsymptomatic

Bone scan +scapula and humerus

Sled runner track

Diagnosis:Ollier disease

Sled runner track

Male, 46 y.o., humeral

pathological fxt, Ollier Disease...

HG sarcoma

Herget et al. Neoplasma 61, 4, 2014

Secondary central chondrosarcoma

Herget et al. Neoplasma 61, 4, 2014

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%

Secondary central chondrosarcomas

Only 50% of the patients had their first event before the

age of 35 yrs

Secondary central chondrosarcomas

Cumulative probability of secondary transformation over a lifetime is

different according to distribution patterns of enchondroma

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)

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

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

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

Grazie