Maffucci Syndrome: Enchondromatosis, Haemangiomas and Malignancy Surveillance

Maffucci syndrome is a rare, usually sporadic skeletal dysplasia/tumour-predisposition syndrome characterised by multiple enchondromas and multiple soft-tissue vascular malformations, classically described as haemangiomas. The enchondromas are benign cartilaginous lesions arising near growth plates, while the vascular lesions may be superficial, intramuscular or deep.

The condition is usually recognised in childhood when skeletal lesions cause asymmetry, swelling, deformity or fracture. The vascular component may become evident later or may be subtle. Disease is frequently unilateral or markedly asymmetric, although the exact distribution varies. There is no reliable worldwide prevalence estimate because cases are rare and definitions and ascertainment differ.

Maffucci syndrome is distinct from:

• solitary enchondroma, which is a single lesion without the syndromic pattern;
• Ollier disease, which is multiple enchondromas without the characteristic multiple soft-tissue vascular malformations;
• hereditary multiple exostoses, which produces osteochondromas rather than enchondromas;
• metachondromatosis, which combines enchondromas and osteochondromas and follows a different phenotype;
• generalised venous malformation syndromes, in which the skeletal cartilage lesions are absent.

The transformation risk is not one number, and the variation is not noise - it is anatomy. The largest series in the field (Verdegaal, PMID 22147000: 161 patients, 13 European centres) reports an overall chondrosarcoma incidence of 40 per cent, and then shows what that average conceals:

Enchondromas in the pelvis carry an odds ratio of 3.8 (p = 0.001). So the answer to "what is the risk?" is where is the disease? - and that is what sets the surveillance interval, not a single quoted percentage.

Two cautions on the number itself. Verdegaal's cohort came from sarcoma referral centres, so 40 per cent is an upper bound rather than a population rate; and the authors note it is the incidence so far and is age-dependent, so lifelong risk is higher. Conversely, the "approximately 100 per cent lifetime risk" still repeated in the Maffucci literature (and cited on this page's own Ngai card) is not supportable - it descends from small historical series of patients who entered the literature because they had a malignancy. Quote 40 per cent, stratify it by site, and say which way each bias runs.

Benign skeletal lesion

Surgery can be considered for:

• pathological fracture or nonunion;
• progressive deformity or clinically important limb-length discrepancy;
• pain attributable to mechanical expansion or instability after malignancy has been excluded;
• nerve or tendon compression;
• functional impairment or a lesion that is structurally unsafe.

Curettage and grafting may be appropriate for a selected benign lesion. Fixation is chosen for the mechanical problem, not simply the radiographic presence of cartilage. In a growing child, preserve the physis and plan correction around growth remaining.

Malignant transformation

Suspected or confirmed chondrosarcoma requires a sarcoma MDT. Treatment is usually wide resection with reconstruction selected by site, grade, contamination, joint involvement, vessels, nerves and patient function. Curettage is not adequate for a lesion with malignant imaging or pathology. Chondrosarcoma is generally treated surgically; chemotherapy and radiotherapy are histology- and site-specific rather than routine substitutes for complete resection.

Vascular lesion

Operate or intervene when there is pain, recurrent thrombosis or bleeding, ulceration, functional restriction, nerve compression, cosmetic burden after informed discussion, or a defined lesion that can be safely controlled. Confirm the flow characteristics and relationship to major vessels before choosing excision.

Maffucci surgery is complicated by the coexistence of abnormal bone and abnormal vessels.

• Enchondromas expand the medullary canal, thin cortex and may distort the physis, metaphysis or neurovascular corridor.
• Hand lesions can displace digital nerves, arteries, flexor tendons and extensor mechanisms. A small incision through a vascular nodule may bleed disproportionately.
• Long-bone deformity changes the location of the medullary canal and the safe corridor for an intramedullary implant.
• A deep venous malformation may cross multiple tissue planes and fill when the limb is dependent. Plan positioning and tourniquet use with vascular specialists.
• Pelvic or skull-base lesions are close to major vessels, cranial nerves and viscera; observation can be safer than aggressive resection when asymptomatic and radiologically indolent.
• A biopsy tract must be placed within the planned oncological resection field. In a hand or foot, coordinate the tract with a sarcoma surgeon before sampling.

The surgical team should know whether a vascular lesion is high-flow or low-flow, whether the bone lesion is benign-appearing or aggressive, and whether the planned operation is curative, reconstructive or palliative.

Maffucci syndrome is generally caused by post-zygotic mosaic mutations affecting the isocitrate dehydrogenase pathway, most often IDH1 or IDH2. The mutation occurs after fertilisation, so only a subset of cells carries it. This explains the segmental distribution, asymmetry and variable involvement of bone, cartilage and soft tissue.

Genetic counselling points

• Most patients have no affected first-degree relatives.
• The usual mosaic mechanism means that routine blood testing can be negative when the mutation is confined to lesional tissue.
• Testing an affected enchondroma or vascular lesion may have greater diagnostic yield than testing peripheral blood, but a negative result does not exclude the clinical diagnosis.
• The reproductive risk is not equivalent to an autosomal dominant germline disorder; explain the uncertainty through clinical genetics rather than assigning a simple Mendelian percentage.
• A positive IDH1/IDH2 result supports the diagnosis but does not by itself predict which lesion will transform.

Pathological model

1. Abnormal chondrocyte differentiation produces multiple medullary cartilaginous lesions.
2. The same or related mosaic developmental disturbance affects vascular tissues.
3. Lesions disrupt normal growth plates and the mechanical axis, producing deformity and limb-length discrepancy.
4. Additional molecular changes may accumulate in an enchondroma and drive malignant transformation to central chondrosarcoma.

Maffucci syndrome is not simply a collection of unrelated benign masses. The mosaic distribution should guide imaging, examination and interpretation of new lesions.

Skeletal manifestations

• palpable or radiographic enchondromas in the hands and feet;
• shortening, angulation or rotation of a digit or limb;
• limb-length discrepancy from asymmetric growth disturbance;
• pathological fracture through a weakened bone;
• joint stiffness, altered loading and early degenerative change;
• nerve compression from a lesion or deformity;
• pain from fracture, mechanical overload, a vascular lesion or malignant transformation.

Hand lesions often become apparent as nodular enlargement or shortened, bowed digits. Long-bone lesions may remain silent until deformity or fracture. The disease can be more extensive than the clinically obvious side suggests, so baseline mapping matters.

Vascular manifestations

Vascular lesions may be blue or violaceous, compressible, tender or associated with local swelling. Phleboliths or soft-tissue calcification may be visible on radiographs. Deeper lesions can cause pain, bleeding, thrombosis, nerve compression or difficulty with a surgical approach. The term haemangioma is historically common, but modern vascular-anomaly classification may identify venous, lymphatic or mixed malformations; involve a vascular anomalies team when the diagnosis or treatment is uncertain.

Extra-skeletal neoplasia and symptoms

Patients with enchondromatosis syndromes have reported associations with non-skeletal tumours, including gliomas and mesenchymal ovarian tumours. The absolute risk and optimal screening strategy are not uniform. Do not order indiscriminate repeated whole-body imaging in an asymptomatic patient without a multidisciplinary rationale. Investigate new neurological, visual, endocrine, abdominal, pelvic or reproductive symptoms on their merits.

Natural history

Disease severity is variable. Lesions may be recognised in childhood, become less active with skeletal maturity and then remain stable, or cause progressive deformity and complications. Malignant transformation can occur in adulthood, but it may occur earlier or later depending on lesion burden and biology. A stable historical diagnosis does not make a newly painful or enlarging lesion safe.

A typical, stable, asymptomatic enchondroma does not need biopsy merely because it occurs in Maffucci syndrome. Biopsy is indicated when imaging or clinical behaviour raises concern for malignancy, when the diagnosis is uncertain, or when tissue will change treatment.

Biopsy rules

1. Discuss the case with the sarcoma MDT first.
2. Review the MRI and planned resection route before choosing the entry point.
3. Place a small longitudinal tract in a compartment that can be excised en bloc.
4. Avoid crossing joints, major neurovascular bundles or multiple compartments.
5. Obtain adequate core tissue from the enhancing or aggressive component, not only necrotic centre or superficial cartilage.
6. Control bleeding carefully, especially when a vascular lesion is nearby.
7. Mark the tract and document it for the definitive surgeon.

Pathology should distinguish benign enchondroma from central chondrosarcoma using architecture, cellularity, atypia, permeation of host bone and radiological correlation. Small samples can under-grade a heterogeneous lesion; a benign-looking fragment does not overrule aggressive imaging.

Name the vascular lesion precisely. The vascular component of Maffucci syndrome is usually a spindle cell haemangioma - the entity formerly called spindle cell haemangioendothelioma - and not an ordinary infantile or capillary haemangioma. This is not pedantry: Pansuriya's molecular work found the same IDH1 or IDH2 mutation in 70 per cent of spindle cell haemangiomas and 87 per cent of enchondromas, with 14 of 16 patients carrying identical mutations in separate lesions, which is what establishes the two lesion types as manifestations of one post-zygotic mosaic disease rather than a coincidental association. A report of "haemangioma" is therefore compatible with the syndrome but does not confirm the specific lesion; ask for the precise entity, and have vascular lesions classified by a vascular anomalies pathologist where possible. Note also that spindle cell haemangioma is benign and locally recurrent - it is not the lesion that carries the malignant risk on this page, which sits with the cartilage.

General inspection

Record height, weight, body proportions, asymmetry, gait and limb-length discrepancy. Photograph visible lesions with consent and document their location and size. Look for multiple subcutaneous nodules, blue discoloration, compressibility, scars, healed fractures and muscle wasting.

Limb examination

For each affected limb:

1. inspect the mechanical axis and rotational profile;
2. measure segment lengths and total limb length using a block test or tape and confirm with standing imaging when treatment is contemplated;
3. assess swelling, skin temperature, compressibility and tenderness of vascular lesions;
4. palpate bony masses and identify whether the lesion is hard, fluctuant, compressible or pulsatile;
5. measure adjacent joint range and document fixed deformity;
6. test motor, sensory and vascular function distal to a lesion;
7. assess gait, shoe wear, grip, pinch and activities limited by the condition.

Vascular lesion assessment

Do not repeatedly compress a deep or pulsatile lesion. Note refill, compressibility, bruit, thrill, positional change, thrombosis-like pain and relation to a nerve or major vessel. A duplex ultrasound can assess flow and venous communication; MRI defines extent and relationship to muscle, tendon, bone and neurovascular structures.

Malignancy screen by history and examination

Ask specifically about:

• new pain in a previously painless lesion;
• pain at rest or at night;
• enlargement or a change in consistency;
• new neurological deficit;
• unexplained fracture;
• fever, weight loss or constitutional symptoms;
• functional decline out of proportion to mechanical deformity.

Examine the entire lesion and regional nodes where appropriate. Do not use absence of fever or a normal inflammatory marker to exclude chondrosarcoma.

The practical diagnosis is a clinicoradiological pattern rather than a single laboratory result.

Other differentials include neurofibromatosis with bony dysplasia, segmental overgrowth syndromes, vascular malformation syndromes without enchondromas, dysplasia epiphysealis hemimelica, fibrous dysplasia and multifocal chondrosarcoma. The imaging pattern and pathology, not a memorable label, should drive the work-up.

There is no universally validated one-size-fits-all surveillance schedule. A useful plan is individualised by age, lesion burden, symptoms, anatomical site, previous malignancy and vascular phenotype.

Baseline plan

• record a complete skeletal and vascular map;
• photograph and measure accessible vascular lesions with consent;
• document baseline pain, function, limb length, deformity and neurological status;
• review previous radiographs and operations;
• establish which team will receive alerts for new pain or growth;
• provide written red-flag advice to the patient and family.

Stable lesions

Observe clinically and radiologically when the lesion is asymptomatic, non-aggressive and mechanically safe. The interval should be decided by the treating MDT; shorter review is appropriate for a new, large, deep, growing or anatomically high-risk lesion. Avoid serial CT when MRI or radiographs answer the clinical question.

Mechanical care

Use physiotherapy for strength, range and gait. Correct shoe wear, use orthoses, manage body weight and protect a fragile bone during periods of pain. Treat a pathological fracture with a plan that considers lesion curettage, grafting, fixation and the possibility of malignancy; do not assume every fracture through an enchondroma is benign.

Vascular care

Compression, analgesia, physiotherapy and activity modification may help low-flow venous malformations. Sclerotherapy, ablation or excision requires a vascular anomalies team and pre-procedure imaging. Anticoagulation, if thrombosis occurs, is a specialist risk-benefit decision rather than an automatic treatment.

The following PIPADRAW framework is a planning checklist, not a substitute for case-specific oncological and vascular review.

A suspected malignant lesion follows a different sequence:

1. Position and imaging: plan the biopsy and definitive resection using the MRI, staging studies and the sarcoma MDT.
2. Preparation: consent for biopsy only or biopsy with later wide resection; prepare for bleeding from vascular lesions and avoid contaminating uninvolved compartments.
3. Approach: use a short longitudinal tract that can be excised en bloc; avoid transverse incisions, joint violation and drains that create additional contamination.
4. Dissection: obtain image-directed core samples from the viable aggressive component; control bleeding without spreading tumour.
5. Pathology: label the site and provide clinical/radiological information; await expert bone tumour pathology.
6. Decision: choose wide resection, reconstruction or palliation according to grade, site, margins, metastasis and function.
7. Failure plan: if the biopsy is non-diagnostic but imaging remains aggressive, repeat through the same corridor or revise the plan with the MDT; do not reassure on an inadequate benign fragment.

Reconstruction options include osteoarticular allograft, endoprosthesis, allograft-prosthetic composite, arthrodesis, biological graft and rotationplasty depending on the site and patient. The tumour operation takes priority over preserving a diseased segment.

Skeletal complications

• pathological fracture;
• deformity recurrence during growth;
• limb-length discrepancy;
• nonunion or delayed union after osteotomy or fracture fixation;
• graft resorption or cavity recurrence;
• infection and wound breakdown;
• nerve or tendon injury;
• implant loosening, breakage or periprosthetic fracture.

Oncological complications

• missed or delayed malignant transformation;
• non-diagnostic or poorly placed biopsy;
• intralesional excision of a sarcoma;
• positive margin and local recurrence;
• pulmonary or other metastasis;
• second primary or extra-skeletal tumour.

Vascular complications

• uncontrolled intraoperative bleeding;
• thrombosis or painful thrombophlebitis;
• ulceration or recurrent malformation after treatment;
• nerve compression or skin necrosis;
• high-flow shunt physiology in a lesion not correctly classified.

Failure response

A new painful mass after reconstruction requires repeat history, examination, radiographs and MRI; compare with preoperative images and obtain tissue through the established MDT route if transformation or recurrence is possible. A painful stable implant with a healed osteotomy may be mechanical, but cancer and infection must be excluded before revision.

Evidence base. Maffucci syndrome is rare and management is derived from cohort studies, imaging reviews, case series and sarcoma principles rather than a single universally adopted guideline. The strongest consistent recommendations are to recognise the vascular phenotype, map lesions, monitor for malignant transformation, investigate red flags and refer suspected sarcoma before biopsy or surgery [1-4].

International practice principles

• Use a sarcoma MDT for aggressive or uncertain lesions.
• Use modern vascular-anomaly classification and specialist imaging for deep vascular disease.
• Offer clinical genetics counselling even though the disorder is usually sporadic and mosaic.
• Record lesion site, imaging phenotype, symptoms, operations, pathology, vascular treatment and malignant events in a longitudinal registry.
• Avoid over-treatment of stable asymptomatic lesions and avoid under-treatment of new aggressive behaviour.

Registries. Rare-disease and sarcoma registries can capture lesion burden, age at diagnosis, IDH status, chondrosarcoma transformation, non-skeletal tumours, vascular interventions, reconstruction, recurrence and survival. A useful local registry should also record whether a biopsy was MDT-planned and whether the lesion was treated intralesionally or with a wide margin.

Global practice. Access to MRI, molecular testing, vascular anomalies services, expert pathology and sarcoma reconstruction varies. Where resources are limited, the safety priorities remain the same: plain radiographic mapping, careful clinical red-flag assessment, referral before biopsy and avoiding unplanned curettage of an aggressive lesion.

Read this page with the one that owns the whole spectrum. Enchondromatosis (Ollier Disease and Maffucci Syndrome) is the canonical page and covers both syndromes together, with the classification, the IDH biology and the management algorithm. This page keeps what that one does not carry in operative form: the examination sequence, surgical anatomy and structures at risk, biopsy and pathology, and two separate operative blocks.

The lesion, and what it becomes. Enchondroma - the solitary lesion, and the comparison that gives the syndromic risk its meaning. Chondrosarcoma - what 40 per cent of these patients develop, most often low grade. Dedifferentiated Chondrosarcoma - the outcome that makes a sudden change in a long-stable lesion an emergency rather than a surveillance finding.

Distinguish it from. Multiple Hereditary Exostoses - multiple lesions in a young patient with malignant potential, but osteochondromas, and unlike enchondromatosis it is genuinely inherited, which changes the family conversation entirely. Haemangioma of Bone and Haemangioma - the vascular lesions that make this Maffucci rather than Ollier.

Doing the operations on this page. Biopsy Principles and Techniques - a badly placed biopsy tract in a patient who may need a later resection is the avoidable disaster here. Pathological Fractures of the Femur - the commonest presentation of a long-bone enchondroma. Megaprosthesis and Non-Oncologic Salvage - the reconstruction after a distal femoral resection. Limb Lengthening Principles and Causes of Limb-Length Discrepancy - asymmetric physeal involvement makes discrepancy and deformity the commonest non-oncological problem these patients bring to clinic.

The page's central number was contested by its own sources and neither card said so. One review cited approximately 40 per cent secondary chondrosarcoma; another asserted an approximately 100 per cent lifetime risk. Because both cards were written without numbers, a reader could not see that they disagreed by a factor of two and a half. The paper that settles it was already in this page's reference list and is now the first card below: the answer is that the risk depends on where the enchondromas are, and that is what selects who needs screening.

1. Sharif B, Lindsay D, Saifuddin A. Update on the imaging features of the enchondromatosis syndromes. Skeletal Radiol. 2022;51:747-762. PMID: 34302201. DOI: 10.1007/s00256-021-03870-0.
2. Ngai C, Ding DY, Rapp TB. Maffucci Syndrome. An Interesting Case and a Review of the Literature. Bull Hosp Jt Dis (2013). 2015;73:282-285. PMID: 26630472.
3. Silve C, Jüppner H. Ollier disease. Orphanet J Rare Dis. 2006;1:37. PMCID: PMC1592482. PMID: 16995932. DOI: 10.1186/1750-1172-1-37.
4. Oushy S, Peris-Celda M, Van Gompel JJ. Skull Base Enchondroma and Chondrosarcoma in Ollier Disease and Maffucci Syndrome. World Neurosurg. 2019;130:e356-e361. PMID: 31233929. DOI: 10.1016/j.wneu.2019.06.087.
5. Verdegaal SHM, Bovée JVMG, Pansuriya TC, et al. Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients. Oncologist. 2011;16:1771-1779. PMCID: PMC3248776. PMID: 22147000. DOI: 10.1634/theoncologist.2011-0200.
6. Pansuriya TC, van Eijk R, d'Adamo P, et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet. 2011;43(12):1256-1261. PMCID: PMC3427908. PMID: 22057234. DOI: 10.1038/ng.1004.
7. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. 5th ed. Lyon: International Agency for Research on Cancer; 2020.
8. International Society for the Study of Vascular Anomalies. ISSVA classification of vascular anomalies. Updated classification and terminology resource.
9. Gelderblom H, Hogendoorn PCW, Dijkstra SD, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13(3):320-329. PMID: 18378543. DOI: 10.1634/theoncologist.2007-0237.
10. Andreou D, Gilg MM, Gosheger G, et al. Metastatic potential of grade I chondrosarcoma of bone: results of a multi-institutional study. Ann Surg Oncol. 2016;23(1):120-125. PMID: 26350369. DOI: 10.1245/s10434-015-4852-1.

Three corrections made after resolving every entry against PubMed. Reference 6 previously named its third author as "d'Haens G", who is not an author of that paper — the correct third author is d'Adamo P. Reference 10 previously read "Andreou D, Bielack SS, Carrle D, et al. The role of surgery in the management of chondrosarcoma. J Surg Oncol. 2011;103" — no paper of that title exists, and the entry was truncated mid-page-number. It has been replaced with Andreou's actual multi-institutional study of grade I chondrosarcoma, which is the more relevant paper for this page in any case. Reference 9 carried the DOI suffix 2008-0237, which does not resolve; the registered DOI is 10.1634/theoncologist.2007-0237 (the journal's DOI year tracks submission, not the issue). All other entries resolved exactly as stated.