Fibrous dysplasia: Difference between revisions
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*Patients with FD usually appear normal unless the is any bony deformity or skin is involved. | *Patients with FD usually appear normal unless the is any bony deformity or skin is involved. | ||
*Physical examination may be remarkable according to the classification of disease: | *Physical examination may be remarkable according to the classification of disease: | ||
:* | :Monostetic | ||
:* | :* Single bone involved | ||
:* | :* Mostly affects rib, femur, and tibia. | ||
:* | :* Carinofasical bone and humorus bone | ||
:* | :* Fracture at age of 10 years | ||
:* | :* Bone defrmity less sever | ||
:* painless swelling of jaw | |||
:* swelling involve buccal and labial plate | |||
:* Protuberance of inferior border of mandible | |||
:Polyostetic | |||
:* Multiple bones involved | |||
:* Involve rib, femur, clavicle, femur, lumber spine and tibia. | |||
:* Asymmetrical involvement | |||
:* Mainly maalignment of bones | |||
:* Tenderness over involved bone | |||
:* Bowing of weight bearing bone and increased curvature of femur and tibia | |||
:Cranofasical | |||
:* Involvement of maxilofascial bones | |||
:* Maladjustment | |||
:* Tappering | |||
:* Daisplacemnt | |||
:* Intact over lesion | |||
:* Maxillary sinus and Zygomatic bone involved mostly | |||
:* Floor of orbit may extend to skull | |||
:* No extracranial involvement | |||
:* Hypertelorisum, facial asymmetry, visual impairment, expothalmus and blindness | |||
:* Vestibular dysfuntion, hearing loss and tinnitus. | |||
:McCune-Albright syndrome | |||
:* Involves all the bone of body | |||
:* Cafe au lait spots | |||
:* Endocrine abnormality of parathyroid hormone, gonadotropins Mazabraud syndrome | |||
:* Involve variable number of bones | |||
:* Cafe au lait spots | |||
: | |||
=== Laboratory Findings === | === Laboratory Findings === | ||
*There are no specific laboratory findings associated with | *There are no specific laboratory findings associated with FD however we may find normal PTH, Ca levels, and increased levels of ALK phosphate due to increased bone turn over and increased BMR. | ||
===Imaging Findings=== | ===Imaging Findings=== | ||
* | *Radiology is the imaging modality of choice for FD. | ||
*On Xray, FD is characterized by | |||
**Network of fine bone trabeculae | |||
*On | **Increased trabeculation | ||
* | **Opaque trabeculation forming ground glass appearance | ||
**Cortical thinning | |||
**Root of teeth separated | |||
=== Other Diagnostic Studies === | === Other Diagnostic Studies === | ||
* | *Work up of FD may also be involve using MRI and CT. | ||
* | *Bone biopsy will revel the histological findings of as: | ||
**Curvilinear trabeculae (Chinese letters) of metaplastic woven bone (never matures) in hypocellular, | |||
**fibroblastic stroma | |||
**No osteoblastic rimming (due to maturation arrest), 20% of cases have cartilaginous nodules (particularly in femoral neck region) | |||
**Also myxoid areas, rapidly growing secondary aneurysmal bone cysts, hemorrhage, foamy macrophages, calcified spherules (similar to cementifying fibromas), cellular areas, focal hyaline cartilage or cystic areas | |||
== Treatment == | == Treatment == | ||
=== Medical Therapy === | === Medical Therapy === | ||
*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2]. | *The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2]. | ||
*[Medical therapy 1] acts by [mechanism of action 1]. | *[Medical therapy 1] acts by [mechanism of action 1]. |
Revision as of 16:45, 20 April 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Fibrous dysplasia is a disorder of bones which may occur with or without endocrinological and skin disorders. It may cause bony pain, deformity, fracture and / or entrapment of nerves, It is basically the acquired mis-sense mutation of gene coding for the α-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. It leads to immature or poor differentiation of body tissue at the time of ossification and replacement of bone by fibrous tissue. Diagnosis depends on radiology and biopsic specimen.
Historical Perspective
- Fibrous dyspepsia was first observed in bone radiography by Von Recklinghausen in 1891.
- It was then entitled as separate entity by american pathologist Dr. Louis Lichtenstein in 1938 as fibrous dyspepsia polyostotic.
- In 1942, Dr Lichtenstein and Dr. Jaffe together labeled syndrome named McCune-Albright syndrome (fibrous dysplasia-café au lait spots-endocrine dysfunction) or Mazabraud syndrome (fibrous dysplasia-myxomas).
Classification
- Fibrous dyspepsia may be classified according to number of bony sites involved into two groups:
- Monoostiotic
- Polyostiotic
- Other variants of FD include McCune-Albright syndrome, and Mazabraud syndrome.
Pathophysiology
The pathophsiology of FD is based on mechanism mutation of Gs protein.
Genetics
- The somatic mutation in GNAS1 gene located on the long arm (q) of chromosome 20 (20q13.2) has been associated with the development of FD, involving the gain-of-function mutation pathway.
- As it is somatic mutation that is why it is not heritable, post fertilization mutation occurring due to unknown reason.
- Mutation of GNAS1 gene results in the overproduction of this G-protein, which in turn increases cyclic adenosine monophosphate (cAMP).
- cyclic adenosine monophosphate (cAMP) is important regulatory molecule of differentiation modulating osteoblasts and osteoclasts while ossification and remodeling of bones.
- Improper differentiation of osteoblasts due to mutation of the GNAS1 gene is the cause of FD.
- Osteoclasts removes ossified bones and creates space for immature osteoblasts to produce fibrous tissue and occupy space which may entrap nerves causing pain or nurological deficit depending on the site involved.
- On gross pathology, Well circumscribed, intramedullary,Tan-white-yellow, gritty, Large lesions distort bone, Cortical bone often thin and expanded are characteristic findings of FD.
- On microscopic histopathological analysis :
- Curvilinear trabeculae (Chinese letters) of metaplastic woven bone (never matures) in hypocellular,
- fibroblastic stroma
- No osteoblastic rimming (due to maturation arrest), 20% of cases have cartilaginous nodules (particularly in femoral neck region)
- Also myxoid areas, rapidly growing secondary aneurysmal bone cysts, hemorrhage, foamy macrophages, calcified spherules (similar to cementifying fibromas), cellular areas, focal hyaline cartilage or cystic areas
- Usually abrupt transition of normal to abnormal bone
- No/rare mitotic figures, no atypia (rarely is degenerative)
- Overall resembles endochondral ossification in skull are characteristic findings of FD.
Clinical Features
There are four varriets of FD and the clinical features are pertaining to that specific feature.
- Monoostiotic
- Polyostiotic
- McCune-Albright syndrome
- Mazabraud syndrome
Differentiating Fibrous dyspepsia from other Diseases
- Fibrous dyspepsia must be differentiated from other diseases that cause bone pain, deformity, and extra-skeletal involvement, such as:
Disease | Bone involvement | Bone pain | Fever | Fractures | Mechanisum | ALK levels | Diagnosis |
---|---|---|---|---|---|---|---|
ossifying sarcoma | single | yes | no | yes | neoplasm | normal | radiology and biopsy |
paget's disease | multiple | yes | no | yes | malfunction of
osteoblast |
high | biopsy |
osteosarcoma | single | yes | no | yes | neoplasm | normal | radiology and biopsy |
cherubism | single | yes | no | no | malfunction of
osteoblas |
high | radiology and biopsy |
hyperparathyroidisum | multiple | yes | yes | yes | high PTH | normal | hormone workup |
solitary endocytosis | single | yes | no | no | neoplasm | normal | radiology and biopsy |
osteoblastoma | single | yes | no | yes | neoplasm | high | radiology and biopsy |
osteomyelitis | single | yes | yes | no | infection | normal | radiology and biopsy |
brodie's abscess | single | yes | yes | no | infection | normal | radiology and biopsy |
Epidemiology and Demographics
- The prevalence and incidence of FD is not known exactly.
Age
- FD is more commonly found in age group from 3 -15 years of life.
- Polyostiotic does not become symptomatic before age 10 years.
- Monostiotic is asymptomatic until age of 20-30 years of life.
Gender
- FD affects men and women equally.
Race
- There is no racial predilection for FD.
Risk Factors
- Common risk factor in the development of PD is gain in function mutation.
Natural History, Complications and Prognosis
- The majority of patients with FD remain asymptomatic for first decade of life.
- Early clinical features include bone pain, bony deformity, fever, pathological fractures, and skin/endocrine/malignancies depending on the variant.
- Common complications of FD include neurological deficit, endocrine abnormality, and in rare cases soft tissue tumors.
- Prognosis is generally good, and the patients with polyostetic form may have frequent fractures.
Diagnosis
Diagnostic Criteria
- The diagnosis of FD is made when on the basis of history, radiology findings and genetic testing to verify presence og GNAS mutation.
Symptoms
- FD is usually asymptomatic.
- Symptoms of FD may include Early clinical features include bone pain, bony deformity, fever, pathological fractures, and skin/endocrine/malignancies depending on the variant. Common complications of FD include neurological deficit, endocrine abnormality, and in rare cases soft tissue tumors
Physical Examination
- Patients with FD usually appear normal unless the is any bony deformity or skin is involved.
- Physical examination may be remarkable according to the classification of disease:
- Monostetic
- Single bone involved
- Mostly affects rib, femur, and tibia.
- Carinofasical bone and humorus bone
- Fracture at age of 10 years
- Bone defrmity less sever
- painless swelling of jaw
- swelling involve buccal and labial plate
- Protuberance of inferior border of mandible
- Polyostetic
- Multiple bones involved
- Involve rib, femur, clavicle, femur, lumber spine and tibia.
- Asymmetrical involvement
- Mainly maalignment of bones
- Tenderness over involved bone
- Bowing of weight bearing bone and increased curvature of femur and tibia
- Cranofasical
- Involvement of maxilofascial bones
- Maladjustment
- Tappering
- Daisplacemnt
- Intact over lesion
- Maxillary sinus and Zygomatic bone involved mostly
- Floor of orbit may extend to skull
- No extracranial involvement
- Hypertelorisum, facial asymmetry, visual impairment, expothalmus and blindness
- Vestibular dysfuntion, hearing loss and tinnitus.
- McCune-Albright syndrome
- Involves all the bone of body
- Cafe au lait spots
- Endocrine abnormality of parathyroid hormone, gonadotropins Mazabraud syndrome
- Involve variable number of bones
- Cafe au lait spots
Laboratory Findings
- There are no specific laboratory findings associated with FD however we may find normal PTH, Ca levels, and increased levels of ALK phosphate due to increased bone turn over and increased BMR.
Imaging Findings
- Radiology is the imaging modality of choice for FD.
- On Xray, FD is characterized by
- Network of fine bone trabeculae
- Increased trabeculation
- Opaque trabeculation forming ground glass appearance
- Cortical thinning
- Root of teeth separated
Other Diagnostic Studies
- Work up of FD may also be involve using MRI and CT.
- Bone biopsy will revel the histological findings of as:
- Curvilinear trabeculae (Chinese letters) of metaplastic woven bone (never matures) in hypocellular,
- fibroblastic stroma
- No osteoblastic rimming (due to maturation arrest), 20% of cases have cartilaginous nodules (particularly in femoral neck region)
- Also myxoid areas, rapidly growing secondary aneurysmal bone cysts, hemorrhage, foamy macrophages, calcified spherules (similar to cementifying fibromas), cellular areas, focal hyaline cartilage or cystic areas
Treatment
Medical Therapy
- The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
- [Medical therapy 1] acts by [mechanism of action 1].
- Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
Surgery
- Surgery is the mainstay of therapy for [disease name].
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
- [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
Prevention
- There are no primary preventive measures available for [disease name].
- Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
- Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].