Bone & joints

Osteogenic giant cell rich tumors

Giant cell tumor of bone



Topic Completed: 13 September 2021

Minor changes: 12 October 2021

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PubMed search: Giant cell tumor of bone[TI] pathology free full text[sb]

Borislav A. Alexiev, M.D.
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Cite this page: Alexiev BA. Giant cell tumor of bone. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonegiantcelltumor.html. Accessed October 25th, 2021.
Definition / general
  • Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastasizing neoplasm composed of neoplastic mononuclear stromal cells admixed with macrophages and osteoclast-like giant cells
  • A small subset of cases are malignant
Essential features
  • Bone tumor with compatible imaging
  • Osteolytic circumscribed tumor involving the epiphysis and metaphysis, generally in skeletally mature individual
  • Mononuclear cell neoplastic component without atypia together with numerous osteoclasts
  • Detection of H3.3 pGly34 mutated cells / H3.3 pGly34Trp (G34W) immunoreactivity
Terminology
  • Not recommended: osteoclastoma
ICD coding
  • ICD-10: 9250/1 - giant cell tumor of bone NOS
  • ICD-11: 2F7B & XH4TC2 - neoplasms of uncertain behavior of bone or articular cartilage & giant cell tumor of bone NOS
Epidemiology
Sites
Pathophysiology
  • GCTB related clonal aberrations occur in a background of epigenetic histone modifications (especially the G34W mutation of H3F3A gene) (Hum Pathol 2018;81:1)
  • Neoplastic mononuclear stromal cells in GCTB express receptor activator of NFκβ ligands (RANKLs) and various chemokines and cytokines associated with monocyte recruitment and reactive multinucleated giant cells (osteoclastogenesis) (Hum Pathol 2018;81:1)
  • Activation of Wnt / beta catenin pathway in GCTB tumorigenesis (Pathol Res Pract 2009;205:626)
  • Clonal telomeric associations (tas) were found in GCTB (Genes Chromosomes Cancer 2009;48:583)
  • Transformation to malignancy may occur after therapeutic irradiation (Indian J Pathol Microbiol 2002;45:273)
  • TP53 and HRAS mutations have been identified in malignant GCTB not associated with prior radiation (Histopathology 2001;39:629)
Etiology
Diagrams / tables

Images hosted on other servers:

Anatomical distribution

Clinical features
Diagnosis
  • In many cases, the diagnosis of GCTB is suggested by the tumor location and appearance on Xray, computed tomography and magnetic resonance scans
  • A definitive diagnosis usually requires a biopsy
Radiology description
  • Typical appearance of GCTB is best demonstrated on conventional radiographs, which show a lytic lesion that has a well defined but nonsclerotic margin, is eccentric in location, extends to the subchondral bone and occurs in patients with closed physes (Radiographics 2013;33:197)
  • CT and MR imaging allow superior delineation of GCTB
  • Cortical thinning of bone is invariably apparent at radiography performed at clinical presentation (Radiographics 2001;21:1283)
  • Expansile remodeling of bone is also frequently seen (47 - 60% of cases)
  • Cortical penetration is seen in 33 - 50% of cases, often with an associated soft tissue mass (Radiographics 2001;21:1283)
  • Aneurysmal bone cyst components in GCTB are relatively common (14% of lesions)
  • Campanacci et al classified the GCTB into 3 grades, depending on their radiographic appearance:
    • Grade 1 lesion (latent) has a well defined margin and an intact cortex (J Bone Joint Surg Am 1987;69:106)
    • Grade 2 lesion (active) has a relatively well defined margin but no radiopaque rim and the cortex is thinned and moderately expanded
    • Grade 3 lesion (aggressive) has indistinct borders and cortical destruction
  • It has been suggested that the Campanacci classification scheme may more easily guide treatment; however, it is doubtful whether this classification accurately predicts the aggressiveness of GCTB (SICOT J 2017;3:54)
  • No correlation exists between the grading system and incidence of local recurrence and metastases (SICOT J 2017;3:54, Int Orthop 2012;36:2521)
Radiology images

Contributed by Borislav A. Alexiev, M.D.
Lytic lesion

Lytic lesion

Expansile solid lesion

Expansile solid lesion

Mass with extraosseous component

Mass with extraosseous component

Prognostic factors
  • Pulmonary metastasis in ~2% of cases; they are very slow growing (nonaggressive) and may spontaneously regress; metastases have same morphology as the bone lesion (Pathol Int 1998;48:723)
  • Local recurrence, a high Campanacci grade and curettage are possible high risk factors for pulmonary metastasis (J Bone Oncol 2017;7:23)
  • Secondary malignancy in giant cell tumor of bone (arising after treatment of a benign giant cell tumor) has a poor prognosis, akin to other high grade sarcomas and much worse than primary malignancy in giant cell tumor of bone (Cancer 2003;97:2520)
Case reports
Treatment
Clinical images

Images hosted on other servers:

Right proximal humerus tumor

Gross description
  • Typical gross lesion is a soft, friable, slightly brownish or red-tan, somewhat poorly defined neoplasm in the end of a long bone (AJR Am J Roentgenol 1985;144:955, Arch Bone Jt Surg 2016;4:2, Diagn Pathol 2014;9:111)
  • Yellow and firm white areas corresponding to xanthomatous change and fibrous tissue are common
  • Surrounding cortex is often thinned and may be destroyed completely
  • Destructive tumors may extend into soft tissue
  • Subchondral bone plate can be focally involved
  • Extensive cystic hemorrhagic areas corresponding to aneurysmal bone cyst-like changes may be seen
  • Cut surface of malignant GCTB is typically firm and fleshy
Gross images

Contributed by Borislav A. Alexiev, M.D. and Mark R. Wick, M.D.
Left distal femur lesion

Left distal femur lesion

Distal femur

Distal femur

Frozen section description
  • Highly cellular lesion composed of large number of osteoclast-like giant cells, between which mononuclear cells are embedded (Int Orthop 2006;30:484, Diagn Pathol 2014;9:111)
  • Due to the complex histological composition of GCTB, differential diagnosis is required to exclude the diagnosis of other lesions also containing giant cells, such as aneurysmal bone cyst, nonossifying fibroma, chondroblastoma, brown tumor of hyperparathyroidism and giant cell rich osteosarcoma (Int Orthop 2006;30:484)
  • In addition to the histological findings, precise details regarding age, localization and radiology findings within the framework of GCTB differential diagnosis is vital (Int Orthop 2006;30:484)
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Borislav A. Alexiev, M.D.
Osteoclasts-rich bone lesion

Osteoclasts-rich bone lesion

Typical features

Typical features

Reactive bone formation

Reactive bone formation

Aneurysmal change

Aneurysmal change

Neoplastic mononuclear cells

Neoplastic mononuclear cells

Residual tumor

Residual tumor


Depletion of giant cells

Depletion of giant cells

Reactive bone formation

Reactive bone formation

Complete response with hemorrhage

Complete response with hemorrhage

Spindle cell proliferation

Spindle cell proliferation

Complete response with fibrosis

Complete response with fibrosis

G34W IHC

G34W IHC


p63 IHC

p63 IHC

Cytology description
  • Smear preparations demonstrate oval to spindled mononuclear cells in cohesive clusters bordered by multiple multinucleated giant cells (Cancer Cytopathol 2018;126:552, Diagn Cytopathol 2004;30:14)
  • Mononuclear cells have spindled or plump cell bodies with moderate amounts of cytoplasm and well defined cytoplasmic membranes; oval nuclei demonstrate fine, evenly distributed chromatin and small nucleoli
  • Multinucleated cells are osteoclast-like and are associated with clusters of mononucleated cells or lying freely
  • They have a well demarcated cytoplasm and contain from a few to several dozen monomorphic nuclei (Diagn Cytopathol 1985;1:111)
Cytology images

Contributed by Lucy Jager, M.D.
Cellular smears

Cellular smears

Mononuclear and MGCs

Mononuclear and MGCs

Electron microscopy description
Molecular / cytogenetics description
Sample pathology report
  • Left distal femur, curettage:
    • Giant cell tumor of bone (see comment)
    • Comment: Radiology images of the left femur demonstrates a 5.2 x 5.9 x 5.2 cm expansile heterogeneous mass centered in the lateral femoral condyle. There is cortical breakthrough and an extraosseous component along the posterosuperior margin. Histologically, the neoplasm is cellular and composed of a large number of osteoclast-like giant cells, between which mononuclear round to oval cells and spindled cells with pale eosinophilic cytoplasm and nuclei with dispersed chromatin and small nucleoli are embedded. Scattered mitotic figures and no necrosis are seen (11 mitoses / 10 high power fields). There are aneurysmal change, clusters of hemosiderophages and fibrosis. The cortical bone is focally destroyed and replaced by a reactive rim of woven bone at the tumor periphery. Immunohistochemical stains for H3.3 G34W and p63 are positive in mononuclear cells. Overall, the appearance on computed tomography and magnetic resonance scans, morphological features and immunohistochemical profile support the diagnosis of giant cell tumor of bone.
    • Giant cell tumor of bone can be locally aggressive and it has a propensity to recur locally after curettage alone. Furthermore, in approximately 3 - 7% of cases, distant metastases occur, most often to the lungs.
Differential diagnosis
Board review style question #1

A 31 year old man presented with a left distal femur metadiaphyseal expansile, predominantly solid, enhancing lesion measuring 6.6 cm in greatest dimension. There is medial distal femur diffuse cortical thinning overlying the lesion and periosteal edema and enhancement. No convincing extraosseous component is seen.

Hematoxylin eosin stains demonstrate a cellular lesion composed of a large number osteoclast-like giant cells, between which mononuclear cells are embedded. The mononuclear cells exhibit a variety of morphological appearances, including round to oval cells and spindled cells with pale eosinophilic cytoplasm and nuclei with dispersed chromatin and small nucleoli. Scattered mitotic figures and no necrosis are seen (7 mitoses / 10 high power fields). There is reactive woven bone formation, aneurysmal changes with hemosiderin deposition and fibrosis. The cortical bone is eroded; however, there is no complete cortical bone destruction. Immunohistochemical stains for H3.3 G34W and p63 are positive in mononuclear cells. P53 expression is wild type (no mutation).

Which of the following is most likely the correct diagnosis?

  1. Aneurysmal bone cyst
  2. Chondroblastoma
  3. Giant cell tumor of bone
  4. Osteoblastoma
  5. Osteosarcoma
Board review style answer #1
C. Giant cell tumor of bone

Comment Here

Reference: Giant cell tumor of bone
Board review style question #2
Which of the following is true about giant cell tumor of bone (GCTB)?

  1. GCTB is composed of neoplastic osteoclast-like giant cells and nonneoplastic mononuclear stromal cells
  2. GCTB is positive for HG34W
  3. GCTB is positive for HK36M
  4. GCTB treated with denosumab shows a striking increase of osteoclast-like giant cells
  5. GCTB typically affects the diaphysis of long bones
Board review style answer #2
B. GCTB is positive for HG34W

Comment Here

Reference: Giant cell tumor of bone
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