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

Written1999-12John A. Martignetti
Mount Sinai School of Medicine, Departments of Human Genetics, Pediatrics, 1425 Madison Ave, Box 1498, New York, NY 10029, USA

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Identity

Other namesBone dysplasia with medullary fibrosarcoma
Bone dysplasia with malignant fibrous histiocytoma
Hereditary bone dysplasia with malignant change
Atlas_Id 10056
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
 
  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.

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.
  •  
      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

    Note the gene has been mapped by linkage analysis to a 3 cM region on chromosome 9p21-22; all families used in the study generated positive LOD scores in this region and all affecteds had similar phenotypic findings consistent with the syndrome being genetically homogeneous; a number of genes in the region, including p15and p16, have been excluded as the DMS-MFH gene by DNA sequencing analysis; under the hypothesis that hereditary and sporadic MFH tumors are genetically identical, the DMS-MFH tumor-suppressor gene region has been further narrowed to 1.5 cM using loss of heterozygosity analysis; the continued search for the common minimally deleted region in MFH tumors should provide the most powerful method for gene identification

    Bibliography

    Hereditary bone dysplasia with sarcomatous degeneration. Study of a family.
    Arnold WH
    Annals of internal medicine. 1973 ; 78 (6) : 902-906.
    PMID 4713573
     
    Hereditary bone dysplasia with malignant change. Report of three families.
    Hardcastle P, Nade S, Arnold W
    The Journal of bone and joint surgery. American volume. 1986 ; 68 (7) : 1079-1089.
    PMID 3745248
     
    Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome.
    Norton KI, Wagreich JM, Granowetter L, Martignetti JA
    Pediatric radiology. 1996 ; 26 (9) : 675-677.
    PMID 8781110
     
    Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22.
    Martignetti JA, Desnick RJ, Aliprandis E, Norton KI, Hardcastle P, Nade S, Gelb BD
    American journal of human genetics. 1999 ; 64 (3) : 801-807.
    PMID 10053015
     
    Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect.
    Martignetti JA, Gelb BD, Pierce H, Picci P, Desnick RJ
    Genes, chromosomes & cancer. 2000 ; 27 (2) : 191-195.
    PMID 10612808
     

    Citation

    This paper should be referenced as such :
    Martignetti, JA
    Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)
    Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):219-221.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/DiaphysStenosID10056.html


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