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Chondro-osseous tumours (view source)

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'''Bone tumours''' occasionally cross the desk of the pathologist.  Primary bone tumours are rare; the most common bone tumour is metastases.<ref name=Ref_WMSP632>{{Ref WMSP|632}}</ref> 
[[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]].  


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.
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.


==General==
==General==
*Diagnosis should not be made without radiologic & clinical information.
*Diagnosis of a primary bone tumour should not be made without radiologic & clinical information!
*Metastasis:primary bone tumours = >20:1.<ref name=Ref_WMSP632>{{Ref WMSP|632}}</ref>
*Metastasis:primary bone tumours = >20:1.<ref name=Ref_WMSP632>{{Ref WMSP|632}}</ref>


===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]].  
Line 20: Line 23:
***[[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.
*Chondrosarcoma -> from enchondroma or osteochrondroma -- patients over 40 yrs.
*Chondrosarcoma -> from enchondroma or osteochrondroma -- patients over 40 yrs.
*Multiple myeloma -> most common primary bone tumour in adults.
*[[Multiple myeloma]] -> most common primary bone tumour in adults.


===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>


=Cartilage=
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>
==Chondrosarcoma==
===Microscopic===
===Summary tables===
Features:<ref>IAV. 26 February 2009.</ref>
====Bone tumours====
*Abnormal cartilage.
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Nuclear atypia.
! Entity
**Nuclear clearing.
! Key feature
**Nucleoli.
! Other features
! Radiology / gross
! Clinical
! Stains / other
! 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]]
| osteoblastic rimming
| anastomosing bony trabeculae
| 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
| IHC / other
| [[Image:Osteoid_osteoma_-_high_mag.jpg |thumb|center|150px| Osteoid osteoma. (WC)]]
|-
| [[Osteoblastoma]]
| osteoblastic rimming
| anastomosing bony trabeculae
| must be >1 cm,<ref name=pmid25224389/> often >=2 cm, metaphysis
| not painful
| IHC / other
| [[Image:Osteoblastoma_-_high_mag.jpg|thumb|center|150px|Osteoblastoma. (WC)]]
|-
| [[Ewing sarcoma]]
| [[small round blue cell tumour]]
| cytoplasmic clearing (due to glycogen)
| usu. diaphysis
| pediatric, typically 1-10 years
| PAS+, PASD-, [[chromosomal translocations]] (usually t(11;22)(q24;q12)) 
| [[Image:Ewing_sarcoma_-_PAS_-_high_mag.jpg |thumb|center|150px| Ewing sarcoma. [[PAS stain]]. (WC)]]
|-
| [[Osteosarcoma]]
| osteoid
| +/-hemorrhage, +/-cartilage
| distal femur, prox. tibia, prox. humerous
| typically 10-30 years, pain, swelling
| no stains; many subtypes
| [[Image:Osteosarcoma_-_very_high_mag.jpg |thumb|center|150px|Osteosarcoma. (WC)]]
|-
| [[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
| [[Image:Giant_cell_tumour_of_bone_-_high_mag.jpg|thumb|center|150px|Giant cell tumour. (WC)]]
|-
|}


=Bone=
====Cartilage tumours====
==Osteoid osteoma==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
===General===
! Entity
*Benign bone lesion.
! 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''
| [[Image:Enchondroma_-_very_high_mag.jpg |thumb|center|150px| Enchondroma. (WC)]]
|-
| [[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
| [[Image:Chondroblastoma_-_very_high_mag.jpg |thumb|center|150px| Chondroblastoma. (WC)]]
|-
| [[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
| [[Image:Chondrosarcoma_%282%29.jpg |thumb|center|150px|Chondrosarcoma. (WC)]]
|-
|}


===Microscopic===
====Other====
Features:
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Rimming of osteoblasts.
! Entity
**Cells line-up at edge of bone.
! 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
| [[Image:Adamantinoma_-_intermed_mag.jpg |thumb|center|150px|Adamantinoma. (WC)]]
|-
| [[Diffuse tenosynovial giant-cell tumour]] ([[AKA]] [[PVNS]])
| pigmented giant cells
| nodules
| Radiology / gross
| Clinical
| IHC / other
| [[Image:Pigmented_villonodular_synovitis_low_mag.jpg |thumb|center|150px| PVNS. (WC)]]
|-
| [[Brown tumour]]
| fibrosis, +/-giant cells
| unaffected bone incr. osteoblasts and osteoclasts
| Radiology / gross
| due to hypercalcemia; not a neoplasm
| IHC / other
| [[Image:Brown_tumour_-_low_mag.jpg |thumb|center|150px| Brown tumour. (WC)]]
|-
|}


Image:
====Radiology====
*[http://library.med.utah.edu/WebPath/COW/COW211.html Osteoid osteoma (med.utah.edu)].
=====Radiologic features=====
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! 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",<br> "onion skin", Codman's triangle
|}


==Ewing sarcoma==
=====Location=====
===General===
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*AKA EWS/PNET:
! Diagnosis
**EWS = Ewing sarcoma.
! [[Epiphysis]]
**PNET = Primative neuroectodermal tumour.
! [[Metaphysis]]
*EWS and PNET were once thought to be different tumours.
! [[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
How to remember the primary bone lesions:
*Painful.
#''Ewing sarcoma'' is the only malignant primary bone tumour of the diaphysis.
*Usually younger than 20 years.
#''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.


====Radiology====
How to remember the primary cartilaginous lesions:
Features:<ref name=Ref_WMSP650>{{Ref WMSP|650}}</ref>
#''Chondroblastoma'' is epiphyseal. The chicken wire goes around the chicken coop.
*Long bones, diaphyses.
#The others are diaphyseal.
*Destructive.
*"Onion-skin" periosteal reaction.


===Microscopic===
=Cartilage=
Features:<ref>PST. 22 February 2010.</ref>
==Chondroma==
*Scant clear cytoplasm (contain glycogen - PAS +ve, PAS-D -ve).
{{Main|Chondroma}}
*Lack nucleoli.
*Round small nucleus.


Notes:
==Chondroblastoma==
*It is a [[small round cell tumour]].
{{Main|Chondroblastoma}}


===[[IHC]]===
==Chondromyxoid fibroma==
Features:<ref name=Ref_WMSP651>{{Ref WMSP|651}}</ref>
{{Main|Chondromyxoid fibroma}}
*CD99 +ve (plasma membrane staining).
*CD45 -ve.
**Done to r/o [[lymphoma]].
*+/-Neural markers (NSE, synaptophysin, CD57 (??? CD56 ???), S100).
*+/-Cytokeratins.
*Caveolin-1.<ref>PST. 22 February 2010.</ref>
**New kid on the block.


Notes:<ref>PST. 22 February 2010.</ref>
==Chondrosarcoma==
*CD99 +ve (plasma membrane) tumours:
{{Main|Chondrosarcoma}}
**Lymphoblastic lymphoma/leukemia.
**Angiomatoid fibrous histiocytoma.
**Desmoplastic small round cell tumour.


===Molecular diagnostics===
=Bone=
Common features:
==Osteoma==
*''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>PMID: 3163261</ref>
{{Main|Osteoma}}
**Often detected by RT-PCR (with EWS 5' and FLI-1 3' primers).


Notes:
==Osteoid osteoma==
*The ''t(11;22)(q24;q12)'' is seen in ~90% of EWS/PNET... but also in:
{{Main|Osteoid osteoma}}
**Olfactory neuroblastoma.
**Small cell osteogenic sarcoma.
**Polyphenotypic tumours.
**Rhbdomyosarcoma.
**Neuroblastoma (possibly).
*Several other translocations exist.


==Osteosarcoma==
==Osteoblastoma==
===General===
{{Main|Osteoblastoma}}
*Terry Fox was afflicited by this tumour.


====Definition====
==Ewing sarcoma==
*Tumour that makes osteoid.
{{Main|Ewing sarcoma}}
**Osteoid = (extracellular) organic component of bone, normally produced by osteoblasts (cells which make bone matrix).


===Microscopic===
==Osteosarcoma==
Features:
{{Main|Osteosarcoma}}
*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:
==Giant cell tumour of bone==
*[http://commons.wikimedia.org/wiki/File:Osteosarcoma_-_intermed_mag.jpg Osteosarcoma - intermed. mag. (WC)].
{{Main|Giant cell tumour of bone}}
*[http://commons.wikimedia.org/wiki/File:Osteosarcoma_-_very_high_mag.jpg Osteosarcoma - very high mag. (WC)].


=Other=
=Other=
==Pigmented villonodular synovitis==
This section collects stuff that doesn't neatly fit into the ''bone'' or ''cartilage'' category.
*Commonly abbreviated: ''PVNS''.
*Course: benign.


===Microscopic===
==Notochordal tumors==
Features:<ref>URL: [http://www.wheelessonline.com/ortho/pigmented_villonodular_synovitis http://www.wheelessonline.com/ortho/pigmented_villonodular_synovitis].</ref>
Notochordal tumors arise from notochordal remnants and thus are seen in the clivus or sacrum.
*Subsynovial nodules composed of cells with:
{{Main|Chordoma}}
**Abundant cytoplasm.
**Pale nuclei.
*Multinucleated giant cells.
*Hemosiderin-laden macrophages.
*Foam cells.


Images:
==Osteochondroma==
*[http://commons.wikimedia.org/wiki/File:Pigmented_villonodular_synovitis_low_mag.jpg PVNS - low mag. (WC)].
{{Main|Osteochondroma}}
*[http://commons.wikimedia.org/wiki/File:Pigmented_villonodular_synovitis_high_mag.jpg PVNS - high mag. (WC)].


==Adamantinoma==
==Diffuse tenosynovial giant-cell tumour==  
===General===
*[[AKA]] ''tenosynovial giant-cell tumour, diffuse type''.
Features:<ref name=Ref_WMSP650>{{Ref WMSP|650}}</ref>
*Previously known as ''pigmented villonodular synovitis'' (PVNS).<ref>{{Ref PBoD8|1247}}</ref>  
*Rare: < 1% of bone tumours.
{{Main|Diffuse tenosynovial giant-cell tumour}}
*25-35 years old.
*Tibia, fibula.
*Benign, may be locally aggressive.
*Cousin of [[ameloblastoma]]. (???)


===Radiology===
==Giant cell tumour of tendon sheath==
*Intracortical, radiolucent.
*Abbreviated ''GCT of tendon sheath''.
{{Main|Giant cell tumour of tendon sheath}}


===Microscopic===
==Adamantinoma==
Features:
{{Main|Adamantinoma}}
*Biphasic tumour:
*#Fibrous/spindle cell component.
*#Epithelial component.


Images:
==Brown tumour==
*[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>
===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>  
==Brown cell tumour==
**If ''tumour'' is understood as a synonym for ''neoplasm'', the name is a misnomer.
===Etiology===
**May (clinically) mimic a true neoplasm.
*Due to hyperparathyroidism - usually parathyroid adenoma.
*Due to hyperparathyroidism - usually [[parathyroid adenoma]].
**Usually secondary to chronic renal failure.


===Microscopy===
====Hypercalcemia DDx====
Features:
Mnemonic ''GRIMED'':<ref>{{Ref TN2006 |Emerg.}}</ref>
*Fibrosis.
 
===Hypercalcemia DDx===
Mnemonic ''GRIMED'':<ref>TN06 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).


==Giant cell tumour==
===Microscopic===
===General===
Features:
Features:<ref name=Ref_WMSP648>{{Ref WMSP|648}}</ref>
*Fibrosis.
*Approximately 5% of primary bone tumours.
*+/-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>
*Typical age: 20-45 years.
*Bone unaffected by tumour - increased numbers of the following:
**Multinucleated cells (osteoclasts).
**Mononuclear cells around the bony trabeculae (osteoblasts).


===Clinical===
DDx:
*May present with joint pain, immobility.
*[[Giant cell tumour of bone]] and other [[giant cell lesions]].


===Microscopic===
====Images====
Features:<ref name=Ref_Klatt420>{{Ref Klatt|420}}</ref>
<gallery>
*Giant cells.
Image:Brown_tumour_-_low_mag.jpg | Brown tumour - low mag. (WC)
*Mononuclear cells, with nuclei similar to those in giant cells - '''key feature'''
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 216: Line 408:
{{reflist|2}}
{{reflist|2}}


=External links=
*[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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