Post on 01-Nov-2020
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Bone Pathology for the Surgical Pathologist
UCSF Current Issues in Pathology 2019
Andrew Horvai MD PhDClinical Professor, PathologyUCSF, San Francisco, CA
DisclosureCompany Relationship typePresage Biosciences Consultant
Outline
• Approach to bone pathology• Decalcification• Osteomyelitis• Avascular necrosis• Infected arthroplasty
Diseases of bone
Trauma76%
Developmental1% Inflammatory
4%
Metabolic17%
Metastatic1%
Primary<1%
Neoplasm
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Clinical
Imaging
Pathology
Approach to bone diagnosis Approach to bone diagnosisClinical
Imaging
Pathology ClinicalImaging
Pathology
FractureOsteoporosis
Metastatic carcinomaMyeloma, lymphoma
Anatomyepiphysis
metaphysis
diaphysis
Physis(growthplate)
cortex
http://classes.midlandstech.edu
medulla
osteon
periosteum
Haversiancanal
trabeculae
Volkmanncanal
Composition – Osteoid: • Collagen (mostly type I) • Other proteins
– Mineral • Carbonated calcium hydroxylapatite• Ca10(PO4)6(OH)2
osteoid
bone
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Decalcification
• Bone = Protein + Carbonated Calcium hydroxylapatite
[Ca10(PO4)6(OH)2]
• Calcium crystals in tissue are hard to cut
• Acid decalcifiers destroy nucleic acids
Product Constituents UCSF useEasy-Cut Formic Acid + HCl Non-neoplastic bone (toes etc.),
cortical bone
Formical2000 Formic Acid + EDTA Bone biopsy, intramedullary bone
tumor
Decal-Stat EDTA + HCl Bone marrow
IED Formic Acid + HCl + exchange
resin
Histology
Immunocal Formic acid Not used at UCSF
EDTA Pure EDTA Not used at UCSF
Sample case
A 16 year old girl with travel to Costa Rica several weeks ago sustained an insect bite on the right leg. This evolved into a presumed septic arthritis which was managed with antibiotics in Costa Rica. She returned to the US with persistent right leg pain and sustained a fracture of the left femur 3 days ago. Imaging revealed a pathologic fracture which was biopsied.
Bone Radiology: Opacity
BLytic Sclerotic
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Radiology: BorderJJ L
CircumscribedMarginated PermeativeJ
Histology: what is “normal”?
lamellar
Evenly spaced cement lines
Remodeling <20% of surface
Marrow: fat and hematopoetic cells only
Blue nuclei in lacunae
Always abnormal: woven bone
• Neoplasms• Osteoblastoma• Osteosarcoma
• Inflammatory• Osteomyelitis
• Metabolic/Developmental• Osteogenesis Imperfecta• Osteopetrosis
WovenLamellarPaget disease
Always abnormal: excess cement lines
• Neoplasms• Low-grade osteosarcoma
• Inflammatory• Paget disease• Necrosis
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Always abnormal: Marrow replacedChondrosarcoma
• Neoplasms• Chondrosarcoma• Metastasis• Hematolymphoid
• Inflammatory• Osteomyelitis
• Metabolic/Developmental• Fibrous dysplasia• Xanthomatosis
HyperparathyroidismAlways abnormal: Excess remodeling
• Inflammatory• Paget disease• Chronic osteomyelitis
• Metabolic/Developmental• Hyperparathyroidism• Renal osteodystrophy
Empty lacunae
Always* abnormal: Empty lacunae
• Inflammatory• Bone infarct• Osteomyelitis
• Trauma• *Normal: interstitial lamellae• *Artifact: over-decalcification
Sample case: biopsyEmpty lacunae
Marrow replaced
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Acute osteomyelitis• Clinical: Wide distribution of age and location, often
no pain, or fever; hematogenous or direct.
• Radiology: Lytic, moth eaten and permeative– Children: does not cross physis (dual vascular supply)
– Infants and adults: can cross physis
• Histology:
1. Neutrophils
2. dead bone (sequestrum) or unequivocal destruction of bone and/or cartilage (scalloping)
– Optional: New, woven bone (involucrum), bacteria, fungi, chronic inflammation
Sequestrum
Involucrum
Acute osteomyelitis: sequestrum Acute osteomyelitisLacunae not empty but destruction of bone and cartilage by neutrophils
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Acute osteomyelitis: involucrum
Acute osteomyelitis
S. aureus
Polymicrobial
Other gram +
Other gram -
Nonbacterial
Chronic osteomyelitis
• Clinical: All ages, painless, often no fever– Progression/reactivation of acute, TB/fungus
– Some variants culture negative (CRMO, CNO, SAPHO)
• Radiology: Lytic -> sclerotic, permeative
• Histology: – Very nonspecific, no gold standard
– Plasma cells predominate
– Sequestrummay persist for months
– Involucrum becomes sclerotic (dense, without medullary spaces)
– Medullary space may be fibrotic, cellular
• DDx: Rosai Dorfman (xanthoma + plasma), myeloma, lymphoma, Langerhans, old bone infarct, nonspecific changes
Chronic osteomyelitis
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Chronic osteomyelitis Chronic osteomyelitis
Chronic osteomyelitis Chronic osteomyelitis
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Empty lacunae
• Osteonecrosis– Osteomyelitis– Trauma– Avascular necrosis (sterile)
• Physiologic: interstitial lamellae• Artifact: excess decalcification
Avascular necrosis
• Clinical: Pain with activity then at rest, any age
– Drugs: Glucocorticoids, alcohol, bisphosphonates (?)
– Systemic: Hyperbarism, sickle cell, Gaucher
– Childhood: Osteochondroses (Legg-Calve-Perthe, Osgood
Schlatter, etc.)
• Radiology:
– Geographic or wedge shaped lucency
– Subchondral collapse
• Histology
– Central: empty lacunae, fat necrosis
– Peripheral: Ingrowth of granulation tissue, creeping
substitution, calcified rim
– Cortex and cartilage usually viable
Bone infarct (avascular necrosis)Bone infarct
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Bone infarct: central Bone infarct
Bone infarct: peripheral Bone infarct: creeping substition
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Bone infarct: peripheral calcification
Empty lacunae
• Osteonecrosis– Acute osteomyelitis– Trauma– Avascular necrosis (sterile)
• Physiologic: interstitial lamellae• Artifact: excess decalcification
Necrosis in interstitial lamellae: not “always” abnormal
Empty lacunae
• Osteonecrosis– Acute osteomyelitis– Trauma– Avascular necrosis (sterile)
• Physiologic: interstitial lamellae• Artifact: excess decalcification
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Do not overdiagnose over-decalcification as osteonecrosis
Decalcification Osteonecrosis
Do not overdiagnose over-decalcification as osteonecrosis
Decalcification Osteonecrosis
Sample case• A 61 year old man with a prior
left hip arthroplasty noted increased pain over 2 months
• Loosening of the hardware is noted clinically and radiographically
• A specimen arrives in the frozen section lab “rule out infection”
Infected arthroplastyEarly Late
Time <3 months > 24 months
Organisms S. AureusE. Coli
Coag – StaphP. Acnes
Route Direct Hematogenous
Clinical Fever↑ WBCPain
LooseningInstabilityPain
• A “delayed” form (3-24 months) has overlapping features between Early and Late.
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Hardware loosening• Aseptic loosening
(85%)– Wear induced particle
debris– Stress shielding
(atrophy)– Hardware failure
• Septic loosening (15%)• Late infection
Immediate replacement
RemovalAntibiotic cement spacer6 weeks IV antibiotics
Septic loosening
• Gold standard: Positive culture from multiple sites
• Intraoperative: Neutrophils in capsule, synovium or granulation tissue
Criterion Sensitivity Specificity
Feldman 5 neutrophils/hpf in > 5 hpf* 25% 98%Athanasou 10 neutrophils / 10 hpf 70% 64%
*hpf: 400X high power field.
Bori G et al. J Bone Joint Surg 2007 89:1232
PMNs in capsule or granulation tissue :YES PMNs in fibrin : NO
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PMNs in vessels : NO Common re-do arthroplasty findingsBarium (black flakes) Foam cells
Common re-do arthroplasty findingsWear debris reaction (polyethylene, Methyl methacrylate, Silastin)
Take home messages• Bone lesions require radiographic and clinical
information for accurate diagnosis• Woven bone, excess cement lines, marrow
replacement, excess turnover and empty lacunae are (almost) always abnormal
• Do not mistake over decalcification for osteonecrosis
• Do not count neutrophils in fibrin for septic loosening