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'''Chondro-osseous tumours''' occasionally cross the desk of the pathologist.  They are grouped together as [[bone]] may develop from [[cartilage]].
[[Image:Osteosarcoma - very high mag.jpg|thumb|250px|right|A chondro-osseous tumour ([[osteosarcoma]]). [[H&E stain]].]]
'''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.<ref name=Ref_WMSP632>{{Ref WMSP|632}}</ref>   
Primary bone tumours are rare; the most common bone tumour is [[metastases]].<ref name=Ref_WMSP632>{{Ref WMSP|632}}</ref>   


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.
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.
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===Common malignant===
===Common malignant===
*Osteosarcoma.
*[[Osteosarcoma]].
*Chondrosarcoma.
*[[Chondrosarcoma]].
*Ewing's sarcoma.
*[[Ewing's sarcoma]].
*Multiple myeloma.
*[[Multiple myeloma]].
*Metastases.
*[[Metastases]].
**Most common tumours metastatic to bone (mnemonic: ''BLT with Ketchup & Pickles''):  
**Most common tumours metastatic to bone (mnemonic: ''BLT with Ketchup & Pickles''):  
***[[Breast]].  
***[[Breast]].  
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***[[Prostate gland]].  
***[[Prostate gland]].  


Epidemiology:<ref>TN05 OR42.</ref>
Epidemiology:<ref name=Ref_TN2005_OR42>{{Ref TN2005 |OR42}}</ref>
*Osteosarcoma -> 2nd decade.  
*Osteosarcoma -> 2nd decade.  
*Ewing's ->5-20 yrs.
*Ewing's ->5-20 yrs.
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===Malignant bone tumours by age===
===Malignant bone tumours by age===
Most common by age:<ref>TN05 OR42.</ref>
Most common by age:<ref name=Ref_TN2005_OR42>{{Ref TN2005 |OR42}}</ref>
*<1 year old - [[neuroblastoma]].
*<1 year old - [[neuroblastoma]].
*1-10 years old - Ewing's of tubular bones.
*1-10 years old - [[Ewing sarcoma|Ewing's]] of tubular bones.
*10-30 years old - osteosarcoma, Ewing's of flat bones.  
*10-30 years old - osteosarcoma, Ewing's of flat bones.  
*30-40 years old - reticulum cell sarcoma, fibrosarcoma, parosteal osteosarcoma, malignant giant cell tumour, lymphoma.
*30-40 years old - [[reticulum cell sarcoma]], [[fibrosarcoma]], parosteal osteosarcoma, [[malignant giant cell tumour]], [[lymphoma]].
*>40 years old - mets, multiple myeloma, chondrosarcoma.
*>40 years old - mets, [[multiple myeloma]], [[chondrosarcoma]].


===Benign aggressive bone tumours===
===Benign aggressive bone tumours===
*Giant cell tumours.
*[[Giant cell tumour of bone]].
*Osteoblastoma.
*[[Osteoblastoma]].
**Thought to be related to osteoid osteoma.
**Thought to be related to [[osteoid osteoma]].
**If in long bones often diaphyseal.
**If in long bones often diaphyseal.
Ref.:<ref>TN05 OR41.</ref><ref>URL: [http://www.emedicine.com/RADIO/topic494.htm http://www.emedicine.com/RADIO/topic494.htm].</ref>
 
Ref.:<ref name=Ref_TN2005_OR41>{{Ref TN2005 |OR41}}</ref><ref>URL: [http://www.emedicine.com/RADIO/topic494.htm http://www.emedicine.com/RADIO/topic494.htm].</ref>
   
   
===Summary tables===
===Summary tables===
====Bone tumours====
====Bone tumours====
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
| Entity
! Entity
| Key feature
! Key feature
| Other features
! Other features
| Radiology / gross
! Radiology / gross
| Clinical
! Clinical
| Stains / other
! Stains / other
| Image
! Image
|-
| [[Osteoma]]
| normal bone (???)
| other features (???)
| radiology / gross (???)
| ?
| no stains / may be assoc. with [[FAP]]
| [[Image:Osteoma -- intermed mag.jpg |thumb|center|150px| Osteoma. (WC)]]
|-
|-
| [[Osteoid osteoma]]
| [[Osteoid osteoma]]
| osteoblastic rimming
| osteoblastic rimming
| anastomosing bony trabeculae
| anastomosing bony trabeculae
| <= 1.5 cm
| must be <2 cm,<ref name=pmid25224389>{{Cite journal  | last1 = Yalcinkaya | first1 = U. | last2 = Doganavsargil | first2 = B. | last3 = Sezak | first3 = M. | last4 = Kececi | first4 = B. | last5 = Argin | first5 = M. | last6 = Basdemir | first6 = G. | last7 = Oztop | first7 = F. | title = Clinical and morphological characteristics of osteoid osteoma and osteoblastoma: a retrospective single-center analysis of 204 patients. | journal = Ann Diagn Pathol | volume = 18 | issue = 6 | pages = 319-25 | month = Dec | year = 2014 | doi = 10.1016/j.anndiagpath.2014.08.006 | PMID = 25224389 }}</ref> metaphysis
| painful, NSAIDs remove pain, young
| painful, NSAIDs remove pain, young
| IHC / other
| IHC / other
| [http://commons.wikimedia.org/w/index.php?title=File:Osteoid_osteoma_-_low_mag.jpg low mag.], [http://commons.wikimedia.org/w/index.php?title=File:Osteoid_osteoma_-_high_mag.jpg high mag.]
| [[Image:Osteoid_osteoma_-_high_mag.jpg |thumb|center|150px| Osteoid osteoma. (WC)]]
|-
|-
| [[Osteoblastoma]]
| [[Osteoblastoma]]
| osteoblastic rimming
| osteoblastic rimming
| anastomosing bony trabeculae
| anastomosing bony trabeculae
| > 1.5 cm
| must be >1 cm,<ref name=pmid25224389/> often >=2 cm, metaphysis
| not painful
| not painful
| IHC / other
| IHC / other
| [http://commons.wikimedia.org/wiki/File:Osteoblastoma_-_low_mag.jpg low mag.], [http://commons.wikimedia.org/wiki/File:Osteoblastoma_-_high_mag.jpg high mag.]
| [[Image:Osteoblastoma_-_high_mag.jpg|thumb|center|150px|Osteoblastoma. (WC)]]
|-
|-
| [[Ewing sarcoma]]
| [[Ewing sarcoma]]
| [[small round blue cell tumour]]
| [[small round blue cell tumour]]
| cytoplasmic clearing (due to glycogen)
| cytoplasmic clearing (due to glycogen)
| Radiology / gross
| usu. diaphysis
| pediatric
| pediatric, typically 1-10 years
| PAS+, PASD-  
| PAS+, PASD-, [[chromosomal translocations]] (usually t(11;22)(q24;q12)) 
| [http://commons.wikimedia.org/wiki/File:Ewing_sarcoma_-_intermed_mag.jpg intermed. mag.], [http://commons.wikimedia.org/wiki/File:Ewing_sarcoma_-_PAS_-_high_mag.jpg high mag. - PAS]
| [[Image:Ewing_sarcoma_-_PAS_-_high_mag.jpg |thumb|center|150px| Ewing sarcoma. [[PAS stain]]. (WC)]]
|-
|-
| [[Osteosarcoma]]
| [[Osteosarcoma]]
| osteoid
| osteoid
| Other features
| +/-hemorrhage, +/-cartilage
| Radiology / gross
| distal femur, prox. tibia, prox. humerous
| Clinical
| typically 10-30 years, pain, swelling
| no stains; many subtypes
| no stains; many subtypes
| [http://commons.wikimedia.org/wiki/File:Osteosarcoma_-_very_high_mag.jpg very high mag.]
| [[Image:Osteosarcoma_-_very_high_mag.jpg |thumb|center|150px|Osteosarcoma. (WC)]]
|-
|-
| [[Giant cell tumour of bone]]
| [[Giant cell tumour of bone]]
| abundant giant cells
| abundant giant cells
| nuclei of surrounding cells similar to those in giant cells
| nuclei of surrounding cells similar to those in giant cells
| Radiology / gross
| growth plate of long bones
| Clinical
| 20-45 years old, +/-joint pain, +/-immobility
| IHC / other
| IHC / other
| [http://commons.wikimedia.org/wiki/File:Giant_cell_tumour_of_bone_-_high_mag.jpg high mag.]
| [[Image:Giant_cell_tumour_of_bone_-_high_mag.jpg|thumb|center|150px|Giant cell tumour. (WC)]]
|-
|-
|}
|}
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====Cartilage tumours====
====Cartilage tumours====
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
| Entity
! Entity
| Key feature
! Key feature
| Other features
! Other features
| Radiology / gross
! Radiology / gross
| Clinical
! Clinical
| Stains / other
! Stains / other
| Image
! Image
|-
|-
| [[Enchondroma]]
| [[Chondroma]]
| Key feature
| ctyologically benign cells
| Other features
| equally spaced nests
| Radiology / gross
| usu. diaphysis
| Clinical
| benign / DDx: chondroma, well-diff. chondrosarcoma
| IHC / other
| IHC / bone marrow cavity chondroma = ''enchondroma''
| Image
| [[Image:Enchondroma_-_very_high_mag.jpg |thumb|center|150px| Enchondroma. (WC)]]
|-
|-
| [[Chondroblastoma]]
| [[Chondroblastoma]]
| Key feature
| abundant extracellular material, abundant eosinophilic cytoplasm
| Other features
| calcifications surround cells nests ("chickenwire" appearance) - '''classic'''
| Radiology / gross
| epiphysis
| Clinical
| DDx: [[giant cell tumour of bone]]
| IHC / other
| S100+ve, vimentin +ve
| Image
| [[Image:Chondroblastoma_-_very_high_mag.jpg |thumb|center|150px| Chondroblastoma. (WC)]]
|-
|-
| [[Chondrosarcoma]]
| [[Chondrosarcoma]]
| Key feature
| cartilaginous appearance +/- nuclear atypia
| Other features
| lack osteoid, if present -> osteosarcoma
| Radiology / gross
| usu. diaphysis, classically hip; almost never distal extremity
| Clinical
| >40 years old
| IHC / other
| IHC / may be histologically benign looking
| Image
| [[Image:Chondrosarcoma_%282%29.jpg |thumb|center|150px|Chondrosarcoma. (WC)]]
|-
|-
|}
|}
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====Other====
====Other====
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
| Entity
! Entity
| Key feature
! Key feature
| Other features
! Other features
| Radiology / gross
! Radiology / gross
| Clinical
! Clinical
| Stains / other
! Stains / other
| Image
! Image
|-
|-
| [[Osteochondroma]]
| [[Osteochondroma]]
| Key feature
| benign bone and cartilage
| Other features
| Other features
| Radiology / gross
| metaphyseal lesions
| Clinical
| Clinical
| IHC / other
| IHC / other
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| bisphasic - stroma & epithelium
| bisphasic - stroma & epithelium
| Other features
| Other features
| Radiology / gross
| tibia, fibula, intracortical, radiolucent
| Clinical
| Clinical
| IHC / other
| IHC / other
| Image
| [[Image:Adamantinoma_-_intermed_mag.jpg |thumb|center|150px|Adamantinoma. (WC)]]
|-
|-
| [[Diffuse tenosynovial giant-cell tumour]] ([[AKA]] [[PVNS]])
| [[Diffuse tenosynovial giant-cell tumour]] ([[AKA]] [[PVNS]])
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| Clinical
| Clinical
| IHC / other
| IHC / other
| Image
| [[Image:Pigmented_villonodular_synovitis_low_mag.jpg |thumb|center|150px| PVNS. (WC)]]
|-
|-
| [[Brown tumour]]
| [[Brown tumour]]
| Key feature
| fibrosis, +/-giant cells
| Other features
| unaffected bone incr. osteoblasts and osteoclasts
| Radiology / gross
| Radiology / gross
| due to hypercalcemia; not a neoplasm
| due to hypercalcemia; not a neoplasm
| IHC / other
| IHC / other
| Image
| [[Image:Brown_tumour_-_low_mag.jpg |thumb|center|150px| Brown tumour. (WC)]]
|-
|-
|}
|}


=Cartilage=
====Radiology====
==Enchondroma==
=====Radiologic features=====
===General===
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Benign thingy.
! Features
*Usu. legs and feet.
! Benign
*May be difficult to separate from chondrosarcoma.
! Malignant
*Multiple chondromas = ''enchondromatosis''; three distinct syndromes.<ref name=emed_enchondroma>URL: [http://emedicine.medscape.com/article/389224-overview http://emedicine.medscape.com/article/389224-overview]. Accessed on: 25 December 2010.</ref>
|-
| 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",<br> "onion skin", Codman's triangle
|}


Radiology:<ref name=emed_enchondroma>URL: [http://emedicine.medscape.com/article/389224-overview http://emedicine.medscape.com/article/389224-overview]. Accessed on: 25 December 2010.</ref>
=====Location=====
*Lytic lesion.
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Usu. close to a growth plate.
! 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 of 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{{fact}} <!-- PMID 12873205 questions this -->
| most common
| common
| [[bone]]/[[cartilage]]
|-
| [[Osteoid osteoma]]
| uncommon
| common
| common<ref name=wheelessonline>URL: [http://www.wheelessonline.com/ortho/osteoid_osteoma http://www.wheelessonline.com/ortho/osteoid_osteoma]. Accessed on: 7 May 2012</ref>
| [[bone]]
|-
| [[Osteosarcoma]]
| rare
| most common
| uncommon
| [[bone]]
|}


Clinical:<ref name=emed_enchondroma>URL: [http://emedicine.medscape.com/article/389224-overview http://emedicine.medscape.com/article/389224-overview]. Accessed on: 25 December 2010.</ref>
How to remember the primary bone lesions:
*Pain.
#''Ewing sarcoma'' is the only malignant primary bone tumour of the diaphysis.
#''Giant cell tumour of bone'' is the only primary bone lesion of the epiphysis.
#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.


===Microscopic===
How to remember the primary cartilaginous lesions:
Features:
#''Chondroblastoma'' is epiphyseal.  The chicken wire goes around the chicken coop.
*Ctyologically benign cells is spaced nests.
#The others are diaphyseal.


Images:
=Cartilage=
*[http://commons.wikimedia.org/wiki/File:Enchondroma_-_intermed_mag.jpg Enchondroma - intermed mag. (WC)].
==Chondroma==
*[http://commons.wikimedia.org/wiki/File:Enchondroma_-_very_high_mag.jpg Enchondroma - very high mag. (WC)].
{{Main|Chondroma}}


==Chondroblastoma==
==Chondroblastoma==
===General===
{{Main|Chondroblastoma}}
*Growth plate lesion.
*Sclerotic margin.
*"Young" = growth plates open.
 
===Microscopic===
Features:<ref name=Ref_WMSP_642>{{Ref WMSP|642}}</ref>
*Abundant extracellular material - pink on [[H&E stain]] - looks vaguely like cartilage.
*Chondroblasts:
**Nuclear morphology variable: ovoid, folded or grooved.
**Moderate-abundant eosinophilic cytoplasm.
*+/-Calcifications surround cells nests ("chickenwire" appearance) - '''classic feature'''.
*+/-Giant cells.
**May lead to confusion with ''giant cell tumour''.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Chondroblastoma_-_intermed_mag.jpg Chondroblastoma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Chondroblastoma_-_very_high_mag.jpg Chondroblastoma - very high mag. (WC)].
*[http://img.medscape.com/pi/emed/ckb/orthopedic_surgery/1230552-1254949-996.jpg Chondroblastoma (medscape.com)].<ref name=emed_chondroblastoma>URL: [http://emedicine.medscape.com/article/1254949-diagnosis http://emedicine.medscape.com/article/1254949-diagnosis]. Accessed on: 31 December 2010.</ref>
*[http://img.medscape.com/pi/emed/ckb/orthopedic_surgery/1230552-1254949-997.jpg Chondroblastoma with "chickenwire" appearance (medscape.com)].<ref name=emed_chondroblastoma>URL: [http://emedicine.medscape.com/article/1254949-diagnosis http://emedicine.medscape.com/article/1254949-diagnosis]. Accessed on: 31 December 2010.</ref>


===IHC===
==Chondromyxoid fibroma==
Features:<ref name=Ref_WMSP_642>{{Ref WMSP|642}}</ref>
{{Main|Chondromyxoid fibroma}}
*S100 +ve.
*Vimentin +ve.<ref name=emed_chondroblastoma>URL: [http://emedicine.medscape.com/article/1254949-diagnosis http://emedicine.medscape.com/article/1254949-diagnosis]. Accessed on: 31 December 2010.</ref>


==Chondrosarcoma==
==Chondrosarcoma==
===General===
{{Main|Chondrosarcoma}}
*Usually a good prognosis.


Clinical/epidemiologic features:<ref name=pmid17976362>{{cite journal |author=Skubitz KM, D'Adamo DR |title=Sarcoma |journal=Mayo Clin. Proc. |volume=82 |issue=11 |pages=1409–32 |year=2007 |month=November |pmid=17976362 |doi= |url=http://www.mayoclinicproceedings.com/content/82/11/1409.long}}</ref>
=Bone=
*Usually arise in a (benign) abnormality of cartilage (e.g. osteochondroma, enchondroma).
==Osteoma==
*May be associated with a syndrome:
{{Main|Osteoma}}
**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 chondrosarcoma.
===Microscopic===
Features:<ref>IAV. 26 February 2009.</ref><ref name=Ref_Klatt417>{{Ref Klatt|417}}</ref>
*"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.<ref>BD. 28 April 2011.</ref>
Images:
*[http://commons.wikimedia.org/wiki/File:Chondrosarcoma_(1).jpg Chondrosarcoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Chondrosarcoma_(2).jpg Chondrosarcoma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Chondrosarcoma_(3).jpg Chondrosarcoma - high mag. (WC)].
DDx:
*[[Chordoma]].
*[[Enchondroma]].
====Variants====
=====Mesenchymal chondrosarcoma=====
*Arise in soft tissue; this is where the name comes from.<ref name=pmid14161087>{{cite journal |author=Dowling EA |title=Mesenchymal chondrosarcoma |journal=J Bone Joint Surg Am |volume=46 |issue= |pages=747–54 |year=1964 |month=June |pmid=14161087 |doi= |url=http://www.ejbjs.org/cgi/reprint/46/4/747.pdf}}</ref>
*Rare variant of chondrosarcoma.
Microscopic:
Features:
*"White clouds in a blue sky".
Image:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/S0A001-PQ01-M.htm Mesenchymal chondrosarcoma (ouhsc.edu)].
=====Myxoid chondrosarcoma=====
Microscopic:
Features:
*[[Chordoma]]-like:
**Myxoid background.
**Small cells with eosinophilic cytoplasm.
DDx:
*Chondroid [[syringoma]].
*Parachordoma.<ref name=pmid10809219>{{cite journal |author=Fisher C |title=Parachordoma exists--but what is it? |journal=Adv Anat Pathol |volume=7 |issue=3 |pages=141–8 |year=2000 |month=May |pmid=10809219 |doi= |url=}}</ref>
*[[Chordoma]]. (???)
Image:
*[http://www.cttr.org/large/03113.jpg Extraskeletal myxoid chondrosarcoma (cttr.org)].<ref>URL: [http://www.cttr.org/cms/?p=736 http://www.cttr.org/cms/?p=736]. Accessed on: 1 May 2011.</ref>
====Grading====
Features:<ref name=Ref_WMSP643>{{Ref WMSP|643}}</ref>
*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=
==Osteoid osteoma==
==Osteoid osteoma==
===General===
{{Main|Osteoid osteoma}}
*Benign bone lesion.
 
Clinical:<ref name=Ref_Sternberg4_285>{{Ref Sternberg4|285}}</ref>
*Extremely painful.
**Relieved by NSAIDS.
 
===Microscopic===
Features:<ref name=Ref_Sternberg4_285>{{Ref Sternberg4|285}}</ref>
*Anastomosing bony [[trabeculae]] with:
**Variable mineralization.
***Mineralization (calcium '''p'''hosphate) = '''p'''urple on [[H&E stain]].
**Osteoblasts rimming.
***Cells line-up at edge of bone.
 
Images:
*[http://library.med.utah.edu/WebPath/COW/COW211.html Osteoid osteoma - CT scan (med.utah.edu)].
*[http://www.sciencephoto.com/images/imagePopUpDetails.html?pop=1&id=700030210&pviewid=&country=67&search=gschmeissners&matchtype=FUZZY Osteoid osteoma (sciencephoto.com)].
*[http://commons.wikimedia.org/w/index.php?title=File:Osteoid_osteoma_-_low_mag.jpg Osteoid osteoma - low mag. (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Osteoid_osteoma_-_high_mag.jpg Osteoid osteoma - high mag. (WC)].
 
Notes:
*Histomorphologically near identical/indistinguishable from ''osteoblastoma''.<ref name=Ref_Sternberg4_286>{{Ref Sternberg4|286}}</ref>


==Osteoblastoma==
==Osteoblastoma==
===General===
{{Main|Osteoblastoma}}
*Benign bone tumour.
 
===Microscopic===
Features:<ref name=Ref_Sternberg4_285>{{Ref Sternberg4|285}}</ref>
*Anastomosing bony [[trabeculae]] with:
**Osteoblasts rimming.
***Cells line-up at edge of bone.
 
Notes:
*Histomorphologically near identical/indistinguishable from ''osteoid osteoma''.<ref name=Ref_Sternberg4_286>{{Ref Sternberg4|286}}</ref>
*'''Must''' be greater 1.5 cm by definition.<ref name=Ref_Sternberg4_286>{{Ref Sternberg4|286}}</ref>
 
Images:
*[http://commons.wikimedia.org/w/index.php?title=File:Osteoblastoma_-_high_mag.jpg Osteoblastoma - high mag. (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Osteoblastoma_-_low_mag.jpg Osteoblastoma - low mag. (WC)].


==Ewing sarcoma==
==Ewing sarcoma==
*[[AKA]] EWS/pPNET, AKA (confusingly) EWS/PNET:
{{Main|Ewing sarcoma}}
**EWS = Ewing sarcoma.
**pPNET = peripheral primitive neuroectodermal tumour.
*EWS and pPNET were once thought to be different tumours.
 
Notes:
*''Peripheral primitive neuroectodermal tumour'' should not be confused with ''[[primitive neuroectodermal tumour]]'', commonly abbreviated ''PNET'', a (supertentorial) brain tumour with similarities to [[medulloblastoma]].
 
===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:<ref>PST. 14 February 2011.</ref>
*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.<ref name=pmid20953407>{{cite journal |author=Lin PP, Wang Y, Lozano G |title=Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma |journal=Sarcoma |volume=2011 |issue= |pages= |year=2011 |pmid=20953407 |pmc=2952797 |doi=10.1155/2011/276463 |url=}}</ref>
 
====Radiology====
Features:<ref name=Ref_WMSP650>{{Ref WMSP|650}}</ref>
*Long bones, diaphyses.
*Destructive.
*"Onion-skin" periosteal reaction.
 
===Microscopic===
Features:<ref>PST. 22 February 2010.</ref>
*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:
*It is a [[small round cell tumour]].
*[[Rhabdomyosarcoma]] occasionally has cytoplasmic clearing (due to glycogen).<ref name=PST14feb11>PST. 14 February 2011.</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Ewing_sarcoma_-_very_high_mag.jpg ES - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Ewing_sarcoma_-_PAS_-_very_high_mag.jpg ES - PAS - very high mag. (WC)].
 
===[[IHC]]===
Features:<ref name=Ref_WMSP651>{{Ref WMSP|651}}</ref>
*CD99 +ve -- 1. diffuse, 2. plasma membrane staining; both required -- most specific.
*FLI-1 +ve.<ref name=pmid15001993>{{cite journal |author=Rossi S, Orvieto E, Furlanetto A, Laurino L, Ninfo V, Dei Tos AP |title=Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody |journal=Mod. Pathol. |volume=17 |issue=5 |pages=547–52 |year=2004 |month=May |pmid=15001993 |doi=10.1038/modpathol.3800065 |url=http://www.nature.com/modpathol/journal/v17/n5/full/3800065a.html}}</ref>
*CD45 -ve.
**Done to r/o [[lymphoma]].
*+/-Neural markers (NSE, synaptophysin, CD57 (??? CD56 ???), S100).
*+/-Cytokeratins.
*Caveolin-1 +ve in ~ 85% of EWS.<ref>PST. 14 February 2011.</ref>
 
Notes:<ref>PST. 22 February 2010.</ref>
*CD99 +ve
**Plasma membrane staining tumours:
***[[Lymphoblastic lymphoma]]/leukemia.
***Angiomatoid fibrous histiocytoma.
***[[Desmoplastic small round cell tumour]].
**Weak/cytoplasmic staining:
***[[Synovial sarcoma]].
***[[Rhabdomyosarcoma]].
***[[Rhabdoid tumour]].
*FLI-1 +ve:<ref name=pmid15001993/>
**Vascular neoplasms.
**-/+[[Merkel cell carcinoma]].
**-/+Melanoma.
 
===Molecular diagnostics===
Common features:
*''EWS/FLI-1 fusion gene'' formation due to translocation: ''t(11;22)(q24;q12)''.<ref>URL: [http://atlasgeneticsoncology.org/Tumors/Ewing5010.html http://atlasgeneticsoncology.org/Tumors/Ewing5010.html]. Accessed on: 23 February 2010.</ref><ref name=pmid3163261>{{cite journal |author=Turc-Carel C, Aurias A, Mugneret F, ''et al.'' |title=Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12) |journal=Cancer Genet. Cytogenet. |volume=32 |issue=2 |pages=229–38 |year=1988 |month=June |pmid=3163261 |doi= |url=}}</ref>
**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:
**[[Olfactory neuroblastoma]].
**Small cell osteogenic sarcoma (small cell variant of [[osteosarcoma]]).
**Polyphenotypic tumours.
**[[Rhabdomyosarcoma]].
**[[Neuroblastoma]] (possibly).
*Several other translocations exist.
*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==
==Osteosarcoma==
*[[AKA]] osteogenic sarcoma.
{{Main|Osteosarcoma}}
 
===General===
*Most common malignant bone tumour in children.
 
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).
 
===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.<ref>{{cite journal |author=Papalas JA, Balmer NN, Wallace C, Sangueeza OP |title=Ossifying dermatofibroma with osteoclast-like giant cells: report of a case and literature review |journal=Am J Dermatopathol |volume=31 |issue=4 |pages=379-83 |year=2009 |month=June |pmid=19461244 |doi=10.1097/DAD.0b013e3181966747 |url=}}</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Osteosarcoma_-_intermed_mag.jpg Osteosarcoma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Osteosarcoma_-_very_high_mag.jpg Osteosarcoma - very high mag. (WC)].
 
====Subtypes====
*Many subtypes exist.
 
Subclassification:<ref>{{Ref WMSP|638}}</ref><ref>URL: [http://bestpractice.bmj.com/best-practice/monograph/780/basics/classification.html http://bestpractice.bmj.com/best-practice/monograph/780/basics/classification.html]. Accessed on: 7 April 2011.</ref>
*Conventional osteosarcoma (high grade).
**Osteoblastic.
**Fibroblastic - [[undifferentiated pleomorphic sarcoma]]-like/[[MFH]]-like.
**Chondroblastic - may be confused with [[chondrosarcoma]].
*Small cell - may mimic (other) [[small round cell tumours]].
*Telangiectatic - extremely vascular.
*Parosteal.
**Low grade.
**Arises from surface of bone.<ref>{{Ref WHOSTAB|279}}</ref>
*Periosteal.
*Low grade central.
*High grade surface.
*Secondary - arise due to something else (e.g. [[Paget disease of the bone]] (~80% of secondary osteosarcomas),  radiation (~15% of secondary osteosarcomas)).<ref>URL: [http://www.rsna.org/REG/publications/rg/afip/privateM/1997/0017/0005/1205/6.htm http://www.rsna.org/REG/publications/rg/afip/privateM/1997/0017/0005/1205/6.htm]. Accessed on: 8 April 2011.</ref>
*Gnathic - jaw bones; usu. chondroblastic.


==Giant cell tumour of bone==
==Giant cell tumour of bone==
===General===
{{Main|Giant cell tumour of bone}}
Features:<ref name=Ref_WMSP648>{{Ref WMSP|648}}</ref>
*Approximately 5% of primary bone tumours.
*Typical age: 20-45 years.


====Clinical====
=Other=
*May present with joint pain, immobility.
This section collects stuff that doesn't neatly fit into the ''bone'' or ''cartilage'' category.
 
Note:
*Several types of giant cell tumours exist.
 
===Microscopic===
Features:<ref name=Ref_Klatt420>{{Ref Klatt|420}}</ref>
*Giant cells with abundant 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'''.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Giant_cell_tumour_of_bone_-_high_mag.jpg GCT of bone - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Giant_cell_tumour_of_bone_-_low_mag.jpg GCT of bone - low mag. (WC)].


===IHC===
==Notochordal tumors==
*p63 +ve in scattered mononuclear cells.<ref name=pmid18311114>{{cite journal |author=Dickson BC, Li SQ, Wunder JS, ''et al.'' |title=Giant cell tumor of bone express p63 |journal=Mod. Pathol. |volume=21 |issue=4 |pages=369–75 |year=2008 |month=April |pmid=18311114 |doi=10.1038/modpathol.2008.29 |url=}}</ref>
Notochordal tumors arise from notochordal remnants and thus are seen in the clivus or sacrum.
**This seems to be contradicted by another paper.<ref name=pmid20012988>{{cite journal |author=Alberghini M, Kliskey K, Krenacs T, ''et al.'' |title=Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone |journal=Virchows Arch. |volume=456 |issue=1 |pages=97–103 |year=2010 |month=January |pmid=20012988 |doi=10.1007/s00428-009-0863-2 |url=}}</ref>
{{Main|Chordoma}}


=Other=
This section collects stuff that doesn't neatly fit into the ''bone'' or ''cartilage'' category.
==Osteochondroma==
==Osteochondroma==
===General===
{{Main|Osteochondroma}}
*Benign metaphyseal lesions.
*Very common.
*Abnormal outgrowth of bone and cartilage.
 
===Microscopic===
Features:
*Normal bone and cartilage.


==Diffuse tenosynovial giant-cell tumour==  
==Diffuse tenosynovial giant-cell tumour==  
*[[AKA]] ''tenosynovial giant-cell tumour, diffuse type''.
*[[AKA]] ''tenosynovial giant-cell tumour, diffuse type''.
*Previously known as ''pigmented villonodular synovitis'' (PVNS).<ref>{{Ref PBoD8|1247}}</ref>  
*Previously known as ''pigmented villonodular synovitis'' (PVNS).<ref>{{Ref PBoD8|1247}}</ref>  
{{Main|Diffuse tenosynovial giant-cell tumour}}


===General===
==Giant cell tumour of tendon sheath==
*Course: benign.
*Abbreviated ''GCT of tendon sheath''.
*''Giant cell tumor of the tendon sheath'' is considered to be the soft-tissue counterpart of PVNS.<ref>URL: [http://emedicine.medscape.com/article/1253223-overview http://emedicine.medscape.com/article/1253223-overview]. Accessed on: 6 January 2011.</ref>
{{Main|Giant cell tumour of tendon sheath}}
 
===Microscopic===
Features:<ref>URL: [http://www.wheelessonline.com/ortho/pigmented_villonodular_synovitis http://www.wheelessonline.com/ortho/pigmented_villonodular_synovitis].</ref>
*Subsynovial nodules composed of cells with:
**Abundant cytoplasm.
**Pale nuclei.
*Multinucleated giant cells.
*Hemosiderin-laden macrophages.
*Foam cells.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Pigmented_villonodular_synovitis_low_mag.jpg PVNS - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Pigmented_villonodular_synovitis_high_mag.jpg PVNS - high mag. (WC)].


==Adamantinoma==
==Adamantinoma==
===General===
{{Main|Adamantinoma}}
Features:<ref name=Ref_WMSP650>{{Ref WMSP|650}}</ref>
*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:
*#Fibrous/spindle cell component.
*#Epithelial component.
 
Images:
*[http://southbaypath.org/CaseImages/sb5260/AdamantinomaBiopsy3.jpg Adamantinoma (southbaypath.org)].<ref>URL: [http://southbaypath.org/CaseImages/sb5260/sb5260.htm http://southbaypath.org/CaseImages/sb5260/sb5260.htm]. Accessed on: 7 December 2010.</ref>
*[http://commons.wikimedia.org/wiki/File:Adamantinoma_-_intermed_mag.jpg Adamantinoma - intermed. mag. (WC)].
 
DDx:<ref name=pathcon_adam>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970057-2 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970057-2]. Accessed on: 28 April 2011.</ref>
*Vascular tumours ([[Epithelioid hemangioendothelioma]]).
*Metastatic carcinoma.
 
===IHC===
Features:<ref name=pathcon_adam/>
*CK14 +ve (HMWK).<ref>URL: [http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm]. Accessed on: 28 April 2011.</ref>
*CK19 +ve (LMWK).
*CK8/18 -ve (LMWK).


==Brown tumour==
==Brown tumour==
===General===
===General===
*''Not'' a true neoplasm,<ref name=pmid16775919>{{cite journal |author=Meydan N, Barutca S, Guney E, ''et al.'' |title=Brown tumors mimicking bone metastases |journal=J Natl Med Assoc |volume=98 |issue=6 |pages=950–3 |year=2006 |month=June |pmid=16775919 |pmc=2569361 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569361/?page=1 }}</ref> i.e. the name is a misnomer.
*''Not'' a true neoplasm.<ref name=pmid16775919>{{cite journal |author=Meydan N, Barutca S, Guney E, ''et al.'' |title=Brown tumors mimicking bone metastases |journal=J Natl Med Assoc |volume=98 |issue=6 |pages=950–3 |year=2006 |month=June |pmid=16775919 |pmc=2569361 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569361/?page=1 }}</ref>  
**If ''tumour'' is understood as a synonym for ''neoplasm'', the name is a misnomer.
**May (clinically) mimic a true neoplasm.
**May (clinically) mimic a true neoplasm.
*Due to hyperparathyroidism - usually parathyroid adenoma.
*Due to hyperparathyroidism - usually [[parathyroid adenoma]].
**Usually secondary to chronic renal failure.
**Usually secondary to chronic renal failure.


====Hypercalcemia DDx====
====Hypercalcemia DDx====
Mnemonic ''GRIMED'':<ref>TN06 Emerg.</ref>
Mnemonic ''GRIMED'':<ref>{{Ref TN2006 |Emerg.}}</ref>
*Granulomatous disease (tuberculosis, [[sarcoidosis]]).
*Granulomatous disease (tuberculosis, [[sarcoidosis]]).
*Renal disease.
*Renal disease.
*Immobility.
*Immobility.
*Malignancy (esp. squamous cell carcinoma, [[plasmacytoma]]).
*Malignancy (esp. [[squamous cell carcinoma]], [[plasmacytoma]]).
*Endocrine (primary hyperparathyroidism - leads to brown cell tumour).
*Endocrine ([[parathyroid gland|primary hyperparathyroidism]] - leads to [[brown tumour]]).
*Drugs (thiazides ... others).
*Drugs (thiazides ... others).


Line 607: Line 381:
Features:
Features:
*Fibrosis.
*Fibrosis.
*+/-Giant cells.
*+/-Giant cells with round to oval nuclei and nucleoli.<ref>URL: [http://path.upmc.edu/cases/case139/micro.html http://path.upmc.edu/cases/case139/micro.html]. Accessed on: 6 January 2012.</ref>
*Bone unaffected by tumour - increased numbers of the following:
**Multinucleated cells (osteoclasts).
**Mononuclear cells around the bony trabeculae (osteoblasts).


DDx:
DDx:
*[[Giant cell tumour of bone]] and other [[giant cell lesions]].
*[[Giant cell tumour of bone]] and other [[giant cell lesions]].
====Images====
<gallery>
Image:Brown_tumour_-_low_mag.jpg | Brown tumour - low mag. (WC)
Image:Brown_tumour_-_intermed_mag.jpg | Brown tumour - intermed. mag. (WC)
Image:Brown_tumour_-_high_mag.jpg | Brown tumour - high mag. (WC)
</gallery>
www:
*[http://wwwold.path.utah.edu/classes/webpath/bonehtml/bone053.htm Brown tumour (utah.edu)].
*[http://www.mda-sy.com/pathology/BONEHTML/BONE054.HTM Brown tumour (mda-sy.com)].
*[http://path.upmc.edu/cases/case139/micro.html Brown tumour - several images (upmc.edu)].


=See also=
=See also=
Line 622: Line 410:
=External links=
=External links=
*[http://www.medpath.info/MainContent/Skeletal/Bone_07.html Bone lesions (medpath.info)].
*[http://www.medpath.info/MainContent/Skeletal/Bone_07.html Bone lesions (medpath.info)].
*[http://www.radiologyassistant.nl/en/494e15cbf0d8d Bone radiology (radiologyassistant.nl)].


[[Category:Chondro-osseous tumours]]
[[Category:Weird stuff]]
[[Category:Weird stuff]]
Michael
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