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Giant Cell lesions of Bone
tumour of bone
Presenter: Dr Himachal Mishra
Giant Cell tumour of bone
Contents
1.Basics of giant cell
2.Classification
3.Approach
4.Detail Description of Lesions
5.Summary
6.References
NORMAL ANATOMY
• A giant cell is a cell that is larger in dimension than the cells
that are routinely encountered in histology.
• They are involved in many physiologic and pathological
processes.
• A multinucleated giant cell is formed by the union of several
distinct cells.
GIANT CELL
• In chronic inflammation, if macrophages fail to deal with
particles that has to be removed; fuse together and form
multinucleated giant cells.
• These cells sequester persistent pathogens and prevent
further spread of infection.
• Usually contain 10 to 20 nuclei per cell and are found on
• bone surfaces
• on the endosteal surfaces within the haversian
system
• on the periosteal surface beneath the periosteum
Formation of multinucleated giant cells
Types of Giant cells
REACTIVE BENIGN MALIGNANT
Brown tumor GC Tumor Osteosarcoma
Giant Cell reparative
granuloma
Aneurysmal Bone Cyst Clear cell
chondrosarcoma
Myositis ossificans Chondroblastoma
Tubercular
osteomyelitis
Chondromyxoid Fibroma
Non ossifying Fibroma
Langerhans Cell
Histiocytosis
Benign fibrous
histiocytoma of bone
GCT of tendon sheath
Osteoid Osteoma
Giant cell lesion-Classification
Categorization
APPROACH
Age Group
(Yrs)
Tumors
10-20 Non Ossifying Fibroma, ABC,
Osteosarcoma, SBC
Osteoid osteoma
10-25 Chondroblastoma, Osteoblastoma
15-30 Myossitis Ossificans
20-40 Langhans cell Histiocytosis
Clear cell chondrosarcoma
GCT
>40 Osteosarcoma
Radiological information
Narrow Zone- Slow growth
Wide zone- sign of aggressive growth
Transition zone/margin
Location
.
.
An Approach
Look for stromal cell background
Brown Tumor
Mononuclear Plump cells
Uniformly distributed giant
cells+
Age>25 yrs
Epiphyseal lesion
-Soap bubble appearance
Giant cell Tumor(Benign)
Stromal cells –nuclear
pleomorphism, atypical mitosis
? Malignant Giant cell Tumor
Cells with polygonal nuclei
- Sharp border, nuclear groove
Chondroblastoma
Age<25 yrs
Iregular distribution of giant
cells, Calcifications+ ,S100 +
Site:Jaw PTH Level
Fibroblastic Stromal cells
Areas of Hemorhage,
hemosiderin, fibrosis,
Irregular distribution of
giant cells
Dilated blood filled spaces+
Age<25 yrs
USP & gene rearragement
Vertebra/long bone
Aneursymal Bone cyst
Giant cell rich lesions??
Age-20-40 yrs
Giant cell Granuloma
Reactive Giant cell Lesions
• Intraosseous proliferation characterized by aggregates of
giant cells in a fibrovascular stroma
• Site- Craniofacial, small bones of hands and feet
• Children and young adults
• Radiographic Features
Expansile, purely lytic lesion with cortical thinning
GIANT CELL REPARATIVE
GRANULOMA
GIANT CELL REPARATIVE GRANULOMA
Gross
• Curettage produces fragments
of reddish brown friable tissue
Microscopy
• Irregular distribution of giant
cells
• Spindle cells within
collagenous stroma and
multinucleated giant cells
D/D:
Lesions Differentiating Features
Brown tumor Elevated S. calcium and PTH levels
Giant Cell Tumor Greater numbers of evenly distributed
giant cells without clustering.
Aneursymal Bone
Cyst
In tumors of the hands and feet, presence
of solid foci of stromal & giant cells is
more consistent with giant cell reparative
granuloma
• Self-healing lesion, characterized by heterotopic ossification.
• Age: Adolescents and young adults, after trauma
• Site: Upper extremity flexors, quadriceps, thigh adductors,
gluteal muscles, soft tissues of hand
• Radiologically: zonal ossification pattern with a shell of
calcifications at the periphery of a well demarcated mass
MYOSITIS OSSIFICANS
MYOSITIS OSSIFICANS
well-circumscribed lesion with
peripheral calcification and
central lucency
well-circumscribed lesion
Central- hemorrhagic & surrounding firmer, YG tissue
Peripheral- rim of bone.
zoning phenomenon
gradual evolution in appearance from plump spindle cells through
immature woven bone to mature lamellar bone-
MYOSITIS OSSIFICANS
A
B C
Myositis ossificans
 cytological features:
Osteoblast-like cells
• Proliferating myofibroblasts
• Osteoclast-like multinucleated
giant cells
• Small calcifications
Extraosseous osteosarcoma:
Rare
>40 yrs
Malignant cytology
Atypical mitotic figures
Differential diagnosis
• Bone tumor composed of non neoplastic reactive tissue
that occurs in setting of hyperparathyroidism
• Age: 3rd & 4th decades
• Site- pelvis, ribs, clavicles, and extremities
• Severe Hyperparathyroidism- Increased bone cell activity,
peritrabecular fibrosis & cystic brown tumor-
• Known as Generalised osteitis Fibrosa Cystica
BROWN TUMOR OF
HYPERPARATHYROIDISM
Brown tumor
Gross-
Well-circumscribed, reddish-brown
hemorrhagic mass with lobular architecture
Thins and expands cortex
Radiology
• Expansile,
• Well circumscribed,
• Lytic lesion
Brown tumor
•Lobular pattern
• Groups and clusters of osteoclast-like multinucleated giant cells
•Vascular fibroblastic stroma
•Tunneling resorption of adjacent uninvolved bone
Brown tumor
Dispersed or clustered spindle cells.
variable amounts of osteoclast-like giant cells and haemosiderin-laden macrophages
Lesion Differentiating features
GCT Uniform distribution of giant cells.
Solid ABC USP6 gene rearrangement on FISH
Differential diagnosis
Benign Giant cell Lesions
• A benign but locally aggressive neoplasm composed of
uniformly distributed osteoclast-like giant cells
• Site:
Ends of long bones in the mature skeleton
occasionally –Metaphysis
• Age: 3rd- 5th decade
• Most common in female
GIANT CELL TUMOR
Pathogenesis
• 95% of giant cell tumors- H3-3A (H3F3A) gene mutations
Neoplastic cells are primitive osteoblast precursors
Express high level of RANKL
Proliferation highly destructive bone resorption of osteoclast
GCT
• Radiolucent lesion involving
epiphysis and metaphysis.
• Lesion- well circumscribed, lacks
surrounding reactive bone
• Cut surface- solid or friable
• Variegated red–brown and yellow
appearance
GCT
• Components -stromal & Giant
cells
• Giant cells- evenly dispersed
among mononuclear stromal
cells.
• Mitoses- prominent in stromal
cells
GCT
Abundant material,
A double cell population: mononuclear spindle cells and giant cells of osteoclastic type,
Giant cells are attached to the periphery of the clustered spindle cells.
MALIGNANCY IN GCT
• PRIMARY MALIGNANT GCT-
• Tumor that contains foci of GCT and pleomorphic
sarcoma at first diagnosis
SECONDARY MALIGNANT GCT-
• Initial tumor has appearance of classic GCT
Sarcomatous transformation:
after local recurrence/following RT
Differential diagnosis
Lesions Differentiating features
Giant cell–reparative
granuloma
• Lacks uniform distribution of giant
cells
• Stroma is more fibrotic and more
abundant hemosiderin and hemorrhage
• Stromal cells are spindle shaped rather
than round
Aneurysmal bone cyst • Not typically involve epiphyses
• Giant cells are arranged around cystic
spaces
Giant cells rich
Osteosarcoma
• Delicate strands of osteoid surrounding
aggregates of pleomorphic mononuclear
cells
• Atypical mitotic activity
• Destructive, expansile benign neoplasm of bone
characterized by multiloculated, blood-filled cystic spaces
• Age: 2nd and 3rd decade of life
• SITE-
• Metaphysis of long bones of upper and lower
extremities
• Posterior elements of vertebra
• Small bones of hands and feet
• Craniofacial skeleton
ANEURYSMAL BONE CYST
Pathogenesis
. Translocation, t(16;17)(q22;p13)
cytogenetic rearrangements of the USP6 gene at
chromosome band 17p13.2
Fusion of CDH11 with USP6
Upregulation of USP6 transcription
Regulates expression of metalloprotein
Cystic bone resorption
ABC
• Radiolucent lesion with
thin shell of reactive
periosteal bone.
Aneursymal bone cyst
• Spongy, hemorrhagic mass
• covered by a thin shell of
reactive bone.
ABC
• Large spaces filled with blood,
separated by cellular septa
• Septa- No true endothelial lining.
• Osteoclast-like giant cells- align
along the bloody spaces.
GENETIC TESTING-
• FISH using break-apart probe for USP6 can detect rearrangement
D/D:
Lesion Differentiating Features
GCT • Located in the epiphyses in skeletally mature bones
• Stromal mononuclear cells and numerous evenly spaced
multinucleated giant cells
Solitary bone
cyst
• Fibrous septa -hypocellular, with foci of occasional giant
cells
• Fibrous septa lack inflammatory cells, osteoid & chondroid
tissue
Telangiectatic
OS
• Uncommon in vertebrae, craniofacial bones, hands & feet
• Anaplastic tumor with production of tumor osteoid
• May show complex karyotypic abnormalities
• Age: 10-20 yrs
• Site: Distal femur, proximal tibia
Eccentrically in the metaphysis
• Associated syndrome: Neurofibromatosis type 1,
JaffeCam- Panacci syndrome
• Prognosis: Excellent
NONOSSIFYING FIBROMA
Pathogenesis
• Mutations in KRAS & FGFR1
• Neoplasms driven by
activated MAPK signaling.
66
NONOSSIFYING FIBROMA
• Eccentric, sharply delimited
radiolucent lesions in the
metaphyseal cortex
• Granular and brown or dark red.
NONOSSIFYING FIBROMA
• Cellular masses of fibrous tissue arranged in a storiform pattern.
• Scattered osteoclasts with collections of foamy and hemosiderin-laden
macrophages
D/D-
Lesion Differentiating Features
GCT • Occurs in skeletally mature patients
• Located in the epiphysis
Benign fibrous
histiocytoma
Features of nonossifying fibroma are found in
ribs, vertebrae, or flat bones
BENIGN FIBROUS HISTIOCYTOMA
• Infiltration by Langerhans cell with variable admixture of
eosinophils, giant cells, neutrophils, foamy cells & areas of
fibrosis
• Site
• Skull>femur>pelvis>ribs
• Solitary bone involvement >>Multiple bone
• Multiple organ involvement:
Hand–Schüller– Christian, Letterer-Siwe disease
LANGERHANS CELL
HISTIOCYTOSIS
Pathogenesis
MAPK pathway activation -central role in LCH pathogenesis.
Pluripotent haematopoietic Tissue-restricted Local precursor level
High-risk multisystem Multifocal low-risk Unifocal LCH
Misguided myeloid differentiation
Disrupted cell migration and apoptosis inhibition
Tissue site accumulation
Langerhans Cell Histiocytosis
Well-circumscribed,
Punched out radiolucent lesions
“Hole in a hole”
Sharply circumscribed lesion
greenish brown color
Langerhans Cell Histiocytosis
• Dendritic cells and other inflammatory cells- eosinophils, giant cells, neutrophils,
foamy histiocytes, and accompanied by areas of fibrosis.
• Langerhans cells: Nuclei- lobulated or indented, longitudinal groove
Eosinophilic cytoplasm
Langerhans Cell Histiocytosis
• Dendritic cells and other inflammatory cells seen with areas of fibrosis
Differential diagnosis
lesions Differentiating features
Granulomatous osteomyelitis when a prominent number of
osteoclast-type giant cells are
present
Osseous manifestations of
Rosai-Dorfman disease
Emperipolesis
strongly immunoreactive for S-
100 protein
• Skeletally immature individuals, 10-25 years
• Site: Epiphyseal end of long bones
Distal end of the femur
• Proximal end of the humerus
• Proximal end of the tibia
CHONDROBLASTOMA
Pathogenesis
pLys36Met substitutions in H33B gene on chr 17
Mutation Inhibit H3K36 Mehyltransferases NSD2 and SETD2
Reduced Global H3K36 Mehylation
Block Mesenchymal differentatiation
Tumorogenesis
Chondroblastoma
• Well-defined eccentric lesions
with a thin sclerotic rim
• Soft to rubbery with gritty and
haemorrhagic areas
Chondroblastoma
• Composed of islands of
immature cartilage, mononuclear
chondroblasts & multinucleated
giant cells.
• Chondroblasts
sharply cytoplasmic borders.
Nuclei- vary, round to indented
& lobulated.
• Presence of small zones of
calcification
Chondroblastoma
• Fragments of chondroid matrix,
• Multinucleated osteoclast-like cells,
• Mononuclear, rounded cells with distinct cell borders and rounded nuclei
(chondroblasts).
Differential diagnosis
Lesion Differentiating features
Chondromyxoid
Fibroma
• Usually involves the metaphyses
• Lacks calcifications
• Prominent lobulated myxoid stroma
Giant Cell Tumor • Skeletally mature patients
• Stromal cells with nuclear grooves are absent
• Lacks chondroid matrix & calcification
Clear Cell
Chondrosarcoma
• Usually seen in older patients
• Composed of cells with clear-staining cytoplasm
• Chondrocytic cells with cytologic malignant features
• Heavily calcified than chondroblastoma
Chondroblastic
Osteosarcoma
• Rarely involve epiphyses & mimic chondroblastoma
• Contains tumor osteoid
• Site: Long bones
• Young adults- 2nd to 3rd decade oflife
Pathogenesis
CHONDROMYXOID FIBROMA
Recombination of the GRM1 gene with several 5' partner genes
Upregulated expression of GRM1 coding region---Driver event
High level in chondromyxoid fibroma.
Chondromyxoid fibroma
• Sharply defined
• Pronounced shell of surrounding
reactive bone.
• Located in the medullary portion
of the bone
• Solid and yellowish white or tan.
• Replaces bone
• Thins the cortex
Chondromyxoid fibroma
Chondromyxoid Fibroma
• Distinctly lobular.
• Lobules show paucicellular
myxochondroid matrix
• Matrix separated by intersecting
bands of highly cellular
fibroblast-like spindle cells and
osteoclast
D/D-
Lesions Differenting features
Chondroblast
oma
• Typically involves the epiphyses
• Calcifications - both radiographically &
histologically (chicken-wire appearance)
Medullary
Chondrosarco
ma
• Occur in older patients and in axial skeleton
• Radiographically-poorly circumscribed &
calcifications
• May cause a soft tissue mass
Simple Bone cyst
• Site: Proximal humerus, femur & tibia.
Small bones of hands & feet
• Age- 10-20 yrs
• Intramedullary, unilocular cystic bone lesion lined by a fibrous
membrane and filled with serous or Serosanguineous fluid
Simple Bone cyst
• Location- Metaphysis adjacent to
the growth plate.
• Growth plate grows away from the
lesion resulting in the appearance
that the cyst has migrated.
• Fallen fragment sign
Simple Bone cyst
• Clear or yellow fluid
• Lined by a smooth fibrous
membrane
• Fluid may be hemorrhagic if a
previous fracture has occurred.
Simple Bone cyst
• Cyst is lined by a thin fibrous
membrane.
• Well-vascularized connective
tissue containing hemosiderin
and cholesterol clefts.
• Fibrin deposits within the wall
gets calcified, resemble
cementum-like material
Cytology
Aspiration - colourless to amber fluid
Cellularity: Scant
Cells: histiocytes, chronic inflammatory cells & giant cells
D/D
Lesion Differenting features
Aneurysmal Bone
Cyst
• Hemorrhagic cyst contents contain osteoid and
chondroid tissue with fibromyxoid features & giant
cells
Giant Cell Tumor • Occurs in epiphyses of bones in skeletally mature
patients
• Composed of mononuclear stromal cells and more
giant cells.
Tenosynovial GCT
Age- young and middle aged
Site: hands. Fingers & feet
Localised or Diffuse
Pathogenesis
Reciprocal somatic Chromosomal translocation, t(1;2)p13;q37)
Fusion of type VI collagen a-3 promoter of MCSF gene
Tumor cell over express MCSF
Stimulate proliferation of macrophages similar to GCT
Tenosynovial GCT
GROSS
• Tumors are small circumscribed
Color : brown to yellowish
MICROSCOPY
• Tumors- mononuclear cells,
foamy histiocytes, and
multinucleated giant cells
containing hemosiderin
• Mitoses may be prominent, and
zones of hyalinization seen
Differential Diagnosis
Epithelioid sarcoma- Presence of granuloma-like formations
Necrosis
Invasiveness,
Epithelioid features
keratin immunoreactivity
Osteoid osteoma
Benign bone-forming tumour characterized by small size < 2 cm.
Site-Long bones, small bones of the hands and feet & spine.
Age group- children and adolescents
Pathogenesis:
Rearrangement of FOS gene
Resulting in nuclear immunoreactivity in the osteoblastic cell
Osteoid osteoma
• Radiolucent central nidus
<2 cm
• Nidus is surrounded by
peripheral sclerotic
reaction.
Osteoid osteoma
• Sharply delineated central nidus is
composed of calcified osteoid and
woven bone lined by plump
osteoblasts.
• Highly vascularized connective
tissue, without evidence of
inflammation
Osteoblastoma
Age group- 10–30 yrs
Site: Vertebrae, tibia, femur, humerus, pelvis, ribs
Medulla of metaphysis
Microscopy
• Irregular interlacing network
of osteoid with prominent
osteoblastic rimming
• Osteoid separated by
fibrovascular stroma containing
multinucleated osteoclast-like
giant cells
Differential diagnosis
Osteoid osteoma Osteoblastoma
Size < 2cm >2cm
pain Severe Less pain
Response to aspirin Relieved Not relieved
Central nidus Tiny osteoid islands
lined by osteoblasts
Less organised
osteoid pattern
Sclerotic bone Dense surrounds
nidus
less
Progressive growth No evidence Present
Lesion Features
GCT Epiphyses of long bones,
Rare in vertebra (Arch not involved)
ABC Reactive osteoid- small foci
MALIGNANT
GC LESIONS
• Age groups: bimodal
• Male>female
OSTEOSARCOMA
Site: Metaphyseal region of the long bones:-
• Lower end of femur
• Upper end of tibia
• Upper end of humerus
Several subtypes
• Site of origin (intramedullary, intracortical, or surface)
• Histologic grade (low, high)
• Primary (underlying bone is unremarkable) or
secondary: Paget disease, bone infarcts, radiation
• Subtype in the metaphysis of long bones:
primary, intramedullary, osteoblastic, and high grade
Pathogenesis
Syndromes- Li-Fraumeni syndrome, hereditary retinoblastoma
Genetics
Gains of chromosome arms 6p, 8q and 17p-50%
Mutated genes in TP53 and RB1 > 90%
• Inactivating mutations of TP53
Inability to mediate cell-cycle arrest, apoptosis, and cellular senescence
Errors in mitotic chromosome segregation
Affects chromosomal regions
• Chromothripsis and amplification
Result in the generation of cancer driver events- CDK4hz amplification
Osteosarcoma
Codman triangle or a
sunburst appearance
Often large (>5 cm),
fleshy or hard tumor,
centered within the metaphysis
Depending on predominant stromal component:
(1) Gray-tan & granular: osteoblastic
(2) Translucent bluish: chondroblastic
(3) Firm off-white mass: Fibroblastic
GROSS
Osteosarcoma
• Immature bone or osteoid by neoplastic cells
• Histological subtype of conventional osteosarcoma:
Osteoblastic,Chondroblastic ,fibroblastic- Common
• Less common-Giant cell rich, clear cell & Chondroblastoma
like
• Microscopic variants: Telangiectatic, small cell, low grade
central & Parosteal osteosarcoma
Osteosarcoma
Microscopic Features
• Defined as-Direct production of immature bone or osteoid by
neoplastic cells
• Conventional osteosarcomas- composed of a mixture of
osteoblastic, fibroblastic & chondroblastic foci.
• Telangiectatic osteosarcoma.- numerous blood-filled spaces
separated by septa containing highly pleomorphic mononuclear
and multinucleated giant cells accompanied by abundant mitotic
activity.
• Small cell osteosarcoma- composed of small, uniform, round or
spindled cells
• Low-grade central osteosarcoma- a fibroblastic osteosarcoma
with minimal cytologic atypia and minimal mitotic activity.
• Parosteal osteosarcoma -composed of bland fibrous stroma
containing disorganized, immature bone.
• Periosteal osteosarcomas are largely chondroblastic in
appearance
Osteosarcoma
CYTOLOGY-
• Variable cellularity
• Tumour cells-pleomorphic spindle, rounded, ovoid,
polygonal and often large, osteoblast like
• Multinucleated tumour giant cells.
• Strands of osteoid matrix between tumour cells in
clusters.
• Benign osteoclast-like giant cells are numerous in
giant-cell-rich osteosarcoma.
Osteosarcoma
Tumor cells are singly or small groups in a myxoid background matrix
IHC
Strong positive cytoplasmic staining
for ALP
Expression of osteonectin
D/D-
Lesions Differentiating features
Dedifferentiated
chondrosarcoma
• Low grade chondrosarcoma
• IDH1 Mutation
Fibro sarcoma • No production of tumor osteoid
Osteoblastoma • Lacks atypical mitoses
• Infiltrative pattern
• Destructive growth pattern
CHONDROSARCOMA
• Malignant tumor of chondroid differentiation
• Divided into 2 major categories on the basis of
microscopic criteria:-
Conventional chondrosarcoma
Chondrosarcoma variant-
 Clear cell chondrosarcoma
 Myxoid chondrosarcoma
 Dedifferentiated chondrosarcoma
 Mesenchymal chondrosarcoma
CENTRAL
CHONDROSARCOMA
PERIPHERAL
CHONDROSARCOMA
Location Medullary cavity of flat or
long bones
De novo or from cartilaginous
cap of a pre existing
osteochondroma
Radiogra
phy
Osteolytic lesion with
splotchy calcification
Ill defined margins Fusiform
thickening of the shaft
Perforation of the cortex
Large tumors with a Calcified centre
surrounded by a lesser denser
periphery with splotchy calcification
CONVENTIONAL
CLEAR CELL CHONDROSARCOMA
• A low-grade, cartilage-producing cells with
characteristic large, clear cytoplasm
• Younger patients
• SITE- Epiphysis of proximal femur, proximal
humerus, and distal femur
Pathogenesis
Loss or structural aberrations of chr 9 & gain of chr 20
CDKN2A alterations
Lacked expression of p16 (CDKN2A)
Clear cell chondrosarcoma
Diagnostic sign:
Ill-defined margins
Fusiform expansile remodeling of bone with endosteal scalloping
cortical destruction with a soft tissue mass
Clear cell chondrosarcoma
• Large cells with a clear or
vacuolated abundant cytoplasm
and a central or paracentral
nucleus.
• Myxoid background matrix
Gross-
• Large bulky tumors
• Pale blue matrix, softer than normal
hyaline cartilage
• Abundant gritty calcifications
• Larger tumors: destructive with
extensive soft tissue
Clear cell chondrosarcoma
• Tumor cells with an abundant
clear or ground glass cytoplasm.
• Sharply defined borders.
• Interspersed small trabeculae of
woven bone, numerous
multinucleated giant cells & foci
of cartilage
ELECTRON MICROSCOPY
•Ultrastructurally, neoplastic cells contain abundant
intracytoplasmic glycogen
GENETICS
• Lacks IDH1 and IDH2 mutations
D/D-
Lesions Differentiating feature
Chondroblastoma • Lacks prominent clear cells and bony trabeculae
Osteoblastoma • Lacks chondroid differentiation
Aneurysmal Bone
Cyst
• Clear cells and cartilaginous differentiation are absent
Intramedullary
Chondrosarcoma
• Multinucleated giant cells and reactive bony
trabeculae are absent
Summary
• Giant cell lesions are a group of diverse entities.
• These lesions are morphologically related due to
presence of multinucleated osteoclast like giant cells.
• For making a diagnosis, apart from from clinical and
histopathological, radiological data is equally
important.
• In ambiguous cases- diagnosis can be done by
additional studies like- IHC, FISH & sequencing.
REFERENCES
1. Unni K.K., Mertens F. (Eds.): World Health Organization Classification of
Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. 2020;5
:370-434.
2. Rosai, Juan, and Lauren Vedder Ackerman. Rosai And Ackerman's Surgical
Pathology.2018;11:1722-1764.
3. Fletcher C, Carrie Y. Inwards, AndrĂŠ M. Oliveira. Diagnostic
histopathology of tumors. 2013: 1884-1890)
4. Field, Andrew S, and Svante R Orell. Orell & Sterrett's Fine Needle
Aspiration Cytology. 2015.;5: 412-427)
5. Kumar v,Abbas KA,Aster C J. Robbins and cotran pathological basis of disease.
2020; 10: 1171-1199.
6. Video Lecture by Dr Shantveer G Uppin on giant cell lesion of bone
7. Matcuk GR Jr, Chopra S, Menendez LR. Solid aneurysmal bone cyst of the
humerus mimics metastasis or brown tumor. Clin Imaging. 2018 Nov-
Dec;52:117-122. doi: 10.1016/j.clinimag.2018.07.020. Epub 2018 Jul 24. PMID:
30056289
8. Patricia J. Brooks, Glogauer M, McCulloch CA. An Overview of the Derivation
and Function of Multinucleated Giant Cells and Their Role in Pathologic
Processes. The American Journal of Pathology, 2019; 189(6): 1145-115
THANK YOU
• Route- hematogenous
• More common than primary bone tumors
• Primary sites: lung, breast, prostate, kidney & thyroid
• Involved bones: skull, spine, ribs, pelvis, humerus & femur
• Prostatic adenocarcinoma- Blastic
• Kidney,lung,GIT &malignant melanoma- Lytic
METASTATIC TUMORS
Metastatic tumors
Histopathology
• Morphology: resembles primary lesion
• Osteoblastic metastasis shows abundant reactive woven bone
• Secondary changes: hemorrhage, fibrosis & osteoclast-type giant
cell reaction
Gross Finding
• Haemorrhagic and friable tissue -thyroid or kidney.
• Hard due to reactive bone sclerosis - Prostate and breast
• Dark, pigmented - Melanoma.

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Giant cell lesion.pptx

  • 1. Giant Cell lesions of Bone tumour of bone Presenter: Dr Himachal Mishra Giant Cell tumour of bone
  • 2. Contents 1.Basics of giant cell 2.Classification 3.Approach 4.Detail Description of Lesions 5.Summary 6.References
  • 4. • A giant cell is a cell that is larger in dimension than the cells that are routinely encountered in histology. • They are involved in many physiologic and pathological processes. • A multinucleated giant cell is formed by the union of several distinct cells. GIANT CELL
  • 5. • In chronic inflammation, if macrophages fail to deal with particles that has to be removed; fuse together and form multinucleated giant cells. • These cells sequester persistent pathogens and prevent further spread of infection. • Usually contain 10 to 20 nuclei per cell and are found on • bone surfaces • on the endosteal surfaces within the haversian system • on the periosteal surface beneath the periosteum
  • 8. REACTIVE BENIGN MALIGNANT Brown tumor GC Tumor Osteosarcoma Giant Cell reparative granuloma Aneurysmal Bone Cyst Clear cell chondrosarcoma Myositis ossificans Chondroblastoma Tubercular osteomyelitis Chondromyxoid Fibroma Non ossifying Fibroma Langerhans Cell Histiocytosis Benign fibrous histiocytoma of bone GCT of tendon sheath Osteoid Osteoma Giant cell lesion-Classification
  • 10.
  • 12. Age Group (Yrs) Tumors 10-20 Non Ossifying Fibroma, ABC, Osteosarcoma, SBC Osteoid osteoma 10-25 Chondroblastoma, Osteoblastoma 15-30 Myossitis Ossificans 20-40 Langhans cell Histiocytosis Clear cell chondrosarcoma GCT >40 Osteosarcoma
  • 14. Narrow Zone- Slow growth Wide zone- sign of aggressive growth Transition zone/margin
  • 16. An Approach Look for stromal cell background Brown Tumor Mononuclear Plump cells Uniformly distributed giant cells+ Age>25 yrs Epiphyseal lesion -Soap bubble appearance Giant cell Tumor(Benign) Stromal cells –nuclear pleomorphism, atypical mitosis ? Malignant Giant cell Tumor Cells with polygonal nuclei - Sharp border, nuclear groove Chondroblastoma Age<25 yrs Iregular distribution of giant cells, Calcifications+ ,S100 + Site:Jaw PTH Level Fibroblastic Stromal cells Areas of Hemorhage, hemosiderin, fibrosis, Irregular distribution of giant cells Dilated blood filled spaces+ Age<25 yrs USP & gene rearragement Vertebra/long bone Aneursymal Bone cyst Giant cell rich lesions?? Age-20-40 yrs Giant cell Granuloma
  • 18. • Intraosseous proliferation characterized by aggregates of giant cells in a fibrovascular stroma • Site- Craniofacial, small bones of hands and feet • Children and young adults • Radiographic Features Expansile, purely lytic lesion with cortical thinning GIANT CELL REPARATIVE GRANULOMA
  • 19. GIANT CELL REPARATIVE GRANULOMA Gross • Curettage produces fragments of reddish brown friable tissue Microscopy • Irregular distribution of giant cells • Spindle cells within collagenous stroma and multinucleated giant cells
  • 20. D/D: Lesions Differentiating Features Brown tumor Elevated S. calcium and PTH levels Giant Cell Tumor Greater numbers of evenly distributed giant cells without clustering. Aneursymal Bone Cyst In tumors of the hands and feet, presence of solid foci of stromal & giant cells is more consistent with giant cell reparative granuloma
  • 21. • Self-healing lesion, characterized by heterotopic ossification. • Age: Adolescents and young adults, after trauma • Site: Upper extremity flexors, quadriceps, thigh adductors, gluteal muscles, soft tissues of hand • Radiologically: zonal ossification pattern with a shell of calcifications at the periphery of a well demarcated mass MYOSITIS OSSIFICANS
  • 22. MYOSITIS OSSIFICANS well-circumscribed lesion with peripheral calcification and central lucency well-circumscribed lesion Central- hemorrhagic & surrounding firmer, YG tissue Peripheral- rim of bone.
  • 23. zoning phenomenon gradual evolution in appearance from plump spindle cells through immature woven bone to mature lamellar bone- MYOSITIS OSSIFICANS
  • 24. A B C Myositis ossificans  cytological features: Osteoblast-like cells • Proliferating myofibroblasts • Osteoclast-like multinucleated giant cells • Small calcifications
  • 25. Extraosseous osteosarcoma: Rare >40 yrs Malignant cytology Atypical mitotic figures Differential diagnosis
  • 26. • Bone tumor composed of non neoplastic reactive tissue that occurs in setting of hyperparathyroidism • Age: 3rd & 4th decades • Site- pelvis, ribs, clavicles, and extremities • Severe Hyperparathyroidism- Increased bone cell activity, peritrabecular fibrosis & cystic brown tumor- • Known as Generalised osteitis Fibrosa Cystica BROWN TUMOR OF HYPERPARATHYROIDISM
  • 27. Brown tumor Gross- Well-circumscribed, reddish-brown hemorrhagic mass with lobular architecture Thins and expands cortex Radiology • Expansile, • Well circumscribed, • Lytic lesion
  • 28. Brown tumor •Lobular pattern • Groups and clusters of osteoclast-like multinucleated giant cells •Vascular fibroblastic stroma •Tunneling resorption of adjacent uninvolved bone
  • 29. Brown tumor Dispersed or clustered spindle cells. variable amounts of osteoclast-like giant cells and haemosiderin-laden macrophages
  • 30. Lesion Differentiating features GCT Uniform distribution of giant cells. Solid ABC USP6 gene rearrangement on FISH Differential diagnosis
  • 31. Benign Giant cell Lesions
  • 32. • A benign but locally aggressive neoplasm composed of uniformly distributed osteoclast-like giant cells • Site: Ends of long bones in the mature skeleton occasionally –Metaphysis • Age: 3rd- 5th decade • Most common in female GIANT CELL TUMOR
  • 33. Pathogenesis • 95% of giant cell tumors- H3-3A (H3F3A) gene mutations Neoplastic cells are primitive osteoblast precursors Express high level of RANKL Proliferation highly destructive bone resorption of osteoclast
  • 34. GCT • Radiolucent lesion involving epiphysis and metaphysis. • Lesion- well circumscribed, lacks surrounding reactive bone • Cut surface- solid or friable • Variegated red–brown and yellow appearance
  • 35. GCT • Components -stromal & Giant cells • Giant cells- evenly dispersed among mononuclear stromal cells. • Mitoses- prominent in stromal cells
  • 36. GCT Abundant material, A double cell population: mononuclear spindle cells and giant cells of osteoclastic type, Giant cells are attached to the periphery of the clustered spindle cells.
  • 37. MALIGNANCY IN GCT • PRIMARY MALIGNANT GCT- • Tumor that contains foci of GCT and pleomorphic sarcoma at first diagnosis SECONDARY MALIGNANT GCT- • Initial tumor has appearance of classic GCT Sarcomatous transformation: after local recurrence/following RT
  • 38. Differential diagnosis Lesions Differentiating features Giant cell–reparative granuloma • Lacks uniform distribution of giant cells • Stroma is more fibrotic and more abundant hemosiderin and hemorrhage • Stromal cells are spindle shaped rather than round Aneurysmal bone cyst • Not typically involve epiphyses • Giant cells are arranged around cystic spaces Giant cells rich Osteosarcoma • Delicate strands of osteoid surrounding aggregates of pleomorphic mononuclear cells • Atypical mitotic activity
  • 39. • Destructive, expansile benign neoplasm of bone characterized by multiloculated, blood-filled cystic spaces • Age: 2nd and 3rd decade of life • SITE- • Metaphysis of long bones of upper and lower extremities • Posterior elements of vertebra • Small bones of hands and feet • Craniofacial skeleton ANEURYSMAL BONE CYST
  • 40. Pathogenesis . Translocation, t(16;17)(q22;p13) cytogenetic rearrangements of the USP6 gene at chromosome band 17p13.2 Fusion of CDH11 with USP6 Upregulation of USP6 transcription Regulates expression of metalloprotein Cystic bone resorption
  • 41. ABC • Radiolucent lesion with thin shell of reactive periosteal bone.
  • 42. Aneursymal bone cyst • Spongy, hemorrhagic mass • covered by a thin shell of reactive bone.
  • 43. ABC • Large spaces filled with blood, separated by cellular septa • Septa- No true endothelial lining. • Osteoclast-like giant cells- align along the bloody spaces.
  • 44. GENETIC TESTING- • FISH using break-apart probe for USP6 can detect rearrangement D/D: Lesion Differentiating Features GCT • Located in the epiphyses in skeletally mature bones • Stromal mononuclear cells and numerous evenly spaced multinucleated giant cells Solitary bone cyst • Fibrous septa -hypocellular, with foci of occasional giant cells • Fibrous septa lack inflammatory cells, osteoid & chondroid tissue Telangiectatic OS • Uncommon in vertebrae, craniofacial bones, hands & feet • Anaplastic tumor with production of tumor osteoid • May show complex karyotypic abnormalities
  • 45. • Age: 10-20 yrs • Site: Distal femur, proximal tibia Eccentrically in the metaphysis • Associated syndrome: Neurofibromatosis type 1, JaffeCam- Panacci syndrome • Prognosis: Excellent NONOSSIFYING FIBROMA
  • 46. Pathogenesis • Mutations in KRAS & FGFR1 • Neoplasms driven by activated MAPK signaling.
  • 47. 66 NONOSSIFYING FIBROMA • Eccentric, sharply delimited radiolucent lesions in the metaphyseal cortex • Granular and brown or dark red.
  • 48. NONOSSIFYING FIBROMA • Cellular masses of fibrous tissue arranged in a storiform pattern. • Scattered osteoclasts with collections of foamy and hemosiderin-laden macrophages
  • 49. D/D- Lesion Differentiating Features GCT • Occurs in skeletally mature patients • Located in the epiphysis Benign fibrous histiocytoma Features of nonossifying fibroma are found in ribs, vertebrae, or flat bones
  • 51. • Infiltration by Langerhans cell with variable admixture of eosinophils, giant cells, neutrophils, foamy cells & areas of fibrosis • Site • Skull>femur>pelvis>ribs • Solitary bone involvement >>Multiple bone • Multiple organ involvement: Hand–SchĂźller– Christian, Letterer-Siwe disease LANGERHANS CELL HISTIOCYTOSIS
  • 52. Pathogenesis MAPK pathway activation -central role in LCH pathogenesis. Pluripotent haematopoietic Tissue-restricted Local precursor level High-risk multisystem Multifocal low-risk Unifocal LCH Misguided myeloid differentiation Disrupted cell migration and apoptosis inhibition Tissue site accumulation
  • 53. Langerhans Cell Histiocytosis Well-circumscribed, Punched out radiolucent lesions “Hole in a hole” Sharply circumscribed lesion greenish brown color
  • 54. Langerhans Cell Histiocytosis • Dendritic cells and other inflammatory cells- eosinophils, giant cells, neutrophils, foamy histiocytes, and accompanied by areas of fibrosis. • Langerhans cells: Nuclei- lobulated or indented, longitudinal groove Eosinophilic cytoplasm
  • 55. Langerhans Cell Histiocytosis • Dendritic cells and other inflammatory cells seen with areas of fibrosis
  • 56. Differential diagnosis lesions Differentiating features Granulomatous osteomyelitis when a prominent number of osteoclast-type giant cells are present Osseous manifestations of Rosai-Dorfman disease Emperipolesis strongly immunoreactive for S- 100 protein
  • 57. • Skeletally immature individuals, 10-25 years • Site: Epiphyseal end of long bones Distal end of the femur • Proximal end of the humerus • Proximal end of the tibia CHONDROBLASTOMA
  • 58. Pathogenesis pLys36Met substitutions in H33B gene on chr 17 Mutation Inhibit H3K36 Mehyltransferases NSD2 and SETD2 Reduced Global H3K36 Mehylation Block Mesenchymal differentatiation Tumorogenesis
  • 59. Chondroblastoma • Well-defined eccentric lesions with a thin sclerotic rim • Soft to rubbery with gritty and haemorrhagic areas
  • 60. Chondroblastoma • Composed of islands of immature cartilage, mononuclear chondroblasts & multinucleated giant cells. • Chondroblasts sharply cytoplasmic borders. Nuclei- vary, round to indented & lobulated. • Presence of small zones of calcification
  • 61. Chondroblastoma • Fragments of chondroid matrix, • Multinucleated osteoclast-like cells, • Mononuclear, rounded cells with distinct cell borders and rounded nuclei (chondroblasts).
  • 62. Differential diagnosis Lesion Differentiating features Chondromyxoid Fibroma • Usually involves the metaphyses • Lacks calcifications • Prominent lobulated myxoid stroma Giant Cell Tumor • Skeletally mature patients • Stromal cells with nuclear grooves are absent • Lacks chondroid matrix & calcification Clear Cell Chondrosarcoma • Usually seen in older patients • Composed of cells with clear-staining cytoplasm • Chondrocytic cells with cytologic malignant features • Heavily calcified than chondroblastoma Chondroblastic Osteosarcoma • Rarely involve epiphyses & mimic chondroblastoma • Contains tumor osteoid
  • 63. • Site: Long bones • Young adults- 2nd to 3rd decade oflife Pathogenesis CHONDROMYXOID FIBROMA Recombination of the GRM1 gene with several 5' partner genes Upregulated expression of GRM1 coding region---Driver event High level in chondromyxoid fibroma.
  • 64. Chondromyxoid fibroma • Sharply defined • Pronounced shell of surrounding reactive bone. • Located in the medullary portion of the bone
  • 65. • Solid and yellowish white or tan. • Replaces bone • Thins the cortex Chondromyxoid fibroma
  • 66. Chondromyxoid Fibroma • Distinctly lobular. • Lobules show paucicellular myxochondroid matrix • Matrix separated by intersecting bands of highly cellular fibroblast-like spindle cells and osteoclast
  • 67. D/D- Lesions Differenting features Chondroblast oma • Typically involves the epiphyses • Calcifications - both radiographically & histologically (chicken-wire appearance) Medullary Chondrosarco ma • Occur in older patients and in axial skeleton • Radiographically-poorly circumscribed & calcifications • May cause a soft tissue mass
  • 68. Simple Bone cyst • Site: Proximal humerus, femur & tibia. Small bones of hands & feet • Age- 10-20 yrs • Intramedullary, unilocular cystic bone lesion lined by a fibrous membrane and filled with serous or Serosanguineous fluid
  • 69. Simple Bone cyst • Location- Metaphysis adjacent to the growth plate. • Growth plate grows away from the lesion resulting in the appearance that the cyst has migrated. • Fallen fragment sign
  • 70. Simple Bone cyst • Clear or yellow fluid • Lined by a smooth fibrous membrane • Fluid may be hemorrhagic if a previous fracture has occurred.
  • 71. Simple Bone cyst • Cyst is lined by a thin fibrous membrane. • Well-vascularized connective tissue containing hemosiderin and cholesterol clefts. • Fibrin deposits within the wall gets calcified, resemble cementum-like material
  • 72. Cytology Aspiration - colourless to amber fluid Cellularity: Scant Cells: histiocytes, chronic inflammatory cells & giant cells D/D Lesion Differenting features Aneurysmal Bone Cyst • Hemorrhagic cyst contents contain osteoid and chondroid tissue with fibromyxoid features & giant cells Giant Cell Tumor • Occurs in epiphyses of bones in skeletally mature patients • Composed of mononuclear stromal cells and more giant cells.
  • 73. Tenosynovial GCT Age- young and middle aged Site: hands. Fingers & feet Localised or Diffuse Pathogenesis Reciprocal somatic Chromosomal translocation, t(1;2)p13;q37) Fusion of type VI collagen a-3 promoter of MCSF gene Tumor cell over express MCSF Stimulate proliferation of macrophages similar to GCT
  • 74. Tenosynovial GCT GROSS • Tumors are small circumscribed Color : brown to yellowish MICROSCOPY • Tumors- mononuclear cells, foamy histiocytes, and multinucleated giant cells containing hemosiderin • Mitoses may be prominent, and zones of hyalinization seen
  • 75. Differential Diagnosis Epithelioid sarcoma- Presence of granuloma-like formations Necrosis Invasiveness, Epithelioid features keratin immunoreactivity
  • 76. Osteoid osteoma Benign bone-forming tumour characterized by small size < 2 cm. Site-Long bones, small bones of the hands and feet & spine. Age group- children and adolescents Pathogenesis: Rearrangement of FOS gene Resulting in nuclear immunoreactivity in the osteoblastic cell
  • 77. Osteoid osteoma • Radiolucent central nidus <2 cm • Nidus is surrounded by peripheral sclerotic reaction.
  • 78. Osteoid osteoma • Sharply delineated central nidus is composed of calcified osteoid and woven bone lined by plump osteoblasts. • Highly vascularized connective tissue, without evidence of inflammation
  • 79. Osteoblastoma Age group- 10–30 yrs Site: Vertebrae, tibia, femur, humerus, pelvis, ribs Medulla of metaphysis Microscopy • Irregular interlacing network of osteoid with prominent osteoblastic rimming • Osteoid separated by fibrovascular stroma containing multinucleated osteoclast-like giant cells
  • 80. Differential diagnosis Osteoid osteoma Osteoblastoma Size < 2cm >2cm pain Severe Less pain Response to aspirin Relieved Not relieved Central nidus Tiny osteoid islands lined by osteoblasts Less organised osteoid pattern Sclerotic bone Dense surrounds nidus less Progressive growth No evidence Present Lesion Features GCT Epiphyses of long bones, Rare in vertebra (Arch not involved) ABC Reactive osteoid- small foci
  • 82. • Age groups: bimodal • Male>female OSTEOSARCOMA Site: Metaphyseal region of the long bones:- • Lower end of femur • Upper end of tibia • Upper end of humerus
  • 83. Several subtypes • Site of origin (intramedullary, intracortical, or surface) • Histologic grade (low, high) • Primary (underlying bone is unremarkable) or secondary: Paget disease, bone infarcts, radiation • Subtype in the metaphysis of long bones: primary, intramedullary, osteoblastic, and high grade
  • 84. Pathogenesis Syndromes- Li-Fraumeni syndrome, hereditary retinoblastoma Genetics Gains of chromosome arms 6p, 8q and 17p-50% Mutated genes in TP53 and RB1 > 90% • Inactivating mutations of TP53 Inability to mediate cell-cycle arrest, apoptosis, and cellular senescence Errors in mitotic chromosome segregation Affects chromosomal regions • Chromothripsis and amplification Result in the generation of cancer driver events- CDK4hz amplification
  • 85. Osteosarcoma Codman triangle or a sunburst appearance
  • 86. Often large (>5 cm), fleshy or hard tumor, centered within the metaphysis Depending on predominant stromal component: (1) Gray-tan & granular: osteoblastic (2) Translucent bluish: chondroblastic (3) Firm off-white mass: Fibroblastic GROSS
  • 87. Osteosarcoma • Immature bone or osteoid by neoplastic cells • Histological subtype of conventional osteosarcoma: Osteoblastic,Chondroblastic ,fibroblastic- Common • Less common-Giant cell rich, clear cell & Chondroblastoma like • Microscopic variants: Telangiectatic, small cell, low grade central & Parosteal osteosarcoma
  • 88. Osteosarcoma Microscopic Features • Defined as-Direct production of immature bone or osteoid by neoplastic cells • Conventional osteosarcomas- composed of a mixture of osteoblastic, fibroblastic & chondroblastic foci. • Telangiectatic osteosarcoma.- numerous blood-filled spaces separated by septa containing highly pleomorphic mononuclear and multinucleated giant cells accompanied by abundant mitotic activity.
  • 89. • Small cell osteosarcoma- composed of small, uniform, round or spindled cells • Low-grade central osteosarcoma- a fibroblastic osteosarcoma with minimal cytologic atypia and minimal mitotic activity. • Parosteal osteosarcoma -composed of bland fibrous stroma containing disorganized, immature bone. • Periosteal osteosarcomas are largely chondroblastic in appearance
  • 91. CYTOLOGY- • Variable cellularity • Tumour cells-pleomorphic spindle, rounded, ovoid, polygonal and often large, osteoblast like • Multinucleated tumour giant cells. • Strands of osteoid matrix between tumour cells in clusters. • Benign osteoclast-like giant cells are numerous in giant-cell-rich osteosarcoma.
  • 92. Osteosarcoma Tumor cells are singly or small groups in a myxoid background matrix
  • 93. IHC Strong positive cytoplasmic staining for ALP Expression of osteonectin
  • 94. D/D- Lesions Differentiating features Dedifferentiated chondrosarcoma • Low grade chondrosarcoma • IDH1 Mutation Fibro sarcoma • No production of tumor osteoid Osteoblastoma • Lacks atypical mitoses • Infiltrative pattern • Destructive growth pattern
  • 95. CHONDROSARCOMA • Malignant tumor of chondroid differentiation • Divided into 2 major categories on the basis of microscopic criteria:- Conventional chondrosarcoma Chondrosarcoma variant-  Clear cell chondrosarcoma  Myxoid chondrosarcoma  Dedifferentiated chondrosarcoma  Mesenchymal chondrosarcoma
  • 96. CENTRAL CHONDROSARCOMA PERIPHERAL CHONDROSARCOMA Location Medullary cavity of flat or long bones De novo or from cartilaginous cap of a pre existing osteochondroma Radiogra phy Osteolytic lesion with splotchy calcification Ill defined margins Fusiform thickening of the shaft Perforation of the cortex Large tumors with a Calcified centre surrounded by a lesser denser periphery with splotchy calcification CONVENTIONAL
  • 97. CLEAR CELL CHONDROSARCOMA • A low-grade, cartilage-producing cells with characteristic large, clear cytoplasm • Younger patients • SITE- Epiphysis of proximal femur, proximal humerus, and distal femur
  • 98. Pathogenesis Loss or structural aberrations of chr 9 & gain of chr 20 CDKN2A alterations Lacked expression of p16 (CDKN2A)
  • 99. Clear cell chondrosarcoma Diagnostic sign: Ill-defined margins Fusiform expansile remodeling of bone with endosteal scalloping cortical destruction with a soft tissue mass
  • 100. Clear cell chondrosarcoma • Large cells with a clear or vacuolated abundant cytoplasm and a central or paracentral nucleus. • Myxoid background matrix
  • 101. Gross- • Large bulky tumors • Pale blue matrix, softer than normal hyaline cartilage • Abundant gritty calcifications • Larger tumors: destructive with extensive soft tissue
  • 102. Clear cell chondrosarcoma • Tumor cells with an abundant clear or ground glass cytoplasm. • Sharply defined borders. • Interspersed small trabeculae of woven bone, numerous multinucleated giant cells & foci of cartilage
  • 103. ELECTRON MICROSCOPY •Ultrastructurally, neoplastic cells contain abundant intracytoplasmic glycogen GENETICS • Lacks IDH1 and IDH2 mutations
  • 104. D/D- Lesions Differentiating feature Chondroblastoma • Lacks prominent clear cells and bony trabeculae Osteoblastoma • Lacks chondroid differentiation Aneurysmal Bone Cyst • Clear cells and cartilaginous differentiation are absent Intramedullary Chondrosarcoma • Multinucleated giant cells and reactive bony trabeculae are absent
  • 105. Summary • Giant cell lesions are a group of diverse entities. • These lesions are morphologically related due to presence of multinucleated osteoclast like giant cells. • For making a diagnosis, apart from from clinical and histopathological, radiological data is equally important. • In ambiguous cases- diagnosis can be done by additional studies like- IHC, FISH & sequencing.
  • 106. REFERENCES 1. Unni K.K., Mertens F. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. 2020;5 :370-434. 2. Rosai, Juan, and Lauren Vedder Ackerman. Rosai And Ackerman's Surgical Pathology.2018;11:1722-1764. 3. Fletcher C, Carrie Y. Inwards, AndrĂŠ M. Oliveira. Diagnostic histopathology of tumors. 2013: 1884-1890) 4. Field, Andrew S, and Svante R Orell. Orell & Sterrett's Fine Needle Aspiration Cytology. 2015.;5: 412-427) 5. Kumar v,Abbas KA,Aster C J. Robbins and cotran pathological basis of disease. 2020; 10: 1171-1199. 6. Video Lecture by Dr Shantveer G Uppin on giant cell lesion of bone 7. Matcuk GR Jr, Chopra S, Menendez LR. Solid aneurysmal bone cyst of the humerus mimics metastasis or brown tumor. Clin Imaging. 2018 Nov- Dec;52:117-122. doi: 10.1016/j.clinimag.2018.07.020. Epub 2018 Jul 24. PMID: 30056289 8. Patricia J. Brooks, Glogauer M, McCulloch CA. An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathologic Processes. The American Journal of Pathology, 2019; 189(6): 1145-115
  • 108. • Route- hematogenous • More common than primary bone tumors • Primary sites: lung, breast, prostate, kidney & thyroid • Involved bones: skull, spine, ribs, pelvis, humerus & femur • Prostatic adenocarcinoma- Blastic • Kidney,lung,GIT &malignant melanoma- Lytic METASTATIC TUMORS
  • 109. Metastatic tumors Histopathology • Morphology: resembles primary lesion • Osteoblastic metastasis shows abundant reactive woven bone • Secondary changes: hemorrhage, fibrosis & osteoclast-type giant cell reaction Gross Finding • Haemorrhagic and friable tissue -thyroid or kidney. • Hard due to reactive bone sclerosis - Prostate and breast • Dark, pigmented - Melanoma.

Editor's Notes

  1. Adult bones, according to their shape- long, flat and short bones Long bones are divided into 3 regions: Diaphysis, Metaphysis and Epiphysis
  2. They were first reported in tuberculous granulomas by Rokitansky and Langhans size of giant cells varies greatly, but is usually between 40 Îźm and 120 Îźm.
  3. Formation of multinucleated giant cells from various types of monocyte differentiation
  4. Radio, ortho &pathologist
  5. AGE LOCATION SYMPTOM DURATION
  6. Area btwn lesion & normal bone SBC- SIMPLE BONE CYST
  7. May occur in normal bone or in pre-existing lesions, such as brown tumor
  8. Gross specimen shows a large red-brown lesion, friable, gritty 2.-appearance of a lesion that contains several multinucleated giant cells in a fibrogenic stroma and osteoid
  9. Iin mature lesions on radiology
  10. Well circumscribed, soft center, gritty periphery
  11. B-Mature bone at periphery, fibrous tissue resembling nodular fasciitis at center, osteoid in between C-Osteoblasts have large nuclei with prominent nucleoli, Osteoid is broader than in osteosarcoma
  12. A- mixture of reactive osteoblasts and myofibroblasts B-Reactive osteoblasts C- multinucleated osteoclast-like giant cell and reactive osteoblasts Differential diagnosis- Osteosarcoma Important diagnostic sign- The zonal ossification pattern
  13. VON RECKLINGHAUSEN DISEASE OF BONE
  14. Expansile, well circumscribed, lytic, and thin with subtle osteopenia Severe osteopenia with resorption of tufts Subperiosteal resorption of the proximal and middle phalanges -A lytic lesion in the 5th proximal phalanx 3. Lateral view of the skull shows significant osteoporosis producing a salt and pepper appearance of the cortices Large, blood-filled cysts may develop (osteitis fibrosa cystica) Peripheral shell of reactive bone may be present
  15. A-Low power view of nodule exhibiting giant cells B-Vascular fibroblastic stroma Hemorrhage and hemosiderin deposits Tunneling resorption of adjacent uninvolved bone
  16. D/D- CGCG GCT Solid ABC
  17. Develops in skeletally mature individuals during
  18. Most cell are non neoplastic osteoclast & their precursors Absence of normal feedback btn clats & blast-localised
  19. Eccentric lytic / cystic lesion of a long bone No evidence of periosteal lifting No sclerotic rim predominantly hemorrhagic to soft and fleshy Gross-Typically, sharp margin between the tumor and surrounding bone Surrounding bone is typically expanded with a thinned cortex texture of a malignant giant cell tumour is typically firm and flesh
  20. A The periphery of the tumour is sharply defined. The cortex is focally completely destroyed and partly surrounded by an eggshell-like rim "reactive bone. B Typical features of a giant cell tumour. The osteoclast-like giant cells dominate, between which are the mononuclear neoplastic cells. 2 Primary malignant giant cell tumour. A Features of giant cell tumour of bone (lower right) tissue juxtaposed to a high-grade sarcoma (upper left). B H3.3 p.Gly34Trp inniunoreactivity is seen in the giant cell tumour of bone component, whereas this is lacking in the sarcomatous component.
  21. Cohesive cell cluster bordered by mx Mxnucleated giant cell A-MGG, B- HE C-Mononuclear cells are rounded ovoid or spindly with slightly pleomorphic nuclei D- Cell block-aspirated material corresponds well with mini
  22. GCT- regarded as low grade malignancies due to its tendency to recur and occasional capacity to metastasize High-grade sarcoma is seen developing at the site of a previously treated GCT
  23. D/D- Benign fibrous histiocytomas located in the epiphysis in the mature skeleton are now generally considered to represent giant cell tumour of bone and those in the metaphysis to represent non-ossifying fibroma. The differential diagnosis of malignant iant cell tumour is undifferentiated sarcoma of bone and giant cell-rich osteosarcoma
  24. Female commonly affected
  25. USP- Ubiquitin specific protease
  26. radiograph demonstrates an expansile multiloculated lytic lesion in the distal tibia
  27. A-Gross image of a resected specimen from the pelvic bone showing multiple haemorrhagic cystic spaces with intervening septatio B- Sppecimen removed from rib – Mx cyst separated by septa of different width.
  28. cellular septa containing fibrovascular tissue, inflammatory cells & giant cells Low-power appearance it contains several twisted septa of varying sizes. Blucking by woven bone around cystic areas. bone is often densely calcified, basophilic metaplastic matrix so-called blue bone- seen in 1/3 cases
  29. not found in aneurysmal bone cyst
  30. Extremely common, Half are bilateral or multiple Often small, that grow to 5 or 6 cm in size are classified as Nonossifying fibromas
  31. Schema of signalling pathways involved in pathogenesis of non-ossifying fibromas. NOFs appear to be related to giant cell lesions of the jaws, as they share histological and genetic alterations
  32. 1. Both fibrous cortical defect and nonossifying fibroma produce sharply demarcated radiolucencies, surrounded by a thin rim of sclerosis 2. The solid red-brown tumor has resulted in expansion of the bone and thinning of the cortex
  33. . A Non-ossifying fibroma composed of spindle-shaped cells arranged in a storiform growth pattern, with scattered cells. B Non-ossifying fibroma with large collections of foamy histiocytes. D/D- GCT Solid ABC
  34. Site-in a non- metaphyseal location Excellent prognosis, curettage/ simple excision
  35. Young adults It is an infiltration by a cell of the accessory immune system known as. Histo- lobulated with longitudinal groove with eosinophilic cytoplasm HSC- Chroic ottis media, DI & Proptosis
  36. cell of origin : myeloid dendritic cell
  37. angerhans cell histiocytosis involving the skull has a greenish-brown color resulting from the high number of eosinophils found within the lesional tissue.
  38. A.Low-power image of bone Langerhans cell histiocytosis with clusters of Langerhans cells and large numbers of eosinophils and osteoclast-like giant cells. B High-power image of Langerhans cell histiocytosis showing distinctive morphology of intermediate-sized cells with nuclear grooves, irregular nuclear contours, and pale eosinophilic cytoplasm.
  39. A-Histiocytes with abundant cytoplasm and rounded or ovoid nuclei mixed with neutrophilic and eosinophilic leucocytes. B & C- Lobulated or ‘coffee-bean’ nuclei
  40. A-Intramedullary, well-defined tumor with sclerotic margins, radiolucent with internal calcifications B-Gray-pink, well circumscribed firm tissue with gritty calcifications and hemorrhage, <5 cm, sharply marginated from surrounding bone
  41. A Sheets of chondroblastic oval to polygonal cells, osteoclast-like giant cells, and an area of matrix calcification. B Oval to polygonal chondi blasts with well-defined cytoplasmic borders, merging with an area of eosinophilic cartilaginous matrix. C Chondroblastic cells with nuclear indentation and grooves. The top-ngr' corner shows chicken-wire pericellular calcification. D H3.3 p.Lys36Met (K36M) diffuse nuclear expression in the chondroblastic cells. Note that the osteoclast-like giant cells show no expression
  42. A cluster of chondroblast-like cells embedded in a chondromyxoid matrix,giemsa
  43. Tumor within metaphysis of proximal tibia- sclerotic & scalloped rim, typical of chondromyxoid Gross-A- yellow white lobulated appearance B-Grey whte lobulated myxoid appearance
  44. A Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left. B Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
  45. A-demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion Falling of portion of cortical bone to the bottom of the cyst
  46. A ThE lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels. B Foci of foamy histiocytes are commonly found in the cyst wall
  47. In the absence of a confirmatory curettage, if the fluid has the above characteristics and the clinical and radiological features are consistent with solitary bone cyst, FNA may be considered diagnostic.
  48. Benign neoplasm develops in synovial lining of joints , tendon sheaths &bursae.
  49. , Gross appearance of tenosynovial giant cell tumor. The lesion is small, well circumscribed, solid, and with a brownish cast. B, Whole-mount appearance of the cross section of a lesion located in the finger. Note the lobulated quality. C-polymorphic infiltrate of small histiocytes and multinucleated giant cells is embedded in dense fibrous tissue.
  50. Prostaglandins, especially PGE2, PGI2, and COX-2
  51. Frontal radiograph of the femur demonstrates cortical thickening and sclerosis of the medial femoral shaft. , on gross- gritty 8-mm nidus of the osteoid osteoma A- Well defined nidus surrounded by dense cortical / compact lamellar bone. B Anastomosing trabeculae of woven bone rimmed by plump osteosts in a highly vascular background with numerous osteoclast-like giant cells.
  52. closely related to osteoid osteoma both microscopically and immunohistochemically Gross- size (>2 cm) A- Low-power view shows a sharply circumscribed border. B- Woven bone with prominent osteoblasts, fibrovascular stroma, and ectatic blood vessels characterize osteoblastoma.
  53. Most common primary malignant tumor of bone
  54. Distal femoral osteosarcoma with prominent bone formation extending into the soft tissues. B- Periosteum, which has been lifted, has laid down a proximal triangular shell of reactive bone known as a Codman triangle (arrow).
  55. Classic osteosarcoma- arising in distal femur metaphysis region is shown. The firm, tan white solid mass has transgressed the cortex & extended into the soft tissue. Growth plate not involved.
  56. Osteoid- glassy eosinophilic appearance following decalcification.
  57. A-Conventional osteosarcoma. Fibroblastic osteosarcoma composed of intersecting fascicles of pleomorphic spindle cells with central focus of neoplastic bon B-Telangiectatic Osteosarcoma- blood filled spaces, separated by thin septa, simulating ABC C-Small cell osteosarcoma. Densely packed small blue round cells showing a delicate and immature bone formation. D-Giant cell-rich osteosarcoma. Highly pleomorphic sarcoma with abundant osteoclast-like giant cells.
  58. Atypical mitosis, Occasional necrosis and calcifications
  59. Rather large cells with a clear or vacuolated abundant cytoplasm and a central or paracentral nucleus
  60. bAsed on location Juxtacortical(periosteal)- diaphysis of long bone; spotty calcification, enchondral ossification.
  61. Epiphyseal (unique among chondrosarcomas) Osteolytic or sclerotic Often circumscribed or marginated, suggesting a benign lesion such as chondroblastoma Larger tumors may have soft tissue extension and cortical destruction
  62. large cells with a clear or vacuolated abundant cytoplasm and a central or paracentral nucleus in a myxoid background matrix
  63. This femoral head-CC-CSA-extends to the subchondral bone plate.The well circumscribed, oval tumor is heterogeneous with gray glistening,white,and hemorrhagic areas
  64. B On low magnification, clear cell chondrosarcomas often contain large areas of woven bone and numerous multinucleated giant cells. C The defining cells are large and contain either eosinophilic or clear cytoplasm, large nuclei, and a prominent central nucleolus.
  65. Most common -adenocarcinomas and squamous cell carcinomas