Maffucci¹s syndrome
Synonyms:
Discussion:
Maffucci's syndrome is a nonhereditary syndrome characterized by multiple hemangiomas and enchondromas, first reported by Dr. Angelo Maffucci in 1881 after a 40-year-old woman died from complications following amputation of an arm. Dr. Maffucci (Oct. 27, 1847 - Nov 24, 1903) was an Italian pathologist born in Calitri, Italy. In 1872 he received his doctorate at Naples and later was a professor of pathology in Messina (1882), Catania (1883) and Pisa (1884). At the University of Pisa, he became the school's first director of pathologicalanatomy, and he remained there until his death in 1903.
Enchondromas are benign noncancerous growths of cartilage in bones or in other areas where cartilage is not normally found.
"When multiple enchondromas coexist, the diagnosis of enchondromatosis should be considered.
Multiple enchondromas may occur in 3 distinct disorders:
Diagnosis:
Prevelance:
Maffucci syndrome is rare. Fewer than 100 cases have been reported in the United States.
Maffucci syndrome is rare, with about 160 total case reports in the English literature.
Symptoms:
Complications:
Treatment:
June 8, 2008
-----------------------------------------
Maffucci¹s syndrome
Poels J| Patient | |
| Age: 31 year(s) Sex: M |
|
| Clinical History and Imaging | |
|
The patient, known to have Maffucci's syndrome, was referred to the Orthopaedic Clinic having moved to the area. Initial diagnosis was as a young child. No recent changes had occurred. Clinical examination revealed limb deformities, predominantly in the hands. Blue, subcutaneous haemangiomas, and hard masses adherent to bone were visible and palpable. Plain radiographs of the hands were obtained as a baseline for comparison if a change were to happen. |
|
| Discussion | |
|
Maffucci's syndrome is multiple enchondromas with
subcutaneous haemangiomas. The presence of haemangiomas distinguish it
from Ollier's disease. It has been suggested that Ollier's disease and
Maffucci's syndrome may be part of the same spectrum of mesenchymal
dysplastic disorders. The hands are the most common site affected, and
there is a tendency for the haemangiomas to predominate on one side of
the body. The disease is sporadic with no apparent hereditary
component. It manifests in early childhood at an average age of 2.6
years. Enchondromas arise in the medulla of the phalanges and
metacarpals, most commonly, and they have the capacity to undergo
malignant change. Enchondromas are lytic and expansile with flecks of
calcification, described as "popcorn like". |
|
| Diagnosis | |
|
Maffucci's syndrome |
|
| MESH = A02.835.232 C05.116.099.708.338 | |
| References | |
|
*Link no longer available
......................
MaffucCi’s Syndrome: Report of a Case
and Review of the Literature
Nadia S. Al-Hawashim, FRCPA; Younes N. Bakri, MD
Enchondromatosis is a nonhereditary skeletal disorder, characterized by the persistence of cartilage in several bones that are formed by enchondral ossification. In 1900, Ollier described a condition that resembled the osseous component of the syndrome that Maffucci had described 19 years earlier. In Maffucci’s syndrome (MS), the enchondromas coexist with cutaneous and sometimes visceral hemangiomas. Fewer than 200 cases of Maffucci’s syndrome have been published in the English literature.
Malignant transformation of the skeletal lesions is a common feature of MS, and has been observed in approximately 30% of reported cases, with chondro-sarcomas being the most common.1 The development of various types of neoplasms is a well-known complication of MS, and is recognized as a principal factor affecting prognosis. In 1948, Kuzma and King2 first reported an ovarian mesenchymal tumor associated with MS, and since then, sporadic reports have referred to ovarian tumors of sex-cord stromal derivation in patients with enchondromatosis.3-13 We describe the first case of bilateral ovarian serous cystadenomas and polycystic ovarian disease in a patient with MS, and review previously reported gynecologic pathology seen in association with enchondromatosis.
Case Report
A 19-year-old
single woman known to have Maffucci’s
syndrome, with a three-year history of right flank pain, was referred
to our
institution for evaluation and management of a pelvic abdominal mass
that was
suspected of being a juvenile granulosa cell tumor. Menarche occurred
at the age
of 15 years, and no menstrual disturbances were noted. The family
history
revealed that no other family member was affected. Deformities and
multiple
enchondromas were more conspicuous in the left hemiskeleton than in the
right. A
subcutaneous soft tissue mass in the left arm was
From the Departments of Pathology and Gynecologic Oncology, King Fahad National Guard Hospital, Riyadh, Saudi Arabia.
Address reprint requests and correspondence to Dr. Al-Hawashim: Department of Pathology, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426, Saudi Arabia.
Accepted for publication 31 March 2000. Received 23 November 1999.
diagnosed in early infancy, and had been removed when the patient was six years old. Subsequently, she underwent above-elbow amputation of the left arm for a large disfiguring mass eight months prior to her current presentation. The surgery had been performed at another hospital, and the histology of this mass was not available for review. She had a history of excision of two other subcutaneous hemangiomas.
Laboratory data showed hemoglobin of 10.29 g/dL (normal value, 12.09-16.0 g/dL), with microcytic and hypochromic anemia. Selected tumor markers, including estradiol concentration 164 pmol/L (normal value, 48-903 pmol/L), human chorionic gonadotropin <2.0 IU/L (0.00-10.00 IU/L), and alpha fetoprotein 3.7 µg/L (0.00-10.00 µg/L), were within normal limits. Radiologic examination, including CT scan and MRI of abdomen, showed a multilocular cystic mass extending above the umbilicus. The spleen and abdominal wall showed vascular malformations. Chest scan showed a hemangioma in the lung less than 1 cm in diameter. Exploratory laparotomy showed bilateral ovarian masses without ascites. Left salpingo-oophorectomy and wedge resection of the right ovary were performed. There was no evidence of intra-abdominal spread. Postoperative recovery was uneventful, and the patient was discharged and given an appointment for follow-up.
Pathology
Tissue available for pathologic examination included the left ovarian cystic mass with attached fallopian tube, and two wedge biopsy specimens from the right ovary. The left ovarian cyst was 20 cm in maximal dimension. It was unilocular and the internal surface was smooth gray and lacked any solid or papillary growth. The fallopian tube was stretched over the cyst but was otherwise normal. The two wedge resections from the right ovary measured 4.5 cm and 3.5 cm in maximal dimension. The cut surface revealed multiple cysts ranging in size from barely visible to 1.0 cm in maximal dimension. The intervening tissue was whitish and solid.
Microscopic
examination of the left ovary showed ovarian
tissue containing numerous primordial follicles and some cystic
follicles
(Figure 1). Multiple atretic follicles were identified but no corpora
lutea or
albicantia were seen.
Figure 1. Left ovary with two follicular cysts (H&E, 40x).
Figure 3. Right ovary with two follicular cysts and part of the wall of the serous cystadenoma (H&E, 40x).
The ovarian stroma showed foci of prominent smooth muscle proliferation, and the ovarian cortex was very thick and fibrous. The large cyst was lined by a single layer of cuboidal-to-low columnar ciliated epithelial cells (Figure 2). There was no evidence of any stratification or nuclear atypia. The underlying stroma was dense and fibrous. The two wedge resections from the right ovary showed numerous cystic follicles lined by granulosa cells and having an outer thicker layer of luteinized theca interna cells (Figure 3). The right ovary showed a multilocular cystic lesion, with a lining of a single layer of cuboidal-to-low columnar ciliated epithelial cells. The ovarian stroma showed areas of hyperthecosis, edema and prominent irregular vascular spaces (Figure 4). Few inclusion cysts were seen, with some showing tubal metaplasia. No corpora lutea or albicantia were identified. The diagnosis of synchronous bilateral ovarian serous cystadenomas and polycystic ovarian disease was made.
Figure 2. Wall of the cyst from left ovary showing ciliated single epithelial cell lining (H&E, 100x).
Figure 4. Right ovary with prominent vascular pattern of the stroma (H&E, 100x).
Discussion
Ollier’s disease (OD) is a rare nonhereditary congenital syndrome characterized by multiple enchondromas. When the latter are associated with multiple hemangiomas, the designation Maffucci’s syndrome (MS) is used. The emergence of several neoplasms is a well-known complication of both these diseases, and is recognized as a principal factor affecting patient prognosis. Although chondrosarcoma is by far the most common sarcoma seen in MS,1 a wide variety of non-cartilaginous tumors have been reported. Some enchondromas have been reported to develop into osteosarcoma or dedifferentiated chondrosarcoma.14-18
One of the earliest studies was conducted by Lewis and Ketchum.4 In their extensive review of the world literature of 105 cases of patients who had MS, they found that 15% of them developed chondrosarcoma. Among the various neoplasms which they described, five were gynecologic, two were described as malignant mesenchymal ovarian tumors, one was ovarian thecoma, one was uterine polyp, and another one was uterine fibroid.
In their tri-institutional retrospective study with long-term follow-up, Schwartz et al.19 identified 44 patients with multiple enchondromas. One patient developed an ovarian granulosa cell tumor. They found no evidence of hereditary transmission or of a familial tendency to this syndrome. In addition, they compared the risk of development of malignant neoplasms in patients with MS and those with OD.
The risk of the development of a skeletal or non-skeletal malignant neoplasm for patients with MS is probably close to 100% if they are followed for a long enough period. The risk of the development of a malignant neoplasm in patients with OD is considerably less. In 1993, Kaplan et al.20 reviewed 65 cases of MS. They found that 37% had a malignant lesion, and chondrosarcoma occurred in 30%. There were four cases of ovarian tumors, three mesenchymal (one juvenile granulosa cell tumor, one fibrosarcoma and one adenosarcoma), and one was an adenofibroma. They also found that the number of non-mesodermal tumors was high at 30% (14/49), contrary to the usual belief that MS is mainly a mesodermal dysplasia.
Because the ovarian neoplasm most commonly documented in association with enchondromatosis is juvenile granulosa cell tumor (JGCT), our case was referred with a strong suspicion of this diagnosis. At least 14 cases of JGCT have been reported in association with enchondromatosis, four associated with MS, and the rest with OD.2-13 The accumulation of cases developing ovarian JGCT indicates that this neoplasm appears to be the next most frequent tumor occurring in patients with enchondromatosis. The clinical and morphological features of the tumors and their behavior have not differed significantly from those of JGCTs occurring in patients without these syndromes.12 Single examples of ovarian fibroma21 and fibrosarcoma22 have also been reported in patients with MS. The patient with the fibrosarcoma, who was 17 years old, was re-explored 18 months after left oophorectomy, and there was no evidence of metastatic tumor.
Polycystic ovarian disease has not been previously described in association with MS. Although our patient did not have clinical manifestations of polycystic ovarian disease, it is possible that this was the primary pathology, and the development of bilateral epithelial neoplasms was a secondary phenomenon. This idea was considered by Resta et al.,23 who found that hyperplastic and metaplastic changes of the ovarian surface epithelium and related inclusion cysts can be regarded as morphologic precursors of common epithelial tumors of ovary. The finding of inclusion cysts and tubal metaplasia in the right ovary of our case may support this hypothesis. The right ovary in our patient showed a prominent stromal vascular pattern, which may be related to the generalized hemangiomatosis seen in MS, noting that our patient had both subcutaneous and visceral hemangiomas. It is not clear whether the ovarian pathology seen in our case was only coincidental or whether it could be attributed to a common embryonic meso-ectodermal developmental dysplasia.16,24 This concept is supported by reports of dysplastic conditions seen in association with enchondromatosis, such as bilateral renal agenesis,25 and the congenital anomalies indicative of Goldenhar’s syndrome (oculoauriculovertebral dysplasia).26
Because of the common tendency for development of neoplasms in patients with enchondromatosis, it is important that these patients are followed carefully, with special emphasis on periodic imaging of abdomen and pelvis for occult neoplasms. Additional studies are needed to understand the pattern of transmission and the proposed embryonic meso-ectodermal developmental dysplasia of enchondromatosis.
*Link no longer available
......................
D I S E A S E : Enchondromatosis
Synonym(s)
Maffucci syndrome
Ollier disease
Maffucci's syndrome is characterized by the presence of multiple enchondromas and cutaneous hemangiomas. Intracranial chondrosarcomas may be associated with this syndrome. Immunohistochemical studies are necessary to differentiate chondrosarcomas from chordomas. Its etiology is still unclear. Maffucci's syndrome is a dysembryoplasia of the mesoderm, explaining the dual involvement of cartilage and vascular tissue. The risk of malignant degeneration or associated tumors is probably high in this uncommon disease, suggesting that there is an additional oncogenic factor. * Author: S. Aymé, M.D. (June 1999) *
MIM : 166000
Clnical Signs
asymmetry
of the body (Very frequent sign)
autosomal
dominant inheritance (Very frequent sign)
bowed
diaphysis (Very frequent sign)
haemangioma-cavernous
(Very frequent sign)
restricted
joint mobility (Very frequent sign)
visceral
angiomatosis (Very frequent sign)
mutiple
fractures (Frequent sign)
neoplasia/cancer
(Frequent sign)
decreased
skin pigmentation irregular (Occasional sign)
lymphoedema/oedema
(Occasional sign)
Other Websites
Information for the disease. General public
Site in english
Collège
des Enseignants en Radiologie de France
Information for the disease. Public : health professionals
Site in french
Hemangiomas
and vascular anomalies, USA
Information for the disease. General public
Site in english
National
Organization for Rare Disorders, USA
Information for the disease. Information centers repertory. General
public
Site in english
Site
francophone sur les anomalies vasculaires, Québec
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=296
......................
Important
It is possible that the main title of the report Maffucci Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Synonyms
- Dyschondrodysplasia with Hemangiomas
- Enchondromatosis with Multiple Cavernous Hemangiomas
- Hemangiomatosis Chondrodystrophica
- Kast Syndrome
- Multiple Angiomas and Endochondromas
Disorder Subdivisions
- None
General Discussion
Maffucci Syndrome is a rare genetic disorder characterized by benign overgrowths of cartilage (enchondromas), skeletal deformities, and dark red irregularly shaped patches of skin (hemangiomas). Enchondromas are most often found in certain bones (phalanges) of the hands and feet. Skeletal malformations may include legs that are disproportionate in length and/or abnormal side-to-side curvature of the spine (scoliosis). In many cases, bones may tend to fracture easily. In most cases, hemangiomas appear at birth or during early childhood and may be progressive. Maffucci Syndrome is inherited as an autosomal dominant genetic trait.
Resources
National Organization for Rare Disorders, Inc.
55 Kenosia Ave
PO Box 1968
Danbury, CT 06813-1968
Tel: (203)744-0100
Fax: (203)798-2291
Tel: (800)999-6673
TDD: (203)797-9590
Email: orphan@rarediseases.org
Internet: http://www.rarediseases.orgAmerican Cancer Society, Inc.
1599 Clifton Road NE
Atlanta, GA 30329
USA
Tel: 4043203333
Tel: 8002272345
Email: None.
Internet: http://www.cancer.orgNIH/National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse
1 AMS Circle
Bethesda, MD 20892-3675
USA
Tel: 3014954484
Fax: 3017186366
Tel: 8772264267
TDD: 3015652966
Email: niamsinfo@mail.nih.gov
Internet: http://www.niams.nih.govNIH/National Heart, Lung and Blood Institute
31 Center Drive MSC 2480
Building 31A Rm 4A16
Bethesda, MD 20892-2480
Tel: (301)592-8573
Fax: (301)480-4907
Email: nhlbiinfo@rover.nhlbi.nih.gov
Internet: http://www.nhlbi.nih.gov/NIH/Patient Referral Services Unit
Warren Grant Magnuson Clinical Center
Patient Referral and Recruitment Center
Bldg 61
10 Cloister Ct
Bethesda, MD 20892
United States
Tel: 8004111222
Internet: http://www.cc.nih.gov/Birth Defect Research for Children, Inc.
930 Woodcock Rd
Suite 225
Orlando, FL 32803
USA
Tel: 4078950802
Fax: 4078950824
Email: abcd@birthdefects.org
Internet: http://www.birthdefects.orgFor a Complete Report
This is an abstract of a report from the National Organization for Rare Disorders, Inc. ® (NORD). A copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html
http://www.questdiagnostics.com/kbase/nord/nord433.htm
......................
A case of Maffucci 's syndrome with pleural effusion: ten-year follow-up.PMID: 15175777 [PubMed - indexed for MEDLINE]
......................
Maffucci's syndrome complicated by intracranial chondrosarcoma: two new illustrative cases.
Sept 2007
Department of Neurosurgery, Hospital Centenário, Avenida Theodomiro Porto da Fonseca 799, 93020-080 São Leopoldo, RS, Brazil. lenadrodini@ig.com.br
Maffucci's syndrome is a rare congenital condition, sometimes misdiagnosed as Ollier's disease, characterized by multiple enchondromas combined with hemangiomas and phlebectasia. Coexisting primary malignancies have been described sporadically. We report two cases of Maffucci's syndrome associated with cranial base chondrosarcoma, emphasizing pathophysiological features and the challenging management of intracranial chondrosarcomas. To the best of our knowledge, only twelve similar cases have been reported in the literature.
......................
Maffucci's syndrome with giant tumor of the thoracic wall]......................
Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C.
Dec 2004
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Enchondromatosis (Ollier disease, Maffucci syndrome) is a rare developmental disorder characterized by multiple enchondromas. Not much is known about its molecular genetic background. Recently, an activating mutation in the parathyroid hormone receptor type 1 (PTHR1) gene, c.448C>T (p.R150C), was reported in two of six patients with enchondromatosis. The mutation is thought to result in upregulation of the IHH/PTHrP pathway. This is in contrast to previous studies, showing downregulation of this pathway in other cartilaginous tumors. Therefore, we investigated PTHR1 in enchondromas and chondrosarcomas from 31 enchondromatosis patients from three different European countries, thereby excluding a population bias. PTHR1 protein expression was studied using immunohistochemistry, revealing normal expression. The presence of the described PTHR1 mutation was analyzed, using allele-specific oligonucleotide hybridization confirmed by sequence analysis, in tumors from 26 patients. In addition, 11 patients were screened for other mutations in the PTHR1 gene by sequence analysis. Using both allele-specific oligonucleotide hybridization and sequencing, we could neither confirm the previously found mutation nor find any other mutations in the PTHR1 gene. These results indicate that the PTHR1 gene is not, in contrast to previous suggestions, the culprit for enchondromatosis.
---------------------------------
References:
......................
Enchondroma and Enchondromatosis (1)
Maffucci Syndrome - eMedicine (2)
---------------------------------
Clasifications and Codes:
......................
ICD-10
| Q78.4 | Enchondromatosis | |||||||
| Maffucci's syndrome Ollier's disease |
||||||||
ICD-9
MeSH D004687
eMedicine derm/256
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