Download Cancer Prone Disease Section Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Cancer Prone Disease Section
Mini Review
Diaphyseal medullary stenosis with malignant
fibrous histiocytoma (DMS-MFH)
John A Martignetti
Mount Sinai School of Medicine, Departments of Human Genetics and Pediatrics, 1425 Madison Ave, Box
1498, New York, NY 10029, USA (JAM)
Published in Atlas Database: December 1999
Online updated version : http://AtlasGeneticsOncology.org/Kprones/DiaphysStenosID10056.html
DOI: 10.4267/2042/37573
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 1999 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Phenotype and clinics
Identity
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 nonunion
- Progressive wasting or bowing of the lower
extremities
- bone pain
- Pre-senile cataracts (25%)
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.
Clinics
Note
Radiologic evidence of bone dysplasia not evident in
childhood; X-ray findings become apparent during
adolescence.
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.
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(4)
219
Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)
Martignetti JA
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.
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.
- 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.
Neoplastic risk
Other findings
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.
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).
Treatment
Genes involved and proteins
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.
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,
Evolution
The disease becomes radiologically apparent only in
adolescence: however, retrospectively, clinical signs
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(4)
220
Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)
Norton KI, Wagreich JM, Granowetter L, Martignetti JA.
Diaphyseal medullary stenosis (sclerosis) with bone
malignancy (malignant fibrous histiocytoma): Hardcastle
syndrome. Pediatr Radiol. 1996 Sep;26(9):675-7
including p15 and 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 tumorsuppressor 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.
Martignetti JA, Desnick RJ, Aliprandis E, Norton KI, Hardcastle
P, Nade S, Gelb BD. Diaphyseal medullary stenosis with
malignant
fibrous
histiocytoma:
a
hereditary
bone
dysplasia/cancer syndrome maps to 9p21-22. Am J Hum
Genet. 1999 Mar;64(3):801-7
Martignetti JA, Gelb BD, Pierce H, Picci P, Desnick RJ.
Malignant fibrous histiocytoma: inherited and sporadic forms
have loss of heterozygosity at chromosome bands 9p21-22evidence for a common genetic defect. Genes Chromosomes
Cancer. 2000 Feb;27(2):191-5
References
Arnold WH. Hereditary bone dysplasia with sarcomatous
degeneration. Study of a family. Ann Intern Med. 1973
Jun;78(6):902-6
This article 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.
Hardcastle P, Nade S, Arnold W. Hereditary bone dysplasia
with malignant change. Report of three families. J Bone Joint
Surg Am. 1986 Sep;68(7):1079-89
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(4)
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