Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)

1999-12-01   John A. Martignetti  

Mount Sinai School of Medicine, Departments of Human Genetics, Pediatrics, 1425 Madison Ave, Box 1498, New York, NY 10029, USA

Identity

Name

Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)

Alias

Bone dysplasia with medullary fibrosarcoma , Bone dysplasia with malignant fibrous histiocytoma , Hereditary bone dysplasia with malignant change

Note

DMS-MFH is an hereditary bone dysplasia \/ cancer syndrome

Inheritance

autosomal dominant; rare hereditary cancer syndrome with only four families identified worldwide; etiology unknown
Atlas Image
Photograph A: Lateral X-ray view of the left tibia and fibula of an 18 year old male with DMS-MFH and MFH. Note the extensive diaphyseal cortical thickening, areas of resultant medullary stenosis, endosteal irregularities, overall permeative pattern in the medullary cavity, and metaphyseal striations.

Omim

112250

Mesh

C536169

Orphanet

85182 Diaphyseal medullary stenosis - bone malignancy

Umls

C1300202;C1862177

Clinics

Note

radiologic evidence of bone dysplasia not evident in childhood; X-ray findings become apparent during adolescence

Phenotype and clinics

  • main features include:
    • bone dysplasia (100%)
      • cortical growth abnormalities: diaphyseal medullary stenosis with overlying endosteal cortical thickening and scalloping, metaphyseal striations, scattered sclerotic areas symmetrically affecting the long bones; bilateral mandibular radiolucent and sclerotic lesions
      • bone infarctions
      • pathologic fractures: subsequent poor healing or non-union
      • progressive wasting or bowing of the lower extremities
      • bone pain
      • pre-senile cataracts (25%)
      • bone malignant fibrous histiocytoma (MFH) (35%)
      • diagnosis: X-ray skeletal findings are unique; however, there may be some radiologic overlap with other diaphyseal dysplasias including Camurati-Engelman and Kenny-Caffey diseases and radiation osteitis; no hematologic or urinary markers of disease have been identified; 201Thallium chloride radionucleotide scans may offer discrimination between areas of increased metabolic bone activity found in DMS-MFH patients and malignant change.
    • Atlas Image
    Photograph B: Tibia and MFH of patient shown in Photograph A. The MFH tumor was associated with the infarcted area in the proximal tibia. Hematoxylin and eosin preparation shows removed MFH tumor from infarcted area with typical storiform arrangement of spindle cells throughout the view.

    Neoplastic risk

    thirteen cases of osseous MFH; thirty-five per cent of DMS-MFH patients develop MFH; the age distribution has been from the second to fifth decades; no sex predilection; in its sporadic form, MFH represents approximately 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma

    Treatment

    no known treatment for the dysplasia; the tumors are highly aggressive   treated with surgical ablation and the same chemotherapeutic regimens as osteosarcoma it is believed that preoperative chemotherapy improves surgical outcome

    Evolution

    the disease becomes radiologically apparent only in adolescence: however, retrospectively, clinical signs and symptoms may be evident in childhood; these include unexplained bone pain and pathologic fractures; in some, crippling pain and weakness of the lower extremities ensues following the sixth decade; malignancy occurs most frequently between the second to fifth decades and is particularly aggressive; only two long-term survivors, greater than five years, are known.; pre-senile cataracts have been noted as early as in the third decade

    Other Findings

    Note

    collagen fibrils from the endosteal surface of bones appear frayed and unraveled (npublished results); chemical crosslink analysis of bone biopsy samples reveal altered hydroxylysylpyridinolin (HP) \/ lysylpyridinoline (LP) ratios (unpublished results)

    Genes involved and Proteins

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    47135731973Hereditary bone dysplasia with sarcomatous degeneration. Study of a family.Arnold WH et al
    37452481986Hereditary bone dysplasia with malignant change. Report of three families.Hardcastle P et al
    106128082000Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect.Martignetti JA et al
    87811101996Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome.Norton KI et al

    Citation

    John A. Martignetti

    Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)

    Atlas Genet Cytogenet Oncol Haematol. 1999-12-01

    Online version: http://atlasgeneticsoncology.org/cancer-prone-disease/10056/diaphyseal-medullary-stenosis-with-malignant-fibrous-histiocytoma-(dms-mfh)/