pitfalls in diagnosis of bone lesions · 2019. 8. 6. · pitfalls in diagnosis of bone lesions...
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PITFALLS IN DIAGNOSIS OF BONE LESIONS
Fouad Al Dayel, MD, FRCPA, FRCPathProfessor and Chairman
Department of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre
Riyadh, Saudi Arabia
XXXII International Academy of Pathology Congress14-18 October 2018
Amman, Jordan
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Location and age of patient most important parameters in classifying a primary bone tumor.
Location is determined from plain radiographs.
Location
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Bone TumorsBenign Malignant Other
Birth – 5 yrs Eosinophilic Granuloma Leukemia Osteomyelitis
Unicameral Bone Cyst Metastatic Healing/stress fractureNeuroblastoma
6-18 yrs Unicameral Bone Cyst Ewing’s Sarcoma OsteomyelitisAneurysmal Bone Cyst Osteosarcoma Fibrous Dysplasia
Nonossifying Fibroma Osteofibrous
Eosinophilic Granuloma
Enchondroma
Chondroblastoma
Chondromyxoidfibroma
Osteoblastoma
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Bone TumorsBenign Malignant Other
19-40 yrs Giant Cell Tumor Ewing’s Sarcoma
Eosinophilic granuloma
40 yrs Metastases (lung, breast, prostate, renal, thyroid,colon)
Multiple MyelomaLymphoma
HyperparathyroidismOsteomyelitis
Osteosarcoma Paget’s
Chondrosarcoma
Fibrosarcoma/
Malignant Fibrous
Histiocytoma
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Location
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Multiple vs SolitaryMultiple
metastatic congenital fibrous dysplasia
acquired Paget
Solitary metastatic primary bone tumor,
malignant or benign
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Multiple 50+ y/o
known malignancy? myeloma, get SPEP otherwise, do metastatic work-up
Child to early adult known malignancy? EG? polyostotic fibrous dysplasia? otherwise, do metastatic work-up
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Metastatic carcinoma/sarcomas
Fibrous and fibro-osseous proliferations of bone
Cystic lesions of bone
Non neoplastic osteoid forming lesion (pseudosarcomas)
Conditions that simulate primary bone tumors
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“herald” metastasis:Solitary bone lesion as initial manifestation of internal malignancy.
Metastasis grow faster than primary
Additional metastasis within few weeks
Clinical history is extremely important
Metastasis to Bone
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Metastasis is more common than primary in bone, mainly adenocarcinomas Breast - osteoblastic Prostate- osteoblastic Lung - cytic, small bones of hands Thyroid - latent Kidney - lytic Unknown origin
Metastasis to Bone
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Seminars in Diagnostic Pathology 31 (2014), 53-65
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Small cell neoplasms (adults)- Small cell carcinoma
DD: Ewing sarcomaSmall cell osteosarcomaLymphomaMesenchymal chondrosarcoma
Markers for small cell carcinoma:Keratin +ve, TTF1 +ve, FLI-1(+), CD99 –ve, chromogranin +, synaptophysin +, Ki-67 high
Metastasis to Bone
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Small cell neoplasm (pediatric)- Neuroblastoma younger age group (25 % congenital and 90% by
age of 5 years) neuropil, Homer Wright Rosettes, ganglion cells positive for NSE, PGP 9.5, neurofilament,
chromogranin negative for CD99
Other pediatric tumors with bone metastasis- RMS- Retinoblastoma- Wilm’s tumor
Metastasis to Bone
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Metastasis to BoneUndifferentiated large cell tumor
lung carcinoma kidney carcinoma malignant melanoma
DD: epithelioid sarcoma (keratin +, EMA+, CD34+ [50%]1N11 –ve)
adamantinoma (D2-40 positive) epithelioid hemangioendothelioma epithelioid angiosarcoma (CD31+, CD34+,
FLI-1+, ERG+) Epithelioid leiomyosarcoma chordoma (brachyury+, EM +, CK8+, CK19+,
S100 protein +) epithelioid osteoblastoma
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Clinical History: Five months old referred from outside hospital with right eye swelling and proptosis, irritability and pain.
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There is massive orbital right side tumour with severe and actual completely extra-orbital ocular displacement and distortion with invasion of the globe posterior sclera. Without comparison to the previous examination, the interval post radiation changes are not evaluated.
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H&E
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CTK
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CD34
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Diagnosis
Epithelioid Sarcoma
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Differential DiagnosisGranulomatous Processes Particularly granuloma annulare Lacks infiltrative or invasion growth Lacks coagulative tumor cell necrosis Negative for keratin and EMA Retained nuclear INI1 expression
Squamous Cell Carcinoma Overlying in situ component may be identifiable Prior clinical history may be present Usually more pleomorphic than ES CK5/6(+) and p63(+) Negative for CD34 Retained nuclear INI1 expression
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Differential DiagnosisExtrarenal Rhabdoid Tumor Can show significant morphologic overlap with proximal-
type ES Most common in infants and young children Keratin(+) but less prominent than in ES Consistent loss of nuclear INI1 expression Mutation of SMARCB1 gene
Melanoma Junctional component or prior clinical history may
be present Usually larger, more pleomorphic cells than classic ES S100 protein(+), SOX10(+); variable HMB45(+) or
MART-1(+) Retained nuclear INI1 expression
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Differential DiagnosisEpithelioid Angiosarcoma Can show significant morphologic overlap with proximal-
type ES Foci of vasoformation often present at least focally CD31(+), CD34(+), FLI1(+) May be keratin (+), though usually not diffuse Retained nuclear INI1 expression
Pseudomyogenic (Epithelioid Sarcoma-Like)Hemangioendothelioma Commonly involves multiple tissue planes Predominantly spindled morphology Neutrophilic infiltrate characteristic Keratin (+), CD31(+) Negative for CD34 Retained nuclear INI1 expression
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Differential Diagnosis
Malignant Myoepithelioma(Myoepithelial Carcinoma) Can show significant morphologic overlap with proximal-
type ES Myxoid stroma common Keratin (+), EMA (+), S100 protein (+) Loss of nuclear INI1 expression in subset of cases
Cellular Fibrous Histiocytoma (Dermatofibroma) Can show morphologic overlap with predominantly
spindled forms of ES Negative for keratin Retained nuclear INI1 expression
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Sarcomas with cytokeratin expression True (epithelial differentiation)
- synovial sarcoma (CK7, CK19)- epithelioid sarcoma (CK5, CK6)
Anomalous (no epithelial differentiation)- sarcomas with epithelioid morphology (epithelioid OS, epithelioid leiomysarcoma, epithelioid angiosarcoma, etc.)- small round cell tumors
Ewing’s sarcoma RMSWilms DSRCT
Other sarcomas: e.g. chondrosarcomas
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Metastasis to Bone
Malignant spindle cell and pleomorphic tumors
sarcomatoid renal cell carcinoma sarcomatoid lung carcinoma
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Cystic Lesions of Bone Simulating Neoplasm
Aneurysmal bone cyst Metaphysis of long bones or vertebra (posterior elements) Young, before 3rd decade Solid variant of “ABC” (giant cell reparative granuloma) Secondary ABC
- chondroblastoma- osteosarcoma- osteoblastoma- CMF- GCT
DD: Telangiectatic OSLow grade central OS
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Aneurysmal bone cyst
There is a small lytic lesion at the mid shaft of the right humerus, which shows no interval change in size.
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USP6 Rearrangement
ABC Nodular Fasciitis
MyositisOssificans
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Cystic Lesions of Bone Simulating Neoplasm
Simple Cyst (unicameral bone cyst) First two decades of life
Intramedullary, unilocular
Pathological fracture
Proximal humerus and femur (children) Calcaneus and ilium (adults)
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Simple bone cyst x-ray
There is a lytic lesion seen in proximal right tibia metaphysis eccentric with narrow zone of transition and sclerotic margin not associated with periosteal reaction or soft tissue component, likely benign. Differential diagnosis include chondromyxoid fibroma and non-ossifying fibroma.
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Cystic Lesions of Bone Simulating NeoplasmGiant cell reparative granuloma Jaw bone (mainly mandible) Small bones of hands and feet Can be multiple “cherubism” DD: 1) Giant cell tumor of bone
- epiphyseal involvement- regular distribution of giant cells- mononuclear cell background resembling
the nuclei of giant cells2) Brown tumor of hyperparathyroidism
- diffuse osteopenia of hands and feet on x-ray- abnormal chemistry- identical histology to GCRG
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Seminars in Diagnostic Pathology 31 (2014), 53-65
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Seminars in Diagnostic Pathology 31 (2014), 53-65
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Giant cell reparative granuloma
13 years old boy with swelling of left middle finger
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Giant cell reparative granuloma
There is lytic expansile lesion in the proximal metadiaphyseal region of the proximal phalanx of the left middle finger. The lesion measures 2.6 x 2.2 cm and has thin sclerotic margins with intact cortex. The overlying soft tissues appears slightly swollen by the effect of the tumor. The remainder of the bones appear unremarkable.
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Cystic Lesions of Bone Simulating Neoplasm
Intraosseous ganglion
Hip, tibia, fibulae, carpal bones
Epidemoid cyst
Skull, distal phalanges
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Fibrous and Fibro-esseous Proliferative of the Bone
Fibrous Dysplasia Monostotic
Polyostotic (can be Albright disease)
Craniofacial bones, long bones, pelvis
Risk of malignant transformation
DD: - LGCO (MDM2, CDK4) - solid ABC- desmoplastic fibroma
+ +
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20-year-oldFibrous dysplasia
Two areas of bony prominence, which are projecting outside the skull with intact inner table of skull. In frontal bone just anterior to the coronal suture is about 45 mm long. One is located posteriorly anterior to the lamboid suture and measures 56 mm. Change is most likely due to a benign process with a history of 15-year-old lesion and this most likely fibrous dysplasia.
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Dorfman and Czerniak’s, Bone Tumors, Second Edition
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Case 9SP12‐3292
History:16‐year‐old with history of wrist pain and swelling for nine months.
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SP12-3292
Diagnosis
Desmoplastic fibroma
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Desmoplastic fibroma Resemble fibromatosis 1st three decades of life Long bones, mandible and pelvic bones No catanin expression or mutation
DD: low grade osteosarcoma: +vefor MDM2 and CDK4 fibrous dysplasia: presence of woven bone
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Fibrous and Fibro-esseous Proliferative of the Bone
Corteal osteofibrous dysplasia Affects tibia and fibula Solitary lesion Lucent intracortical mass in diaphysis Isolated stromal positivity for keratin can be
seen ( precursor for adamantinoma) DD: Adamantinoma
- low grade malignant neoplasm- anterior surface of tibia, corticol- presence of basoloid cells, glandular or tubular structure
- positive for keratin- positive for podoplanin (D2-40)
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Dorfman and Czerniak’s, Bone Tumors, Second Edition
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Fibrous and Fibro-esseous Proliferative of the Bone
Metaphyseal fibrous defect (nonossifying fibroma Most patients less than 10 years old
Intracortical, asymptomatic, incidental
DD: Fibrous histiocytoma of bone- diaphyseal- axial skeleton- painful
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Seminars in Diagnostic Pathology 31 (2014), 53-65
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Zoning phenomenon Functional arrangement Maturation cartilages
DD: Perosteal osteosarcomaSoft tissue osteosarcomaSubungual exostosisFlorid reactive periostitisNora disease
Myositis Ossificans
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Dorfman and Czerniak’s, Bone Tumors, Second Edition
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Dorfman and Czerniak’s, Bone Tumors, Second Edition
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Dorfman and Czerniak’s, Bone Tumors, Second Edition
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Usually involves the surface of small bones of hands and feet
Related to subungual exostosis
Nora lesion (Bizarre parosteal osteochondromatous proliferation)
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Thank you