Disclosure UCSF Current Issues in Pathology 2019 Company - PDF document

5/25/19 Disclosure UCSF Current Issues in Pathology 2019 Company Relationship type Presage Biosciences Consultant Bone Pathology for the Surgical Pathologist Andrew Horvai MD PhD Clinical Professor, Pathology UCSF, San Francisco, CA Outline Diseases of bone • Approach to bone pathology Developmental • Decalcification Inflammatory 1% 4% • Osteomyelitis Metabolic • Avascular necrosis 17% Metastatic Trauma • Infected arthroplasty Neoplasm 1% 76% Primary <1% 1

5/25/19 Approach to bone diagnosis Approach to bone diagnosis Pathology Clinical Clinical Imaging Clinical Pathology Pathology Imaging Fracture Metastatic carcinoma Imaging Osteoporosis Myeloma, lymphoma Anatomy Composition osteon – Osteoid: epiphysis Physis (growth • Collagen (mostly type I) plate) metaphysis • Other proteins – Mineral • Carbonated calcium hydroxylapatite periosteum diaphysis trabeculae • Ca 10 (PO 4 ) 6 (OH) 2 Haversian canal bone Volkmann canal osteoid cortex medulla http://classes.midlandstech.edu 2

5/25/19 Decalcification Sample case • Bone = Protein + Carbonated Calcium hydroxylapatite A 16 year old girl with travel to Costa Rica [Ca 10 (PO 4 ) 6 (OH) 2 ] • Calcium crystals in tissue are hard to cut several weeks ago sustained an insect bite on • Acid decalcifiers destroy nucleic acids the right leg. This evolved into a presumed Product Constituents UCSF use septic arthritis which was managed with Easy-Cut Formic Acid + HCl Non-neoplastic bone (toes etc.), cortical bone antibiotics in Costa Rica. She returned to the US Formical2000 Formic Acid + EDTA Bone biopsy, intramedullary bone with persistent right leg pain and sustained a tumor fracture of the left femur 3 days ago. Imaging Decal-Stat EDTA + HCl Bone marrow IED Formic Acid + HCl + exchange Histology revealed a pathologic fracture which was resin biopsied. Immunocal Formic acid Not used at UCSF EDTA Pure EDTA Not used at UCSF Bone Radiology: Opacity Lytic Sclerotic B 3

5/25/19 Histology: what is “normal”? Radiology: Border lamellar J J J L Marginated Circumscribed Permeative Marrow: fat and hematopoetic Remodeling <20% of surface cells only Blue nuclei in lacunae Evenly spaced cement lines Always abnormal: woven bone Always abnormal: excess cement lines Lamellar Woven Paget disease • Neoplasms • Osteoblastoma • Osteosarcoma • Neoplasms • Inflammatory • Osteomyelitis Low-grade osteosarcoma • • Metabolic/Developmental • Inflammatory • Osteogenesis Imperfecta Paget disease • • Osteopetrosis Necrosis • 4

5/25/19 Always abnormal: Excess remodeling Always abnormal: Marrow replaced Hyperparathyroidism Chondrosarcoma • Neoplasms • Inflammatory • Chondrosarcoma • Paget disease • Metastasis • Chronic osteomyelitis • Hematolymphoid • Inflammatory • Metabolic/Developmental • Osteomyelitis • Hyperparathyroidism • Metabolic/Developmental • Renal osteodystrophy • Fibrous dysplasia • Xanthomatosis Always* abnormal: Empty lacunae Sample case: biopsy Empty lacunae Empty lacunae • Inflammatory • Bone infarct Marrow replaced • Osteomyelitis • Trauma • *Normal: interstitial lamellae • *Artifact: over-decalcification 5

5/25/19 Acute osteomyelitis Sequestrum Involucrum • 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 Acute osteomyelitis Acute osteomyelitis: sequestrum Lacunae not empty but destruction of bone and cartilage by neutrophils 6

5/25/19 Acute osteomyelitis: involucrum Acute osteomyelitis Nonbacterial S. aureus Other gram - Other gram + Polymicrobial Chronic osteomyelitis 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 – Sequestrum may 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 7

5/25/19 Chronic osteomyelitis Chronic osteomyelitis Chronic osteomyelitis Chronic osteomyelitis 8

5/25/19 Empty lacunae Avascular necrosis • Clinical: Pain with activity then at rest, any age • Osteonecrosis – Drugs: Glucocorticoids, alcohol, bisphosphonates (?) – Systemic: Hyperbarism, sickle cell, Gaucher – Osteomyelitis – Childhood: Osteochondroses (Legg-Calve-Perthe, Osgood – Trauma Schlatter, etc.) – Avascular necrosis (sterile) • Radiology: • Physiologic: interstitial lamellae – Geographic or wedge shaped lucency – Subchondral collapse • Artifact: excess decalcification • Histology – Central: empty lacunae, fat necrosis – Peripheral: Ingrowth of granulation tissue, creeping substitution, calcified rim – Cortex and cartilage usually viable Bone infarct Bone infarct (avascular necrosis) 9

5/25/19 Bone infarct: central Bone infarct Bone infarct: peripheral Bone infarct: creeping substition 10

5/25/19 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 11

5/25/19 Do not overdiagnose over-decalcification as osteonecrosis Do not overdiagnose over-decalcification as osteonecrosis Decalcification Osteonecrosis Decalcification Osteonecrosis Sample case Infected arthroplasty Early Late • A 61 year old man with a prior left hip arthroplasty noted Time <3 months > 24 months increased pain over 2 months Organisms S. Aureus Coag – Staph E. Coli P. Acnes • Loosening of the hardware is noted clinically and Route Direct Hematogenous radiographically Clinical Fever Loosening • A specimen arrives in the ↑ WBC Instability Pain Pain frozen section lab “rule out infection” • A “delayed” form (3-24 months) has overlapping features between Early and Late. 12

5/25/19 Hardware loosening Septic loosening • Aseptic loosening • Septic loosening • Gold standard: Positive culture from (15%) (85%) multiple sites – Wear induced particle • Late infection • Intraoperative: Neutrophils in capsule, debris synovium or granulation tissue – Stress shielding (atrophy) – Hardware failure Criterion Sensitivity Specificity Feldman 5 neutrophils/hpf in > 5 hpf* 25% 98% Removal Athanasou 10 neutrophils / 10 hpf 70% 64% Antibiotic cement spacer *hpf: 400X high power field. Immediate replacement 6 weeks IV antibiotics Bori G et al. J Bone Joint Surg 2007 89:1232 PMNs in capsule or granulation PMNs in fibrin : NO tissue :YES 13

5/25/19 PMNs in vessels : NO Common re-do arthroplasty findings Barium (black flakes) Foam cells Common re-do arthroplasty findings Take home messages Wear debris reaction (polyethylene, Methyl methacrylate, Silastin) • 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 14