BONE PATHOLOGY

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CHAPTER 7 BONE PATHOLOGY

Bone tumors

Introduction
Osteochondroma
Enchondroma
Chondroblastoma
Chondrosarcoma
Chondromyxoid fibroma
Synovial chondromatosis
Osteoid osteoma
Osteoblastoma
Osteosarcoma
Desmoplastic fibroma of bone
Fibrosarcoma of bone
Benign fibrous histiocytoma of bone
Malignant fibrous histiocytoma of bone
Ewing’s sarcoma (see also PNET)
Giant cell tumor of bone
Chordoma
Adamantinoma
Aneurysmal bone cyst
Simple bone cyst
Fibrous dysplasia of bone
Osteofibrous dysplasia
Langerhans cell disease
Erdheim–chester disease
Chest wall hamartoma of infancy

Non-tumor pediatric osteoarticular disease

Arthritis
Osteomyelitis
Chronic recurrent multifocal osteomyelitis (CRMO)
Osteopetrosis
Myositis ossificans
Ganglion cyst

BONE TUMORS

INTRODUCTION

• In many countries, including the UK, bone tumors are diagnosed and managed by specialist tertiary centers
• In most cases the diagnosis is suspected from clinical and imaging data and hence biopsies and resection specimens will be dealt with by specialist bone tumor centers

image the appropriate handling, blocking and sectioning of such specimens requires specialist equipment and expertise

• Therefore, this section will only briefly cover the main points of entities which may be encountered in a diagnostic pediatric pathology practice and more specialist texts on bone pathology should be consulted
• In general, malignant pediatric bone tumors affect the long bones and include predominantly

image osteosarcomas

– affecting mainly metaphyses of patients in the second decade

image Ewing sarcoma

– affecting mainly diaphyses of similar aged patients

image a range of other pediatric malignancies may metastasize to bone and a bone lesion in a patient under 5 years of age is statistically more likely to be metastatic

• Most bone tumors are not associated with an underlying predisposing factor but a range of associations are reported

image Ollier disease
image Maffuci syndrome
image familial retinoblastoma syndrome
image Rothmund–Thomson syndrome
image multiple osteochondromas
image Paget’s disease of bone
image post-radiation
image other rare entities

• Bone tumors generally present with:

image pain
image swelling
image loss of function
image pathological fracture

• Radiological imaging is essential for adequate interpretation of the histopathological features, in particular:

image the site

– specific bone
– diaphysis vs metaphysis vs epiphysis

image size
image position

– central vs eccentric

image invasiveness and soft tissue involvement
image periosteal reaction
image isolated vs multiple lesions

• In surgical pathology material bone tumors are graded on the basis of cellularity and nuclear features

image see specialist texts for discussion and specific details

OSTEOCHONDROMA

Epidemiology

• First three decades

image common in children

• 15% are multiple
• Malignant transformation in <1%

image increased risk in multiple

Clinical features

• Asymptomatic, painless bony lesion
• Metaphysis of long bones of limbs

Histopathological features (Fig 7.1)

• Pedunculated lesion with cartilage cap and extension of medulla into lesion
• Outer perichondrium
• Underlying cartilage
• Underlying bone
• Endochondral ossification
• No atypia
• Well organized structure
image

Fig 7.1 Photomicrograph of a benign osteochondroma, demonstrating a well-organized structure with a cartilage cap overlying the medullary cavity.

Differential diagnoses and pitfalls

• Myxoid change, atypia, fibrous bands and disorganization may indicate malignant transformation

ENCHONDROMA

Epidemiology

• Common
• Most often present in adults

image children also affected

Clinical features

• Tubular bones

image mainly hands and feet

• Painless swellings
• Pathological fractures

Histopathological features (Fig 7.2)

• Multinodular, intramedullary well-circumscribed cartilage nodules
• Hyaline cartilage matrix
• Bland chondrocytes

image small round nuclei

• May show myxoid change
• No mitoses or atypia
• Normal marrow between nodules
image

Fig 7.2 Photograph of a benign enchondroma in a patient with Maffuci syndrome, demonstrating a nodular lesion composed of mature cartilage.

Differential diagnoses and pitfalls

Periosteal chondroma

• On bone surface

image arises from periosteum

• Long bones

image especially humerus

• Cartilage nodules do not penetrate underlying cortex

Enchondromatosis

• Ollier disease

image multiple enchondromas in childhood

• Maffuci syndrome

image also has vascular lesions of soft tissue

– especially cavernous hemangiomas

• Increased risk of chondrosarcoma

image develops in adulthood

CHONDROBLASTOMA

Epidemiology

• 10–25 years
• M > F

Clinical features

• Mainly long bones epiphyses
• Painful
• Local recurrence 10–20%

Histopathological features (Figs 7.3, 7.4)

• Lesion composed of chondroblasts

image uniform round to ovoid cells
image clear to eosinophilic cytoplasm
image nuclear grooves

– ‘coffee bean’ nuclei

• Scattered osteoclast-like giant cells
• Immature chondroid stroma
• Pericellular ‘chicken wire’ calcification
• Scattered slightly atypical nuclei are normal variant
image

Fig. 7.3

image

Figs 7.3–7.4 Photomicrographs of a chondroblastoma, demonstrating a lesion composed of chondroblasts with areas of immature chondroid stroma and scattered osteoclast-like giant cells.

Differential diagnoses and pitfalls

• Non-progressive lung ‘metastases’ reported in association with benign chondroblastomas

CHONDROSARCOMA

• Malignant mesenchymal tumor with hyaline differentiation

Epidemiology

• Mainly adults

image children reported

Clinical features

• Pelvis, long bones, hands and feet, head and neck (Gadwal et al 2000)
• Swelling, pain

Histopathological features (Figs 7.5–7.6)

• Chondroid matrix
• Lobules of cartilage

image hypercellular
image atypical chondrocytes

– hyperchromatic
– enlarged
– binucleate
– mitoses

image myxoid change
image necrosis

• Grades I–III (grade predicts prognosis)
image

Fig. 7.5

image

Figs 7.5–7.6 Photomicrographs of chondrosarcomas, confirmed on specialist review, demonstrating infiltrating lesions composed of lobules of cartilage with chondroid matrix and atypical chondrocytes.

Periosteal chondrosarcoma

• similar features but in periosteal location

Mesenchymal chondrosarcoma

• Younger age

image usually young adults

• Malignant behavior but long clinical course
• Craniofacial, ribs, vertebrae
• Biphasic pattern

image areas of undifferentiated small round cells

– similar to other SRBCTs

image nodules of hyaline cartilage

Clear cell chondrosarcoma

• Mainly adults

image adolescents also

• Epiphyses of long bones

image mainly humerus and femur

• Lobules of clear cells with distinct membranes
• Focal chondroid differentiation

Immunohistochemical staining

• S100+ in chondroid areas
• SRBCTs of mesenchymal chondrosarcoma are CD99+

Differential diagnoses and pitfalls

• Caution in diagnosing chondrosarcoma in childhood

image rare

• Caution in diagnosing chondrosarcoma in lesions of hands and feet

image in these sites enchondromas may also be hypercellular, binucleate

• Secondary chondrosarcomas develop in benign enchondroma or osteochondroma

image especially Ollier / Maffuci syndromes

• development of increased cellularity and atypia

CHONDROMYXOID FIBROMA

Epidemiology

• Rare
• M > F
• Usually 10–30 years

Clinical features

• Any site

image mainly long bones

• Pain and swelling
• Metaphyseal eccentric lucent lesion
• 15% recurrence

Histopathological features

• Well-demarcated lesions
• Microlobular pattern
• Myxoid stroma
• Stellate and spindle cells

image alternating microscopic cellular and hypocellular areas

• Pleomorphism 20–30%
• Rare mitoses

image not atypical

• With or without cartilage and calcification
• ABC like areas 10%

Immunohistochemical staining

• S100+
• Peripheral cells may be SMA+, CD34+

SYNOVIAL CHONDROMATOSIS

Epidemiology

• Usually adults

image children reported

Clinical features

• Joints

image usually knee

• Pain, swelling, locking, mass

Histopathological features

• Nodules of hyaline cartilage

image variably cellular

• Fibrous outer layer
• With or without synovium and ossification

OSTEOID OSTEOMA

Epidemiology

• Usually children
• M > F

Genetics

• Possible 17q loss

image not in diagnostic use

Clinical features

• Any site

image mainly long bones

• Pain

image especially at night
image relieved by NSAIDS

• Tender
• Swelling
• Well circumscribed cortical lesion

image associated with cortical sclerosis on radiology

Histopathological features

• <2 cm diameter
• Central connective tissue with osteoid

image forming bony trabeculae
image prominent osteoblasts

• Cartilage not usually present
• Hypervascular peripheral sclerotic bone

OSTEOBLASTOMA

Epidemiology

• Usually 10–30 years
• M > F

Clinical features

• Spine and sacrum, limbs and other sites
• Mainly medullary

image rare periosteal
image cementoblastoma in jaw

• Pain
• Swelling
• Local mechanical effects
• Lytic lesion with reactive periosteal shell
• May have ABC-like areas

Histopathological features (Figs 7.7, 7.8)

• >2cm diameter
• Well circumscribed, pushing margin
• Morphologically mimics osteoid osteoma

image randomly arranged central bony trabeculae
image covered by osteoblasts

• Vascular stroma

image ABC-like areas

image

Fig. 7.7

image

Figs 7.7–7.8 Photomicrographs of osteoblastomas, demonstrating randomly arranged bony trabeculae covered by osteoblasts.

Differential diagnoses and pitfalls

• Sample junction with normal bone

image osteoblastomas are not infiltrative

OSTEOSARCOMA

• Malignant mesenchymal tumor producing osteoid

CONVENTIONAL OSTEOSARCOMA

Epidemiology

• All ages

image peak 10–20 years

• M > F

Genetics

• Complex clonal abnormalities

image none yet diagnostic

• Possibly important for prognosis

Clinical features

• Range of sites

image usually metaphysis of long bones

• Pain, mass, tender
• Mechanical features
• Pathological fractures in 5–10%
• Aggressive

image metastases especially to lungs and bones

• 60–80% survival
• Response to preoperative chemotherapy best predictor of outcome

image >90% necrosis = 80–90% survival

• Minority have predisposing syndromes/features

image secondary osteosarcoma

– mainly older patients
– retinoblastoma syndrome
– Li–Fraumeni syndrome
– Paget’s disease of bone
– fibrous dysplasia (McCune–Albright)
– previous radiotherapy

· children with high dose radiotherapy at highest risk (tumors develop in adulthood)

Histopathological features (Fig 7.9)

• Large, variably fleshy destructive bony lesion

image anaplastic, pleomorphic tumor cells
image spindled, epithelioid, clear cell, small round cell variants
image mixed population
image angiocentric pattern of growth

• Stroma

image determines subtype

– osteoid production (amorphous, pale eosinophilic) (osteoblastic)

· highly variable amounts

– bone formation

• High grade atypical fibrous tissue (fibroblastic)
• High grade atypical chondroid (chondroblastic)
image

Fig 7.9 Photomicrograph of an osteosarcoma, demonstrating ovoid to spindled tumor cells with areas of pale osteoid stroma.

Immunohistochemical staining

• Caution in interpretation

image may mimic other tumors

• CD99+

image diffuse cytoplasmic

• Osteopontin / osteonectin+
• May be focally CK+ or SMA+

Special diagnostic investigations

• In osteosarcoma, response to chemotherapy is of vital importance

image the operative specimen must have formal mapping of response and biopsy site

– optimal specimen handling, especially of large primary tumors, should be carried out in specialist centers

Differential diagnoses and pitfalls

• In small biopsies, morphology and immunostaining may mimic other small round cell tumors

image interpretation must be in conjunction with the clinical and radiological findings

TELANGIECTATIC OSTEOSARCOMA

• Pathological fracture more common than classical type
• Destructive, lytic lesion

image usually long bones

• ABC-like on imaging
• ABC-like histology

image cystic, blood-filled spaces
image thin septae

• Foci of atypical osteosarcoma areas at edges

LOW GRADE CENTRAL OSTEOSARCOMA

• Well differentiated intramedullary
• Long bones

image especially femur

• Firm, solid grey white
• Fibroblastic stroma
• Focal osteoid production
• Malignant stroma but

image less cellular
image less pleomorphic

• Bony spicules with intervening spindle cell stroma

PAROSTEAL OSTEOSARCOMA

• Usually young adults
• F > M
• Low grade

image good survival in low grade lesions

• Long bones

image especially femur

• Arising on bone surface
• Well-formed trabeculae
• Hypocellular stroma
• Minimal atypia usually

image 15% are high grade

• 50% show chondroid differentiation

PERIOSTEAL OSTEOSARCOMA

• Long bones diaphysis
• Arises from surface
• Fusiform lesion with perpendicular bony spicules
• Ossified near the cortex with peripheral soft tissue
• Spindle cell lesion peripherally
• Moderately differentiated chondroblastic osteosarcoma

HIGH GRADE SURFACE OSTEOSARCOMA

• Arises from surface
• Erodes cortex
• Areas of high grade cytological atypia

DESMOPLASTIC FIBROMA OF BONE

Epidemiology

• Adolescents and adults

Clinical features

• Any bone

image mainly mandible

• Pain, mass, loss of function
• Firm white, well circumscribed lesion
• Locally aggressive if not excised

Histopathological features

• Spindle cells in variably collagenous stroma
• No atypia
• No or scanty mitoses

FIBROSARCOMA OF BONE

Epidemiology

• Mainly adults

image pediatric cases reported

– including infants

• May be predisposing features

image Paget’s disease
image previous radiation

Clinical features

• Pain, swelling
• Any site, mainly long bones

Histopathological features

• Spindle cells with herringbone or fascicular pattern
• Variably collagenous stroma

image no osteoid or chondroid areas

• Nuclear atypia and mitoses
• Myxoid areas may be present

BENIGN FIBROUS HISTIOCYTOMA OF BONE

Epidemiology

• All ages

image mainly adults

Clinical features

• Any site
• Well-defined lucent medullary defect

Histopathological features

• Sharply demarcated from surrounding bone
• Spindle cells, fibroblasts
• Storiform pattern
• Scattered osteoclast-like giant cells
• No nuclear atypia

image if present ‘atypical fibrous histiocytoma’

• With or without foam cells and lymphocytes

Differential diagnoses and pitfalls

• Histologically similar to non-ossifying fibroma

image needs clinical and radiological features to distinguish

MALIGNANT FIBROUS HISTIOCYTOMA OF BONE

Epidemiology

• Mainly adults

image may occur in adolescents

• Primary or secondary

image Paget’s disease
image radiotherapy

Clinical features

• Mainly long bones

Histopathological features

• Infiltrative margins
• Spindle cell lesion

image atypia
image pleomorphism

• Giant cells
• Variable cellularity
• Focal storiform pattern

Immunohistochemical staining

• Vimentin+
• SMA+ focally

EWING’S SARCOMA (see also PNET)

Epidemiology

• Second most common primary malignant bone tumor of childhood
• Mainly <20 years
• M > F

Genetics

• t(11;22)(q24;q12)

image EWS/FLI1 in majority

• Variants

image EWS/ERG
image EWS/ETV1
image EWS/E1AF

Clinical features

• Diaphysis of long bones, pelvis, ribs

image others rarely

• Poorly defined osteolytic lesion
• Soft tissue extension

Histopathological features (Figs 7.10, 7.11)

• Cellular uniform small round cell tumor
• Round to ovoid cells

image sometimes spindled

• Scanty but variable cytoplasm

image PAS+ glycogen

• Focal rosettes may be present
image

Fig. 7.10

image

Figs 7.10–7.11 Photomicrographs of an intraosseous Ewing sarcoma, demonstrating tumor composed of sheets and nests of uniform small round-ovoid cells.

Immunohistochemical staining

• Uniform strong membranous CD99
• Vimentin+
• Neural markers variable: CD56, NSE
• CK+ in minority

Differential diagnoses and pitfalls

• Note variable morphology and immunophenotype

image other pediatric small round cell tumors may also be CD99+

• ES/PNET may show ‘aberrant’ expression of markers such as CK

GIANT CELL TUMOR OF BONE

Epidemiology

• Usually 20–45

image rare before 10 years

Genetics

• Reduced telomere length
• No diagnostic features

Clinical features

• Usually long bones

image but many sites including pelvis, sacrum and scapula

• Expanding lytic lesion with variable margins
• Local recurrence
• 2% lung metastases
• High grade sarcoma malignant transformation may occur following radiation therapy

Histopathological features

• Sheets of round to ovoid to polygonal cells

image neoplastic component

• May show marked spindle morphology

image even storiform arrangements

• with or without:

image foam cells
image ABC-like areas
image peripheral intravascular plugging

• Admixed numerous osteoclast like multinucleate giant cells

Immunohistochemical staining

• Giant cells demonstrate histiocyte lineage immunophenotype

Differential diagnoses and pitfalls

• May show ABC like areas
• If numerous mitoses and atypia

image giant cell rich sarcoma

CHORDOMA

Epidemiology

• Mainly adults

image rare in children

Clinical features

• Axial spine
• Features depend on site

Histopathological features

• Markedly lobulated

image fibrous septae

• Sheets and cords of cells in prominent myxoid stroma

image abundant pale cytoplasm with vacuolations

– physalipherous cells

image mild–moderate atypia

• With or without:

image chondroid areas
image sarcomatoid / dedifferentiated areas

Immunohistochemical staining

• CK+
• S100+
• EMA+

ADAMANTINOMA

Epidemiology

• All ages

image well reported in children

• Osteofibrous dysplasia-like adamantinoma more common in children

Clinical features

• Long bones

image especially tibia

• Well circumscribed cortical lobulated lesion
• May be multifocal
• Local recurrence
• 10–30% metastases

Histopathological features

Classical

• Epithelial component
• Osteofibrous component
• Intermixed bony trabeculae
• Patterns

image basaloid
image squamoid
image tubular
image spindle cell

• With or without

image foam cells
image myxoid change
image mast cells
image giant cells

Osteofibrous dysplasia like adamantinoma

• Predominant osteofibrous component

image only small scattered epithelial component

Immunohistochemical staining

• Vimentin+
• FGF/R+ stroma
• CK+
• EMA+
• Vimentin+
• EGF/R+ epithelial cells

Differential diagnoses and pitfalls

• Osteofibrous dysplasia-like lesions may have only focal epithelial areas

image require good sampling and specific search

ANEURYSMAL BONE CYST

Epidemiology

• All ages

image mainly adolescents

– median 13 years

Clinical features

• Many sites

image most commonly long bones

• Presents as with other bony lesions

image pain, swelling, pathological fracture

• Benign
• May be primary or secondary to other pathology

Histopathological features

• Well circumscribed lesion

image blood-filled spaces
image connective tissue septa

– fibroblasts
– osteoclast like giant cells

• Reactive bone with osteoblasts
• No atypia
• Solid type

image only septae

– similar to giant cell reparative granuloma

Differential diagnoses and pitfalls

• Secondary changes within another neoplasm may mimic ABC

image including osteosarcoma

SIMPLE BONE CYST

Epidemiology

• Mainly <20 years
• M > F

Clinical features

• Intramedullary unilocular cyst
• Mainly long bones
• Pathological fracture
• 10–20% recurrence

Histopathological features

• Cystic cavity filled with serosanguinous fluid
• Connective tissue lined / septae
• Focal reactive bone
• Hemosiderin laden macrophages
• Fibrin clot
• Giant cells

FIBROUS DYSPLASIA OF BONE

Epidemiology

• Children

Genetics

• Activating GNAS1 mutations (Bianco et al 2000)

image detectable by PCR on paraffin sections
image useful diagnostically in distinguishing from juvenile ossifying fibroma

Clinical features

• Monostotic
• Polyostotic

image associated with McCune–Albright syndrome

– endocrine abnormalities
– skin pigmentation ‘café au lait’ spots

• Association with intramuscular myxoma

image Mazabraud syndrome

• Many sites

image head and neck
image long bones
image ribs

Histopathological features (Figs 7.12–7.14)

• Well circumscribed
• Fibrous and osseous components in variable proportions

image fibrous

– bland spindle cells
– phenotypic features of pre-osteogenic cells
– scattered osteoclast-like cells

image osseous

– irregular curvilinear bony trabecula

· no osteoblastic rimming
· bone due to abnormal osteoblasts (Riminucci et al 1997)

• Three main histological patterns (Riminucci et al 1999)

image Chinese letters

– axial / appendicular

image sclerotic / pagetoid type

– cranial

image sclerotic / hypercellular type

– gnathic

image

Fig. 7.12

image

Fig. 7.13

image

Figs 7.12–7.14 Photomicrographs of cases of fibrous dysplasia of bone, confirmed on molecular testing for GNAS1 mutations, demonstrating variable admixture of fibrous and osseous elements, with irregular bony trabeculae not lined by osteoblasts, and spindle cell stroma, with areas of osteoclast-like giant cells.

Differential diagnoses and pitfalls

• Main differential is juvenile ossifying fibroma

image may be significant diagnostic difficulties even in specialist centers (Ipploito et al 2003)

– analysis of FD-associated GNAS1 mutations is diagnostically useful

OSTEOFIBROUS DYSPLASIA

Epidemiology

• First two decades
• M > F

Clinical features

• Anterior mid-tibia

image rarely radius / ulna

• Painless swelling / bowing of cortex

Histopathological features

• Irregular bony trabeculae

image osteoblastic rimming present

• Bland spindle cell stroma

Differential diagnoses and pitfalls

• OFD-like adamantinoma

image has epithelial component

LANGERHANS CELL DISEASE

Epidemiology

• All ages

image majority present in children

Genetics

• Non-diagnostic

image but infiltrating Langerhans cells are clonal

Clinical features

• Many sites

image especially skull

• Presentation according to site

image unisystem, unifocal
image unisystem, multifocal
image multisystem, multifocal

Histopathological features (Fig 7.15)

• Collections of LCH cells

image ovoid
image grooved / fetiform nuclei
image pale eosinophilic cytoplasm
image minimal atypia

– if atypical consider Langerhans cell sarcoma

• Associated inflammatory cells

image especially eosinophils

image

Fig 7.15 Photomicrograph of a case of Langerhans cell histiocytosis of bone, demonstrating sheets of ovoid LCH cells with numerous admixed eosinophils.

Immunohistochemical staining

• CD1a+
• Langerin+
• S100+
• Classical LCH is fascin, Factor XIIIa, CD68 negative

Special diagnostic investigations

• Electron microscopy shows Birbeck granules

image rarely now required in current practice with immunomarkers

Differential diagnoses and pitfalls

• See cutaneous LCH section for differential with non-Langerhans histocytoses

image not usually an issue with bony disease

• Marrow ‘involvement’ may represent LCH associated hemophagocytic syndrome due to cytokine related macrophage activation

image marrow shows CD68+ macrophages with minimal CD1a+ Langerhans cells

ERDHEIM–CHESTER DISEASE

Epidemiology

• Mainly older adults

image children well reported

Clinical features

• Mainly long bones

image many sites reported

• Visceral involvement in 50%
• Bilateral, symmetric bony sclerosis

Histopathological features

• Diffuse marrow infiltration by foamy macrophages
• Admixed fibrosis, lymphocytes and plasma cells
• Reactive cortical sclerosis

Immunohistochemical staining

• Mac 387+
• CD68+
• CD1a−

CHEST WALL HAMARTOMA OF INFANCY

Epidemiology

• Majority in infants

image may be congenital

• Rare cases in older patients

Clinical features

• Intrathoracic, extrapleural lesion

image arising from ribs

• Expansile mass with rib destruction
• Most posterior and affecting multiple contiguous ribs
• Mass
• May show respiratory distress

Histopathological features

• Intermixed areas of:

image cartilage

– may be immature chondroblastoma like areas
– endochondral ossification

image ABC-like cystic areas in two-thirds (Groom et al 2002)
image fibrous tissue
image osteoclast-like giant cells
image small ovoid cell areas

Differential diagnoses and pitfalls

• If biopsied, usually cartilage and giant cells present

image if only ovoid cell areas exclude chest wall PNET

NON-TUMOR PEDIATRIC OSTEOARTICULAR DISEASE

ARTHRITIS

• Often associated with connective tissue diseases
• Most arthritis in childhood is not investigated by biopsy
• In some cases, atypical infective arthritis and PVNS may be demonstrated
• Other arthritides such as rheumatoid disease show similar features to adult cases

image inflammatory cells

– especially lymphoid aggregates

image synovial hypertrophy

• Neutrophil rich infiltrate suggests:

image infective arthritis
image Behcet’s syndrome
image familial Mediterranean fever

OSTEOMYELITIS

• Usually bacterial infection

image hematogenous or local spread
image >75% Staph aureus

• Rarely biopsied
• Dead bone (sequestrum)
• New bone formation (involucrum)
• Inflammatory infiltration (Figs 7.16–7.17)

image variable mixture of:

– acute inflammatory cells
– plasma cells
– macrophages

image

Fig. 7.16

image

Figs 7.16–7.17 Photomicrographs of cases of acute / subacute osteomyelitis, demonstrating infiltration by numerous acute inflammatory cells.

CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS (CRMO) (Figs 7.18–7.19)

• Older children

image average age 9 years (Job-Deslandre et al 2001)

• Recurrent episodes of pain, swelling, fever and malaise

image usually affects long bones or clavicle

– almost any site can be affected
– usually multifocal

• Most cases are isolated

image may be related to Crohn’s disease in a minority (Girschick et al 2007)

• Genetic linkage with mutations in a susceptibility gene (18q21.3-18q22; Golla et al 2002)
• Mild periosteal / parosteal inflammation

image prominent plasma cells

• Polymorph infiltration is usually not heavy
• No granulomata formation
• Non-specific features

image essentially diagnosis of exclusion

– sterile cultures

image

Fig. 7.18

image

Figs 7.18–7.19 Photomicrographs of a case of chronic recurrent multifocal osteomyelitis (CRMO), demonstrating absence of acute inflammatory cells and numerous plasma cells associated with negative other investigations for infection.

OSTEOPETROSIS (Fig 7.20)

• Group of diseases characterized by lack of osteoclast function

image failure of osteoclasts to resorb immature bone

• May present in adulthood

image ‘malignant’ variants (autosomal recessive) present in infancy and childhood

• Complex genetics

image multiple genes
image autosomal recessive and dominant variants

– autosomal dominant osteopetrosis caused by mutations in the chloride channel 7 (ClCN7) gene (Waguespack et al 2007)

• Leads to abnormal bone marrow cavity formation

image bone marrow failure in ‘malignant’ form
image thickened bony trabeculae with reduced marrow space

– marrow space replaced by osteocartilagenous matrix

• Osteoclasts with absence of ruffled borders on electron microscopy
image

Fig 7.20 Photomicrograph of a case of osteopetrosis, demonstrating thickened bony trabeculae with reduced marrow space, which is partially replaced by osteocartilagenous matrix.

MYOSITIS OSSIFICANS

• Reactive process
• Cellular spindle and stellate cell stroma
• Focal bone and/or cartilage formation
• With maturation zonal phenomenon becomes prominent

image osteoid / bone peripherally
image central stroma

• No cytological atypia

image cf osteosarcoma

GANGLION CYST

• Fibrous tissue wall without synovial lining

image cf bursae / Bakers cysts which have a synovial lining

REFERENCES

Bianco P, Riminucci M, Majolagbe A, et al. Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune–Albright fibrous dysplasia of bone. J Bone Miner Res. 2000;15:120-128.

Gadwal SR, Fanburg-Smith JC, Gannon FH, Thompson LD. Primary chondrosarcoma of the head and neck in pediatric patients: a clinicopathologic study of 14 cases with a review of the literature. Cancer. 2000;88:2181-2188.

Girschick HJ, Zimmer C, Klaus G, Darge K, Dick A, Morbach H. Chronic recurrent multifocal osteomyelitis: what is it and how should it be treated? Nat Clin Pract Rheumatol. 2007;3:733-738.

Golla A, Jansson A, Ramser J, et al. Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility gene located on chromosome 18q21.3-18q22. Eur J Hum Genet. 2002;10:217-221.

Groom KR, Murphey MD, Howard LM, Lonergan GJ, Rosado-De-Christenson ML, Torop AH. Mesenchymal hamartoma of the chest wall: radiologic manifestations with emphasis on cross-sectional imaging and histopathologic comparison. Radiol. 2002;222:205-211.

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