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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