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*Diaphysis = shaft, mid-portion, contains [[bone marrow]].
*Diaphysis = shaft, mid-portion, contains [[bone marrow]].


Image:
===Image===
*[http://commons.wikimedia.org/wiki/File:EpiMetaDiaphyse.jpg Bone (WC)].
<gallery>
Image:EpiMetaDiaphyse.jpg | Bone. (WC)
</gallery>


==Bone Matrix==
==Bone histology==
Two types (based on arrangement of collagen):
Two types (based on arrangement of collagen):
#Woven.
# Woven bone.
#*Always abnormal in adults.
# Lamellar bone.
#*Collagen arranged haphazardly - mechanically weak.  
#Lamellar.
#*Collagen organized in layers (lamellae).


Woven vs. lamellar:
===Woven bone===
*Easiest way to differentiate: polarize; lamellar bone has well-defined layers.
*Always abnormal in adults.
*Collagen arranged haphazardly - mechanically weak.  


Images:
Images:
*[http://www.ajnr.org/cgi/content-nw/full/27/2/274/F4 Woven bone (ajnr.org)].<ref name=pmid16484391>{{cite journal |author=Lin DD, Gailloud P, McCarthy EF, Comi AM |title=Oromaxillofacial osseous abnormality in Sturge-Weber syndrome: case report and review of the literature |journal=AJNR Am J Neuroradiol |volume=27 |issue=2 |pages=274–7 |year=2006 |month=February |pmid=16484391 |doi= |url=}}</ref>
*[http://www.ajnr.org/cgi/content-nw/full/27/2/274/F4 Woven bone (ajnr.org)].<ref name=pmid16484391>{{cite journal |author=Lin DD, Gailloud P, McCarthy EF, Comi AM |title=Oromaxillofacial osseous abnormality in Sturge-Weber syndrome: case report and review of the literature |journal=AJNR Am J Neuroradiol |volume=27 |issue=2 |pages=274–7 |year=2006 |month=February |pmid=16484391 |doi= |url=}}</ref>
*[http://www.brown.edu/Courses/Digital_Path/systemic_path/bone/paget.html Woven bone (brown.edu)].
*[http://www.brown.edu/Courses/Digital_Path/systemic_path/bone/paget.html Woven bone (brown.edu)].
===Lamellar bone===
[[File:Lamella bone H&E and under polarised light.gif|thumb|Animated GIF showing a photomicrograph of lamellar bone. The layers are accentuated under polarised light.]]
*Collagen organized in layers (lamellae).
===Woven versus lamellar===
*Easiest way to differentiate: polarize; lamellar bone has well-defined layers.


==Bone cells==
==Bone cells==
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==Bone marrow==
==Bone marrow==
{{Main|Haematopoiesis}}
{{Main|Haematopoiesis}}
===General===
*One of two ''[[primary lymphoid organs]]'' - the other one is the [[thymus]].<ref>URL: [http://www.life.umd.edu/classroom/bsci423/song/Lab1.html http://www.life.umd.edu/classroom/bsci423/song/Lab1.html]. Accessed on: 28 March 2012.</ref>
*One of two ''[[primary lymphoid organs]]'' - the other one is the [[thymus]].<ref>URL: [http://www.life.umd.edu/classroom/bsci423/song/Lab1.html http://www.life.umd.edu/classroom/bsci423/song/Lab1.html]. Accessed on: 28 March 2012.</ref>
Bone marrow biopsy adequacy:<ref name=pmid16477878>{{Cite journal  | last1 = Rudzki | first1 = Z. | last2 = Partyła | first2 = T. | last3 = Okoń | first3 = K. | last4 = Stachura | first4 = J. | title = Adequacy of trephine bone marrow biopsies: the doctor and the patient make a difference. | journal = Pol J Pathol | volume = 56 | issue = 4 | pages = 187-95 | month =  | year = 2005 | doi =  | PMID = 16477878 }}</ref>
*10 intertrabecular spaces or 10 mm.
===Microscopic===
One should see three cell lines:<ref>URL: [http://emedicine.medscape.com/article/199003-overview http://emedicine.medscape.com/article/199003-overview]. Accessed on: 28 March 2012.</ref>
#Erythroid (red cells).
#Myeloid (white blood cells).
#Megakaryocytic (platelets).
Adipose tissue:
*Fat content (%) ~= age in years.<ref>IAV. 26 Feb 2009.</ref>
*Fat content (%) ~= age in years.<ref>IAV. 26 Feb 2009.</ref>
**e.g. 60 year old will have 60% fatty replacement.
**e.g. 60 year old will have 60% fatty replacement.


*One should see three cell lines:<ref>URL: [http://emedicine.medscape.com/article/199003-overview http://emedicine.medscape.com/article/199003-overview]. Accessed on: 28 March 2012.</ref>
Identifying the cell lines:<ref>[http://upload.wikimedia.org/wikipedia/commons/6/69/Hematopoiesis_%28human%29_diagram.png http://upload.wikimedia.org/wikipedia/commons/6/69/Hematopoiesis_%28human%29_diagram.png]</ref>
*#Erythroid (red cells).
*#Myeloid (white blood cells).
*#Megakaryocytic (platelets).
 
Note: Lymphocytes are considered separately and typically spared in bone marrow failure.<ref>[http://emedicine.medscape.com/article/199003-overview http://emedicine.medscape.com/article/199003-overview]</ref>
 
Identifying the lines:<ref>[http://upload.wikimedia.org/wikipedia/commons/6/69/Hematopoiesis_%28human%29_diagram.png http://upload.wikimedia.org/wikipedia/commons/6/69/Hematopoiesis_%28human%29_diagram.png]</ref>
#Megakaryocytes:
#Megakaryocytes:
#*Big cells ~ 3x the size of a [[RBC]].
#*Big cells ~ 3x the size of a [[RBC]].
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#*Reniform nucleus, i.e. kidney bean shaped nucleus.
#*Reniform nucleus, i.e. kidney bean shaped nucleus.


Images:
Note:  
*[http://commons.wikimedia.org/wiki/File:Bone_marrow_WBC.JPG Myeloid line (WC)].
*Lymphocytes are considered separately and typically spared in bone marrow failure.<ref>[http://emedicine.medscape.com/article/199003-overview http://emedicine.medscape.com/article/199003-overview]</ref>
 
====Organization====
====Organization====
*Mature hematopoeitic cells at the centre (distant from bone).
*Mature hematopoeitic cells at the centre (distant from bone).
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*Immediately adjacent to the bone (paratrabecular)... is where [[follicular lymphoma]] is classically found.<ref name=pmid17284114>{{Cite journal  | last1 = Iancu | first1 = D. | last2 = Hao | first2 = S. | last3 = Lin | first3 = P. | last4 = Anderson | first4 = SK. | last5 = Jorgensen | first5 = JL. | last6 = McLaughlin | first6 = P. | last7 = Medeiros | first7 = LJ. | title = Follicular lymphoma in staging bone marrow specimens: correlation of histologic findings with the results of flow cytometry immunophenotypic analysis. | journal = Arch Pathol Lab Med | volume = 131 | issue = 2 | pages = 282-7 | month = Feb | year = 2007 | doi = 10.1043/1543-2165(2007)131[282:FLISBM]2.0.CO;2 | PMID = 17284114 }}</ref>
*Immediately adjacent to the bone (paratrabecular)... is where [[follicular lymphoma]] is classically found.<ref name=pmid17284114>{{Cite journal  | last1 = Iancu | first1 = D. | last2 = Hao | first2 = S. | last3 = Lin | first3 = P. | last4 = Anderson | first4 = SK. | last5 = Jorgensen | first5 = JL. | last6 = McLaughlin | first6 = P. | last7 = Medeiros | first7 = LJ. | title = Follicular lymphoma in staging bone marrow specimens: correlation of histologic findings with the results of flow cytometry immunophenotypic analysis. | journal = Arch Pathol Lab Med | volume = 131 | issue = 2 | pages = 282-7 | month = Feb | year = 2007 | doi = 10.1043/1543-2165(2007)131[282:FLISBM]2.0.CO;2 | PMID = 17284114 }}</ref>
**Image: [http://www.flickr.com/photos/euthman/5691578596/in/set-72057594114099781 Paratrabecular follicular lymphoma (flickr.com)].
**Image: [http://www.flickr.com/photos/euthman/5691578596/in/set-72057594114099781 Paratrabecular follicular lymphoma (flickr.com)].
===Images===
<gallery>
Image:Bone_marrow_WBC.JPG| Myeloid line. (WC)
</gallery>
===Sign out===
====Essentially normal====
<pre>
Bone Marrow, Posterior Superior Iliac Spine, Biopsy:
- Bone marrow with trilineage hematopoiesis.
- Cellularity within normal limits for age.
- Case will be sent to hematology for consultation and correlation
  with other testing.
</pre>
====Inadequate====
<pre>
Right Posterior Superior Iliac Spine, Bone Marrow Biopsy:
- Predominantly benign dense fibrous tissue with a small
  amount of laminar bone, and minute fragment of marrow (<2 mm).
- Case will be sent to hematopathology for further assessment.
</pre>


=Benign variants=
=Benign variants=
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===Sign out===
===Sign out===
<pre>
LOWER LEG, RIGHT, BELOW KNEE AMPUTATION:
LOWER LEG, RIGHT, BELOW KNEE AMPUTATION:
- ACUTE AND CHRONIC OSTEOMYELITIS.
- ACUTE AND CHRONIC OSTEOMYELITIS.
- MODERATE ATHEROSCLEROSIS.
- MODERATE ATHEROSCLEROSIS.
- SKIN ULCERATION.
- SOFT TISSUE SURGICAL MARGIN WITH FAT NECROSIS AND MUSCULAR ATROPHY.
- NEGATIVE FOR MALIGNANCY.
- NEGATIVE FOR MALIGNANCY.
- SOFT TISSUE SURGICAL MARGIN WITH FAT NECROSIS AND MUSCULAR ATROPHY.
</pre>
 
<pre>
TRAPEZIUM, RIGHT HAND, REMOVAL:
- DEGENERATIVE JOINT DISEASE.
- MARROW SPACE WITH FIBROSIS AND SCATTERED LYMPHOCYTES AND PLASMA CELLS,
  COMPATIBLE WITH MILD CHRONIC OSTEOMYELITIS.
- NO MICROORGANISMS APPARENT WITH ROUTINE STAINS.
- NEGATIVE FOR MALIGNANCY.
</pre>


=Bone tumours=
=Bone tumours=
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A general DDx for cystic bone lesions is found on ''radipedia.com''.<ref>URL: [http://radipedia.com/WikiMedia/index.php?title=Benign_cystic_bone_lesions http://radipedia.com/WikiMedia/index.php?title=Benign_cystic_bone_lesions]. Accessed on: 15 March 2011.</ref>
A general DDx for cystic bone lesions is found on ''radipedia.com''.<ref>URL: [http://radipedia.com/WikiMedia/index.php?title=Benign_cystic_bone_lesions http://radipedia.com/WikiMedia/index.php?title=Benign_cystic_bone_lesions]. Accessed on: 15 March 2011.</ref>
==Sequestrum==
{{Main|Sequestrum}}


==Osteoarthritis==
==Osteoarthritis==
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==Aneurysmal bone cyst==
==Aneurysmal bone cyst==
*Abbreviated ''ABC''.
{{Main|Aneurysmal bone cyst}}
:''Also see [[giant cell reparative granuloma]]'' ([[AKA]] ''solid aneurysmal bone cyst'').
 
===General===
Features:<ref name=emed_abc>URL: [http://emedicine.medscape.com/article/1254784-overview http://emedicine.medscape.com/article/1254784-overview]. Accessed on: 4 February 2011.</ref>
*Benign.
**May grow rapidly.
*Osteolysis -> cystic space -> filled with blood.
*Relatively common; in children second only to [[osteosarcoma]].<ref name=pmid18157043>{{cite journal |author=van den Berg H, Kroon HM, Slaar A, Hogendoorn P |title=Incidence of biopsy-proven bone tumors in children: a report based on the Dutch pathology registration "PALGA" |journal=J Pediatr Orthop |volume=28 |issue=1 |pages=29–35 |year=2008 |pmid=18157043 |doi=10.1097/BPO.0b013e3181558cb5 |url=}}</ref>
 
===Gross/radiologic===
Features:<ref name=pmid22531523>{{Cite journal  | last1 = Parashari | first1 = UC. | last2 = Khanduri | first2 = S. | last3 = Upadhyay | first3 = D. | last4 = Bhadury | first4 = S. | last5 = Singhal | first5 = S. | title = Radiologic and pathologic correlation of aneurysmal bone cysts at unusual sites. | journal = J Cancer Res Ther | volume = 8 | issue = 1 | pages = 103-5 | month =  | year =  | doi = 10.4103/0973-1482.95183 | PMID = 22531523 }}</ref>
*Air-fluid levels (radiology).
*Usually metaphysis of long bones, but uncommonly the femur.
*May have an "aggressive" appearance, i.e. erode bone.
 
===Microscopic===
Features:<ref name=emed_abc/>
*Bony trabeculae ''or'' osteoid tissue.
*Osteoclast [[giant cell]]s.
**Multi-nucleated giant-cells with round randomly arranged nuclei.
*Benign spindle cells (fibroblasts) - surround bone/adjacent to the giant cells - '''important'''.
*Blood +/- surrounded by giant cells.
 
DDx:
*[[Giant cell tumour of bone]] - the nuclei of the cells surrounding the giant cells are similar to those in the giant cells (round nuclei).
*[[Telangiectatic osteosarcoma]].
*Other [[giant cell lesions]].
 
Images:
*WC:
**[http://commons.wikimedia.org/wiki/File:Aneurysmal_bone_cyst_-_intermed_mag.jpg ABC - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Aneurysmal_bone_cyst_-_very_high_mag.jpg ABC - very high mag. (WC)].
*www:
**[http://www.webpathology.com/image.asp?n=4&Case=344 ABC - low mag. (webpathology.com)].
**[http://www.webpathology.com/image.asp?n=5&Case=344 ABC - intermed. mag. (webpathology.com)].
**[http://www.webpathology.com/image.asp?case=344&n=6 ABC - high mag. (webpathology.com)].


==Myositis ossificans==
==Myositis ossificans==
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**Lesion is well-circumscribed.
**Lesion is well-circumscribed.
**Normal muscle is adjacent to the lesion - '''key feature'''.
**Normal muscle is adjacent to the lesion - '''key feature'''.
DDx:
*[[Heterotopic ossification]] - bone, not cellular, no inflammation.


Images:
Images:
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==Paget disease of the bone==
==Paget disease of the bone==
===General===
{{Main|Paget's disease of the bone}}
*Benign - unlike [[Paget disease of the breast]].
*Afflicts ~ 3% of population > 55 years old.<ref name=pmid22396921/>
*Leading cause of ''secondary [[osteosarcoma]]''.
*Uncommonly associated with [[giant cell tumour of bone]].<ref name=pmid17437100>{{Cite journal  | last1 = Hoch | first1 = B. | last2 = Hermann | first2 = G. | last3 = Klein | first3 = MJ. | last4 = Abdelwahab | first4 = IF. | last5 = Springfield | first5 = D. | title = Giant cell tumor complicating Paget disease of long bone. | journal = Skeletal Radiol | volume = 36 | issue = 10 | pages = 973-8 | month = Oct | year = 2007 | doi = 10.1007/s00256-007-0310-x | PMID = 17437100 }}</ref><ref name=pmid21319038>{{Cite journal  | last1 = Karakida | first1 = K. | last2 = Ota | first2 = Y. | last3 = Aoki | first3 = T. | last4 = Akamatsu | first4 = T. | last5 = Kajiwara | first5 = H. | last6 = Hirabayashi | first6 = K. | title = Multiple giant cell tumors in maxilla and skull complicating Paget's disease of bone. | journal = Tokai J Exp Clin Med | volume = 35 | issue = 3 | pages = 112-7 | month = Sep | year = 2010 | doi =  | PMID = 21319038 }}</ref>
*[[Diagnosis]] based on radiology.<ref name=pmid22396921/>
*Genetic component - several genes implicated<ref name=omim602080>{{OMIM|602080}}</ref> including ''TNFRSF11A'' ([[AKA]] PDB2)<ref name=omim603499>{{OMIM|603499}}</ref> and ''PDB4''.<ref name=omim606263>{{OMIM|606263}}</ref>
 
====Clinical====
Presentation:<ref name=pmid22396921>{{Cite journal  | last1 = Britton | first1 = C. | last2 = Walsh | first2 = J. | title = Paget disease of bone - an update. | journal = Aust Fam Physician | volume = 41 | issue = 3 | pages = 100-3 | month = Mar | year = 2012 | doi =  | PMID = 22396921 | URL = http://www.racgp.org.au/afp/201203/201203britton.pdf }}</ref>
*[[Fracture of bone|Fracture]].
*Bone pain.
*Bony deformity.
*Deafness.
*Incidental finding - radiologic or biochemical.
 
Serology:
*Elevated ALP.
 
Clinical features - mnemonic ''PANICS'':<ref>URL: [http://www.medicalgeek.com/orthopedics/2743-orthopedics-mnemonics.html http://www.medicalgeek.com/orthopedics/2743-orthopedics-mnemonics.html]. Accessed on: 30 April 2012.</ref>
*'''P'''ain (bone).
*'''A'''rthralgia and '''A'''LP elevated.
*'''N'''erve compression - deafness.
*'''I'''ncreased bone density.
*'''C'''ardiac failure (high output) - due to AVM formation in bone.
*'''S'''unburst skull on X-ray.
 
====Stage====
Classically divided into three phases:<ref name=emed_paget>URL: [http://emedicine.medscape.com/article/311688-overview http://emedicine.medscape.com/article/311688-overview]. Accessed on: 25 December 2010.</ref><ref>URL: [http://radiopaedia.org/articles/paget-disease-of-bone-1 http://radiopaedia.org/articles/paget-disease-of-bone-1]. Accessed on: 25 December 2010.</ref>
#Lytic (predominantly osteoclasts).
#Mixed lytic (osteoclastic) and blastic (osteoblastic).
#Sclerotic (burned-out).
 
===Microscopic===
Features:<ref name=emed_paget>URL: [http://emedicine.medscape.com/article/311688-overview http://emedicine.medscape.com/article/311688-overview]. Accessed on: 25 December 2010.</ref>
*Bone matrix has jigsaw-puzzle like pattern.
**Jigsaw-puzzle pieces each ~ 100-500 micrometres in size (largest dimension).
*Increased osteoclast activity.
**Osteoclast = macrophage that reabsorbs bone matrix.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Paget_disease_of_bone_-_high_mag.jpg Paget disease - bone - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Paget_disease_of_bone_-_intermed_mag.jpg Paget disease - bone - intermed. mag. (WC)].


==Fibrous dysplasia==
==Fibrous dysplasia==
*[[AKA]] ''osteitis fibrosa''.
*[[AKA]] ''osteitis fibrosa''.
===General===
{{Main|Fibrous dysplasia}}
Classification:
*''Monostotic'' - one bone involved, ~80% of cases.
*''Polyostotic'' - several bones involved, ~20% of cases.
**May be associated with [[McCune-Albright syndrome]].
 
===Microscopic===
Features:<ref>URL: [http://www.pathologypics.com/pictview.aspx?id=104 http://www.pathologypics.com/pictview.aspx?id=104]. Accessed on: 14 April 2011.</ref>
*Woven bone with odd irregular shapes - '''key feature'''.
**Described as "chinese characters".<ref>URL: [http://www.pathcases.com/bone_tumors_and_tumor.htm http://www.pathcases.com/bone_tumors_and_tumor.htm]. Accessed on: 31 May 2011.</ref>
*Fibrous tissue around bone.
 
Notes:
*No osteoblastic rimming.
 
DDx:
*[[Desmoplastic fibroma]] - has lamellar bone.
*Low grade [[fibrosarcoma]].
*[[Low-grade central osteosarcoma]].<ref name=inwards>{{cite journal |author=Inwards, CY |title=Low-grade central osteosarcoma versus fibrous dysplasia |journal=Pathology Case Reviews |volume=6 |issue=1 |pages=22-27 |year=2001 |pmid= |doi= |url= http://journals.lww.com/pathologycasereviews/Fulltext/2001/01000/Low_Grade_Central_Osteosarcoma_Versus_Fibrous.5.aspx }}</ref>
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Fibrous_dysplasia_-_low_mag.jpg Fibrous dysplasia - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Fibrous_dysplasia_-_intermed_mag.jpg Fibrous dysplasia - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Fibrous_dysplasia_-_high_mag.jpg Fibrous dysplasia - high mag. (WC)].
*www:
**[http://www.pathologypics.com/pictview.aspx?id=104 Fibrous dysplasia of bone - high mag. (pathologypics.com)].
**[http://www.pathologypics.com/BigPicViewer.aspx?PictureID=103 Fibrous dysplasia of bone - low mag. (pathologypics.com)].


==Desmoplastic fibroma==
==Desmoplastic fibroma==
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DDx:
DDx:
*[[Fibrous dysplasia]] - has woven bone.
*[[Fibrous dysplasia]] - has woven bone.
*Low grade fibrosarcoma.
*Low grade [[fibrosarcoma]].


==Gaucher disease==
==Gaucher disease==
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*[[Giant cell tumour of bone]].
*[[Giant cell tumour of bone]].


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Central_giant_cell_granuloma_-_intermed_mag.jpg CGCG - intermed. mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Central_giant_cell_granuloma_-_high_mag.jpg CGCG - high mag. (WC)].
Image:Central_giant_cell_granuloma_-_intermed_mag.jpg | CGCG - intermed. mag. (WC/Nephron)
 
Image:Central_giant_cell_granuloma_-_high_mag.jpg | CGCG - high mag. (WC/Nephron)
</gallery>
===Molecular===
===Molecular===
Recurrent [[chromosomal translocation]]:<ref name=pmid22285042/>
Recurrent [[chromosomal translocation]]:<ref name=pmid22285042/>
Line 413: Line 360:
*[[Chondro-osseous tumours]].
*[[Chondro-osseous tumours]].
*[[Femoral head]].
*[[Femoral head]].
*[[Spine]].
*[[Hematopathology]].
*[[Hematopathology]].
*[[Soft tissue lesions]].
*[[Soft tissue lesions]].
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{{reflist|2}}
{{reflist|2}}


[[Category:Weird stuff]]
=External links=
*[http://www.medicalhistology.us/twiki/bin/view/Main/CartilageAndBoneAtlas08 Bone and cartilage histology (medicalhistology.us)].
 
[[Category:Bone]]
Mark
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