Path Flashcards
How do you monitor the disease activity of Paget’s?
What treatment is recommended for asymptomatic Paget’s Disease?
By measuring serum alkaline phosphatase and urine hydroxyproline.
No pharmacological therapy as long as they remain asmyptomatic.
What are the most common sites for UBCs?
Proximal humerus>proximal femur>distal tibia>ilium>calcaneus Occasionally metacarpals, phalanges, or distal radius.
What are unicameral bone cysts?
-non-neoplastic serous filled bone lesion. -Thought to result from temporary failure of medullary bone formation near the physics. -Usually found in patients under the age of 20. -Most are asymptomatic.
What is the most common sarcoma found in the foot?
synovial sarcoma.
Where are Epithelioid sarcomas most commonly found?
forearm and hand.
Multiple Myeloma is a malignancy of what cell?
Monoclonal plasma cell.
What are the two forms of osteopetrosis?
Autosomal recessive form- lethal and causes death in infancy. Autosomal dominant form- more commonly seen. Patients live.
Known mutations that lead to osteoporosis?
carbonic anhydrase II vacuolar proton pump chloride channel 7
Radiographs that show erlenmeyer flask proximal humerus and distal femur and “Rugger jersey spine” are characteristic of what disease?
Osteopetrosis
Also can see loss of medullary canal (bone within a bone) appearance and block femoral metaphysis.
What are manifestations of Osteopetrosis?
Cranial nerve palsies
Osteomyelitis
Long bone fractures
coxa vara
anemia (from marrow encroachement)
What is Paget’s disease caused by?
What is the most important related gene mutation?
Abnormal osteoclasts.
Sequestosome 1 (SQSTM1) Autosomal dominant with high penetrance. It is a scaffold protein in the NF?B signalling pathway.
What disease is paramyxovirus infection thought to contribute to?
Paget’s Disease.
What is the most common diagnosis of a destructive bone lesion in an adult > 40 years?
Metastases.
What treatment option for distal femur ostosarcoma has the highest self-reported outcomes and the lowest revision surgeries in pre-adolescent patients?
Van Nes rotationplasty.
Endoprothetic reconstructions have high degree of success but high reoperation rates.
Amputation is a salvage option but should nto be perfromed initially because of increased oxygen requirements.
What is the difference between SYT-SSX1 vs SYT SSX2 fusion proteins?
SYT-SSX1 Biphasic, larger, more mets, and worse prognosis. More common.
SYT-SSX2 smaller size, fewer metastases, and better prognosis. Monophasic. Less common.
Biphasic refers to epithelial differentiation with glandular epithelial organization with spindle cell stroma.
40 M with a mass in the great toe. Histology from biopsy below.
What is the most liley diagnosis?
synovial sarcoma
hsitology shows biphasic areas of spindle cell stroma and epithelial cells.
Describe the histolgy slide.
THIS IS SPINDLE CELL LIPOMA-found in males between 5th and 7th decade of life. Treated with marginal excision.
Mature adipocytes with numerous bland spindle cells, collagen fibers, some mast cells with areas of myxoid degeneration.
Mitosis or cellular pleomorphism are absent.
CD34 postive staining.
Polyostotic mycobacterial infection.
Biopsy: Shows multiple giant cells with caseous necrosis.
Stain: Ziehl-Neelsen stain that displays mycobacterium as “red snappers” against a blue background.
What will the histology of a rheumatoid nodule show?
fibrous cellular palisade with a center of fibrinoid necrosis.
What is tarsal tunnel syndrome?
What are the sights of compression?
either proximal compression of the tibial nerve of from distal compression of any of the terminal branches.
Describe Mirel’s Criteria
What is the most likely diagnosis given the histology slide?
Resistant to chemotherapy and radiation
Treatment is wide surgical resection with negative margins.
How do you recognize well differentiated liposarcoma?
isointense on T1 and T2 images.
MDM2 amplification.
Treated with marginal resection and no radiation unlike high grade liposarcomas.
What are the histological finding of necrotizing fasciitis?
Necrosis of fascial layer
Microorganisms within fascial layer
PMN infiltration
fibrinous thrombi in arteries and veins and necrosis of arterial and venous walls.
What is the LRINEC Scoring system?
Used to diagnose necrotizing fasciitis.
score > 6 has PPV of 92% of having necrotizing fasciitis.
Based on the attached histology slide what is the most likely disease process?
Eosinophilic granuloma
Slide show Langerhans cells which have eosinophilic cytoplasmic cells that are mononuclear with a coffee bean shaped nuclei.
This slide is consistent with what disease process?
Lyme disease
The slide is of borrelia burgdorferi. Spirochete transmitted by the deer tick Ixodes.
This slide is consistent with what kind of staining?
What is the most likley disease?
Acid fast staining
Mycobacterium tuberculosis
Are the following statements true or false:
Prostate cancer is relatively radiosensitive?
Skeletal related evens are common in metastatic prostate cancer?
If pathologic fractures do occur they are not associated with a fair rate of healing?
True
False, they are relatively uncommon.
False, they are associated with a fair rate of healing.
Are Multiple Myeloma lesions hot or cold on bone scans?
Radionuclide bone scan is unreliable. As these are lytic lesions and 3-50% of the time will be “cold” or siltent on scan.
Perform a skeletal survery instead.
A lesion from what malignancy has the highest rates of pathologic fracture healing?
Multiple Myeloma 67%
True or false renacl cell carcinoma is sensitive to radiation?
Cytotoxic Chemotherapy?
False
False
What is the most common location for malignant transformation of exostoses in MHE?
Pelvis
Second, Scapula.
Proximal lesions more likely to undergo malignant transformation.
Describe the MSTS staging system for bone tumors?
Another name for Enneking staging system.
Two systems one for malignant (roman numerals) one for benign lesions (arabic numerals).
Describe the AJCC staging system?
Used more for soft tissue tumors.
Depends on:
grade- low = G1 and G2. High= G3 and G4.
size- T1 = <8cm T2 = > 8cm
nodes- N0 = no regional nodes N1 = Regional nodes
Metastasis- presence of distant metastasis automatically elevates patient to stage IV disease.
What are the indications for a biopsy?
Aggressive bone or soft tissue lesions
Soft tissue lesions larger than 5cm, deep to fascia, or overlying bone/neurovascular structures.
Unclear diagnosis in a symptomatic patient
Solitary bone lesions in a patient with history of carcinoma
What are the important principles of the open incisional biopsy?
incision should be longitudinal in the extremities and allow for extension for definitive management.
Do note expose neurvascular structures. All tissue exposed during biopsy is considered contaminated with tumor. This goes for post-operative hematomas as well.
Peform through only the involved compartment
If using a drain bring drain out of the skin in line with surgical incision.
What is the mechanism of doxorubicin (adriamycin)?
What is the most concerning side effect?
anthracycline antibiotic commonly used in oncological protools
Functions as a cytostatic agent.
Cardiac toxicity. Leads to congestive heart failure
Dexrazoxane used to mitigate toxicity.
What orthopaedic oncologic conditions does chemotherapy have an integral role?
Osetosarcoma (intramedullary and periosteal)
Ewing’s sarcoma/primative neuroectodermal tumor
Malignant fibrous histiocytoma
Dedifferentiated chondrosarcoma (chemotherapy for soft tissue sarcoma is controversial)
For the specific chemotherapy agents what is the antidote?
Mechlorethamine/cisplatin
Vinca alkaloids (vincristine/vinblastine)
Give sodium thiosulfate
Give hot compress and hyaluronidase. Give cold compress for all other vesicants(agent that causes blistering).
What primary malignant bone tumors is external beam irradiation the primary form of control?
Ewing sarcoma/primative neuroectodermal tumor
Primary Lymphoma of bone
Hemangioendothelioma
Solitary plasmacytoma of bone
In what tumors is external beam irradiation an adjuvant to surgical excision?
What metastatic disease is not radiosensitive?
Soft tissue sarcomas
GI and renal tumors.
Prostate tumors are very radiosensitive.
What is a typical radiation dose per day?
What should you know about total dose and tissue healing?
1 rad = 1 centiGray
Typical dose is 180-200 cGy/day
Radiotherapy is cumulative
Total dose:
< 45 Gray: usually leads to uncomplicated tissue healing.
45-55 Gray: tissue usually heals but with problems.
> 60 Gray: tissue unlikely to heal.
What is the incidence of post-radiation sarcoma?
13%
More frequent in patients with prior chemotherapy.
For the following categories describe the difference between Preoperative radiation and Postoperative radiation.
What is the incidence of post-radiation fractures?
What are risk factors?
25% following soft tissue sarcoma resection and external beam irradiation.
Total rod dose >59gy
Weight bearing bones
Female
Osteoporosis
Age
Periosteal stripping
Anterior femoral compartment resection
Volume of bone receiving it.
Is osteoid osteoma more common in males or females?
Males 3:1
> 80% present before age of 30.
What is the most common location of an osteoid osteoma?
Lower extremity > 50%. Proximal femur > tibia diaphysis
Spine 10-15%
Hand 5-10%
Foot <5%
What is thought to be be the reason for pain with osteoid osteoma?
Increased local concentration of prostaglandin E2 and COX1 & 2 Expression
Increased number and size of unmyelinated nerve fibers within the nidus.
What is the prognosis of Osteoid osteoma without intervention?
What about the spine?
Pain usually resolves after an average of 3 years
The lesion spontaneously resolves in 5-7 years
In the spine, early resection (within 18 months) leads to resolution of scoliosis in young children (<11 years).
What should be on your differential if an osteoid osteoma is > 1.5 cm in size?
Osteoblastoma
Which osteoid osteomas are not amenable to RFA?
Any lesion that is close to skin or a nerve.
Spine lesions assoicated with painful scoliosis.
Spine lesions that are close to the cord or nerve roots.
Digital lesions- RFA carries risk of thermal skin necrosis and injury to digital neurovascular bundle
For the following categories describe the difference between Osteoid Osteoma and Osteoblastoma?
What is the most common patient population and location for an osteoblastoma?
Males > Females 2:1
Majority of patients 10-30 years of age
Most common in posterior elements of spine
What conditions are associated with osteoblastoma?
oncogenic osteomalacia
10-40% associated with secondary ABC
Describe the appearance of osteoblastoma on x-ray?
lytic or mixed lytic-blastic with a radiolucent nidus that is > 2cm.
66% cortically based and 33% medullary based
Often expansile with extension into soft tissues with rim of reactive bone.
Need CT to fully evaluate lesion.
Describe the histology of an osteoblastoma?
Similar to osteoid osteoma but with more giant cells.
Distinct demarcation between nidus and reactive bone.
Nidus of immature osteoid and osteoblasts with abundant cytoplasm and normal nuclei
What treatment is recommended for osteoblastoma?
Curettage or marginal excision with bone grafting is standard of care.
Recurrence 10-20%
Observation is rarely if ever indicated as the lesion will continue to grow
What is the most common malignancy of bone?
What is the most common primary malignancy of bone?
What is the most common primary sarcoma of bone?
Metastatic disease
Myeloma
Intramedullary osteosarcoma
What is the age and location of intramedullary osteosarcoma?
Bimodal distribution: majority occur in the second decade of life. Second peak in occurrence is in elderly patients with Paget’s disease
Most common sites: distal femur>proximal tibia>proximal humerus>proximal femur>Pelvis>axial skeleton
What is the incidence of common sites of metastasis of intramedullary osteosarcoma?
Lung is the most common site of metastasis. 10-20% of patients will present with pulmonary metastases.
Bone is the second most common site.
What is Rothmund Thomson syndrome?
What malignancies are they at increased risk for?
AR inheritance. Mutation in RECQL4 gene, chr 8q24.3
Sun sensitive facial poikiloderma rash (pigmentation, thined skin, prominent blood vessels)
Absent eyelashes, eyegrows, hair
Juvenile cataracts, teeth abnormailities
Osteosarcoma, fibrosarcoma, gastic adenocarcinoma, cutaneous BCC and SCC
What is the long-term prognosis for intramedullary osteosarcoma?
What are poor prognostic factors?
76% long term survival with modern treatment.
Advanced stage of disease (most predictive of survival)
Response to chemotherapy (judged by percent tumor necrosis of resected speciment)
Tumor site and size
Expression of P-glycoprotein, High serum alkaline phophatase, high lactic dehydrogenase
vascular involvement, surgical margins, type of chemotherapy regimen.
What is characteristic of intramedullary osteosarcoma on radiographs?
Blastic and destructive lesion.
Sun-burst or hair on end patternof matrix mineralization .
Periosteal reaction (Codman’s triangle).
Large soft tissue mass with maintenance of bone cortices.
What should be considerd when obtaining advanced imaging of intramedullary osteosarcoma?
MRI: must include entire involved bone to determine soft tissue involvement, neurovascular involvement, and presence of skip metastases.
BONE SCAN: very hot in osteosarcoma. Useful to evaluate extent of local disease and presence of bone metastases.
CT: Chest CT required at presentation to evaluate for pulmonary metastases.
What lab is elevated in intramedullar osteosarcoma?
Alkaline phophatase may be 2-3 times normal.
What does the histology for ostosarcoma typically show?
Tumor cells show significant atypia and produce “lacey” osteoid.
Stroma cells show malignant characteristics with atypia, high nuclear to cytoplasmic ratio, and abnormal mitotic figures.
Giant cells may be present in giant cell rich osteosarcoma and can be confused with giant cell tumor of bone.
May have mixed histology with different combinations of chondroblastic osteoblastic, or fibroblastic looking cells.
What is the treatment for high grade intramedullary osteosarcoma?
Does it differ for a low grade osteosarcoma such as parosteal osteosarcoma?
multi-agent chemotherapy and limb salvage resection. Pre-operative chem for 8-12 weeks forllowed by maintenance chemotherapy for 6-12 months after surgical resection.
Survival is equivalent after limb salvage vs amputation.
Can do wide surgical resection alone for low grade osteosarcoma.
Amputation is indicated if there is a pathologic fracture, encased neurovascular bundle, or if the tumor is enlarging during preop chemo AND adjacent to a neurovascular bundle.
What is the most common patient population and location of a parosteal osteosarcoma?
Females age 30-40
Occurs on surface of metaphysis of long bones.
Most common sites include posterior distal femur (80%), proximal tibia, and proximal humerus.
Ture or false invasion of the medullary cavity by a parosteal osteosarcoma decreases long term survival?
False
95% long term survival when local control has been achieved.
Dedifferentiation of parosteal osteosarcoma is a poor prognostic factor
What is the presentation of a parosteal osteosarcoma?
Painless mass
Limiting joint motion can also be a presenting complaint for characteristic large posterior distal femoral lesions.
What does a parosteal osteosarcoma lool like on radiographs?
What other imaging is indicated?
Heavily ossified, lobulated mass arising from cortex. Appears stuck onto cortex.
CT chest to look for mets.
MRI of entire bone.
Bone scan is mandatory. Will always be hot.
What does histology of parosteal osteosarcoma show?
Treatment for a parosteal osteosarcoma?
Wide local surgical excision is standard of care.
Chemotherapy not indicated unless there is a high grade component.
What is the most common demographics, location, and presentation for periosteal osteosarcoma?
15-25 years of age, more common in females.
Occurs most commonly in the diaphysis of long bones. Femur and tibia are most common.
Pain is the most common presenting symptom. 25% present with a pathologic fracture.
What is the prognosis of periosteal osteosarcoma?
Intermediate. Better than intramedullary, but wors than parosteal.
20-35% chance of pulmonary metastases.
How will a periosteal osteosarcoma present on radiographs?
What other imaging is indicated?
classic “sunburst” or “hair on end” periosteal reaction. Often occurs in an areas of saucerized cortical depression.
CT scan, Bone scan (very hot), and MRI.
What is the histologic appearance of periosteal osteosarcoma?
gross tumor appears lobular and cartilaginous
Chondroblastic matrix on slide. Tumor still produces osteoid though.
If no osteoid is produced the tumor would be classified as a chondrosarcoma.
What is the treatment for periosteal osteosarcoma?
Same as intramedullary.
Multi-agent chemotherapy and limb salvage resection.
8-12 weeks pre-op chemo. 6-12 months of chemo after resection.
telangiectatic osteosarcoma is associated with what mutations?
Tumor suppressor genes: Rb-1 and P53
Oncogenes: HER2/neu, c-myc, and c-fos
Telangiectatic osteosarcoma is similar to what two other bone lesions?
Epidemiology and genetics is similar to classic osteosarcoma. Male > Female
Presentation is similar to ABC. Proximal humerus, proximal femur, distal femur, and proximal tibia are the most common locations.
Prior radiation is a risk factor.
What is the prognosis of telangiectatic osteosarcoma?
Poor.
More chemosensitive than intramedullary osteosarcoma but similar survival.
5 year survival with tumor localized to an extremity is 70%
5 year survival with metastases is 20%
What imgaging is indicated for a telangiectatic osteosarcoma?
How will it appear on imaging?
Radiographs will show a lytic, expansile, destructive lesion where the entire cortex may be compromised.
Need bone scan and MRI.
MRI will show fluid-fluid levels and extensive edema in surroudning tissue.
Notable that a CT is not required, but will likely be obtained.
What will histology show for a telangiectatic osteosarcoma?
High grade sarcoma with mitotic figures is seen in intervening cellular areas.
Lakes of blood mixed with malignant cells (not in ABC).
Not as much osteoid as intramedullary osteosarcoma.
How do you differentiate ABC vs Telangiectatic Osteosarcoma
Diagnosis is difficult and needs to be confirmed by an experience musculoskeletal pathologist.
Key is histology that shows the presence or absence of malignant cells with mitotic bodes.
What treatment is recommended for Telangiectatic Osteosarcoma?
Multi-agent chemotherapy and limb salvage resection.
What is the most common location for an echondroma?
Hands 60% of the time
Most common bone tumor of the hand.
Other locations femur (20%), Proximal humerus 10%, and tibia.
Rare in the pelvis, scapula, and ribs. Suspect condrosarcoma in these locations.
What is the pathophysiology of an echondroma?
chondroblast fragments of the epiphyseal cartilage escape from the physis and displace into the metaphysis and proliferate there.
2nd most common benign cartilage lesion (osteocondroma is the most common).
What is Ollier’s disease?
Multiple enchodromatosis)
Sporadi inheritance with no genetic predispostion.
Enchondromas throughout the metaphyses and diaphyses of long bones- involved bones are dysplastic, with shortening and bowing.
risk of malignant transformation <30%
What is Mafucci’s syndrome?
Multiple enchondromas and soft tissue angiomas
Radiographically enchondromas in Maffucci’s syndrome markedly expand the bone and angiomas are seen as small, round calcified phleboliths.
risk of malignant transformation up to 100%
also has increased risk of visceral malignancies (astrocytoma, GI malignancy)
True or false pain is uncommon with enchondromas?
True
Unlike enchondroma, most chonrosarcomas have non-mechanical pain (rest pain and nocturnal pain)
What are characteristics of an enchondroma on radiographs?
1-10 cm in size
Pop-corn stippling, arcs, whorls, rings
Minimal endosteal erosion (<50% width of cortex)
Cortical expansion may be present in hands and feet but not in femur or tiba
May have a purely lytic appearanc eespecially in hand.
Chonrosarcoma’s display cortical thickening and destruction. endosteal erosions and scalloping >50% of the width of the cortex. Usually are larger (>5cm)
How do you differentiate a bone infarct from an enchondroma on MRI?
Enchondroma on MRI has high T2 signal because of high water content of cartilage.
Bone infarct low signal on T2.
On advanced imaging how do you differentiate a enchondroma from a chondrosarcoma?
Bone scan: enchondromas will have increased uptake but are small and have less uptake than chondrosarcoma.
MRI: Enchondroma will have no bone marrow edema or periosteal reaction.
Medullary fill >90% suggests chondrosarcoma instead of enchondroma.
What is the histology of an enchondroma?
SOLITARY LESIONS IN LONG BONES: hypocellular with bland, matrue hyaline cartilage (blue balls of cartilage) separated by normal marrow.
SOLITARY LESIONS IN SMALL TUBULAR BONES AND FIBULA, OLLIER’S, AND MAFFUCCI’S: Hypercellular with mild chondrocytic atypia.
Chondrosarcomas display: Hypercellularity, with plump nuclei. Multiple binucleate cells, and giant cells with clumps of chromatin.
Treatment for Enchondroma’s?
Observation for vast majority.
Serial radiographs at 6 months and 12 months to confirm radiographic stability.
Long term follow-up for patients with multiple enchondroma syndromes.
INTRALESIONAL CURETTAGE AND BONE GRAFTING: Lesions that show any change on serial x-rays. Symptomatic lesions. Pathologic fractures (immediate curettage and grafting is now favored). Large lesions at risk for recurrent fracture.
Local recurrence is unusual.
What is a periosteal chondroma?
Rare chondroma that occurs on surface of long bones.
Occurs in 10-20 year olds.
59% of lesions in proximal humerus. Also distal and proximal femur. Can be seen in metacarpal or phalanges.
RADIOGRAPHS: well demarcated shallow cortical defect. saucerization of underlying bone.
HISTOLOGY: Similar to enchondroma but increased cellularity and more malignant looking cells.
TREATMENT: For those that are painful and interferring with function. Marginal excision including underlying cortex. Bone graft large defects. Will recur if cartilage is left behind.
What are common locations for osteochondroma’s
On the surface of bones and often at sites of tendon insertion
Knee
Proximal femur
Proximal humerus
Subungal exostosis (occurs most often at hallus)
Solitary osteochondromas can aris because of?
Salter-Harris fracture
Surgery
Radiation therapy
What is the risk of malignant transformation of of an osteochondroma?
<1% with solitary osteochondroma
5-10% with MHE develop secondary chondrosarcoma
When it does occur it is a secondary chondrosarcoma:
Most commonly a low grade tumor (90%)
Occurs in older patients, 50 or older. Rare in pediatric population.
Most common location of secondary chondrosarcoma is the pelvis.
What is Multiple Hereditary Exostosis (MHE)
What is its inheritance?
What is the mutation?
Multiple osteochondromas
Autosomal dominant
Mutation in EXT1, EXT2, and EXT3 tumor suppressor genes. Leads to decreased production of heparin sulfate by chondrocytes found at the physis.
EXT1 is mor severe than EXT2.
5-10% risk of malignant transformation to chondrosarcoma. Proximal lesions more likely to undergo this transformation.
What are the most common deformites in MHE?
Ulnar shortening and radial bowing.
Radial head dislocation
Ulnar deviation of the hand.
What symptom or sign should make you suspicious that an ostechondroma is possibly malignant?
Acue onset of pain in adults with MHE.
What is the difference between sessile and pedunculated osteochondroma lesions?
Sessile (Broad base)- Higher risk of malignant degeneration
Pedunculated (Narrow stalk)- Pain away from the joint.
Have a cartilage cap that is usually thin. If cartilage cap becomes thicker as an adult, need to be concrned for chondrosarcoma transformation.
Operative treatment of osteochondromas?
Only if they become symptomatic.
Surgical excision inculding the cartilage cap.
Try to delay sugery until skeletal maturity.
What is the location and demographics of chondroblastoma?
epiphyseal lesion in young patients
Usually agound 12 years of age.
80% of patients under 25 years of age. M:F = 2:1
Common locations include distal femur and proximal tibia >>>proximal humerus, proximal femur, calcaneus, flat bones, and apophysis or triradiate cartilage of the pelvis.
<1% develop benign pulmonary mets
Local recurrence rate is 10-15%
painful
How will a chondroblastoma appear on radiographs?
Well-cricumbscribed epiphyseal lytic lesion with thin rim of sclerotic bone
Lesions often cross physis into metaphysis
Stippled clacifications within the lesion may be present. Cortical expansion may be present.
soft tissue expansion is rare.
What does the histology of a chondroblastoma show?
Chondroblasts arraged in “cobblestone” or “chickenwire” pattern
Scattered multinucleated giant cells with focal areas of chondroid matrix
Mononuclear stromal cells are distinct. Large central nuclei. Nuclei have longitudinal groove resembling coffee bean.
S100+
1/3 of chondroblastomas have areas of secondary ABC
Treatment for a chondroblastoma?
Extended intralesional curettage and bone grafting.
May do adjuvant treatment with phenol or cryotherapy to decrease local recurrence.
Surgical resection if there are pulmonary mets.
What are the demographics and locations of chondromyxoid fibromas?
Most common in second and third decades of life.
More common in males.
Often affects metaphyseal regions of long bones. Tibia and distal femur most common. Can also be in the pelvis, feet, or hands.
Genetic rearrangement that may affect chromosome 6 (position q13)
NO METS
What is the presentation of chondromyxoid fibroma?
How will it appear on radiographs?
MRI/Bone scan?
long standing pain (months to years)
Lytic eccentric metaphyseal lesion. Sharply demarcated with a scalloped and sclerotic rim. Lesion ranges from 2-10cm.
Low signal on T1. High signal on T2. Increased signal uptake will be seen.
What does the histology of a chondromyxoid fibroma show?
Biphasic appearance.Low power will show. Hypercellular area with lobules of fibromyxoid tissue. Hypocellular area with chondroid material.
Spindle-shaped cells or stellate-shaped cells.
Mutlinucleated giant cells and fibrovascular tissue located between lobules.
HIGHER POWER: Will show myxoid stroma with stellate cells.
What is the treatment ond most common complication of chondromyxoid fibroma?
Intralesional curretage and bone grafting. (Can also use PMMA)
Recurrence- occurs in 25% of cases.
What are the different forms of primary chondrosarcoma
Low and high grade dedifferentiated chondrosarcoma
Clear cell chondrosarcoma
Mesenchymal chondrosarcoma
What are the different forms of secondary chondrosarcoma?
Osteochondroma (<1% risk of malignant transformation)
Multiple hereditary exostosis (1-10% risk of malignant transformation)
Enchondroma (1% risk of malignant transformation)
Ollier’s disease (25-40% risk of malignatn transformation)
Maffucci’s (100% risk of malignant transformation)
What are typically the demographics and location of chondrosarcoma?
Older patients 40-75
Slight male predominance
Most common locations include: Pelvis, proximal femur, distal femur, and scapula.
Tumor location is importatn for diagnosis as the same histiology may be diagnosed as benign in the hand but malignant if located in the long bones.
What are important prognostic variables for chodrosarcoma?
Histologic grade correlates with survival. See image attached.
Axial, pelvis, and proximal extremity lesions have a more aggressive course.
Advanced patient age
Inadequate surgical margins
Increaed telomerase activity as determined by reverse transcriptase-polymerase chain reaction. Show to directly correlate with recurrence.
Briefly describe clear cell chondrosarcoma?
Malignant immature cartilaginous tumor accouting for <2% of all chondrosarcomas
Most common in 3 and 4th decade of life
Presents as an eiphyseal lesion (mistaken for low grade chondroblastoma) with insidious onset of pain.
Locally destructive with potential to metastasize.
Briefly describe mesenchymal chondrosarcoma?
Chondrosarcoma variant which presents with a biphasic pattern of neoplastic cartilage with associated neoplastic small round blue cells.
Occurs in younger patients than typical chondrosarcomas.
May occur at several ciscontinuous sites at presentation and can occur in the soft tissues.
treatment is neo-adjuvant chemotherapy followed by wide surgical resection
True or false chondrosarcoma is diagnosed with a core needle biopsy?
Needle biopsy is not indicated due to difficulties with diagnosis.
Lesions are often heterogenous and difficult to diagnose on histology alone.
Requires clinical, pathologic, and radiographic correlation.
How does chondrosarcoma present on radiographs?
lytic or blastic with reactive thickening of the cortex. 85% will have cortical changes.
LOW GRADE- similar appearance to enchondroma with additional cortical thickening/expansion and endosteal erosion
HIGH GRADE- Cortical destruction and a soft tissue mass.
DE-DIFFERENTIATED- show a lower grade chondroid lesion with superimposed highly destructive area consistent with the high grade dedifferentiated chondrosarcoma
What is helpful about MRI, CT, and BONE SCAN in chondrosarcoma?
MRI to determine marros and soft tissue involvement. Bright on T1.
CT- to determine cortical involvement in low grade lesions. Deep endosteal scalloping suggests chondrosarcoma instead of enchondroma. 90% have cortical breach.
BONE SCAN- Very hot with chondrosarcoma so can be used to distinguish it from enchondroma.
Identify the image?
Biphasic appearance with low grade chondrosarcoma adjacent to small round blue cells.
Mesenchymal chondrosarcoma
Identify the image
Lobular architecture similar to toher cartilage neoplasms, but cells are large and vacuolated.
Clear cell chondrosarcoma.
Typically low to intermediate grade.
What does the histology show for a de-differentiated chondrosarcoma?
Bimorphic histology.
Low grade chondroid component
High grade spindle cell component ( similar histology to osteosarcoma, fibrosarcoma, MFH)
80% are chondrosarcomas with an extra destructive area
What is the treatment for chondrosarcoma?
Chondrosarcoma is generally resistant to radiation and chemotherapy.
Grade 1- intralseional currettage for extremities. Pelvis or axial skeleton most recommend wide excision.
Grade 2 or 3- Wide surgical excision.
What are the recurrence rates for chondrosarcoma?
Grade 1- rare after wide resectionw ith negative margins. 5-15% after curettage with adjuvant treatment
Grade 2- varies depdening on resection margins
Grade 3- 25% local recurrence and >30% rate of metastasis
What are the three forms of lymphoma found in bone?
Primary lymphoma of bone (solitary site)- Most primary lymphomas of bone are Non-Hodgkin’s B-cell lymphomas rather than T-cell variants. Diagnosed when there is only a single node of disease for six months. Very rare to have primary lymphom of bone.
Multiple bony sites (no visceral sites)
Bone and soft tissue lymphoma
What is the incidence, demographics, location, and risk factors for lymphoma?
INCIDENCE: 10-35% of non-Hodgkin’s lymphoma patients have extranodal disease
DEMOGRAPHICS: Males>females. Can occur in all age groups. Most common in patients aged 35-55.
LOCATION: most common are pelvis, spine, and ribs. Bones with peristant red marros. Other common sites include knee, proximal femur, and shoulder girdle.
RISK FACTORS: Immunodeficiency. Viral or bacterial infecions.
True or false primary lymphoma of bone has a better prognosis than secondary involvement of bone in lymphoma?
True
How does a patient with lymphoma of bone present?
25% present with a pathologic fraacture.
Pain unrelieved by rest.
Can have neurologic symptoms from spinal compression.
Fever, nightsweats, and weight loss (common B-cell symptoms)
On physical exam can have warm and swollen large soft tissue masses.
How will lymphoma appear radiographically?
What other imaging is indicated?
Large ill-defined diffuse lytic lesions with a subtle mottled appearance
More common in diaphysis of long bones
“ivory vertebrae
Multiple sites are common. Can show cortical thickening
CT of chest, abdomen, and pelvis for staging.
PET useful to stage and follow the disease.
What study besides imaging is required for staging for lymphoma?
Bone marrow aspiration and biopsy
What does histology show for lymphoma?
Mixed small round blue cell infiltrate
To differentiate from other small round blue cell tumors:
CD20, CD45, and lymphocyte common antigen positive
CD99 negative and absent 11:22 chromosomal translocation
diffuse infiltration of trebeculae as opposed to nodular.
What is the treatment for lymphoma of bone?
Multi-agent chemotherapy +/- local irradiation.
Radiation is used to obtain locatl control in persistent disease.
Chemotherapy alone is effective for most lesions.
70% 5-year survival in disseminated disease
Fracture stabilization or prophylactic management.
What do neoplastic cells in multiple myeloma produce?
immunoglobulins
Heavy Chains: IgG (52%), IgA (21%), and IgM (12%)
Light Chains: Kappa, lambda aka Bence Jones proteins
What are the three forms of multiple myeloma and which has the best prognosis?
Multiple Myeloma
Solitary Plasmacytoma
Osteoclerotic myeloma
solitary plasmacytoma has the best prognosis
What is the demographics and prognosis of multiple myeloma?
Patients > 40 years of age (median age is 60)
Affects males > females
2x more common in African Americans
5 year survival rate of 30%
10 year survival rate of 11%
Median survival is 3 years
Shortest survival is seen in pateints with renal failure.
What is the specific pathophysiology in multiple myeloma?
Osteoclastic stimulation by malignant cells.
Malignant cells bind bone marrow stromal cells to stimulate the production of receptor activator of nuclerar factor-k B ligand (RANKL) and other pro-osteoclastic mediators (macrophage colony-stimulating factor M-CSF, IL-6, IL-11, TNF)
Osteoprotegerin synthesis is suppressed, resulting in further osteoclast activation. OPG competes with RANK to bind to RANKL as a decoy receptor.
What are the CRAB features of Multiple Myeloma?
hyperCalcemia: serum clacium > .25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)
Renal insufficiency: creatinine clearance <40 mL/min or serum creatinine >177 umol/L (>2mg/dL)
Anemia: hemoglobin >20g/L below the lowers limit of normal or hemoglobin <100g/L
Bone lesions: >=1 osteolytic lesion on radiographs, CT, or PET/CT
Describe the diagnostic criteria for multiple myeloma?
Monoclonal plasma cells >10% on bone marrow biopsy or biopsy-proven bony/extramedullary plasmacytoma and greater than or equal to 1 of the CRAB features and myeloma-defining events (MDEs). See the image for a list of those features and events.
What classifies a solitary plamacytoma?
Plasma cell tumor occuring in a single skeletal location and lacking appropriate criteria for diagnosis of multiple myeloma (histologic biopsy confirming plasmacytoma and negative bone marrow biopsy with no plasma cells in the bone marrow).
Sensitive to radiation
Progresses to multiple myeloma in over 50% of patients
Obtain MRI and FDG-PET additional lesions identified in 33% of patients
What classifies a Osteosclerotic myeloma?
What is the radiographic appearance of Multiple Myeloma on radiographs?
Multiple “punched-out” lytic lesions
Only visible once >50% destruction has occurred
Lytic appearance
Absence of sclerotic border because there is a lack of osteoblastic activity.
Bone scans are cold in 30% so obtain a skeletal survery if suspicion for multiple myeloma.
What are the serum and urine labs in Multiple Myeloma?
anemia
elevated creatinine
hypercalcemia- present in 30% of patients due to excessive resorption of bone
ESR often elevated
SPEP (serum protein electrophoresis)- M spike present (50% IfG, 25% IgA)
Beta-2 microglobulin- marker of prognosis/disease severity
URINE: proteinuria. UPEP may show Bence Jones proteins (secreted immunoglobulin kappa and lambda light chains).
What immunohistochemical stain is postive in Multiple Myeloma?
CD38+
What is the distinctive histology of multiple myeloma?
Round plasma cells with an eccentric nucleus, prominent nucleolus, and clock face organization of chromatin.
Characteristic clear area (Hoffa clear zone) next to the nucleus represents the prominent Golgi apparatus involved in immunoglobulin (protein production)
What treatment is recommended for monoglonal gammopathy of unknown signficance…asymptomatic myeloma.
annual surveillance
What is the recommended treatment for multiple myeloma?
Multiagent chemotherapy
+/- stem cell therapy
+/- bisphosphonates
For complete or impending fractures in patients with life expectancy > 3 months -> surgical stabilization and external beam radiation therapy.
Kyphoplasty can be used in thos ewith vertebral fractures that are resistant to radiation.
What are other names for Non-Ossifying Fibroma?
Metaphyseal fibrous defect
Nonosteogenic fibroma
Cortical desmoid
Fibrous cortical defect
Fibromatosis
Fibroxanthoma
All are names for a benign fibrogenic lesion that is related to dysfunctional ossification and is one of the most common benign bone tumors in childhood.
What is the incidence, demographics, and location of non-ossifying fibroma?
occurs in 30-40% of skeletally immature children
More common in males (2:1) and in children 5-15 years old.
Located in the metaphysis of long bones.
80% are in the lower extremity. Distal femur > proximal tibia > distal tibia.
Uncommon in proximal femur and proximal humerus.
usually spontaneously resolves. No malignant or metastatic potential.
What is Jaffe-Campanacci syndrome?
Congenital syndrome of multiple non-ossifying fibromas and:
cafe au lait pigmentation
mental retardation
heart, eyes, gonads involved
How to non-ossifying fibromas appear on radiographs?
Any other imaging that is useful?
Metaphyseal eccentric bubbly lytic lesion surrounded by a sclerotic rim
Cortex may be expanded and thing. Length > width
Migrates to diaphysis and lesions enlarge (1-7cm) as the pateint grows.
quantitative CT shown to be useful in predicting fracture risk.
What should you look for on histology for a non-ossifying fibroma?
Fibroblastic spindle cells in whirled or storiform pattern (helicopter in wheat field)
hemosiderin pigmentation
numerous lipophages and giant cells
Fibroblastic connective tissue backround. Occasional ABC component.
Recommended treatment for non-ossifying fibroma?
Almost all are observation. Most lesion reossify as child enters 2nd and 3rd decade of life.
Radiographs at 6 months, 12 months, and then annually until reossified.
Pathologic fractures treated as you would normally treat the fracture.
Symptomatic and large lesions with > 50-75% cortical involvement can be treated with curettage and bone grafting.
Risk factors for pathologic fracture: >50% of transverse diameter of bone and >33mm in length. 90% occur in lower extremity with 50% in distal tibia.
What is another name for malignant fibrous histiocytoma?
Undifferentiated pleomorphic sarcoma
similar in presentation to osteosarcoma, but histologically different (lacks osteoid formation).
What is the incidence, demographics, body location, and risk factors of pleomorphic sarcoma?
INCIDENCE: second most common bone sarcoma in adults after chondrosarcoma.
DEMOGRAPHICS: Affects individuals 20 to 80 years of age. Highest rates of affected patients in 2nd to 4th decades. male > female (3:2). More common in caucasians than African Americans or Asians.
BODY LOCATION: 75% of cases from appendicular skeleton. Often metaphysis of long bones. Primarily distal femur, proximal tibia, and proximal humerus.
RISK FACTORS: 25% arise as secondary lesion from bone infarct, Paget disease, or prior radiation.
What is the prognosis of malignant fibrous histiocytoma?
50-60% survival at 5 years.
worse prognosis with secondary MFH compared to primary lesions.
pulmonary metastasis common in up to 30%.
good response (> 90% tumor necrosis ) to neoadjuvant chemotherapy found to have a much better prognosis.
age younger than 40 years associated with improved disease-free survival rate.
How does a pleomorphic sarcoma present?
New painful mass
Often has constitutional symptoms as well. Fever, chills, night sweats, and weight loss.
How does a pleomorphic sarcoma (malignant fibrous histiocytoma) appear on radiographs?
lytic(can also be blastic) and destructive
In metaphysis
Cortical destruction with soft tissue extension
MRI: Will show a deep seated heterogeneous mass that is low signal on T1 and high signal on T2. Often associated with internal hemorrhage.
What will histology for a malignant fibrous histiocytoma show?
Pleomorphic spindle cells and histiocytic cells in storiform pattern.
Malignant multinucleated giant cells with grooved or indented nuclei.
Hemorrhagic and necrotic regions not infrequent; suggest high-grade lesion.
Treatment for malignant fibrous histiocytoma (pleomorphic sarcoma)?
neoadjunctive chemotherapy, wide resection, postoperative chemotherapy +/- radiation
Trend towards limb salvage whenever possible.
Radiation used whenever incomplete or questionable margins.
What is the most commo primary malignant spinal tumor in adults?
chordoma
What is the demographics of a chordoma?
Incidence of mets?
Prognosis?
3:1 Male to female.
Usually in patients > 50 years
Metastatic disese in 30-50%- occurs late in the course of the disease so long term follow up required. May spread to lung and rarely to other bony locations.
60% 5 year survival
25% long term survival
Local extension may be fatal.
What are the symptoms and presentation of a chordoma?
insidious onset of pain.
Often complain of bowel or bladder changes. Sensory deficits rare due to distal nature of tumor. Constripation and occassional fecal incontinence.
Motor deficits are rare because most lesions at S1 or distal.
More than 50% of sacral chordomas are palpable on rectal exam.
How will a Chordoma appear on imaging?
Can be difficult to see on radiographs.
CT will show bone destruction and soft tissue mass.
MRI will be bright on T2
What will histology of a chordoma show?
Gross: lobular and gelatinous.
foamy, vacuolated, and physaliferous cell that grows in distinct nodules.
HISTOCHEMICAL STAINING: keratin positive important to distinguish from chondrosarcoma, which is not keratin positive.
weakly S100 positive.
Treatment for chordoma?
Complications/recurrence?
Radiation for inoperable tumors
Wide margin surgical resection +/- radiation. Must be willing to sacrifice sacral nerve roots to obtain adequate surgical margins.
Long term survival 25-50%
en bloc corpectomy has best chance of local control with spinal lesions.
50% local recurrence is common
Loss of bowel/bladder function postoperatively. In order to preserve near normal function need to preserve bilateral S2 nerve roots or unilateral S2, S3, and S4 roots.
Where is a hemangioma most commonly found?
How does it appear on imaging?
Most often occurs in the vertebral bodies and cranio-facial bones.
Lytic lesion with vertical striations giving a “honey-comb” or “jail bar appearance” on radiographs
May be multi-focal.
Bone scan is warm to hot.
How does a hemangioma appear on histology?
What is the recommended treatment?
cavernous lesions with numerous thin walled blood vessels.
Observation as long as they are asymptomatic.
curettage and bone grafting it the lesion is symptomatic and accessible.
Low dose radiation (25 to 40 Gy) if the lesion is symptomatic and inaccessible for above.
What is a unicameral bone cyst?
Most common age of patient and location?
Non-neoplastic serous fluid-filled bone lesion thought to result from temporary failure of medullary bone formation near the physis.
Usually in patients <20 years of age
Most often found in the proximal humerus of young patients.
Can also be found in proximal femur, distal tibia, ilium, calcaneus, and occassionally metacarpals, phalanges, or distal radius.
Arises in the metaphysis adjacent to physis.
What happens to a UBC as a patient ages?
Will often decrease in size and may heal after growth is compelete.
Fracture healing usually does not lead to cyst resolution.
Requires close follow up while in acitve phase due to recurrence and risk of fracture or growth arrest.
How do you classify a UBC as active or latent?
If cyst is adjacent to physis on radiographs then it is active
If normal bone separates cyst from physis then it is latent. see photo.
How will a UBC appear on radiographs?
central, lytic, well-demarcated metaphyseal lesion (2-3% cross physis)
Cystic expansion with symmetric thinning of cortices
“Fallen leaf” sign (pathologic fracture with fallen cortical fragment in base of empty cyst is pathognomonic)
ABC will be more expansive than UBC (UBC is usally not wider than physis).
What are the characteristic findings on histology of a UBC?
Cyst with thin fibrous lining containing fibrous tissue, giant cells, and hemosiderin pigment.
Chronic inflammatory cells may be found in small numbers
Cementum spherules (calcified eosinophilic fibrinous material) in 10%
Uniform opulation of spindle cells without nuclear atypia
Treatment for UBC?
What is a contraindication to operative treatment?
avoid operative treatment in active lesions as communication with physis may lead to growth arrest.
What is the demographics and most common location of an ABC?
75% of patients are < 20 yrs.
25% in spine
20% in long bones, usually in metaphysis.
Metatarsal is the most common location in the foot.
Can be seen in posterior elements of the pelvis.
What are the associated conditions of an ABC?
Associated with other tumors 30% of the time:
Giant cell tumor
Chondroblastoma
Fibrous dysplasia
Chondromyxoid fibroma
NOF
How will an ABC present on imaging?
RADIOGRAPHS: expansile, eccentric and lyic lesion with bony septae (bubbly appearance). Usually in metaphysis.
Often have thin rim of periosteal new bone surrounding lesion.
MRI or CT will show multiple fluid lines.
Can expand into soft tissue
What will histology of an ABC show?
cavernous space
blood filled spaces without an endothelial lining.
Cavity lining can have:
numerous benign giant cells
Spindle cells
Thin strands of woven new bone present.
Recommended Treatment for a ABC?
ABC with acute fracture: Non-operative fracture management until fracture has healed. Once healed treat as you would normally treat an ABC
Symptomatic ABC no fracture: aggressive curettage (+/- adjuvant) and bone grafting.
Adjuvants include phenol, argon beam, and liquid nitrogen.
Local recurrence in up to 25% and more common in children with open physes.
What is fibrous dysplasia?
What genetic mutation is involved?
developmental abnormality caused by failure of the production of normal lamellar bone. Areas of skeleton remain poorly mineralized trabeculae.
GNAS mutation
GS alpha protein (chromosome 20q13) activating mutation affects cAMP signaling pathway leading to increased production of cAMP.
What is the demographics and most common locations of fibrous dysplasia?
Females > males
Found in any and all ages. Onset for 75% of patients at <30 years of age
Any bone can be involved.
Proximal femur is most common follwed by rib, maxilla, and tibia
What conditions are associated with fibrous dysplasia?
Mcune Albright syndrome- Defined by presence of cafe au lait spots in coast of Maine pattern. Endocrine abnormalities -> precocious puberty. Renal phosphate wasting due to FGF-23 (oncogenic osteomalacia). Unilateral polyostotic fibrous dysplasia obtain AP spine radiographs to look for scoliosis.
Mazabraud syndrome- polyostotic fibrous dysplasia. Soft-tissue intrmuscular myxomas.
Osteofibrous dysplasia- rare form that primarily affects the tibia and is confined to the cortices.
nonorthopedic manifestations can include severe cranial deformities with blindness.
What is the risk of a malignant transformation in fibrous dysplasia?
1% risk of malignant transformation to osteosarcoma, fibrosarcoma, or malignant fibrous histiocytoma.
What should be possible disorder should be investigated with this skin disorder?
Cafe au lait spot with large irregular border.
Neurofibromatosis will be smaller and have more defined borders.
What is the radiographic appearance of fibrous dysplasia?
Central lytic lesion in medullary canal. Ground glass appearance
“punched out” lesion with well defined margin of sclerotic bone is common.
May have cortical thinning with expansile lesion.
Shepherd’s crook deformity.
Spine radiograph will show vertebral collapse and kyphoscoliosis.
What will the histology of fibrous dysplasia show?
alphabet soup or chinese letters.
Fibroblast proliferation surrounding islants of woven bone. The woven bone lacks osteoblastic rimmin (osteofibrous dysplasia has osteoblastic rimming)
Treatment for Fibrous dysplasia?
ASYMPTOMATIC- observation
SYMPTOMATIC POLYOSTOTIC- Bisphosphonate therapy. Effective in decreasing pain and recucing bone turnover.
SYMPTOMATIC, IMPENDING/ACTUAL FRACTUES, SEVERE DEFORMITY- internal fixation and bone grafting. Need to use allograft. Intramedullary device is more effective than a plate for coxa var deformities that require an osteotomy.
What is osteofibrous dysplasia?
What is the patient demographics?
Mutation?
Rare form of fibrous dysplasia that primarily affects the tibia and is confined to the cortices.
Also knonw as ossifying fibroma and Campanacci lesion.
Males > females. Usually found in younger children (< 10 years old)
Does NOT have GS alpha activating mutation like fibrous dysplasia.
lesions usually regress and do not cause problems in adulthood.
What is the usual presentation of osteofibrous dysplasia?
Painless swelling.
anterior or anterolateral bowing of the tibia.
Pseudoarthrosis develops in 10-30% of patients. In these cases they have local tenderness and pain.
How does osteobifrous dysplasia present on radiographs.
anterior eccentric lytic tibial lesion in a child that often leads to tibial bowing.
Confined to anterior cortex, diaphyseal, with no periosteal reaction.
Need to differentiate from adamantinoma.
What dos the histology show for osteofibrous dysplasia?
Histology similar to dibrous dysplasia EXCEPT osteoblastic rimmin is present
fibroblast proliferation surrounding islands of woven bone with osteoblastic rimmin
May have giant cells
mitotic figures are common.
What treatment is recommended for osteofibrous dysplasia?
Observation is first line of treatment for most patients.
Bracing if deformity is significant and interferes with walking.
Deformity correction with osteotomy in rare cases. perform after skeletal maturity
What is thought to be the cause of Paget’s Disease?
Thought to be due to a slow virus infection (intra-nuclear nucleocapsid-like structure) such as paramyxovirus or RSV.
Increased osteoclastic bone resorption is the primary cellular abnormality.
What is the epidemiology and genetics of Paget’s Disease?
Peak incidence in the th decade of life.
Common in caucasians (northern european/anglo-Saxon descent
Males = Females
May be monostotic or polyostotic.
Common sites include femur > pelvis > tibia > skull > spine
Most cases are spontaneous but familial clusters with 40% autosomal dominant transmission has been reproted.
What non-orthopaedic condition is associated with Paget’s disease?
High output heart failure.
What is the incidence of malignancy in Paget’s disease?
Prognosis?
Less than 1% develop malignant Paget’s sarcoma
Osteosarcoma > fibrosarcoma and chondrosarcoma
Most common in pelvis, femur, and humerus.
Poor prognosis 5-year survival for metastatic Paget’s Sarcoma < 10%
Treatment includes chemotherapy and wide surgical resection.
What are the three phases of Paget’s Disease?
LYTIC PHASE- intense osteoclastic resorption
MIXED PHASE- resorption and compensatory bone formation
SCLEROTIC PHASE- ostoeblastic bone formation predominates
All three phases may co-exist in the same bone
How do patients with Paget’s Disease normally present?
frequently asymptomatic and found incidently
Pain may be presenting symptom due to stress fractures and increased vascularity and warmth.
New intense pain and swelling is suspicious for Paget’s Sarcoma.
Can present with high-output cardiac failure particularly if large/multiple lesions & pre-existing diminished cardiac function.
How does Paget’s Disease present on Radiographs.
Coarsened trabeculae which five the bone a blastic appearance.
Because of the three different phases can have both increased and decreased density.
lytic phase- “blade of grass” or “flame shaped” lucent advancing edge.
Remodeled cortices.
Long bone bowing
osteitis circumscripta (cotton wool exudates in skull)
Bone scan accurately marks site of disease very hot in lytic and mixed phase, less hot in sclerotic phase.
laboratory findings in Paget’s Disease?
elevated serum ALP
elevated urinary collagen cross-links
elevated urinary hydroxyproline (collagen breakdown marker)
Increased urinary N-telopeptide, alpha-C-telopeptide, and deoxypyridinoline
Normal calcium levels.
Histology for Paget’s disease?
woven bone and irregular broad trabeculae with disorganized cement lines in a mosaic pattern.
Profound bone resorption- numerous large osteoclasts with multiple nuclei per cell
virus-like inclusion bodies in osteoclasts
Paget’s osteoclasts larger, more nuclei than typical osteoclasts.
Treatment for Paget’s disease?
Nonoperative?
Operative?
What are the three general presentations of Eosinophilic Granuloma (Histiocytosis X)
Eosinophilic granuloma- usually a single self-limited lesion found in younger patients. Most commonly occurs in children < 20 years 80% of the time.
Hand-Schuller-Christian Disease- Chornic disseminated form with bone and visceral lesions. Also known as langerhans cell histiocytosis with visceral involvement. Children > 3 yrears of age
Prognosis depends on response to chemotherapy. Generally worse prognosis with extraskeletal involvement.
Letterer Siwe disease- Fatal form that occurs in yound children. children < 3 years of age
What is the most common location of eosinophilic granuloma?
Commonly presents in the skull, ribs, clavicle, scapula, and mandible.
Isolated lesions of the spine (thoracic most common)
Can also occur in diaphyseal regions of long bones and the pelvis.
Hand-Schuller-Christian disease- Multiple bony sites, multiple lytic skull lesions. visceral involvement of the lungs, spleen, liver, skin, and lymph nodes.
What is the classic triad of Hand-Schuller-Christian disease?
Multiple lytic skull lesions
Diabetes insipidus
Exopthalmos
Patients will also present with diffuse or nonspecific abdominal or chest pain.
How does eosinophilic granuloma present of radiographs?
Known as “the great mimicker” as it appears similar to many lesions
DIAPHYSEAL LESIONS: well defined intramedullary lytic or “punched-out” lesion. Cortex may be thinned, expanded, or destroyed. May have periosteal reaction.
METAPHYSEAL LESIONS: Extend up to but not through physis. Less central location than diaphyseal lesions.
SPINAL LESIONS: vertebra plana (flattened vertebrae) in spine. Increased kyphosis.
What does histology of eosinophilic granuloma show?
Langerhan’s cells: mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm.
A prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
Eosinophilic cytoplasm (pink generally)
Stain with CD1A. Shows up as a brown pigmentation similar to hemosiderin.
Giant cells are present.
Lack of nuclear atypia and atypical mitoses- differentiates this condition from malignant conditions such as Ewings Sarcoma, lymphoma of bone, and metastatic neuroblastoma, which may look similar based on the round cells alone.
What does thi picture demonstrate?
electronmicroscopy shows birbeck granules seen inside Langerhan’s cells.
Found in patients with eosinophilic granuloma.
Treatment for eosinophilic granuloma?
For most observation as this is a self limited process.
Bracing for spine kyphosis which will correct in 90%. The other 10% will have spinal deformity correction.
Low dose irradiation (600-800cGy) for lesions in the spine that are causing issues but not amenable to injectio or open treatment.
Chemotherapy for diffuse HSC.
Corticosteroid injections for isolated lesions.
curretage and bone grafting for lesions that endanger the articular surface or are at risk for impending fractures.
What is myositis ossificans?
A reactive process that is characterized by a well circumscribed proliferation of fibroblasts, cartilage, and bone within muscle.
Form of HO that is the result of direct trauma or intramuscular hematoma.
Must differentiate from tumors
What is fibrodyslpasia ossificans progressiva (FOP)?
What is the mutation?
How do you differentiate it from MHE?
Rare subtype of heterotopic ossification
Involves mutation of the ACVR1 gene (activin A type I receptor gene, a BMP type-1 receptor)
Has numerous areas of extraskeletal ossification.
Hallmark is rigid deformed spine.
What is the epidemiology and prognosis of myositis ossificans?
Most common in young active males 15-35 years of age.
Most common locations are quadriceps, brachialis, and gluteal muscles.
Usually self limiting. Mass begins to decrease in size after 1 year.
How does myositis ossificans appear on radiographs?
Peripheral bone formation with central lucent area. May appea as “dotted veil” pattern.
MRI with gadolinium will who rim enhancement within the first 3 weeks.
CT scan lesion has an eggshell appearance.
What does histology of myositis ossificans show?
PERIPHERY OF LESION- mature trabeculae of lamellar and woven bone. Calcification seen on xray
CENTER OF THE LESION- irregular mass of immature fibroblasts. cartilage component may be present. No cellular atypia.
Treatment for myositis ossificans?
Rest, ROM (avoid passive stretching, needs to be active motion with PT), and activity modification.
Radiographic monitoring to confirm maturation of the lesion
Surgical excision only if it remains a problem after maturation.
Do not operate in the acute phase. Excision of the lesion within 6 to 12 months predisposes to local recurrence.
What is Melorheostosis?
Most common patient and location?
Rare benign painful disorder of the extremities characterized by formation of periosteal new bone?
Usually presents before age 40. No gender preference.
More common in the lower extremities but can appear in any bones.
Patients will present with pain, reduced ROM, and joint contractures.
Physical exam will show fibrosis of skin with significant induration and erythema.
Painful hyperostoses
What will radiographs and histology show for Melorheostosis?
Cortical hyperostosis. This may flow across joints.
dripping candle wax appearance with dense hyperostosis that flows along the cortex of the bone.
HISTOLOGY: normal haversian systems with enlarged bone trabeculae and without cellular atypia or mitotic figures.
Treatment for melorheostosis?
MILD SYMPTOMS WITH ADEQUATE MOTION: observation bisphosphonates show to help with pain and swelling.
SEVERE CONTRACTURES WITH LIMITED MOBILITY AND PAIN: resection of the hyperostotic bone with contracture release.
What is the risk of malignancy with a giant cell tumor?
What mutation is associated with those metastatic lesions?
PRIMARY MALIGNANT GIANT CELL TUMOR: Metastatic to lung in 2-4% of cases
wrist and hand lesions have a greater chance of metastasis
SECONDARY MALIGNANT GIANT CELL TUMOR: occurs following radiation or multiple resections of giant cell tumor
c-myc oncogene or p53
metastatic GCT has a 5 year 76% disease-free survival rate and a 17% mortality rate.
What is the most common demographics and location of giant cell tumors?
More common in females (unlike most bone tumors which show male predominance)
Ages 30-50 years
Distal femur > proximal tibia > distal radius > sacral ala
50% occur around knee
10% in sacrum and vertebrae (vertebral body) with the sacral ala most common site in axial skeleton
Phalanges of the hand is also a very common location
What imaging is indicated in cases of giant cell tumors?
Radiographs including chest x-ray. Eccentric lytic epiphyseal/metaphyseal lesion that borders subchondral bone.
Chest CT ot look for pulmonary mets.
MRI. Will be dark on T1 and very bright on T2 with clear demarcation.
What is responsible for the significant bone destruction in giant cell tumors?
Tumor cell activation of osteoclasts.
Likely accomplished through the RANK pathway and requires tumor cells to secrete or stimulate osteoblast to produce RANKL.
The multinuclear giant cells and the osteocytic stromal cells of giant cell tumor are locally aggressive, but they do not have the capcity to dissolve bone.
Nonoperative treatment for giant cell tumors?
RADIATION THERAPY: only indicated for inoperable (sacral or vertebral body) or multiply recurrent lesions
MEDICAL MANAGEMENT: denosumab or bisphosphanates. Excellent response has been seen with denosumab (85-90% destruction of giant cells)
Post-surgical treatment with bisphosphonate has shown to lower recurrence rates by 25-30%
Operative treatment for giant cell tumors?
Extensive curettage, adjuvant treatment, and reconstruction. Majority of lower extremity lesions, hand lesions are most controversial. Outcomes 20-40% recurrence with curettage alone versus 3-10% with adjuvatn treatment.
Complete resection and reconstruction. When currettage is not possible due to structural compromise. Extensive involvement of vertebral body -> total en bloc spondylectomy.
Amputation. Hand lesions with cortical breathrough which are not amendable to intercalary resection. has the lowers incidence of recurrence.
What are some of the complications of denosumab use in giant cell tumors?
What is a contraindication to its use?
nasopharyngitis and arthralgias
contrainidcation is severe hypocalcemia.
What are acceptable forms of adjuvant treatment for giant cell tumors?
Phenol, liquid nitrogen, hydrogen peroxide, argon beam, and high-speed burr.
High-speed burr without any other adjuvant has recurrence rate of 12%
Liquid nitrogen has been associated with an increased incidence of pathologic fracture and vascular injury.
Can a giant cell tumor transform into a high grade sarcoma?
Yes but it is very rare <1% of the time.
9 years from previous radiation treatment
19 years from spontaneous transformation
What is the incidence of secondary ABC with giant cell tumors?
How do you differentiate it from a primary ABC?
between 10-14%
Differentiate from primary ABC because of enhancing soft-tissue component in GCT (not present in primary ABC)
If heterotopic ossification is going to occur after brain or spinal cord injury when will it occur?
within 2 months of neurologic injury.
Hip is most common for both brain and spine injury.
Occurs on affected (spastic) side.
elbow HO is more common following brain trauma.
True or false there is a genetic disposition to Heterotopic ossification?
True
Especially in men with hypertrophic osteoarthritis and women > 65 yrs
What conditions are associated with heterotopic ossification?
ORTHOPAEDIC MANIFESTATIONS: Pathologic fractures, nerve impingement, soft tissue contractures, CRPS, and joint ankylosis
Nonorthopaedic conditions- skin maceration and hygiene problems.
For the table or risk factors give an explanation of the risk of heterotopic ossification and if possible a percent risk?
How do you determine the maturity of heterotopic ossification on radiographs?
The appearance of bony cortex suggests mature HO
Sharp demarcation from surrounding tissue
trabecular pattern.
radiographs are not useful for early diagnosis as calcium is not deposited until 7-10 dyas later than symptom onset.
What is most useful for early diagnosis of heterotopic ossification?
Triphasic bone scan is the most commonly used diagnostic study.
Ultrasound can also be used.
What lab changes are consistent with heterotopic ossification?
Elevated serum alkaline phosphatase. ALP removes inhibitors of mineralization. Elevated 12 wks after surgery is a predictor.
Elevated CRP. correlates with inflammatory activity of HO better than ESR. normalization of CRP may correlate with maturity of HO.
Elevated ESR. 12wks after THA is predictor
Elevated CK- correlates with extent of muscle involvement.
Prophylactic treatment of heterotopic ossification?
bisphosphonates & NSIADs despite not much literature to support its use. Indomethacin is most commonly used. 75mg/day for 10 days to 6 weeks.
Perioperative radiation. Also commonly used despite not much literature supports. A single perioperative dose of 700 cGy can be given either 4 hours preop or within 72 hours postoperatively.
What is the appropriate timing of wide exposure and surgical resection for heterotopic ossification?
Indicated if there is severe loss of motion and decreased function.
TIMING OF RESECTION (CONTROVERSIAL):
Should be a marked decrease in bone scan activity AND normalization of ALP.
6 months following general trauma
1 year following SCI
1.5 years following TBI (most controversial of the three).
Postop give indomethacin, irradiate, and perform gentle ROM.
What are some of the complications of HO resection?
INFECTION- higher rate of infection folloiwng joint arthroplasty if HO is present.
FRACTURES- of osteoporotic bone- can be intraop or during PT
RECURRENCE- recurrence rates correlate with neurolgoical injury
AVN- if extensive dissection or stripping is required.
What is tymoral calcinosis?
Rare and poorly understood hereditary metabolic dysfunction of phosphate regulation associated with massive periarticular calcinosis in the extracapsular soft tissues.
More common in females and African-Americans
Hip (trochanteric bursa is most common location then shoulder
onset in childhood or early adolescence
What genetic defect leads to familial hyperphosphatemic tumoral calcinosis?
FGF-23
inborn abnormality of phosphorus metabolism
How will tumoral calcinosis appear on imaging?
Radiographs- amorphos, cystic, lobular (circular or oval) well-demarcated calcification in periarticular location. direct involvement of the bones or joints is rare.
CT- may demonstrate fluid-fluid levels within some of these masses. calcium layering (“sedimentations sign”)
MRI- Also may show fluid-fluid levels with alternating areas of high signal intensity and signal void.
What will labs and histology show for tumoral calcinosis?
normal or slightly elevated renal, parathyroid function
normal or slightly elevated serum calcium, phosphorus, uric acid, and alkaline phosphatase.
HISTOLOGY: lobulated soft tissue masses with well defined capsules and thick septae. Masses are filled with calcareous material(calcium phophate, calcium carbonate, and calcium hydroxyapatite) and fluid
What should be included in your differential for tumoral calcinosis?
Treatment for tumoral calcinosis?
Obersvation treatment of choice for non-symptomatic lesions.
If symptomatic compete surgical excision to decrease rate of local recurrence. Risk of recurrence is greater if lesion is poorly circumscribed or if excision is performed while lesion is actively growing.
What test can differentiate Ewing sarcoma from other small round cell lesions?
PCR can identify the fusion protein EWS-FLI1 that is formed by the 11:22 translocation.
What is the demographics and common location for Ewing Sarcoma?
typically found in patients from 5-25 years of age
Second most common malignant bone tumor in children.
Uncommon in African Americans and Chinese
50% are found in the diaphysis of long bones- Most common locations pelvis, distal femur, proximal tibia, femoral diaphysis, and proximal humerus.
What are the 5 year and 10 year survival rates for Ewing Sarcoma?
What are poor prognostic factors? What is the most important prognostic indicator?
5 yr- 65-80% for localized disease and 25-40% for metastatic disease
10 yr survival- 60% for localize disease and 30% for metastatic disease
See image for complete list. Metastases most important prognostic indicator. Lung mets better prognosis than bone/marrow mets. Skip mets better prognosis than distant.
What studies are requried for work-up of Ewing Sarcoma?
Bone scan- will show very hot lesion(s)
MRI- required to identify soft-tissue extension and marro involvement. Often shows a large soft tissue component.
CT chest- required to look for pulmonary metastasis
Bone Marrow biopsy- required as part of workup to rule out metastasis to the marrow
How does Ewing Sarcoma appear on radiographs?
Large destructive lesion in the diaphysis or metaphysis with a permeative moth-eaten appearance
Lesion may be purely lytic or have variable amounts of reactive new bone formation
Periosteal reaction may five “onion skin” or “sunburst” appearance
What will labs show in a patient with Ewings Sarcoma?
Often mimics an infection
ESR and WBC is elevated
Anemia is common
Elevated lactic dehydrogenase- high levels >200 is a poor prognostic indicator.
What histology of Ewing’s Sarcoma show?
Gross appearance may have liquid appearance mimicking pus
CHARACTERISTIC: sheets of monotonous small round blue cells. Prominent nuclei and minimal cytoplast. May have pseudo-rosettes (circle of cells with necrosis in center)
IMMUNOSTAINING: Postive- CD99 (in 95%), MIC2, vimentin, PAS positive (intracellular glycogen), neuron specific enolase (NSE) S100, and Leu7.
Negative- cytokeratin, reticulin (positive in lymphoma), neurofilament (positive in neuroblastoma)
List small-round-cell tumor differentials by age?
< 5 yrs: neuroblastoma or leukemia
5-10 yrs: eosinophilic granuloma
5-30 yrs: Ewing’s sarcoma
> 30 yrs: lymphoma
> 50 yrs myeloma
Treatment for Ewing Sarcoma?
Chemotherapy and radiation- for non-resectable tumors or where functional deficit is unacceptable. However trend is increasingly towars surgical resection because of morbidity and risk of secondary malignancies associated with Ewing Sarcoma.
OPERATIVE: Chemotherapy with limb salvage resection +/- adjuvant radiation is the stnadard of care.
Chemo for 8-12 weeks pre-op and then 6-12 months after resection.
Radiation if there are positive margins, widely metastatic disease, or where chemotherapy response if poor.
Complications associated with Ewing Sarcoma?
Secondary neoplasm- 10-20% risk of bone sarcoma at 20 yrs with radiation. Dose dependent. > 60Gy confers 20% risk while < 48Gy has no risk.
acute myeloid leukemia/myelodysplasia from chemotherapy in 2% of survivors. Arises around 5 years after diagnosis.
Recurrence- extremely poor prognosis <10% survival at 5 yrs after recurrence.
METS- 25-30% have macromets on presentation. CURE RATES WITH CHEMO: 10% have bone mets at presentation. Cure rates with chemo 30% for lung mets alon. 20% for bone mets. 15% for combined lung and bone.
What is the incidence, demographics, and general prognosis of adamantinoma?
Less than 300 cases have been documented
Occurs in young adults 20-40 years of age
May metastasize to the lungs in 25% therefore long term follow-up is recommended.
Recurrence is uncommon with negative margin excision.
Historically it was thought that osteofibrous dysplasia was a precurssor but current studies doubt this.
How will an adamantinoma appear on radiographs?
Multiple sharply circumscribed lucent lesions (“soap bubble” appearance) with interspersed sclerotic bone in mid tibia
Some lesions may destroy cortex, this is greatest differentiator on imaging from osteofibrous dysplasia.
May see bowing of the tibia.
No periosteal reaction unlike other primary bone tumors.
What will you see on histology for an adamantinoma?
Biphasic- contains both epithelial and ribrous mesenchymal cells.
Nests of epithelial-like cells arranged in palisading or glandular pattern. Stains for keratin.
Notice the epithelial islands in the image.
Background of fibrous stroma.
What is the treatment for adamantinoma?
Wide margin surgical resection.
Low grade so radiotherapy or chemotherapy is not typically used.
Often requires placement of an intercallary graft or megaprosthesis.
What cancer’s most commonly metastasize to bone?
BLT Kosher Pickle
Breast
Lung
Thyroid
Kidney
Prostate
Bone is the third most common site for metastatic disease behind Lung and Liver.
What is the most common location in bone for metastatic carcinoma?
Most common site is the thoracic spine
2nd most common site is proximal femur.
Proximal femur is the most common location for pathologic fracture with 50% in the femoral neck. 65% nonunion rate.
What kind of disease has Endothelin 1 been shown to be a crucial protein in?
osteoblastic bone metastases like those caused by prostate cancer or certain types of breast cancer.
What is a medical condition associated with bony metastatic disease where the patient presents with confusion, muscle weakness, nausea/vomiting, and dehydration?
How is it treated?
Metastatic hypercalcemia other major symptom is polyuria and plydipsia.
Hydration, loop diuretics, and bisphosphonates.
What is the median survival for patients with the following metastatic bone diseases?
Thyroid:
Prostate:
Breast:
Kidney:
Lung:
Thyroid: 48 months
Prostate: 40 months
Breast: 24 months
Kidney: variable but can be as short as 6 months
Lung: 6 months
What are the steps and factors involvend in the mechanism of metastasis to bone?
What is the mechanism for vacular spread of meastasis?
Batson’s vertebral plexus- valveless venous plexus of the spine that provides a route of metastasis from organs to axial structure including vertebral bodies, pelvis, skull, and proximal limb girdles.
Arterial tree metastasis- mechanism by which lung and renal cancer spread to the distal extremities.
What is the mechanism of bone lysis if mestatic cancer?
oncogenic cell releases cytokines IL-6, IL-11, PTHrP, and TGF-beta.
PTHrP and TGF-beta activate osteoblasts
Osteoblasts secrete RANKL, that binds to RANK on osteoclasts and activates osteoclasts.
What is the mechanism of bone sclerosis in prostate and breast mets?
prostate cancer cells secrete endothelin 1 (ET-1)
ET-1 binds to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts
ET-1 decreases WNT suppressor DKK-1 -> activates WNT pathway, increasing osteoblast activity.
What work-up should be performed for a patient that has a single bone lesion and unknown primary?
Radiographs
CT chest/abdomen/pelvis
technetium bone scan to detect extent of disease- myeloma and thyroid carcinoma are oftne cold on bone scan. evaluate with a skeletal survery.
LABS: CBC, ESR, BMP, LFTs, Ca, Phos, Alkaline phosphatase, SPEP, and UPEP.
in patients where a primary carcinoma is not identified, obtaining a biopsy is necessary to rule out a primary bone lesion.
metastatic adenocarcinoma not identified by CT of the chest, abdomen, and pelvis is most likely from a small lung primary tumor.
Cortical mets are most common in what cancer?
Lung cancer
Lung is also the most common cause of acral mets and lesions distal to elbow and knee.
What are characteristic histological findings of mestatic carcinoma to bone?
The following immunohistochemical stains are positive in what malignancies?
Keratin
CK7
TTF1
Epitherlial cells in clumps or glands in a fibrous stroma.
Keratin- positive in epithelial cells, so all metastatic carcinoma
CK7- breast and lung cancer
TTF1- lung cancer
What is the general treatment recommended for metastatic carcinoma to bone?
bisphosphonate therapy- IV pamidronate most commonly used.
Stabilization of complete fracture with postoperative radiation. All patients require postop radiation unless imminent death or area has been previously irradiated. Area should inclued the entire fixation device. start after surgery.
See table of treatment based on cancer type.
What carcinoma other than renal may need preoperative embolization?
Thyroid carcinoma prior to operative intervention.
How would you treat metastatic lesions to bone in the following scenarios?
Femoral head fracture.
peritrochanteric fracture without femoral neck or head involvement.
Impending fracture of femoral head and neck.
Cemented hemiarthroplasty. Only perfrom THA if there is acetabular involvement.
Cephalomedullary nail with currettage and cement. As long as it doesn’t involve the femoral head can consider nail for both complete and impending fractures.
hemiarthroplasty vs THA. Take into account age of patient. Any existing arthritic disease. Life expectancy. Morbidity of the surgery and stability of the patient.
What malignancy is associated with Stuart-Treves syndrome?
Angiosarcoma
What is the demographic and location of most soft tissue sarcomas?
Males > Females
85% occur in patients > 15 years old
60% occur in extremities
What malignancies are associated with the following translocations?
t(x;18)
t(2;13)
t(12;16)
Synovial sarcoma (SYT-SSX fusion)
Rhabdomyosarcoma (alveolar)
Myxoid liposarcoma
Where is the most common metastasis in soft tissue sarcoma?
What is the rate of lymph node metastasis?
Lung
5% (most commonly epitheliod, synovial, angiosarcoma, rhabdomyosarcoma, clear cell)
What is the most important prognostic variable for soft tissue sarcoma(STS)?
What is the most common error in treatment of STS
tumor stage
Unplanned excision- referral to orthopaedic oncologist for multidisciplinary workup and repeat excision is critical.
True or false all soft tissue sarcomas have the same general presentation, imgaing, and differential diagnosis?
True, even though there are over 50 subtypes recognized the generally present the same.
Histologic findings and molecular signatures are used to distinguish the individual types.
How will a soft tissue sarcoma present on MRI?
isointense with msucle on T1
T2 will have high signal intensity.
IV gadolinium: peripheral enhancing zone and non-enhancing necrotic center.
MRI can be diagnostic for lipomas, neurilemoma (schwannoma), and intramuscular myxoma.
If MRI is diagnostic can be removed withouth a biopsy.
What treatment is standard of care in most cases for soft tissue sarcomas?
What about for lung mets?
Wide surgical resection & radiation therapy.
eliptical incision is used to incorporate biopsy and drain sites.
50 Gy pre-operative and 66 Gy postoperative radiation is standard dose.
Chemotherapy is controversial for soft tissue sarcomas. Is used regularly for rhabdomyosarcoma and Ewings Sarcoma.
Surgical resection of lung mets is standard of care if the preop evaluation shows that complete resection is possible. curative in up o 25% of patients.
What are the radiation (early and late) and recurrence complications associated with soft tissue sarcoma?
Radiation induced: pre-operative radiotherapy associated with a > 30% risk for wound complications. However, post-operative radiation is associated with greater radiation induced morbidity and risk of radiation-induced sarcoma.
EARLY effects: desquamation, delayed wound healing, and infection
LATE effects: fibrosis, post-radiation fracture, possibly secondary sarcoms
Recurrence: local recurrence <10% with radiation and surgery. The most common location for recurrene of a low-grade STS is locally.
What is a neurilemmoma?
age and Location?
Mutation?
Benign encapsulated tumor composed of Schwann cells on the surface of a peripheral nerve.
also known as a schwannoma
peak incidence is in the 3rd to 6th decades of life.
Often occurs on flexor surfaces of extremities, head, and neck. Large lesions may occur in pelvis.
Associated with mutation affecting NF2 gene.
Malignant transformation is extremely rare.
How will a neurilemmoma appear on MRI?
dark T1
Bright T2
diffuse enhancement with gadolinium
May show string sign
difficult to differentiate from neurofibroma.
What will histology of a neurilemmoma show?
Verocay bodies is pathognomonic composed of two rows of aligned nuclei in a palisading formation. depicted below.
Will also have Antoni A (a pattern of spindle cells arranged in intersecting bundles also referred to as a spindle cell battle formation. depicted on the image on the reverse of the car.
There is also Antoni B which are areas with less cellularity with loosely arranged cells.
strongly uniform S100 antibody staining.
Treatment for neurilemmoma?
observation for asymptomatic lesions.
Marginal excision if symptoms are interfering with quality of life.
Nerve function may be preserved with careful dissection, excising the lesion parallel to the nerve fascicles so the lesion may be extruded. Small risk of sensory deficits. Recurrence is rare.
What is synovial chondromatosis?
Who is usually affected?
What is the most common location?
proliferative disease of the synovium that results in multiple intra-articular loose bodies.
usually younger adults 30-50 years of age. 2:1 Male to Female.
Knee is most common location
Slow progression of pain, swelling, and decreased ROM.
How does synovial chondromatosis appear on radiographs and histology?
may or may not show on radiographs depending on stage of disease. May show stippled calcifications.
Initially cartilage nodules are only visible on MRI with a lobular appearance. In later stages signal drops off due to clacification.
HISTOLOGY: shows discrete hylaine cartilage nodules in various stages of calcification. Chondrocytes with mild atypia, binucleate cells, and occassional mitoses.
Operative treatment for synovial chondromatosis?
observation if symptoms are mild.
Open or arthroscopic synovectomy and loose body resection is symptoms are severe and affecting ROM. May prevent degenerative joint changes.
True of False synovial carcinoma is due to a malignant transformation of a cell within the synovium?
False.
cellular origin is unkown but it is not a synovial cell.
Arises near joints, but is rarely within joints.
What is the incidence of metases in synovial sarcoma?
What is the overall prognosis of synovial sarcoma?
May develop in 30-60% of patients.
Lung is the most common location.
Rare soft tissue sarcoma that can metastasize to lymph nodes ( others include epitheliod sarcoma, angiosarcoma, rhabdomyosarcoma, and clear cell sarcoma)
Lung mets still worse prognosis than lymph mets.
Overall prognosis is poor. 5 year survival is 50% 10 year survival is approximately 25%
SYT-SSX2 fusion type better prognosis.
How will a synoial sarcoma appear on imaging?
may see mineralization in tumor on radiograph that resembles HO.
CT can show calcifications.
MRI reveals a heterogenous mass that is typically dark on T1 and bright on T2.
What will histology of a synovial sarcoma show?
Classically will hsow biphasic appearnace with spindle cells and epithelial cells.
STAINS POSITIVE FOR: Vimentin, epithelial membrane antigen, sporadic S-100, and epithelial cells will stain positive for keratin.
What is treatment for synovial sarcoma?
Wide surgical resection with adjuvatn radiotherapy.
What two soft tissue sarcomas is chemotherapy actually standard of care.
Rhabdomyosarcoma and Ewing sarcoma
What is PVNS?
Is it neoplastic?
Genetic component?
Demographics?
idiopathic monoarticular neoplastic synovial disease. Characterized by exuberant proliferation of synovial villi and nodules
Now thought to be neoplastic.
5q33 chromosomal rearrangement. Increased expression of CSF1 gene.
Ages 30-40 but can occur at any age. Equal male to female.
What are the different types of PVNS?
Localized (intra-articular or classic form). Knee is the most common site of involvement (80%) Knee > hip > ankle > shoulder > elbow
Diffuse (extra-articular extension)
Giant cell tumor of tendon sheath- occurin galong tendon sheaths of hands and feet.
50% of patients will have prior history of trauma to the area.
How will PVNS appear on imaging?
RADIOGRAPHS: cystic erosion with sclerotic margins on both sides of joint.
MRI: Low signal intensity on both T1 and T2 due to hemosiderin deposits
“blooming artifact” signal loss on gradient-echo sequencs because of the hemosiderin deposits.
Allows evaluation of both intra-articular and extra-articular disease.
What will gross path and histology show for PVNS
Gross appearnce will be brownish or reddish inflamed synovium
HISTOLOGY: mononuclear stromal cells infriltrating the synovium
hemosiderin stained multinucleated giant cells
highly vascular milli with hyperplastic synovial cells.
pigmented foam cells (lipid-laden histiocytes)
What is the treatment for PVNS?
no role for obervation if disease is even minimally symptomatic.
Total synovectomy (classified as marginal excision)
Recurrence is common. External beam irradiation when combined with a total synovectomy can reduce rate of recurrence to 10-20%
draw back of arthroscopic treatment is difficult to access posterior portions of joint and cannot address extraarticular disease.
For diffuse PVNS can do arthroscopic anterior and open posterior synovectomy.
What is the most common complication in PVNS?
Recurrence- 30% despite compete synovectomy. Same rates for arthroscopic vs open.
Reduced by external beam radiation.
What is another name for a malignant peripheral nerve sheath tumor?
demographics?
Genetics?
Prognosis?
Also knonw as neurofibrosarcoma or malignant schwannoma.
Arises from a peripheral nerve or neurofibroma
30-55 yrs for solitary neurofibromas
20-40 years for neurofibromatosis type 1
Most cases associated with NF-1 mutation
5 year survival solitary lesion 75%
5 year survival associated with NF-1 is 30%
How will neurofibromasarcoma (malignant peripheral nerve sheath tumor) appear on MRI and histology?
MRI: T1- low intensity. T2-high intensity
spindle cells with vavy nuclei resembling fibrosarcoma.
Postivie S100 and keratin staining.
Treatment for neurofibrosarcoma?
Wide surgical excision with radiation.
In general treated as high-grade sarcoma.
Wide resection should inlcude entire affected nerve.
Preop radiation.
What is the difference between a schwannoma and a neurofibroma?
Schwannoma involves schwann cells alon.
Neurofibroma is also a benign nerve sheat tumor but it has multiple cell types.
nonmyelinating Schwann cells, fibroblasts (predominant cell type), and perineural cells.
What is the pathophysiology/molecular biology of neurofibroma?
Arise in nonmyelinating Schwann cells with biallelic inactivation of NF1 tumor-suppressor gene.
Loss of expression of protein neurofibromin: neurofibromin negatively regulates RAS-mediated pathway -> loss of neurofibromin leads to increased RAS activity. -> affects RAS-dependent MAPK activity which is essential for osteoclast function and survival.
Rapid hyperplasia of nonmyelinating Schwann cells into neurofibromas after NF1 inactivation -> recruits perineural cells, fibroblasts, mast cells, and endothelial cells.
What are the two disease processes that lead to neurofibromas?
What are the subtypes of neurofibromas?
What are the types of Schwann cells?
What will be seen on physical exam in a patient with neurofibromatosis?
What is the NIH criteria for neurofibromatosis?
What other things are associated with NF1?
See image for physical exam and NIH criteria.
Associated with NF1:
dystrophic kyphoscoliosis
rib penciling
intraspinal neurogibromas and dumbbell lesions
Dural ectasia
Meningiomas.
How will a neurofibroma present on MRI?
Solitary neurofibromas are found central to the nerve fibers
Schwannoma are found eccentric to the nerve fibers
nerve continuity sign- fusiform tumor in continuity with the neurovascular bundle
split fat sign- fusiform tumor surrounded by a thin margin of fat because the mass within the neurovascular bundle enlarges and displaces the adjacent intramuscular fat
target sign- lesion of high signal intensity peripherally and low signal centrally (on coronal STIR)
How does a neurofibroma present on histology?
overall hypocellular with predominantly fibroblasts with some Schwann cells, mast cells, and lymphocytes. Elongated wavy nuclei
Stroma is a rich wire-like collagen fiber netwrok.
Distorted structures resembling Pacini or Meissner corpuscles.
Variable S100 staining.
Treatment for a neurofibroma?
observe for most if very symptomatic then can consider surgical excision.
May require nerve grafting.
How common is leiomyosarcoma of bone?
Very rare. Fewer than 100 case reports of extra-fascial leiomyosarcoma of bone.
thought to arise from the smooth muscle cells linging small blood vessels.
Occurs in soft tissue (ex. uterus) or bone.
When in bone most commonly in metaphysis of long bones with most frequent locations femur, tibia, ilium, and humerus.
25% recurrence rate. 25% mets rate. 75% survival at 3 years with treatment.
How will a leiomyosarcoma present on imaging?
RADIOGRAPHS: purely osteolytic lesions with ill-distinct margins, moth-eaten, or permeative pattern of bone destruction. Primarily extramedullary but can extend into soft tissues.
Chest radiograph and CT of chest in all patients to look for mets.
MRI: dark on T1 (similar to muscle tissue). Heterogeneous on T2 with areas of increased signal intensity.
Contrast causes diffuse enhancement of signal within the lesion.
How will a leiomyosarcoma appear on histology?
spindle cell neoplasm
cigar-shaped nuclei
cells arranged into fascicles along with myofibrils running parallel
presence of actin and vimentin immunoreactivity. See image on other side of card.
Treatment for leiomyosarcoma?
chemotherapy- diffuse metastatic disease to the lungs. Large pelvic masses with neurovascular involvement that preculde safe resection. Variable response. Better with combined chemo and surgery than surgery alone.
radiation- controversial, may be used for contaminated resection bed.
operative- early wide resection of primary lesion and secondary reconstruction is the standard of care. +/- chemo and radiation
What is the most common sarcoma in children?
Rhabdomyosarcoma- A malignatn tumor of the primitive mesenchyme.
FOUR SUB-TYPES: Embryonal- occurs in infants and young children
Alveolar- occurs in adolescents and young adults
Botryoid- occurs in infants and young children, typically in the vagina (aka Sarcoma botryoides or “bunch of grapes”
Pleomorphic- tends to occur in older patients 40-70 yrs.
What is the genetic translocation and fusion protein in rhabdomyosarcoma?
Mets?
Prognosis?
t(2;13) translocation. forms Pax3-FKHR fusion protein
nodal metastasis are known to occur with rhabdomyosarcoma. consider sentinel lymph node biopsy as part of treatment.
bone marrow biopsy is required for staging.
PROGNOSIS: 5 year survival for the following sub-types.
embryonal- 80%
Alveolar- 60%
Botryoid- uniformly fatal, less than 30% of patients live 5 years from the time of diagnosis
Pleomorphic- 25%
Where to most rhabdomyosarcoma lesions occur?
Head/neck, genitourinary system, or retroperitoneum.
How does rhabdomyosarcoma appear on imaging?
Histology?
MRI- like most other STS dark on T1 and bright on T2.
Need CT of chest for staging.
Histology differs depending on subtype:
embryonal- small round blue cell, skeletal muscle like cross-striations can occur. depicted in image
alveolar- poorly differentiated round cells with multinucleated giant cells. Cellular aggregates are surrounded by dense fibrous septae.
pleomorphic- multiple cell types are present. difficult to differentiate from other pleomorphic sarcomas.
IMMUNOHISTOCHEMISTRY +: MyoD1, myoglobin, myosin, desmin, and vimentin.
Treatment for rhabdomyosarcoma?
Chemotherapy alone in select patients with widespread metastatic disease. common agents include vincristine, dactinomycin, and cyclophosphamide.
Radiation for unresectable tumors or close/positive margins.
wide surgical excision with chemotherapy is stnadar of care.
chemotherapy is not effective for adult rhabdomyosarcoma. Use surgery and radiation.
What is the epidemiology and common locations of an extra-abdominal desmoid tumor?
A fibrogenic lesion that is the most locally invasive of all benign soft tissue tumors.
Female > male 3:1. Found in patients 25-35 years of age.
Higher incidence in familial adenomatous polyposis (FAP) and Gardner syndrome (4-30%)
Most common shoulder (20%) > chest wall/back (17%) > thigh (13%). >50% are extra-abdominal.
May have multiple lesions in the same extremity.
Appears in sites of previous surgery or scared
elevated levels of beta catenin in all tumors.
trisomy in chromosome 8 or 20.
What are the associated conditions with extra-abdominal desmoid tumor?
What is the overall prognosis?
Dupuytrens contractures, Ledderhose disease, FAP, and Gardner syndrome
High risk of recurrence and lesions are highly unpredictable.
No risk of metastatis or malignant transformation unless related to radiation.
How will and extra-abdominal desmoid tumor preset on physical exam?
enlarging mass with possible nerve compression.
Will have a distinctive rock hard feel on palpation because tumor is fixed to surrounding tissues.
Poorly circumscribed and may be painful and limit motion around joint.
How will an extra-abdominal desmoid tumor appear on MRI?
dark on T1
dark to isointense on T2
Gadolinium enhances appearance.
Infiltrates muscle
5-10cm in size
May erode bone locally
How will an extra-abdominal desmoid tumor appear on Histology?
Gross specimen will be gritty, white, and poorly encapsulated.
Micro will show well differentiated fibroblasts, uniform spindle cells with elongated nuclei and occasional mitoses. Abundant collagen
Tumor infiltrates adjacent tissue.
POSITIVE: 100% for estrogen receptor beta. Somatostatin, cathepsin D, Ki-67, and c-Kit.
NEGATIVE: estrogen receptor alpha, progesterone receptor, HER2.
Treatment for Extra-abdominal desmoid tumor?
Recurrence?
low dose-chemo only/famoxifen- inoperable lesions. tamoxifen favored for failed/poor candidates for standard chemotherapy.
operative- wide surgical resection with chemotherapy for symptomatic or recurrent lesions. Recurrence is reduced by radiotherapy.
negative margins: 28% with surgery alone and 6% with addition of radiation.
Positive margin: 39% surgery alone and 25% with addition of radiation.
What is the most common soft tissue neoplasm of the foot?
Plantar fibromatosis (Ledderhose Disease)
More common in males and the middle aged to elderly.
Malignant transformation is rare.
Recurrence is common and it usually recurs as a more agressive lesion.
MRI will be dark on T1 and medium signal on T2. Will have “comb sign” on Ultrasound.
Can be treated with observation if small or not very symptomatic
Excision for symptomatic +/- radiation. Total fasciectomy is prefferred due to risk of recurrenct. 0-50% risk with total fasciectomy compared to 57-100% with local excision.
What is nodular fasciitis?
How does it appear on imaging?
Histology?
Treatment?
Common reactive lesion that usually occurs in upper extremities of young people age 15-35 years. most common fibrous soft tissue lesion.
common locations volar forearm, back, chest wall, head, and neck.
May be painful or painless. Rapidly enlarging over 1-2 weeks. Generally not bigger than 2cm.
MRI: most commonly superifical mass with extension along fascial planes. avid enhancement with gadolinium.
HISTOLOGY: short irregular bundles and fascicles. Dense reticulum network. small amounts of mature collagen.
Marginal resection.
What is dermatofibrosarcoma protuberans?
What are its variants?
Demographics?
Location?
rare low-grade fibrogenic cutaneous sarcoma that occurs in early to midadult life.
Variants include: Bednar tumor- pigmented variant that is 7.5x more common in African Americans. Fibrosarcomatous- more aggressive variant with poor prognosis.
Patients aged 20-50 yrs old. Slightly more common in males. 2:1 African Americans to Caucasians.
Most common locations trunk > proximal extremities > head/neck
What mutation is associated with dermatofibrosarcoma protuberans?
Incidence of mets?
Overall prognosis?
t(17;22)- encodes for PDFG-beta chain (PDGFB)/collagen type I alpha 1 (COL1A1) fusion protein.
distant mets is rare <5%: lung is the most common site. usually preceded by multiple local recurrences.
Worse prognosis is seen with:
regional lymph node involvement, fibrosarcomatous variant, age > 50 yrs
Worse prognosis with the following histologic features: high number of mitotic figures, increased cellularity, DNA aneuploidy, TP53 gene overexpression.
How does dermatofibrosarcoma appear on histology?
Biopsy is required for diagnosis.
Classically appears as uniform fibroblasts arranged in storiform pattern around an inconspicuous vasculature.
Bednar- variant has scattered melanin-containing dendritic cells.
Fibrosarcomatous- variant has a characteristic herringbone pattern.
Treatment for Dermatofibrosarcoma Protuberans?
Nonoperative- adult patients with unresectable, recurrent, and/or metastatic DFSP.
uses imatinib which inhibits PDGF-receptor tyrosine kinase. 65% response rate. No response in patients who lack the t(17;22) mutation.
Operative- wide surgical resection +/- adjuvant radiation therapy. Done for patients with resectabel DFSP.
Obtain 2-3cm margins. Need to dissect deep to and excise all tissue including the fascia.
15.7% recurrence for lesions on the body. 51.8% recurrence rate for lesions on the head/neck.
What are the different common variants of lipoma?
Spindle cell lipoma- common in males 45-65 years. Treated with marginal excision.
Pleomorhpic lipoma- common in middle aged patients. May be confused with liposarcomas.
Angiolipoma- unique in that it is painful when palpated. Often present with small nodules in the upper extremity.
Intramuscular lipoma- Often symptomatic and requires marginal resection
Hibernoma- tumor of bown fat. Affects younger patients (20-40 yrs). See image.
How will a lipoma appear on MRI?
Bright on T1
Bright on T2
Dark on STIR of fat saturated sequences.
How will lipomas appear on histology?
Include the common variants.
In general show bland acellular stroma with neoplastic cells that lack cellular atypia.
Hibernoma are reddish brown becuase of rich vascular supply in addition to high numbers of mitochondria.
Spindle cell lipoma- mucoid matrix with varying numer of birefringent collagen fibers. Will see spindle cells.
Pleomorphic lipoma- lipocytes, spindle cells, and scattered atypical giant cells.
Angiolipoma- mature fat cells with nests of small arborizing vessels.
Intramuscular lipoma- lipoblasts and muscle infiltration. See image.
When is operative treatment recommended for a lipoma?
symptomatic.
mass is rapidly growing.
Tumors located deep to the fascia or in the retroperitoneum. These have a higher likelyhood to become atypical lipomatous tumors.
In the retroperitoneum referred to as well-differentiated liposarcoma.
In the extremities referred to as atypical lipomas
Spindle cell/pleomorphic lipomas are treated by marginal resection.
Recurrence is uncommon < 5%
What is the hallmark on histology of a liposarcoma?
Signet ring-type cell
What is the common patient age and location of a liposarcoma?
Older individuals 50-80 yrs
Males more than females
More common in the lower extremity than upper extremity.
Usually occur deep to fascia and are common in the retroperitoneum.
What genetic mutation or translocation is found in liposarcomas?
What is their malignant potential?
In general what is the prognosis?
Well-differentiated liposarcoma- amplification MDM2
Myxoid liposarcoma -> t(12;16)
Metastasis risk correlates with grade/sub-type of liposarcoma: low grade (well differentiated) <1%
Intermediate grade (myxoid) 10-30%. High grade rate of >50%
PROGNOSIS: Well differentiated <10% local recurrence and almost complete survival
Intermediate and high grade 20% local recurrence but 5 year survival is 25-50%
What kind of liposarcoma is depicted in the image?
Myxoid liposarcoma.
Most common- 50% of all liposarcomas.
What needs to be obtained in the work-up of a myxoid liposarcoma?
CT chest/Abd/Pelvis
they have a tendency for abnormal metastasis outside of the lungs, such as spread to the retroperitoneum.
How will liposarcomas appear on MRI?
Well-differentiated or atypical will loo similar to lipomas. Bright on T1 and dark on T2. (isointense with fat).
High grade liposarcomas will be similar to all other sarcomas. Dark on T1 and Bright on T2
How will liposarcoma and the different sub-types appear on histology?
Treatment for liposarcoma?
marginal resection without radiotherapy- well differentiated liposarcoma
wide surgical resection with adjuvant radiotherapy- Intermediate and high grade liposarcomas
Radiation decreases recurrence.
Chemotherapy generally not used.
What is Kasabach-Merritt Syndrome?
Rare complications of soft tisse hemangioma caused by entrapped platelets that can lead to a possibly fatal coagulopathy.
What is the demographics, common location, and prognosis of soft tissue hemangiomas?
More common in patients <30 years of age.
Common in the hand
intramuscular is commonly found deep in the lower extremities.
Most commonly found as isolated lesions, except for diffuse hemangioma (a rare childhood form which extensively involves a single limb.
No incidence of malignant transformation. Infantile forms involute by age 7.
Mass will vary in size depending on activity level and between supine and standing position.
How will a soft tissue hemangioma appear on imaging?
Radiographs may show small phleboliths (calcifications) inside the lesion and erosion into adjacent bone.
MRI WITH GADOLINIUM: Increased signal on both T1 and T2 sequences.
Heterogeneous lesion with numerous small blood vessels adn fatty infiltration (bag of worms).
Focal areas of low signal are a sing of blood flow or calcifications.
Helps differentiate these benign lesions from arteriovenous malformations and angiosarcomas.
How will a soft tissue hemangioma appear on histology?
gross speciment will vary from red to tan to yellow.
No malignant cells.
Many vascular dilations with large nuclei filled with erythrocytes.
Vascular lumens infiltrated with muscle fibers
Cavernous type shows large vessels with lots of fatty tissue.
What is treatment for soft tissue hemangiomas?
First line and childhood lesions -> observation, NSAIDs, vascular stockings, and activity modification.
Large painful lesions that fail the above can undergo sclerotherapy of embolization with IR.
OPERATIVE: Small lesions of the hand -> marginal excision
Wide surgical resection for lesions resistant to nonoperative management.
What is the demographic, common location, and prognosis of angiosarcoma?
Male > female
elderly
60% near long bones
Osseous involvement in <10%
Poor, high local failure rate and amputation is often required.
Propensity for lymphatic spread.
Metastases to lung is common.
What will angiosarcoma show on histology?
Vascular channels with variable degrees of anaplasia.
Malignant cells associated with vascular structures.
Treatment for angiosarcoma?
Wide surgical excision is treatment of choice. Often end up with amputation to achieve local control of disease.
Relatively insesitive to chemotherapy and radiation.
What is the most common subungual malignancy?
Not glomus tumor its squamous cell carcinoma.
What are risk factors for development of squamous cell carcinoma?
Incidence of mets?
primary risk factor is exposure to ultraviolet radiation.
actinokeratosis
Chronic osteomyelitis
Marjolin’s ulcer is a squamous cell carcinoma resulting from chronic draining wounds or burns or scars.
Relatively high incidence of mets. Higher than basal cell carcinoma.
Also metastases to lymph nodes.
Treatment for squamous cell carcinoma?
Wide surgical resection +/- skin graft +/- radiation standard of treatment.
adjunctive radiatio when: lesions >2cm wide. 4mm deep. perineural invasion. Lymph node metastases.
Mohs microsurgery- indicated for smaller lesions. High cure rate. Lymph node biopsy may be necessary.
What is a glomus tumor?
Demographics?
Location?
Rare benign tumor of the glomus body(perivascular temperature regulating structure that is frequently located at the tip of a digit) that often occurs in the subungual region
Also called a paraganglioma.
May involve soft tissue or bone.
Patients 20 to 40 years of age.
75% occur in hand. 50% are subungual. 50% have erosions of distal phalanx.
Less common locations are palm, wrist, forearm, and foot.
What is the classic triad of symptoms of a glomus tumor?
What will you see on physical exam?
TRIAD: paroxysmal pain, exquisite tenderness to touch, and cold intolerance.
Physical exam: small bluish nodule. Often difficult to see especially when it is under the nail.
Nail ridging or discoloration is common.
Love test: pressure to the area with a pinhead elicits exquisite pain. 100% sensitive and 78% accurate.
Hildreth test: tourniquet inflation reduces pain/tenderness and abolishes tenderness to the love test. 92% sensitive and 91% specific.
How will a glomus tumor appear on imaging and histology?
On radiographs can see pressure erosion of the underlying bone and an associated deformity of the bone cortex.
MRI: dark on T1 and bright on T2
Well defined lesion with samll round cells and dark nuclei.
associated small vessels in a hyaline/myxoid stroma
Can show gland-like or nest structures, separated by stromal elements.
Treatment for a glomus tumor?
Marginal excision is curative. Done if symptoms affecting quality of life.
Recurrence is uncommon (20%). Can become malignant.
Reconstruction of nail bed contour with autologous fat graft is done for large defects after resection.
What is a epithelioid sarcoma?
Age of patients & common locations?
Mets?
Prognosis?
rare malignant slow growing nodular soft tissue tumor.
2:1 Male to female age 10-35 years
Most common soft tissue sarcoma of the hand and wrist. also occurs in the forearm, buttock/thigh, knee, and foot.
Can be deep( attached to tendons or fascia) or superficial where is can ulcerate and mimic skin carcinoma, rheumatoid nodules, or granulomas.
Regional lymph node mets is common. Lung mets can also occur.
extremely poor prognosis
How will epithelioid sarcoma appear on imaging and histology?
RADIOGRAPHS: erosion of adjacent bone is sometimes foung. Calcification in 10-20%
MRI: dark on T1 and bright on T2. May visualize it attached to tendon sheath.
HISTOLOGY: nodular pattern with central necrosis within granulomatous area.
epithelial appearance with ovoid or polygonal cells with eosinophilic cytoplastm.
dense hyalinized collage deposits intercellularly
Keratin positive staining.
Treatment for epithelioid sarcoma?
Wide excision with adjuvant radiotherapy for all operable tumors.
perform a sentinel lymph node biopsy to evaluate for regional lymph node metastasis.
Amputation may be necessary to prevent spread of disease in cases of multiple recurrences.
What is a intramuscular myxoma?
Demographics?
Common locations?
Mets?
Prognosis?
Benign soft tissue tumor that presents as a slow growing deeply seated mass confined to skeletal muscle. Likely develop from premature mesenchymal stem cells which differentiate into benign fibroblasts.
40 to 60 year olds with slight female predilection.
Commonly located in thigh, shoulder, buttock, or upper arm.
Mets are uncommon.
Prongosis is good.
What conditions are associated with intramuscular myxomas?
Mazabraud’s syndrome- a syndrome characterized by multiple intramuscular myxomas associated with monostotic or polyostotoic fibrous dysplasia.
Myxoid liposarcomas- important to differentiate from a myxoid liposarcoma which occurs in an intermuscular location.
How will a intramuscular myxoma appear on imaging?
Histology?
MRI: Will have homogenous appearance. Dark T1 and Bright on T2.
key is the intramuscular location!
myxoid liposarcoma will occur in an intermuscular location.
HISTOLOGY: characterized by a bland and hypo-cellular myxoid stroma
No cellular atypia or atypical mitosis.
Treatment for intramuscular myxoma?
observation for asymptomatic lesions.
Marginal excision for symptomatic lesions. Recurrence and mets is very uncommon.
True or False a PET-CT can differentiate neurofibromas from malignant nerve sheath tumors?
True.
What condition does the image depict?
Lucency of the medial corticla border of the metaphysis.
Pathognomonic for focal fibrocartilaginous dysplasia?
Occurs in humerus, ulna, and femur.
Can spontaneously resolve but often requires corrective osteotomy.
What are general external beam radiation doses for the following:
Post-op for HO prevention
Adjuvant for soft tissue sarcoma
Palliative therapy for metastatic disease
6 Gy
60 Gy
30 Gy
Where may proton beam therapy be utilized instead of photon therapy?
Proton beam radiotherapy offers the added value of avoiding the exit dose and therfore is often used in the context of spinal column tumors or tumors immediately adjacent to the spinal elements.
Conventional radiation most often utilized photon radiotherapy.
