Bone Tumors in Children and Adolescents-f

7/29/2019 Bone Tumors in Children and Adolescents-f

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Bone tumors in children andadolescents

Benign childhood bone tumors


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MALIGNANT BONE TUMORS Incidence : 8.7/million children under 20yearsComprises of about 6% of childhood cancer

In the US, 650-700 children and adolescents younger than 20 yearsof age are diagnosed with bone tumors each year, of whichapproximately 400 are osteosarcoma and 200 are Ewings sarcoma.

The two types of malignant bone cancer that predominated inchildren were osteosarcomas and Ewings sarcomas , about 56%and 34% of the malignant bone tumors, respectively


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For all bone cancer combined, a steady rise in incidence ratesoccurred with increasing age between ages 5 and 10 , and a steeper rise began at age 11 until age 15 coinciding with the adolescentgrowth spurt. The peak incidence of bone cancer (19/million)occurred at age 15, after which rates showed a decline ( see figurebelow).


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Rates did not differ much by sex among younger children, butmales had higher incidence than females during adolescence

For osteosarcoma, black children had a higher overall rate than did white children . For Ewings sarcoma the racial variation in rates was dramatic: white children had an approximate 6-fold higherincidence rate than black children

The most frequent site of bone cancer development was the long bones of the lower limbs for osteosarcomas and the central axis forEwings sarcomas


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Current knowledge on causes of bone tumors Known risk factors osteosarcoma

Prior treatment for childhood cancer with radiation therapyand/or chemotherapy

Hereditary retinoblastoma,,Li-Fraumeni syndrome, andRothmund-Thomson syndrome

Radium :High doses

Known risk factors Ewings sarcoma

Race: ES is almost exclusively a disease of white children.Rates in whites are approximately 9 times those in

blacks.


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Benign childhood bone tumors Static lesions :e.g. nonossifying fibromaslocally aggressive lesions :e.g. aneurysmalbone cysts

Most benign bone tumors have characteristicradiographic features and can be diagnosed

with plain radiographs


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Approach to Bone tumors1. Clues by appearance of lesion

2. Clues by location of the lesion

3. Clues by density of the lesion

4. Other clues


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1. Clues by appearance of lesion A. Patterns of bone destructionB. Periosteal reactionC. Tumor matrixD. Expansile lesion of bone


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A. Patterns of bone destruction

I. Geographic :Destructive lesion with sharply definedborderImplies a less aggressive,more slow-growing, benign process

Narrow transition zonee.g. Non-ossifying fibroma

Chondromyxoid fibromaEosinophilic granuloma


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I. Geographic.contd Example: Non-ossifying fibroma


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II. Moth-Eaten bone destruction

Areas of destruction with ragged bordersImplies more rapid growth, probablymalignancy

e.g. Ewings sarcoma Lymphoma

Multiple myelomaMetastases


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III. Permeative pattern:Ill- defined lesion, with multiple worm -wholes Spreads through marrow space

Wide transition zoneImplies an aggressive malignancy

e.g. Round cell lesions or tumors

Lymphoma,Leukemia,Ewings sarcoma, Neuroblastoma,Oteomyelitis


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Permeative pattern: contde.g. Leukemia


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Patterns of bone destruction ( SUMMARY)

Less malignant More malignant

GeographicMoth-eaten Permeative


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B. Periosteal reactionBenign

.None . Solid

Non-ossifying fibroma Chronic Osteomyelitis


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B. Periosteal reaction.contd More Aggressive or Malignant

Lamellated or

onion peel

e.g. Ewings sarcoma


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B. Periosteal reaction.contd Sunburst

e.g. Osteosarcoma


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Codmans trangle

e.g. Osteosarcoma


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B.Periosteal reactioncontd

Less malignant More malignant

Solid onion peelsunburst Codmans traingle


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C.Tumor MatrixOsteoblastic Fluffy, cotton-like or cloudy-like densities

e.g. Osteosarcoma

CartileginousComma-shaped, punctate, annular, popcorn-like

e.g.Enchondroma, chondrosarcoma,chondromyxoid fibroma


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C.Tumor matrix.contd

Cloud-like bone formation in Osteosarcoma (left)

a.Oseoblastic


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C.Tumor matrix.contd Cartileginous (Chondroid matrix )

Enchondroma chondrosarcoma Chondrosarcoma of the rib.


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D.Expansile lesion of boneEnchondroma

Aneurysmal Bone cystFibrous dysplasiaMultiple myeloma

MetastasisBrown tumor


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2. Clues by location of the lesionIn the transverse planeIn the longitudinal planeCharacteristic Locations by tumorsCharacteristic tumors by body sitee.g. Pelvic lesion

Expansive rib lesionLesions of the spine


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2.Clues by locationcontd In the

transverseplane

.

.

.


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2.Clues by locationcontd In the longitudinal planeEpiphyseal

e.g. GCT, ChondroblastomaMetaphyseal

e.g.Osteosarcoma, ChondrosarcomaDiaphyseal

e.g. Round cell lesions, enchondroma


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2.Clues by locationcontd Characteristic locationsby tumors

Simple bone cyst Proximal humerus

Chondroblastoma Epiphyses

Giant Cell tumor Epiphyses

Adamantinoma Tibia

Chordoma Sacrum, clivus

Osteoblastoma Spine, posterior

Adamantinoma, Tibia


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3.Clues by density of the lesionSclerotic cortical lesions

Lytic lesions

Blastic lesions


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3.Clues by density of the lesion..contd Sclerotic cortical lesions

e.g. Osteoid osteoma :a benign bone lesion with a small nidus surroundedby a zone of reactive sclerosis.


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3.Clues by density of the lesion..contd

Lytic lesions

e.g. Fibrous Dysplasia


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3. Clues by density of the lesion..contd Blastic lesions

e.g. lymphoma


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4.Other cluesSoft tissue extensionUsually implies malignancy

More likely to form discrete soft tissue mass

Benign conditions with soft tissueextension

OsteomyelitisUsually infiltration of fat


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4.Other cluescontd Benign

vs.

Malignant


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Clinical cases n explanationCase#1

A 17-year-old male presented with increasing pain in the right

upper arm of approximately 3 months' duration and a recentonset of low-grade fever. On physical examination, there wassome local tenderness and soft tissue swelling over the distaland mid thirds of the right humerus.Shown below is the radiographic finding and histopathology of the lesion.


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Thank You!


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case


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Case #1. Describe both the x-ray finding and the histopathology

2. What are your DDx and most likely diagnosis

3. How common is this lesion in children and what is the c/p

4. The parents asked you to explain to them what it will be like the nextstep in terms of managing the condition and its long term outcome


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Diagnosis: Ewing's Sarcoma (ES)

ES and PNET are " small round blue cell " tumors of children andyoung adults occurring in 80% of cases between the ages of 5 and 20 years

Most common skeletal sites include diaphyses of femur, tibia andhumerus, and also pelvis and ribs ( Askin tumor of the chest). Associated soft tissue mass is a common finding.


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Key facts Most common presentation: ill-defined osteolytic lesion withmultiple small holes in the diaphysis of a long bone in a child

with a large soft tissue mass.Presentation with pain, mass, fever, anemia and leukocytosis .Most common location: femur, iliac bone, fibula, rib, tibia.Differential diagnosis: Osteosarcoma, lymphoma, infection

and EG.Frequently aggressive type of periosteal reaction, but never abenign type.


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Ewing's Sarcoma (ES)contd

The following studies are required to support the diagnosis of ESand PNET :Demonstration of t(11;22) or EWS-FLI-1 fusion transcript (present in both ESand PNET)Immunostains (both ES and PNET are positive for CD99/O13. Inaddition, PNET shows positive staining with neural markers)

EM (ES cells are undifferentiated and show prominent glycogendeposits; PNET shows neural differentiation)


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TreatmentSurgery : Local for control

Chemotherapy Radiation therapy

Prognostic Factors for Ewing Sarcoma PretreatmentTreatment response factors.


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Ewing's Sarcoma (ES)contd PretreatmentSite : distal ext > prox. Ext > centeral/pelvic sitesSize : Cutoffs of either 100 mL or 200 mL are used to define

larger tumors. Large trs- portend bad PxAge :Infants and younger patients (


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Treatment response factors to preoperativetherapy

No or minimal Residual tr after surgery or decreasedPET uptake following CTx Good Px or event free survival

NB. The ff have no Pxc importance Histopathology , Molecular pathology and Pathologic fracture


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Case # 3 An 11-year-old male was seen in consultation for an increasingly painful proximalhumeral lesion associated with a soft tissue mass since the last 3 1/2 months. Hasa h/o trauma while playing football 4 months ago Radiological findings:

Plain radiograph shows an ill-defined destructive tumor in the proximalhumerus(see below)Laboratory results:

On admission, the patient's temperature was 37.5 C. His WBC was 8.5 (4.5 - 9.5) with a normal differential. His electrolytes and liver function tests were normal,

and the alkaline Phosphatase was 1020 (up to 740). The erythrocytesedimentation rate was 52 (up to 15) and the protein C was 0.72 (up to 0.5). Onexamination, his left proximal armand shoulder joint was enlarged and slightly tender. There were no neurovascular or cutaneous abnormalities, except for somedistended superficial veins. The ROM of the extremity was unimpaired.


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Case #3.contd


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Case #3.contd

Q1. What is your diagnosis?1. Osteosarcoma,2. GCT

3. Aggressive osteoblastoma4. MFH

Q2. What is the distinguishing and diagnostic feature of this tumor?

1. Highly pleomorphic mesenchymal cells2. Tumor osteoid3. Characteristic immunophenotype4. Characteristic chromosomal abnormality


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Case #3.contd

Q3. How would you manage this patient?

Q4. Prognosis depends on1.Tumor response to pre-operative chemotherapy 2. Surgical stage3. Skeletal site of involvement

4. All of the above


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Osteosarcoma

The most common primary malignantneoplasm of bone that occurs in children

and young adults Accounts for 60% of malignant bonelesions in the first two decades of life


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StatisticsOn average, 400 cases are diagnosed per year.The overall survival rate for patients diagnosedbetween 1974 and 1994 is 63%.Occurrence is slightly higher in AA than inWhites and higher in males than in females.

The highest occurrence in adolescence is 15 to19 years old.


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Symptoms

Pain and swelling of the affected area arethe most common clinical findings

On rare occasions, fever and night sweatsmay occur,but more so in Ewings sarcomathan osteosarcoma


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Diagnostic Imaging

Radiographicappearance (plain x-ray)of proximal humeral

Osteosarcoma .


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Diagnostic Imaging

MRI appearance (T1-weighted image) of Osteosarcoma of theproximal humerus.Note dramatic tumorextension intoadjacent soft tissueregions


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TreatmentPreoperative and/or postoperativechemotherapy

Resection - A procedure performed forthe specific purpose of removal

Allograft replacement - the process of transplanting tissues and organs


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PrognosisFactors that seem to negatively impact prognosis are:

Site (axial locations fare worse),Larger tumor size,Poor response to chemotherapy andPresence of metastatic disease .

The most consistent and clinically relevant of theseis presence of detectable metastases


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Case #4 A 15-year-old female was seen in consultation for a lesion in the proximal femur.She complained of chronic mild to moderate pain in her right hip and was walking

with a noticeable limp. Physical examination revealed hip deformity and minimallimb length discrepancy.She also c/o of pain in the left lower leg.

Plain film shows a large, elongated, well-defined intramedullary lesion of the proximal femur with "shepherd's crook" deformity (lateral bowing) due to a healed pathologic fracture. Thelesion is partially surrounded by a sclerotic rim and has a complex appearance with lytic areas,multiple foci of " ground glass " density, and radiopaque areas. Curettage specimen consisted of pieces of firm, white-gray, gritty tissue,with a thin, wavyspicules of woven bone (" Chinese characters " )Following is the plain film,histopathology and picture taken of the patient :


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Case #4..contd


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Case #4.contd

Q.1 What is your diagnosis?

1. Enchondroma2. Fibrous dysplasia3. Osteosarcoma, Grade II4. Simple Bone cyst

Q2. What other complications is this patient at risk for ?

Q3. What is the mode of inheritance and the molecular defect of these problem?


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Diagnosis: Fibrous Dysplasia

Fibrous dysplasia is a common benign fibro-osseouslesion , which occurs sporadically during the period of skeletal growth (ages 10 to 25).

It is a hamartoma and is characterized by the intramedullary

location. There are two forms of the disease: monostotic (80% of cases) and polyostotic.


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Fibrous dysplasia contd

Polyostotic involvement may be a part of McCune-

Albright syndrome (fibrous dysplasia, patchy cutaneous pigmentation, and precocious puberty),

Most common locations include the long bones (femur,

tibia and humerus), the ribs, cranio-facial bones and pelvis.

In the long bones, the lesion is found in the metaphysis ordiaphysis.


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Molecular Genetics

McCune Albright syndrome is a rare, sporadically occurring genetic disorder

McCune Albright syndrome is the result of a postzygotic

somatic mutation in the GNAS complex locus. This locus,located on chromosome 20, codes for multiple proteins,one of which is the Gs-alpha, the alpha subunit of theheterotrimeric stimulatory G protein


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Case #5

A bone lesion, in the distal tibial meta-diaphysis of the right leg ,was discovered incidentally in a 13-year-old boy. The lesion was totally asymptomatic. Plain radiograph shows a sharply demarcated, lucent, loculated, meta-diaphyseal lesion surrounded by a rim of scleroticbone (see below).


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Case #5..contd

The parents got worried so much after you showed them the x-ray and wanted you to tellthem what it is and how commonly this thing occurs.They also wanted to know what willbe done next.What would you tell them?Late at night(the same day) they called at your cell phone to hear your opinion.They tellyou that from what they have read on the internet, they think ,what their son has is aGCTwhat would be your response? Would you confirm to them that their suspicion isindeed right ? If not,how would you convince them otherwise ? They also want to hearyour opinion about the chance of his lesion transforming in to a cancer? Please explain


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Diagnosis: Non-Ossifying Fibroma (NOF)

NOF is a common, non-neoplastic, self-healing lesionoccuring in skeletally immature individuals , usually between the ages of 5 and 20 years

Small lesions are usually incidental radiological findings. Thelarger lesions may present with a pathologic fracture.

In most cases, NOF presents as a solitary lesion in themetaphysis or meta-diaphysis of the long bone at theknee (distal femur, proximal tibia or fibula), distal tibia and

proximal humerus


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X-ray characteristics of NOF:*Geographic

* Lytic

* Multilobulated

* Metaphyseal

* Usually intramedullary

* Eccentric

* Well-marginated

* Sclerotic rim


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Management considerations NOF

The following considerations should be keptin mind:

Does the lesion involve more than 50% of the transversediameter of the bone? Prophylactic surgery may beindicated, as the risk of fracture is higher in this

circumstance.

Is the lesion becoming larger and more symptomatic? Amore aggressive therapy may be considered.


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Management considerations NOF

Is the location of the lesion particularly associated withhigh risk for pathologic fracture (eg, femoral neck)?

Localization around the femoral neck is associated withan increased risk of pathologic fracture, producing avascular necrosis of the femoral head. Therefore,stabilization may be indicated.


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Case #6

A 16-year-old boy was seen in consultation for increasing pain inthe mid upper arm. Characteristically, the pain intensified at nightand subsided with aspirin after 20 to 30 minutes. Plain radiographshows the a small, intracortical, radiolucent focus (nidus),surrounded by dense reactive periosteal bone

Histopathologic specimen:


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Case#6


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Case#6 Which of the following is the most likely lesion in this patient?

1) GCT2) Osteosarcoma3) Osteoid Osteoma

4) Enchodroma

Discuss the treatment plan and prognosis


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Osteoid Osteoma is a benign bone lesion with a nidus of lessthan 2 cm surrounded by a zone of reactive bone.

Osteoid osteoma has a distinct clinical picture of dull pain thatis worse at night and disappears within 20 to 30 minutes of treatment with NSAIDs medication.Most frequently (50% of cases), arise in the femur and tibia4 diagnostic features include:(1) a sharp round or oval lesion(2) less than 2 cm in diameter,(3) has a homogeneous dense center(4) a 1-2 mm peripheral radiolucent zone.


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Case#7

14-year-old female presented with a 3 months history of increasing pain in her elbow , proptosis of the left eye and adandruff like scalp lesion. Shown Below is the patients picture and skull radiograph. Also included is the histology of a sample of tissue from the affected site


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Case#7

1) What are your differentials?

2) The parents asked you the prognosis. What wouldbe your response

3) What would be most diagnostic of this patientslesion?


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Diagnosis: Eosinophilic Granuloma (EG)

Eosinophilic granuloma (EG) is the benign form of the 3clinical variants of Langerhans cell histiocytosis

1) Eosinophilic granuloma (localized form of disease at singleskeletal sites)

2) Hand-Schuller-Christian disease (extensive, multifocal,symptomatic disease with predominantly skeletalinvolvement)

3) Letterer-Siwe disease (aggressive systemic form of diseasethat involves multiple organs and systems and leads tofunctional impairment of the affected sites).


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Eosinophilic Granuloma..contd

EG commonly occurs in individuals younger than 30 years and hasthe highest incidence in the first decade of life.

Location .. Any bone can be involved, but the most common sitesinclude the skull, mandible, spine, ribs, and long bones Extraskeletallesions most commonly arise in the lungs and lymph nodes.

Clinical behavior . EG is a benign, self-limited disorder.Progression to systemic disease occurs exclusively in the first twoyears of life. Lesions usually begin to regress after approximately 3months, but they may take as long as 2 years to resolve.

The prognosis is usually excellent, with spontaneous resolution by fibrosis occurring within 1-2 years.


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Eosinophilic Granuloma..contd

The Langerhans cells are pathognomonic and clonal. They arecharacterized by histiocyte-like appearance and indented or grooved nuclei.

Unlike histiocytes, these cells show strong positivity for S-100 andCD1a , and contain Birbeck granules (rod-shaped and tennis racquet-shaped cytoplasmic inclusions), which can be demonstrated by

electron microscopy.

DDx include osteomyelitis, granulomatous inflammation, Hodgkin'sand non-Hodgkin's lymphoma, neuroblastoma

Bone Tumors in Children and Adolescents-f

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