Update: Maffucci syndrome

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome).

Additionally, neuroendocrine tumors including pituitary adenomas have been described in patients with Maffucci syndrome.

The rate of malignant transformation in Maffucci syndrome is high, with enchondromas transforming into chondrosarcomas and the development of secondary neoplasms, including pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, and brain tumors such as glioma. However, hematopoietic malignancies arising in Maffucci syndrome are rare 1)

Etiology

The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2)2).

Case series

2017

Cerebral MRI was routinely performed in Ollier-Maffucci patients followed-up in tertiary centers. Patients with previous history of skull base or intracranial tumors were excluded from the study. Clinical and radiological datas were retrospectively collected. The occurrence rate and nature of abnormal cerebral MRIs were determined.

Twelve patients were included. A glioma-looking lesion was found in one patient (8%), while skull base lesions were evidenced in 3 others (25%). A regular MRI follow-up was recommended for each patient, with a time interval varying between 1year and 3years depending on the likelihood of tumoral evolutivity, as infered from the MRI findings.

All in all, the high rate of intracranial and skull base lesions with a malignant potential warrants to include cerebral MRI in the routine follow-up of Ollier-Maffucci patients 3).

Case report

2016

A report describes a patient with Maffucci syndrome who presented with skull base tumors and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors.

This report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci syndrome. In patients who are newly diagnosed with Maffucci syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction 4).


A 39-year-old woman who was diagnosed with Maffucci syndrome together with intrahepatic cholangiocarcinoma (IHCC). Heterozygous somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes are associated with a number of different tumor types (e.g. IHCC) and also with Maffucci syndrome. For IHCC, mutations in IDH1/IDH2 are associated with higher survival rates. IHCC tissue as well as normal liver tissue and peripheral blood were analyzed for IDH1/IDH2-mutations in our patient. In the tumor sample, we identified a recurrent somatic IDH1-mutation affecting Arg132, while in normal liver tissue and peripheral blood, no variants were detected, as expected.

This case report presents the second patient in the literature exhibiting the features of Maffucci syndrome along with cholangiocarcinoma. This supports the hypothesis that IDH1/2-mutations, which can be present in different types of tumor tissue simultaneously, arise during embryonic development in a mosaic pattern; as a result, a more aggressive follow-up is proposed in patients with Maffucci syndrome to exclude neoplasms 5).

2009

First case of Maffucci syndrome associated with a pituitary adenoma and a probable brainstem glioma

A 35-year-old woman with Marfucci syndrome (diagnosed when she was 22 years old) who presented with complaints of decreased visual acuity and visual field defect. Neuroimaging revealed a pituitary macroadenoma and a suspected brainstem tumor. The macroadenoma was partially removed. There were no postoperative complications and the patient experienced rapid improvement in visual acuity. On follow-up examination 2 years later, the lesion in the pons showed the same dimensions. No sarcomatous changes of enchondromas or hemangiomas occurred. To the authors’ knowledge, including the present case, only 7 cases of Maffucci syndrome associated with glioma and 7 cases associated with pituitary adenoma have been reported in the literature. This report emphasizes that patients with this disease are at a higher risk for primary intracranial tumors and reinforces the concept of the multiplicity of tumors that may arise in this syndrome. It also underscores the importance of early diagnosis, regular clinical surveillance, and follow-up studies of these patients 6).

1)

Akiyama M, Yamaoka M, Mikami-Terao Y, Ohyama W, Yokoi K, Arakawa Y, Takita J, Suzuki H, Yamada H. Somatic mosaic mutations of IDH1 and NPM1 associated with cup-like acute myeloid leukemia in a patient with Maffucci syndrome. Int J Hematol. 2015 Dec;102(6):723-8. doi: 10.1007/s12185-015-1892-z. Epub 2015 Oct 27. PubMed PMID: 26508204.

2)

Pansuriya TC, van Eijk R, d’Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet. 2011 Nov 6;43(12):1256-61. doi: 10.1038/ng.1004. PubMed PMID: 22057234; PubMed Central PMCID: PMC3427908.

3)

Mandonnet E, Anract P, Martin E, Roujeau T, Spena G, Cormier-Daire V, Duffau H, Baujat G; Collaborators. Brain and skull base MRI findings in patients with Ollier-Maffucci disease: A series of 12 patient-cases. Clin Neurol Neurosurg. 2017 Jul 18;160:147-151. doi: 10.1016/j.clineuro.2017.07.011. [Epub ahead of print] PubMed PMID: 28750360.

4)

Hao S, Hong CS, Feng J, Yang C, Chittiboina P, Zhang J, Zhuang Z. Somatic IDH1 mutation in a pituitary adenoma of a patient with Maffucci syndrome. J Neurosurg. 2016 Jun;124(6):1562-7. doi: 10.3171/2015.4.JNS15191. Epub 2015 Oct 16. PubMed PMID: 26473790.

5)

Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H. Maffucci syndrome and neoplasms: a case report and review of the literature. BMC Res Notes. 2016 Feb 27;9(1):126. doi: 10.1186/s13104-016-1913-x. PubMed PMID: 26920730; PubMed Central PMCID: PMC4769492.

6)

Ruivo J, Antunes JL. Maffucci syndrome associated with a pituitary adenoma and a probable brainstem tumor. J Neurosurg. 2009 Feb;110(2):363-8. doi: 10.3171/2008.8.JNS08150. Review. PubMed PMID: 18976063.

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