Genetic disorder with dysplasia of the long bones
associated with a high risk for transition in malignant histiocytoma.
Diaphyseal Medullary Stenosis with Malignant Fibrous
Histiocytoma; Bone Dysplasia with Medullary Fibrosarcoma; Hereditary Bone
Dysplasia with Malignant Fibrous Histiocytoma.
Unknown but rare. Only four families with this syndrome
have been reported in the literature since its first recognition by Arnold
Autosomal dominant pattern of inheritance with
probable variable penetration of the gene. Gene linkage studies have
isolated the syndrome to 9p22-p21.
Precise pathophysiology is unknown, but the region
of chromosome 9 has been linked to the syndrome. It contains a number of genes whose
protein products are involved in growth regulation, protein synthesis, and
breakdown. At a cellular level, abnormal fibroblast function is the most
likely cause of dysplasia.
Made by clinical features and characteristic radiologic
findings, which include diffuse diaphyseal medullary stenosis with overlying
endosteal cortical bone thickening, scalloping, metaphyseal striations,
infarctions, scattered sclerotic bone areas, and decrease of metaphyseal
bone density with sparing of the epiphysis. Family members at risk are
advised to have yearly radiographs of the lower limbs after puberty, and
those with abnormalities on plain radiographs should have yearly bone
scintigraphy scans thereafter (scintigraphy scanning will detect tumors
within areas of dysplasia). Biochemical and parathyroid screening are
Characterized by bone dysplasia with cortical
growth abnormalities, which symmetrically affects the long tubular bones of
the extremities. Spine and pelvis are unaffected. Radiographic evidence of
the bone dysplasia has been reported from puberty onward, with a peak
between the second and fifth decade of life. Of affected individuals, 35%
develop malignant fibrous histiocytoma, a highly malignant bone sarcoma.
Survival following diagnosis of malignant fibrous histiocytoma is very poor
(usually less than 2 years). Morbidity results from pathologic fractures
(prolonged healing and nonunion occur), bowing of the limbs, wasting of
affected limbs, and painful debilitation. An association with presenile
cataracts has been reported. Death is most often caused by multiple
metastases (brain, lung, liver, kidney, heart, and bone). Current treatment
is directed toward early diagnosis of malignant changes in dysplastic areas
followed by amputation with or without chemotherapy.
Detailed clinical history and
examination to determine the extent of bone dysplasia and evidence of
malignant changes and tumor metastases. If indicated (metastatic disease),
assess cardiac function (ECG, echocardiography), pulmonary function (chest
radiograph, spirometry, arterial blood gases), liver function, and renal
function (blood urea nitrogen, electrolytes). CT or MRI scans (brain, lungs,
heart, liver, kidney, bones) and hematologic screening (complete blood count
and clotting screen) may be required.
Anesthetic technique is influenced by the
metastatic disease and depends on the affected organs. Care with patient
positioning must be taken because even minimal trauma may cause bone fracture.
All routine medications should be
continued preoperatively unless contraindicated. No other specific
pharmacological considerations except for patients receiving chemotherapy