Difference between revisions of "Chondro-osseous tumours"

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| osteoblastic rimming
| osteoblastic rimming
| anastomosing bony trabeculae
| anastomosing bony trabeculae
| <= 1.5 cm
| <= 1.5 cm, metaphysis
| painful, NSAIDs remove pain, young
| painful, NSAIDs remove pain, young
| IHC / other
| IHC / other
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| osteoblastic rimming
| osteoblastic rimming
| anastomosing bony trabeculae
| anastomosing bony trabeculae
| > 1.5 cm
| > 1.5 cm, metaphysis
| not painful
| not painful
| IHC / other
| IHC / other

Revision as of 20:23, 30 April 2012

Chondro-osseous tumours occasionally cross the desk of the pathologist. They are grouped together as bone may develop from cartilage.

Primary bone tumours are rare; the most common bone tumour is metastases.[1]

Bone tumours occasionally are lumped with soft tissue tumours. Soft tissue tumours are dealt with in the soft tissue lesions article. An introduction to bone is found in the bone article. An introduction to cartilage is found in the cartilage article.

General

  • Diagnosis of a primary bone tumour should not be made without radiologic & clinical information!
  • Metastasis:primary bone tumours = >20:1.[1]

Common malignant

Epidemiology:[2]

  • Osteosarcoma -> 2nd decade.
  • Ewing's ->5-20 yrs.
  • Chondrosarcoma -> from enchondroma or osteochrondroma -- patients over 40 yrs.
  • Multiple myeloma -> most common primary bone tumour in adults.

Malignant bone tumours by age

Most common by age:[2]

Benign aggressive bone tumours

Ref.:[3][4]

Summary tables

Bone tumours

Entity Key feature Other features Radiology / gross Clinical Stains / other Image
Osteoma normal bone (???) other features (???) radiology / gross (???) ? no stains / may be assoc. with FAP Image (???)
Osteoid osteoma osteoblastic rimming anastomosing bony trabeculae <= 1.5 cm, metaphysis painful, NSAIDs remove pain, young IHC / other low mag., high mag.
Osteoblastoma osteoblastic rimming anastomosing bony trabeculae > 1.5 cm, metaphysis not painful IHC / other low mag., high mag.
Ewing sarcoma small round blue cell tumour cytoplasmic clearing (due to glycogen) usu. dialysis pediatric, typically 1-10 years PAS+, PASD- intermed. mag., high mag. - PAS
Osteosarcoma osteoid +/-hemorrhage, +/-cartilage distal femur, prox. tibia, prox. humerous typically 10-30 years, pain, swelling no stains; many subtypes very high mag.
Giant cell tumour of bone abundant giant cells nuclei of surrounding cells similar to those in giant cells growth plate of long bones 20-45 years old, +/-joint pain, +/-immobility IHC / other high mag.

Cartilage tumours

Entity Key feature Other features Radiology / gross Clinical Stains / other Image
Chondroma ctyologically benign cells equally spaced nests usu. diaphysis benign / DDx: chondroma, well-diff. chondrosarcoma IHC / bone marrow cavity chondroma = enchondroma very high mag.
Chondroblastoma abundant extracellular material, abundant eosinophilic cytoplasm calcifications surround cells nests ("chickenwire" appearance) - classic epiphysis DDx: giant cell tumour of bone S100+ve, vimentin +ve very high mag.
Chondrosarcoma cartilaginous appearance +/- nuclear atypia lack osteoid, if present -> osteosarcoma usu. diaphysis, classically hip; almost never distal extremity >40 years old IHC / may be histologically benign looking high mag.

Other

Entity Key feature Other features Radiology / gross Clinical Stains / other Image
Osteochondroma benign bone and cartilage Other features metaphyseal lesions Clinical IHC / other Image
Adamantinoma bisphasic - stroma & epithelium Other features tibia, fibula, intracortical, radiolucent Clinical IHC / other (WC)
Diffuse tenosynovial giant-cell tumour (AKA PVNS) pigmented giant cells nodules Radiology / gross Clinical IHC / other (WC)
Brown tumour fibrosis, +/-giant cells unaffected bone incr. osteoblasts and osteoclasts Radiology / gross due to hypercalcemia; not a neoplasm IHC / other Image

Radiology

Radiologic features
Features Benign Malignant
Bone changes sclerotic rim tumour perforation
Circumscription pushing margins ill-defined/moth-eaten
Soft tissue involvement no common
Periosteal reaction no "hair-on-end" or "sunburst",
"onion skin", Codman's triangle
Location
Diagnosis Epiphysis Metaphysis Diaphysis Type of lesion
Aneurysmal bone cyst common most common rare bone
Chondroblastoma most common rare extremely rare cartilage
Chondrosarcoma uncommon common most common cartilage
Chondromyxoid fibroma rare most common common other
Enchondroma rare common common cartilage
Ewing sarcoma rare common most common bone
Giant cell tumour most common rare extremely rare bone
Metastatic carcinoma rare common most common other
Non-ossifying fibroma extremely rare most common common other
Osteoblastoma rare most common uncommon bone
Osteochondroma extremely rare most common common bone/cartilage
Osteoid osteoma uncommon common uncommon bone
Osteosarcoma rare most common uncommon bone

How to remember the primary bone lesions:

  1. Ewing sarcoma is the only primary bone lesion of the diaphysis.
  2. Giant cell tumour of bone is the only primary bone lesion of the epiphysis.
  3. The rest of the primary bone lesions are metaphyseal.
    • Osteochondroma is bone first and cartilage second. It behaves like most primary bone lesions; it is usually metaphyseal.

How to remember the primary cartilaginous lesions:

  1. Chondroblastoma is epiphyseal. The chicken wire goes around the chicken coop.
  2. The others are diaphyseal.

Cartilage

Chondroma

General

  • Benign thingy.
  • Usual legs and feet.
  • May be difficult to separate from chondrosarcoma.
  • Multiple chondromas = enchondromatosis; three distinct syndromes:[5]
  • Enchondroma = chondroma in the marrow space.

Clinical:[5]

  • Pain.

Radiology

Features:[5]

  • Lytic lesion.
  • Usual close to a growth plate.

Microscopic

Features:

  • Ctyologically benign cells is spaced nests.

Images:

Chondroblastoma

General

  • Growth plate lesion.
  • Sclerotic margin.
  • "Young" = growth plates open.
  • Typically painful.[7]

Gross

  • Well-defined lesion.

Image:

Microscopic

Features:[8]

  • Abundant extracellular material - pink on H&E stain - looks vaguely like cartilage.
  • Chondroblasts:
    • Nuclear morphology variable: ovoid, folded or grooved.
    • Moderate-abundant eosinophilic cytoplasm.
  • +/-Calcification surrounds the cell nests ("chickenwire" appearance) - classic feature.
    • Cell nests have a thin pale blue rimming.
  • +/-Giant cells.

DDx:

Images:

IHC

Features:[8]

  • S100 +ve.
  • Vimentin +ve.[9]

Chondromyxoid fibroma

General

  • Benign.
  • Teenagers or young adults.

Gross

  • Metaphyseal lesion.
  • Well-circumscribed.

Microscopic

Features:[11]

  • Spindle cells or stellate cells in a myxoid or chondroid stroma.

Images:

Chondrosarcoma

General

  • Usually a good prognosis.

Clinical/epidemiologic features:[12]

  • Usually arise in a (benign) abnormality of cartilage (e.g. osteochondroma, enchondroma).
  • May be associated with a syndrome:
    • Olier disease (multiple enchondromatosis).
    • Maffucci syndrome (multiple enchondromas and hemangiomas).

Notes:

  • Review article (from oncology perspective): PMID 17545802.

Subtypes

Several subtypes exist:

  • Chondrosarcoma not otherwise specified (NOS).
  • Juxtacortical chondrosarcoma.
  • Myxoid chondrosarcoma.
  • Mesenchymal chondrosarcoma.
  • Clear cell chondrosarcoma.
  • Dedifferentiated chondrosarcoma.

Microscopic

Features:[13][14]

  • "Abnormal cartilage":
    • +/-Nuclear atypia - high grade lesions.
      • High grade lesions:
        • Nuclear clearing.
        • Nucleoli.
        • Hyperchromasia.
      • Low/intermediate grade lesions:
        • Bi-nucleation.
        • Hypochromatic enlarged nuclei.
        • Infiltration of lamellar bone ("invasion") - not common - diagnostic.
    • Increased cellularity.
      • More cellular than cartilage... but relatively paucicellular compared to other sarcomas.
    • Irregular spacing of chondrocytes.

Notes:

  • Low grade chondrosarcoma are not cytologically malignant; the diagnosis rests mostly on radiologic findings.
    • The exception is infiltration of lamellar bone -- this is diagnostic of chondrosarcoma.[15]

DDx:

Images:

Variants

Mesenchymal chondrosarcoma
  • Arise in soft tissue; this is where the name comes from.[16]
  • Rare variant of chondrosarcoma.

Microscopic: Features:

  • "White clouds in a blue sky".

Image:

Myxoid chondrosarcoma

Microscopic: Features:

  • Chordoma-like:
    • Myxoid background.
    • Small cells with eosinophilic cytoplasm.

DDx:

Extraskeletal myxoid chondrosarcoma
  • Originally thought to be a variant of myxoid chondrosarcoma of bone; however, may not be a chondrosarcoma at all.[18]
  • Characteristic chromosomal translocation: t(9;22) CHN-EWS.

DDx:

  • Chordoma.[18]
    • S-100 +ve (strong).
    • EMA +ve.

Image:

Dedifferentiated chondrosarcoma

Clinical:

  • Abysmal to poor prognosis.
    • In one series (22 patients) 5-year survival ~20%.[20]
    • All dead in two years in another series (25 patients).[21]

Features:[21]

  1. Poorly differentiated (mesenchymal) malignancy.
  2. Well-differentiated cartilaginous component.

Images:

Grading

Features:[22]

  • Grade I: mild-to-moderate increase of cellularity +/- binucleated cells.
  • Grade II: between Grade I and Grade III.
  • Grade III: nuclear pleomorphism, mitoses common.

IHC

  • S-100 -ve. (???)

Bone

Osteoma

General

Microscopic

Features:

  • Normal bone.

Osteoid osteoma

General

  • Benign bone lesion.

Clinical:[23]

  • Extremely painful.
    • Relieved by NSAIDS.

Microscopic

Features:[23]

  • Anastomosing bony trabeculae with:
    • Variable mineralization.
      • Mineralization (calcium phosphate) = purple on H&E stain.
    • Osteoblasts rimming.
      • Cells line-up at edge of bone.

Note:

Images:

Osteoblastoma

General

  • Benign bone tumour.

Microscopic

Features:[23]

  • Anastomosing bony trabeculae with:
    • Osteoblasts rimming.
      • Cells line-up at edge of bone.

Notes:

  • Histomorphologically near identical/indistinguishable from osteoid osteoma.[24]
  • Must be greater 1.5 cm by definition.[24]

Images:

Ewing sarcoma

  • AKA EWS/pPNET, AKA (confusingly) EWS/PNET:
    • EWS = Ewing sarcoma.
    • pPNET = peripheral primitive neuroectodermal tumour.
  • EWS and pPNET were once thought to be different tumours.

Notes:

General

Clinical:

  • Painful.
  • Usually younger than 20 years.
  • Second most common malignant bone tumour in children.
    • Most common malignant bone tumour = osteosarcoma (AKA osteogenic sarcoma).

Poor prognostic factors:[25]

  • Age (18 years-old+).
  • Pelvis (extremity = good).
  • >8 cm.
  • Metastases.
  • EWS-FL1 fusion type 2.
  • >90% necrosis.

Etiology:

  • Unknown origin; hypothesis: Ewing sarcoma arises from mesenchymal stem cell.[26]

Radiology

Features:[27]

  • Long bones, diaphyses.
  • Destructive.
  • "Onion-skin" periosteal reaction.

Microscopic

Features:[28]

  • Scant clear cytoplasm (contain glycogen -- PAS +ve, PAS-D -ve) - key feature.
  • Round small nucleus.
    • Usu. lack nucleoli.
    • Usu. minimal-moderate size variation.
  • Mitoses (common).

Notes:

Images:

IHC

Features:[30]

  • CD99 +ve -- 1. diffuse, 2. plasma membrane staining; both required -- most specific.
  • FLI-1 +ve.[31]
  • CD45 -ve.
  • +/-Neural markers (NSE, synaptophysin, CD57 (??? CD56 ???), S100).
  • +/-Cytokeratins.
  • Caveolin-1 +ve in ~ 85% of EWS.[32]
  • WT-1 -ve.[33]

Notes:[34]

Molecular diagnostics

Common features:

  • EWS/FLI-1 fusion gene formation due to translocation: t(11;22)(q24;q12).[35][36]
    • Often detected by RT-PCR (with EWS 5' and FLI-1 3' primers).
    • Type 1 = EWS exon 7 + FLI-1 exon 6; good prognosis.
    • Type 2 = others; poor prognosis.

Notes:

  • The t(11;22)(q24;q12) is seen in ~90% of EWS/PNET... but also in:
  • Several other EWS translocations exist.[37]
    • ERG,[38] ETV1, E1AF and FEV.
  • Lack of molecular findings does not exclude Ewing sarcoma.
  • Testing:
    • A break apart probe for EWS is a common way to look for pathologic change, as it covers almost all variants.

Electron microscopy

  • Primitive cell junctions.
  • Clear zone (glycogen lakes).

Osteosarcoma

  • AKA osteogenic sarcoma.

General

Trivia:

  • Terry Fox was afflicited by this tumour.

Definition

  • Tumour that makes osteoid.
    • Osteoid = (extracellular) organic component of bone, normally produced by osteoblasts (cells which make bone matrix).

Gross

Classic locations:[39]

  • Distal femur ~ 45%.
  • Proximal tibia ~ 20%.
  • Proximal humerous ~ 15%.

Microscopic

Features:

  • Cells with malignant features (e.g. nuclear membrane irregularities, marked nuclear size differences, mitoses) surrounded by delicate strands of osteoid.
    • Osteoid on H&E: pink, homogenous, "glassy".
    • Tumours typically very cellular - when compared to normal bone.
  • Large (multinucleated) osteoclast-like giant cells may be seen.[40]

Images:

Subtypes

Subtypes:[41][42]

  • Conventional osteosarcoma (high grade).
    • Osteoblastic osteosarcoma.
    • Fibroblastic osteosarcoma.
    • Chondroblastic osteosarcoma.
  • Small cell osteosarcoma.
  • Telangiectatic osteosarcoma.
  • Parosteal osteosarcoma.
  • Periosteal osteosarcoma.
  • Low-grade central osteosarcoma.
  • High-grade surface osteosarcoma.
  • Secondary osteosarcoma.
  • Gnathic osteosarcoma - jaw bones - usually chondroblastic.

How to remember:

  • Convention FOC = fibroblastic, osteogenic, chondroblastic.
  • Low-grade central.
  • High-grade surface.
  • Parosteal.
  • Periosteal.
  • Small cell.
  • Secondary.
  • Telangiectatic.
Chondroblastic osteosarcoma
  • Chondroid matrix present - may be prominent; osteoid may be a minor component.
  • May be confused with chondrosarcoma.
Fibroblastic osteosarcoma

Images:

Telangiectatic osteosarcoma
  • Rare.[43]
  • Extremely vascular.
  • Prognosis similar to other types of osteosarcoma.[44]
Parosteal osteosarcoma
  • Arise from surface of bone.[45]
  • Low grade.[46]
Periosteal osteosarcoma
  • Intermediate grade.[46]
Small cell osteosarcoma
Secondary osteosarcoma

Arises in the context of something else - causes:

Images:

Giant cell tumour of bone

General

Features:[48]

  • Approximately 5% of primary bone tumours.
  • Typical age: 20-45 years.

Clinical

  • Location: growth plate of long bones.[49]
    • May present with joint pain, immobility.

Note:

Microscopic

Features:[50]

  • Giant cells with a large number of nuclei (usu. >10 in the plane of section).
    • Usu. have prominent nucleoli.
  • Mononuclear cells and small multinucleated cells with nuclei similar to those in the giant cells - key feature.

Notes:

  • Giant cells typically present in abundance.

DDx:

Images:

IHC

  • p63 +ve in scattered mononuclear cells.[51]
    • This seems to be contradicted by another paper.[52]

Other

This section collects stuff that doesn't neatly fit into the bone or cartilage category.

Osteochondroma

General

  • Benign.
  • Very common.
  • Abnormal outgrowth of bone and cartilage.

Gross

  • Usually metaphyseal lesions - associated with growth plate.[citation needed]

Microscopic

Features:

  • Normal bone and cartilage.

Images:

Diffuse tenosynovial giant-cell tumour

  • AKA tenosynovial giant-cell tumour, diffuse type.
  • Previously known as pigmented villonodular synovitis (PVNS).[53]

General

  • Course: benign.
  • Giant cell tumor of the tendon sheath is considered to be the soft-tissue counterpart of PVNS.[54]

Microscopic

Features:[55]

  • Subsynovial nodules composed of cells with:
    • Abundant cytoplasm.
    • Pale nuclei.
  • Multinucleated giant cells.
  • Hemosiderin-laden macrophages.
  • Foam cells.

Images:

Adamantinoma

Should not be confused with adenomatoid tumour.

General

Features:[27]

  • Rare: < 1% of bone tumours.
  • 25-35 years old.
  • Tibia, fibula.
  • Benign, may be locally aggressive.
  • Cousin of ameloblastoma. (???)

Radiology

  • Intracortical, radiolucent.

Microscopic

Features:

  • Biphasic tumour:
    1. Fibrous/spindle cell component.
    2. Epithelial component.

Images:

DDx:[57]

IHC

Features:[57]

  • CK14 +ve (HMWK).[58]
  • CK19 +ve (LMWK).
  • CK8/18 -ve (LMWK).

Brown tumour

General

  • Not a true neoplasm,[59] i.e. the name is a misnomer.
    • May (clinically) mimic a true neoplasm.
  • Due to hyperparathyroidism - usually parathyroid adenoma.
    • Usually secondary to chronic renal failure.

Hypercalcemia DDx

Mnemonic GRIMED:[60]

Microscopic

Features:

  • Fibrosis.
  • +/-Giant cells with round to oval nuclei and nucleoli.[61]
  • Bone unaffected by tumour - increased numbers of the following:
    • Multinucleated cells (osteoclasts).
    • Mononuclear cells around the bony trabeculae (osteoblasts).


DDx:

Images:

See also

References

  1. ↑ 1.0 1.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 632. ISBN 978-0781765275.
  2. ↑ 2.0 2.1 Yeung, J.C.; Leonard, Blair J. N. (2005). The Toronto Notes 2005 - Review for the MCCQE and Comprehensive Medical Reference (2005 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. OR42. ISBN 978-0968592854.
  3. ↑ Yeung, J.C.; Leonard, Blair J. N. (2005). The Toronto Notes 2005 - Review for the MCCQE and Comprehensive Medical Reference (2005 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. OR41. ISBN 978-0968592854.
  4. ↑ URL: http://www.emedicine.com/RADIO/topic494.htm.
  5. ↑ 5.0 5.1 5.2 URL: http://emedicine.medscape.com/article/389224-overview. Accessed on: 25 December 2010.
  6. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 166000
  7. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 625. ISBN 978-1416054542.
  8. ↑ 8.0 8.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 642. ISBN 978-0781765275.
  9. ↑ 9.0 9.1 9.2 URL: http://emedicine.medscape.com/article/1254949-diagnosis. Accessed on: 31 December 2010.
  10. ↑ URL: http://path.upmc.edu/cases/case494.html. Accessed on: 24 January 2012.
  11. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 642. ISBN 978-0781765275.
  12. ↑ Skubitz KM, D'Adamo DR (November 2007). "Sarcoma". Mayo Clin. Proc. 82 (11): 1409–32. PMID 17976362. http://www.mayoclinicproceedings.com/content/82/11/1409.long.
  13. ↑ IAV. 26 February 2009.
  14. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 417. ISBN 978-1416002741.
  15. ↑ BD. 28 April 2011.
  16. ↑ Dowling EA (June 1964). "Mesenchymal chondrosarcoma". J Bone Joint Surg Am 46: 747–54. PMID 14161087. http://www.ejbjs.org/cgi/reprint/46/4/747.pdf.
  17. ↑ Fisher C (May 2000). "Parachordoma exists--but what is it?". Adv Anat Pathol 7 (3): 141–8. PMID 10809219.
  18. ↑ 18.0 18.1 Aigner, T.; Oliveira, AM.; Nascimento, AG. (Feb 2004). "Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype.". Mod Pathol 17 (2): 214-21. doi:10.1038/modpathol.3800036. PMID 14657948.
  19. ↑ URL: http://www.cttr.org/cms/?p=736. Accessed on: 1 May 2011.
  20. ↑ Mitchell, AD.; Ayoub, K.; Mangham, DC.; Grimer, RJ.; Carter, SR.; Tillman, RM. (Jan 2000). "Experience in the treatment of dedifferentiated chondrosarcoma.". J Bone Joint Surg Br 82 (1): 55-61. PMID 10697315.
  21. ↑ 21.0 21.1 Sopta, J.; Dordević, A.; Tulić, G.; Mijucić, V. (Feb 2008). "Dedifferentiated chondrosarcoma: our clinico-pathological experience and dilemmas in 25 cases.". J Cancer Res Clin Oncol 134 (2): 147-52. doi:10.1007/s00432-007-0262-5. PMID 17653766.
  22. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 643. ISBN 978-0781765275.
  23. ↑ 23.0 23.1 23.2 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 285. ISBN 978-0781740517.
  24. ↑ 24.0 24.1 24.2 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 286. ISBN 978-0781740517.
  25. ↑ PST. 14 February 2011.
  26. ↑ Lin PP, Wang Y, Lozano G (2011). "Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma". Sarcoma 2011. doi:10.1155/2011/276463. PMC 2952797. PMID 20953407. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952797/.
  27. ↑ 27.0 27.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 650. ISBN 978-0781765275.
  28. ↑ PST. 22 February 2010.
  29. ↑ PST. 14 February 2011.
  30. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 651. ISBN 978-0781765275.
  31. ↑ 31.0 31.1 Rossi S, Orvieto E, Furlanetto A, Laurino L, Ninfo V, Dei Tos AP (May 2004). "Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody". Mod. Pathol. 17 (5): 547–52. doi:10.1038/modpathol.3800065. PMID 15001993. http://www.nature.com/modpathol/journal/v17/n5/full/3800065a.html.
  32. ↑ PST. 14 February 2011.
  33. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 286. ISBN 978-0781765275.
  34. ↑ PST. 22 February 2010.
  35. ↑ URL: http://atlasgeneticsoncology.org/Tumors/Ewing5010.html. Accessed on: 23 February 2010.
  36. ↑ Turc-Carel C, Aurias A, Mugneret F, et al. (June 1988). "Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12)". Cancer Genet. Cytogenet. 32 (2): 229–38. PMID 3163261.
  37. ↑ URL: http://www.cancerindex.org/geneweb/EWSR1.htm. Accessed on: 20 November 2011.
  38. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 165080
  39. ↑ Greenwald, J.; Heng, M. (2007). Toronto Notes for Medical Students 2007 (2007 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. OR43. ISBN 978-0968592878.
  40. ↑ Papalas JA, Balmer NN, Wallace C, Sangueeza OP (June 2009). "Ossifying dermatofibroma with osteoclast-like giant cells: report of a case and literature review". Am J Dermatopathol 31 (4): 379-83. doi:10.1097/DAD.0b013e3181966747. PMID 19461244.
  41. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 638. ISBN 978-0781765275.
  42. ↑ URL: http://bestpractice.bmj.com/best-practice/monograph/780/basics/classification.html. Accessed on: 7 April 2011.
  43. ↑ Patibandla, MR.; Uppin, SG.; Thotakura, AK.; Panigrahi, MK.; Challa, S.. "Primary telangiectatic osteosarcoma of occipital bone: a case report and review of literature.". Neurol India 59 (1): 117-9. doi:10.4103/0028-3886.76891. PMID 21339678.
  44. ↑ Weiss, A.; Khoury, JD.; Hoffer, FA.; Wu, J.; Billups, CA.; Heck, RK.; Quintana, J.; Poe, D. et al. (Apr 2007). "Telangiectatic osteosarcoma: the St. Jude Children's Research Hospital's experience.". Cancer 109 (8): 1627-37. doi:10.1002/cncr.22574. PMID 17351949.
  45. ↑ The International Agency for Research on Cancer (Editors: Fletcher, C.D.M.; Unni, K. Krishnan; Mertens, F.) (2006). Pathology and Genetics of Tumours of Soft Tissue and Bone (IARC WHO Classification of Tumours) (3rd ed.). World Health Organization. pp. 279. ISBN 978-9283224136.
  46. ↑ 46.0 46.1 46.2 Carrle, D.; Bielack, SS. (Dec 2006). "Current strategies of chemotherapy in osteosarcoma.". Int Orthop 30 (6): 445-51. doi:10.1007/s00264-006-0192-x. PMC 3172747. PMID 16896870. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172747/.
  47. ↑ URL: http://www.rsna.org/REG/publications/rg/afip/privateM/1997/0017/0005/1205/6.htm. Accessed on: 8 April 2011.
  48. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 648. ISBN 978-0781765275.
  49. ↑ Wülling, M.; Engels, C.; Jesse, N.; Werner, M.; Delling, G.; Kaiser, E. (Aug 2001). "The nature of giant cell tumor of bone.". J Cancer Res Clin Oncol 127 (8): 467-74. PMID 11501745.
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  55. ↑ URL: http://www.wheelessonline.com/ortho/pigmented_villonodular_synovitis.
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  58. ↑ URL: http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm. Accessed on: 28 April 2011.
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  61. ↑ URL: http://path.upmc.edu/cases/case139/micro.html. Accessed on: 6 January 2012.

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