Difference between revisions of "Soft tissue lesions"

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'''Soft tissue lesions''' strike fear in many pathologists as they are uncommon and may be difficult to diagnose.  
'''Soft tissue lesions''' strike fear in many pathologists as they are uncommon and may be difficult to diagnose. Malignant soft tissue lesions, i.e. [[cancer|cancerous]] soft tissue lesions, are usually '''sarcomas'''. Sarcomas are malignancies derived from mesenchymal tissue. 
 
''Bone tumours'' are dealt with in the ''[[bone]]'' article.


=Introduction=
==WHO classification of soft tissue lesions/tumours==
==WHO classification of soft tissue lesions/tumours==
===Morphologic grouping<ref>WMSP PP.601-3.</ref>===
===Morphologic grouping===
#Adipocytic tumours.
These include:<ref name=Ref_WMSP601-3>{{Ref WMSP|601-3}}</ref>
#Fibroblastic/myofibroblastic tumours.
#[[Adipocytic tumours]].
#"Fibrohistiocytic" tumours.
#[[Fibroblastic/myofibroblastic tumours]].
#Smooth muscle tumours.
#[[Fibrohistiocytic tumours|"Fibrohistiocytic" tumours]].
#Skeletal muscle tumours.
#[[Smooth muscle tumours|Smooth muscle tumours]].
#Vascular tumours.
#[[Soft tissue lesions#Skeletal muscle tumours|Skeletal muscle tumours]].
#Perivascular (pericytic) tumours.
#[[Vascular tumours]].
#Chondro-osseous tumours.
#[[Soft_tissue_lesions#Perivascular_tumours|Perivascular (pericytic) tumours]].
#Tumours of uncertain differentiation.
#[[Chondro-osseous tumours]].
#[[Soft tissue lesions#Tumours of uncertain differentiation|Tumours of uncertain differentiation]].


===Biologic potential grouping<ref>WMSP PP.598-604.</ref>===
===Biologic potential grouping===
These include:<ref>{{Ref WMSP|598-604}}</ref>
#Benign.
#Benign.
#Intermediate (locally aggressive).
#Intermediate (locally aggressive).
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*Once upon a time almost everything was called ''malignant fibrous histiocytoma''; thus, it is listed as a common entity in some publications.
*Once upon a time almost everything was called ''malignant fibrous histiocytoma''; thus, it is listed as a common entity in some publications.


===Most common:<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>===
Most common:<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>
*Liposarcoma.
*Liposarcoma.
*Leiomyosarcoma.
*Leiomyosarcoma.


==Molecular testing==
==Molecular testing==
{{Main|Molecular pathology}}
*Molecular testing plays an important role in soft tissue pathology.
*Molecular testing plays an important role in soft tissue pathology.
*It is generally seen as an adjunct test that:<ref name=pmid11454050>{{cite journal |author=Fletcher CD, Fletcher JA, Dal Cin P, Ladanyi M, Woodruff JM |title=Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics? |journal=Histopathology |volume=39 |issue=1 |pages=100–3 |year=2001 |month=July |pmid=11454050 |doi= |url=}}</ref>
*It is generally seen as an adjunct test that:<ref name=pmid11454050>{{cite journal |author=Fletcher CD, Fletcher JA, Dal Cin P, Ladanyi M, Woodruff JM |title=Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics? |journal=Histopathology |volume=39 |issue=1 |pages=100–3 |year=2001 |month=July |pmid=11454050 |doi= |url=}}</ref>
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**May directly affect treatment.
**May directly affect treatment.


=Other=
===Translocations===
==Neurofibromatosis==
{{Main|Chromosomal translocations}}
Comes in two flavours:
*Many tumours in soft tissue pathology are diagnosed inconjunction with the finding of [[chromosomal translocations]].
#NF1 (peripheral).
#NF2 (central).


===NF1===
==Morphohistologic patterns==
Features (need 2/7 to diagnose):<ref>URL: [http://emedicine.medscape.com/article/1177266-overview http://emedicine.medscape.com/article/1177266-overview]. Accessed on: 3 May 2010.</ref>
{{Main|Morphologic patterns}}
*Two or more neurofibromas or one plexiform neurofibroma.
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Café-au-lait spots.
! Name
*Freckles in axilla or inguinal area.
! Description
*Optic nerve glioma.
! DDx
*Iris hamartomas (Lisch nodules).
! Image(s)
*Sphenoid dysplasia or typical long-bone abnormalities (e.g. bowing).
|-
*First-degree relative with NF1.
| Storiform, [[AKA]] patternless pattern<ref name=pmid9704618>{{cite journal |author=Mangano WE, Cagle PT, Churg A, Vollmer RT, Roggli VL |title=The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining |journal=Am. J. Clin. Pathol. |volume=110 |issue=2 |pages=191–9 |year=1998 |month=August |pmid=9704618 |doi= |url=}}</ref>
| whorled, cartwheel-like arrangement
| [[pleomorphic undifferentiated sarcoma]], [[solitary fibrous tumour]], [[dermatofibrosarcoma protuberans]], [[dermatofibroma]]<ref name=pmid224569>{{cite journal |author=Meister P, Höhne N, Konrad E, Eder M |title=Fibrous histiocytoma: an analysis of the storiform pattern |journal=Virchows Arch A Pathol Anat Histol |volume=383 |issue=1 |pages=31–41 |year=1979 |month=July |pmid=224569 |doi= |url=}}</ref>
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| Patternless pattern. (WC)]]
|-
| Herring bone
| like herring bone (technique) for climbing a hill in cross country skiing; books on a shelf, where they have partially fallen over -- on the one shelf to the left and the one below to the right
| [[fibrosarcoma]], [[synovial sarcoma]], [[MPNST]]
| [[Image:Malignant_peripheral_nerve_sheath_tumour_-_intermed_mag.jpg |thumb|center|150px |Herring bone. (WC)]]
|-
| Fascicular
| the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells
| [[leiomyoma]], [[leiomyosarcoma]]
| [[Image:Cutaneous_leiomyosarcoma_-_high_mag.jpg |thumb|center|150px| Fascicular pattern. (WC)]]
|-
| Biphasic
| nests of cells and stroma
| [[synovial sarcoma]], [[DSRCT]], [[alveolar RMS]]
| [[Image:Desmoplastic_small_round_cell_tumour_-_high_mag.jpg|thumb|center|150px| DSRCT. (WC)]]
|- <!--
| name ?
| description ?
| DDx ?
| image ? -->
|}


===NF2===
Notes:
Features (need 1/3 to diagnose):<ref>URL: [http://emedicine.medscape.com/article/1178283-overview http://emedicine.medscape.com/article/1178283-overview]. Accessed on: 3 May 2010.</ref>
*Memory device: herring bone DDx ''MSF'' = MPNST, Synovial sarcoma, Fibrosarcoma.
#Bilateral CNVIII masses on imaging.
#Unilateral CNVIII mass + first-degree relative with NF2.
#First-degree relative with NF2 ''and'' 2/4 of the following:   
## Meningioma.
## Glioma.
## Schwannoma.
## Juvenile cataract.


==Small round blue cell tumours (SRBCT)==
==Grading==
A group of tumours that has a similar histologic appearance. It is a group of tumours that is seen more often in childhood than adulthood.
*Several systems exist.
*The US-CAP advocates the use of the French system over the NCI system.
**The French system is a better predictor metastases and mortality.<ref name=pmid8996162>{{cite journal |author=Guillou L, Coindre JM, Bonichon F, ''et al.'' |title=Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma |journal=J. Clin. Oncol. |volume=15 |issue=1 |pages=350–62 |year=1997 |month=January |pmid=8996162 |doi= |url=}}</ref>


===DDx===
===French system===
*Neuroblastoma.
*Formally known as the grading system from the ''French Federation of Cancer Centres Sarcoma Group'' (FNCLCC).
*Wilm's tumour.
*Alveolar rhabdomyosarcoma.
*Ewing sarcoma/PNET - this entity is dealt with in the ''[[bone]]'' article.
*Lymphoma (diffuse large B cell lymphoma).
*Retinoblastoma.
*Hepatoblastoma.
*Desmoplastic small round cell tumour.


===Microscopic===
====Overview====
Features:
Components - overview:<ref name=pmid8996162/><ref name=uscap_stp>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf]. Accessed on: 12 April 2011.</ref>
*Sheets of cells, very cellular.
#Differentiation (score 1-3).
*Small cells ~ 2X RBC diameter.
#*De facto, this is mostly the ''histologic type''.
*Scant cytoplasm.
#Mitotic rate (score 1-3).
*Coarse chromatin.
#Necrosis (score 0-2)
*Nucleolus (???).
*+/-Vascular.


=Adipocytic tumours=
Obtaining a score:
==Hibernoma==
*Add all the points from the three components.
===General===
*Consists of ''brown fat'' (present in the infants to generate heat).<ref>WMSP P.605.</ref>
*Benign.
*Usually asymptomatic.<ref name=pmid19131775>{{cite journal |author=Ahmed SA, Schuller I |title=Pediatric hibernoma: a case review |journal=J. Pediatr. Hematol. Oncol. |volume=30 |issue=12 |pages=900–1 |year=2008 |month=December |pmid=19131775 |doi=10.1097/MPH.0b013e318184e6dd |url=}}</ref>


===Epidemiology===
Scoring:
*Young adults.
*Grade 1 = 2-3.
*Grade 2 = 4-5.
*Grade 3 = 6-8.


===Gross===
=====Differentiation=====
*Well-circumscribed.
*Standardized for histologic types.
*Lobulated and light-brown on sectioning.
*Most tumours = 3/3.


===Microscopic===
Exceptions:<ref name=uscap_stp/>
Features:<ref>{{cite journal |author=Chen DY, Wang CM, Chan HL |title=Hibernoma. Case report and literature review |journal=Dermatol Surg |volume=24 |issue=3 |pages=393–5 |year=1998 |month=March |pmid=9537018 |doi= |url=}}</ref>
*Well-differentiated liposarcoma = 1.
*Large polygonal/oval cells:
*Myxoid liposarcoma = 2.
**Nucleus - central & small.<ref>[http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70271-6 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70271-6]</ref>
*Conventional [[liposarcoma]] = 2.
***Nucleoli typically prominent.<ref>[http://surgpathcriteria.stanford.edu/softfat/hibernoma/ http://surgpathcriteria.stanford.edu/softfat/hibernoma/]</ref>
*Fibrosarcoma = 2.
**Cytoplasm - multivacuolated, oval, eosinophilic, granular.
*[[Myxofibrosarcoma]] =2.


Image:
A group of tumours is not graded:<ref name=uscap_stp/>
*[http://en.wikipedia.org/wiki/File:Hibernoma1.jpg Hibernoma (WC)].
*[[MPNST]].
*[[Rhabdomyosarcoma]].
*[[Alveolar soft part sarcoma]].
*[[Clear cell sarcoma]].
*[[Extraskeletal myxoid chondrosarcoma]].


==Liposarcoma==
=====Mitotic rate=====
*Most common malignant sarcoma in the retroperitoneum.
*0-9 mitoses/10 HPF.
*10-19 mitoses/10 HPF.
*>=20 mitoses/10 HPF.


===Microscopy===
Notes:
Features:
*1 HPF = 0.1734 mm^2.
*Lipoblasts:
**Most resident microscopes have a field of view = 0.2376 mm^2.
**Large sharply demarcated vacuole.
***Thus, ~7.3 HPFs on a resident microscope corresponds to 10 US-CAP HPFs.
**Nucleus:
***Hyperchromatic (dark staining) nucleus.
***Eccentric location.
***Nuclear indentation.


Images:
=====Necrosis=====
*[http://commons.wikimedia.org/wiki/File:Myxoid_liposarcoma_%2806%29.JPG Myxoid liposarcoma (WC)].
*None = score 0.
*[http://commons.wikimedia.org/wiki/File:Myxoid_liposarcoma_%2805%29.JPG Myxoid liposarcoma (WC)].
*<=50% of tumour = score 1.
*[http://www.john-libbey-eurotext.fr/e-docs/00/04/09/14/texte_alt_jleejd00046_gr5.jpg Lipoblasts (john-libbey-eurotext.fr)].
*>50% of tumour = score 2.


===IHC===
===System used by some at MSH===
*IHC is of limited value.
Some pathologists at [[MSH]] use the system advocated by Costa et al..<ref name=pmid6692258>{{cite journal |author=Costa J, Wesley RA, Glatstein E, Rosenberg SA |title=The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases |journal=Cancer |volume=53 |issue=3 |pages=530–41 |year=1984 |month=February |pmid=6692258 |doi= |url=}}</ref>


*S-100 +ve ~1/3 of the time.
====Scoring====
*Reticulin ???.
*Grade 1 = 1 point.
*Grade 2 = 2 points.
*Grade 3 = 3-4 points.


=Smooth muscle tumours=
====Components====
==Leiomyosarcoma==
Points for each of the following:
See gyne notes.
*Mitotic activity >= 6 / 10 HPF @ 40X - definition suffers from [[HPFitis]].
*Pleomorphism present.
*Cellularity (cells/matrix) > 50%.
*Necrosis >15% - microscopic (without targeting necrosis grossly) ''or'' grossly.


===Microscopy===
==Stage==
Features:
{{Main|Cancer staging systems}}
*Nuclear atypia.
===Lymph node metastases in sarcomas===
*Necrosis.
{{Main|Lymph node metastasis}}
*Mitoses.
*[[Lymph node]] (LN) spread is uncommon in sarcomas; [[lymph node metastases]] are seen in <3% of cases.<ref name=pmid8424704>{{Cite journal  | last1 = Fong | first1 = Y. | last2 = Coit | first2 = DG. | last3 = Woodruff | first3 = JM. | last4 = Brennan | first4 = MF. | title = Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. | journal = Ann Surg | volume = 217 | issue = 1 | pages = 72-7 | month = Jan | year = 1993 | doi =  | PMID = 8424704 | PMC = 1242736}}</ref>
**Many sarcomas are reported in LNs.
***According to the [[CAP checklist]] for soft tissue<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf]. Accessed on: 28 March 2012.</ref> the most common are: [[epithelioid sarcoma]] and [[clear cell sarcoma]].
***According to Fong ''et al.''<ref name=pmid8424704/> the most commonly is: angiosarcoma.


=Fibroblastic/myofibroblastic tumours=
Sarcomas more likely to be found in the lymph nodes - mnemonic ''RACE For MS'':<ref>URL: [http://www.aippg.net/forum/f21/surgery-mnemonics-79897/ http://www.aippg.net/forum/f21/surgery-mnemonics-79897/]. Accessed on: 23 March 2012.</ref>
*[[rhabdomyosarcoma|'''R'''habdomyosarcoma]]
*[[Angiosarcoma|'''A'''ngiosarcoma]].
*[[clear cell sarcoma|'''C'''lear cell sarcoma]].
*[[epithelioid sarcoma|'''E'''pitheliod sarcoma]].
*[[fibrosarcoma|'''F'''ibrosarcoma]].
*[[pleomorphic undifferentiated sarcoma|'''M'''alignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma)]].
*[[synovial sarcoma|'''S'''ynovial cell sarcoma]].


==Proliferative fasciitis==
==DDx by history/site==
*Need to write something here.
===Retroperiteum===
#[[Liposarcoma]].
#[[Undifferentiated pleomorphic sarcoma]].
#[[Leiomyosarcoma]].
#[[MPNST]].


==Solitary fibrous tumour==
Note:
===General===
[[Synovial sarcoma]] and [[fibrosarcoma]] are very rare in the retroperitoneum.
*Grouped with ''hemangiopericytoma'' in the WHO classification; possibly the same tumour (?).<ref name=Ref_WMSP609>{{Ref WMSP|609}}</ref>
*May be benign ''or'' malignant; more commonly benign.<ref>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970528-9 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970528-9]. Accessed on: 25 June 2010.</ref><ref>URL: [http://wjso.com/content/6/1/86 http://wjso.com/content/6/1/86]. Accessed on: 25 June 2010.</ref>


==Hemangiopericytoma==
===Young person - extremity sarcoma===
===General===
#[[Epithelioid sarcoma]].
*Grouped with ''solitary fibrous tumour'' in the WHO classification; possibly the same tumour (?).<ref name=Ref_WMSP609>{{Ref WMSP|609}}</ref>
#[[Synovial sarcoma]].
*Arises from the ''pericyte'', a connective tissue cell of small vessels that is thought to be involved in flow regulation.
*Hematologic spread most common - to lungs.<ref>URL: [http://emedicine.medscape.com/article/1255879-overview http://emedicine.medscape.com/article/1255879-overview]. Accessed on: 2 May 2010.</ref>
*Oncogenic osteomalacia - assoc. with hemangiopericytoma.<ref>URL: [http://emedicine.medscape.com/article/1255879-overview http://emedicine.medscape.com/article/1255879-overview]. Accessed on: 2 May 2010.</ref>


===Presentation===
==Gross characteristics==
*Usually painless mass, slow enlargement.
*Usually non-specific.
*Most sarcomas have a pushing border.
**If there is an infiltrative border think: (1) fibromatosis, (2) carcinoma.


====Radiology====
=Adipocytic tumours=
*Intramedullary lytic mass.
{{Main|Adipocytic tumours}}
*May be well-circumscribed.
*+/-Periosteal reaction.
*+/-Sclerotic border.


May be worked-up with angiography to distinguish from a vascular malformation.<ref>URL: [http://emedicine.medscape.com/article/1255879-diagnosis http://emedicine.medscape.com/article/1255879-diagnosis]. Accessed on: 2 May 2010.</ref>
This category includes:
===Location===
*Lipoma.
*Usually extremities - femur or prox. tibial.<ref>URL: [http://emedicine.medscape.com/article/1255879-overview http://emedicine.medscape.com/article/1255879-overview]. Accessed on: 2 May 2010.</ref>
*Liposarcoma.
*Hibernoma.


===Histology===
=Smooth muscle tumours=
Features:<ref>URL: [http://emedicine.medscape.com/article/1255879-diagnosis http://emedicine.medscape.com/article/1255879-diagnosis]. Accessed on: 2 May 2010.</ref>
{{Main|Smooth muscle tumours}}
*Hypervascular lesion - '''key diagnostic feature'''.<ref name=enzinger>Enzinger & Weiss's Soft Tissue Tumors. 4th Ed. PP.1007-13. ISBN 0-323-01200-0.</ref>
IHC markers: desmin, SMA, H-caldemsin (most specific).
**Abundant thin-walled branching small vessels of variable size.
***May be described as "staghorn vessels" or "antler-like" vasculature.
***Cells may "onion-skin" around thin blood vessels.
*Spindle or ovoid shaped cells in nests or sheets.


===IHC===
==Leiomyosarcoma==
Features:<ref>WMSP P.609.</ref><ref name=enzinger/>
{{Main|Leiomyosarcoma}}
*Vimentin +ve (usually).
*Desmin -ve (typical).
*Factor VIII -ve (marks endothelium).
*CD34 +ve.
**CD34 usu. -ve in synovial sarcoma.
*CD31 -ve (marks benign endothelium).
*vWF (von Willebrand factor) -ve.
 
===DDx===
*Other vascular tumours.
*Vascular malformations.
*Synovial sarcoma.
 
==Desmoplastic fibroblastoma==
*AKA ''collagenous fibroma''.<ref name=pmid18271804>PMID 18271804.</ref>
*Benign lesion.
*Classically found in shoulder region.
 
===IHC===
*Beta-catenin -ve.<ref name=pmid18544056>PMID 18544056.</ref>
**Significance ???
 
=Vascular tumours=
==Kaposi sarcoma==
===General===
*Not really a sarcoma.
*Caused by HHV-8.
*Associated with immunodeficiency, e.g. HIV/AIDS.
 
===Stages===
It is seen in different stages:<ref>URL: [http://www.histopathology-india.net/KS.htm http://www.histopathology-india.net/KS.htm]. Accessed on: 31 January 2010.</ref>
#Patch stage.
#Plaque stage.
#Nodular stage.
#Lymphangioma-like. (???)


===Microscopic===
===Microscopic===
Features:<ref>Klatt. AOP P.23.</ref>
Features (summary):
*Vascular channels that anastomose - '''key feature'''.
*Fasicular cellular spindle cell lesion with:
*+/-Nuclear atypia.
**Nuclear atypia.
*Hyaline globules (intracytoplasmic)<ref name=pmid7528163>{{cite journal |author=del Rosario AD, Bui HX, Singh J, Ginsburg R, Ross JS |title=Intracytoplasmic eosinophilic hyaline globules in cartilaginous neoplasms: a surgical, pathological, ultrastructural, and electron probe x-ray microanalytic study |journal=Hum. Pathol. |volume=25 |issue=12 |pages=1283–9 |year=1994 |month=December |pmid=7528163 |doi= |url=}}</ref> - pale pink globs (that are paler than RBCs) - '''important feature'''.
**[[Necrosis]].
*+/-Hemosiderin deposits.
**High mitotic rate.
 
DDx:
*Angiosarcoma (have many mitoses).


Notes:
=Fibrohistiocytic tumours=
*Hyaline globules have a DDx (hepatocellular carcinoma, lung adenocarcinoma, chondrosarcomas + others).<ref name=pmid7528163/>
''Fibrohistiocytic'' refers (only) to the histomorphologic appearance and therefore may be written in quotation marks; these tumours are not derived from histiocytes (or tissue macrophages), as the name implies.<ref name=pmid20055912>{{Cite journal  | last1 = Luzar | first1 = B. | last2 = Calonje | first2 = E. | title = Cutaneous fibrohistiocytic tumours - an update. | journal = Histopathology | volume = 56 | issue = 1 | pages = 148-65 | month = Jan | year = 2010 | doi = 10.1111/j.1365-2559.2009.03447.x | PMID = 20055912 }}</ref>  


Images:
==Pleomorphic undifferentiated sarcoma==
*[http://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_high_mag.jpg Kaposi sacoma - high mag. (WC)].
*Abbreviated ''PUS''.
*[http://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_low_intermed_mag.jpg Kaposi sarcoma - intermed. mag. (WC)].
*[[AKA]] ''Undifferentiated pleomorphic sarcoma'', abbreviated ''UPS''.
*Previously known as ''malignant fibrous histiocytoma'', abbreviated ''MFH''.<ref>URL: [http://sarcomahelp.org/learning_center/mfh.html http://sarcomahelp.org/learning_center/mfh.html]. Accessed on: 8 April 2011.</ref>
{{Main|Pleomorphic undifferentiated sarcoma}}


===IHC===
=Fibroblastic/myofibroblastic tumours=
*CD31 +ve.
{{Main|Fibroblastic/myofibroblastic tumours}}
*CD34 +ve.
*HHV-8 +ve.


==Angiosarcoma==
This is a very large and important group of soft tissue lesions.  It is covered in a separate article.
===General===
*Malignant tumour.


===Microscopic===
The grouping includes:
Features:
*[[Inflammatory myofibroblastic tumour]].
*Very many small capillaries or irregular shape lined with:
*[[Nodular fasciitis]].
**Atypical nuclei, pleomorphic nuclei.
*[[Desmoid-type fibromatosis]] (Desmoid tumour).
*Mitoses.
*[[Proliferative fasciitis]].
*Cytoplasmic vacuoles.
*[[Solitary fibrous tumour]] ([[Hemangiopericytoma]]).
**Cells trying to form lumina - embryologic.
*[[Desmoplastic fibroblastoma]].
*[[Low-grade fibromyxoid sarcoma]].
*Others.


==Hemangioendothelioma==
=Perivascular tumours=
===General===
This grouping includes only two:<ref name=Ref_WMSP602>{{Ref WMSP|602}}</ref>
*Usually benign.
*[[Glomus tumour]] - both benign and malignant.
*[[Myopericytoma]].


===Microscopic===
=Vascular lesions=
Features:<ref>Klatt. AOP P.23.</ref>
{{Main|Vascular lesions}}
*Well-formed thin vascular channels on a fibrous stroma - '''key feature'''.
Vascular lesions are "too red"; they have too many RBCs.
*+/-Thrombosis.
*+/-Calcification.
*+/-Fibrosis.
*+/-Myxoid change.


===IHC===
They include:
*Factor VIII +ve.
*[[Hemangioma]].
*[[Kaposi sarcoma]].
*[[Masson hemangioma]].
*[[Angiosarcoma]]
*[[Epithelioid hemangioendothelioma]].


=Skeletal muscle tumours=
=Skeletal muscle tumours=
==Rhabdomyoma==
{{Main|Rhabdomyoma}}
==Rhabdomyosarcoma==
==Rhabdomyosarcoma==
*Often abbreviated ''RMS''.
*Abbreviated ''RMS''.
*Most common paediatric sarcoma.
*~6% of all childhood cancer.


Histological subdivision:
{{Main|Rhabdomyosarcoma}}
#Alveolar rhabdomyosarcoma.
Comes it two main flavours:
#*Usually young adults/adolescents.
*Alveolar rhabdomyosarcoma.
#*Early mets common.
*Embryonal rhabdomyosarcoma.
#Embryonal rhabdomyosarcoma.
#*Usual <10 years old.
#*Typically locally invasive.


Molecular and histologic subdivision:
The histology may be that of a [[small round cell tumour]].
#Translocation-positive alveolar RMS.
#Translocation-negative alveolar RMS.
#Embryonal RMS.


Notes:
=Chondro-osseous tumours=
*Translocation-negative alveolar RMS shares characteristics with ''embryonal RMS''.
{{Main|Chondro-osseous tumours}}


===Microscopy===
This grouping includes tumours derived from [[cartilage]] and [[bone]].
Alveolar rhabdomyosarcoma:
*Alveolus-like pattern:
**Fibrous septae lined by tumour cells.
***Space between fibrous sepate may be filled with tumour: ''solid variant of alveolar rhabdomyosarcoma''.
*Eccentric nucleus (???).
*Cytoplasm - dense pink staining on H&E (if well differentiated).
*Usu. nuclear pleomorphism +++.
*Mitoses common.
 
===Molecular diagnostics===
====Alveolar rhabdomyosarcoma====
Common translocations (~80%):
*t(1,13).
**PAX3/FKHR fusion gene.
*t(2,13).
**PAX7/FKHR fusion gene.
 
Several uncommon translocations exist.
 
===IHC===
*Desmin (best marker).
*Actin.


=Tumours of uncertain differentiation=
=Tumours of uncertain differentiation=
==Clear cell sarcoma==
==Angiomatoid fibrous histiocytoma==
*Known among pathologists as "soft-tissue melanoma" and "melanoma of the soft parts", as it has a strong morphological resemblance.<ref name=pmid18300804>{{cite journal |author=Hisaoka M, Ishida T, Kuo TT, ''et al.'' |title=Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases |journal=Am. J. Surg. Pathol. |volume=32 |issue=3 |pages=452–60 |year=2008 |month=March |pmid=18300804 |doi=10.1097/PAS.0b013e31814b18fb |url=}}</ref>
{{Main|Angiomatoid fibrous histiocytoma}}
**Molecular changes and origin distinct from melanoma.
*Incidence: rare soft tissue tumour.


===Clinical===
==Aggressive angiomyxoma==
*Usually - deep soft tissue ''or'' extremities.
*[[AKA]] deep aggressive angiomyxoma.
*Guarded prognosis.
{{Main|Aggressive angiomyxoma}}
*First described in 1965.<ref>URL: [http://www.informaworld.com/smpp/723576818-750600/ftinterface~db=all~content=a789166263~fulltext=713240928 http://www.informaworld.com/smpp/723576818-750600/ftinterface~db=all~content=a789166263~fulltext=713240928]. Accessed on: 5 May 2010.</ref>


===Microscopy===
==Angiomyofibroblastoma==
Features:<ref name=pmid18300804/>
{{Main|Angiomyofibroblastoma}}
*Architecture: sheets or fascicular (bundles) arrangement.
*Cells: Spindle cells or epithelioid cells.
*Prominent nucleoli - basophilic.
*Fibrous septae.
*Uniform


Image:
==Extrarenal malignant rhabdoid tumour==
*[http://commons.wikimedia.org/wiki/File:Clear_cell_sarcoma.Image12.jpg Clear cell sarcoma (WC)].
*Essentially identical to ''[[renal malignant rhabdoid tumour]]''.<ref name=Ref_WMSP627>{{Ref WMSP|627}}</ref>
*[http://www.informaworld.com/ampp/image?path=/713690780/789166263/sonc_a_284443_o_f0003g.jpeg Clear cell sarcoma (informaworld.com)].
{{Main|Extrarenal malignant rhabdoid tumour}}


===IHC===
==Ewing sarcoma/PNET==
Features:<ref name=pmid18300804/>
{{Main|Ewing sarcoma}}
*S100 +ve.
*A [[small round blue cell tumour]] that may be seen in [[bone]]. It is discussed in the context of [[bone tumours]].
*HMB-45 +ve.
*Melan A (MART-1) +ve; sometimes -ve.
*bcl-2 +ve.
*CD57 +ve (usually).


Keratins:
==Epithelioid sarcoma==
*EMA may be +ve.
:Sarcomas with an epithelioid morphology are covered in ''[[epithelioid sarcomas]]''.
*CAM5.2 -ve.
{{Main|Epithelioid sarcoma}}
*AE1/AE3 -ve.


===Molecular studies===
==Alveolar soft part sarcoma==
*Chromosomal translocation t(12;22)(q13;q12).<ref name=pmid18300804/>
{{Main|Alveolar soft part sarcoma}}
**Fusion transcripts:
***EWSR1-ATF1.
***EWSR1-CREB1 (GI tract associated).


==Chondrosarcoma==
==Desmoplastic small round cell tumour==
*May arise from an ''enchondroma''.
{{Main|Desmoplastic small round cell tumour}}
*Usually a good prognosis.


===Microscopic===
==Clear cell sarcoma==
Features:
{{Main|Clear cell sarcoma}}
*Resembles cartilage at low power.<ref>Klatt. AOP P.417.</ref>
*More cellular than cartilage... but relatively paucicellular compared to other sarcomas.
 
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)].
 
====Grading====
Features:<ref>WMSP P.643.</ref>
*Grade I: moderate cellularity +/- binucleated cells.
*Grade III: nuclear pleomorphism, mitoses common.
*Grade II: between Grade I and Grade III.


==Synovial sarcoma==
==Synovial sarcoma==
===General===
{{Main|Synovial sarcoma}}
*Does not arise from cartilage.<ref>WMSP P.627.</ref>
*Young adults or adolescents.


===Microscopic===
=Other=
Comes in three flavours:<ref>WMSP P.627.</ref><ref>{{cite journal |author=Schaal CH, Navarro FC, Moraes Neto FA |title=Primary renal sarcoma with morphologic and immunohistochemical aspects compatible with synovial sarcoma |journal=Int Braz J Urol |volume=30 |issue=3 |pages=210–3 |year=2004 |pmid=15689250 |doi= |url=http://www.brazjurol.com.br/may_june_2004/Schaal_ing_210_213.htm}}</ref>
==Granulocytic sarcoma==
#Spindle cell sarcoma with features of hemangiopericytoma, i.e. staghorn vessels.
*Common alternate terms: extramedullary leukemia,<ref name=pmid21795742>{{Cite journal | last1 = Bakst | first1 = RL. | last2 = Tallman | first2 = MS. | last3 = Douer | first3 = D. | last4 = Yahalom | first4 = J. | title = How I treat extramedullary acute myeloid leukemia. | journal = Blood | volume = 118 | issue = 14 | pages = 3785-93 | month = Oct | year = 2011 | doi = 10.1182/blood-2011-04-347229 | PMID = 21795742 }}</ref> myeloid sarcoma, chloroma.
#Biphasic synovial sarcoma:
*Other terms:<ref name=pmid21556238>{{Cite journal | last1 = Eom | first1 = KS. | last2 = Kim | first2 = TY. | title = Intraparenchymal myeloid sarcoma and subsequent spinal myeloid sarcoma for acute myeloblastic leukemia. | journal = J Korean Neurosurg Soc | volume = 49 | issue = 3 | pages = 171-4 | month = Mar | year = 2011 | doi = 10.3340/jkns.2011.49.3.171 | PMID = 21556238 | PMC = 3085814 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085814/ }}</ref> myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, or myelosarcoma.
##Spindle cells with features of hemangiopericytoma.
{{Main|Granulocytic sarcoma}}
##Epitheliod glands or nests.
#Primative round cell type.
 
Images:
*[http://www.scielo.br/img/revistas/ibju/v30n3/3a06f03.jpg Synovial sarcoma (scielo.br)].
*[http://www.humpath.com/spip.php?page=article&id_article=1965 Synovial sarcoma - collection of images (humpath.com)].
 
===IHC===
Features:<ref>WMSP P.627.</ref>
*Vimentin +ve + cytokeratin and/or EMA +ve.
*CD99 +ve.
 
Others:
*Beta-catenin +ve ~30-70%.<ref name=pmid16740029>{{cite journal |author=Horvai AE, Kramer MJ, O'Donnell R |title=Beta-catenin nuclear expression correlates with cyclin D1 expression in primary and metastatic synovial sarcoma: a tissue microarray study |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=6 |pages=792–8 |year=2006 |month=June |pmid=16740029 |doi= |url=}}</ref>
*Cyclin D1 ~50%.<ref name=pmid16740029/><ref name=pmid15375433>{{cite journal |author=Ng TL, Gown AM, Barry TS, ''et al.'' |title=Nuclear beta-catenin in mesenchymal tumors |journal=Mod. Pathol. |volume=18 |issue=1 |pages=68–74 |year=2005 |month=January |pmid=15375433 |doi=10.1038/modpathol.3800272 |url=}}</ref>
 
===Molecular pathology===
Unique translocation:
*t(X;18)(p11.2;q11.2).<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/300813 http://www.ncbi.nlm.nih.gov/omim/300813]. Accessed on: 30 May 2010.</ref>


=See also=
=See also=
Line 410: Line 315:
*[[Hematopathology]].
*[[Hematopathology]].
*[[Spindle cell lesion]].
*[[Spindle cell lesion]].
*[[Neurofibromatosis]].
*[[Small round cell tumours]].


=References=
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Weird stuff]]
[[Category:Soft tissue lesions]]

Latest revision as of 12:50, 3 November 2015

Soft tissue lesions strike fear in many pathologists as they are uncommon and may be difficult to diagnose. Malignant soft tissue lesions, i.e. cancerous soft tissue lesions, are usually sarcomas. Sarcomas are malignancies derived from mesenchymal tissue.

Introduction

WHO classification of soft tissue lesions/tumours

Morphologic grouping

These include:[1]

  1. Adipocytic tumours.
  2. Fibroblastic/myofibroblastic tumours.
  3. "Fibrohistiocytic" tumours.
  4. Smooth muscle tumours.
  5. Skeletal muscle tumours.
  6. Vascular tumours.
  7. Perivascular (pericytic) tumours.
  8. Chondro-osseous tumours.
  9. Tumours of uncertain differentiation.

Biologic potential grouping

These include:[2]

  1. Benign.
  2. Intermediate (locally aggressive).
  3. Intermediate (rarely metastasizing).
  4. Malignant.

Prevalence

  • All sarcomas are rare buggers.
    • As the classification has been changing over the past years (with more subtypes being recognized/identified) numbers are variable from study-to-study.
  • Once upon a time almost everything was called malignant fibrous histiocytoma; thus, it is listed as a common entity in some publications.

Most common:[3]

  • Liposarcoma.
  • Leiomyosarcoma.

Molecular testing

Main article: Molecular pathology
  • Molecular testing plays an important role in soft tissue pathology.
  • It is generally seen as an adjunct test that:[4]
    • Often is used to confirm the histomorphologic impression/quality control.
    • Frequently has some prognostic significance.
    • May directly affect treatment.

Translocations

Main article: Chromosomal translocations

Morphohistologic patterns

Main article: Morphologic patterns
Name Description DDx Image(s)
Storiform, AKA patternless pattern[5] whorled, cartwheel-like arrangement pleomorphic undifferentiated sarcoma, solitary fibrous tumour, dermatofibrosarcoma protuberans, dermatofibroma[6]
Patternless pattern. (WC)
Herring bone like herring bone (technique) for climbing a hill in cross country skiing; books on a shelf, where they have partially fallen over -- on the one shelf to the left and the one below to the right fibrosarcoma, synovial sarcoma, MPNST
Herring bone. (WC)
Fascicular the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells leiomyoma, leiomyosarcoma
Fascicular pattern. (WC)
Biphasic nests of cells and stroma synovial sarcoma, DSRCT, alveolar RMS
DSRCT. (WC)

Notes:

  • Memory device: herring bone DDx MSF = MPNST, Synovial sarcoma, Fibrosarcoma.

Grading

  • Several systems exist.
  • The US-CAP advocates the use of the French system over the NCI system.
    • The French system is a better predictor metastases and mortality.[7]

French system

  • Formally known as the grading system from the French Federation of Cancer Centres Sarcoma Group (FNCLCC).

Overview

Components - overview:[7][8]

  1. Differentiation (score 1-3).
    • De facto, this is mostly the histologic type.
  2. Mitotic rate (score 1-3).
  3. Necrosis (score 0-2)

Obtaining a score:

  • Add all the points from the three components.

Scoring:

  • Grade 1 = 2-3.
  • Grade 2 = 4-5.
  • Grade 3 = 6-8.
Differentiation
  • Standardized for histologic types.
  • Most tumours = 3/3.

Exceptions:[8]

A group of tumours is not graded:[8]

Mitotic rate
  • 0-9 mitoses/10 HPF.
  • 10-19 mitoses/10 HPF.
  • >=20 mitoses/10 HPF.

Notes:

  • 1 HPF = 0.1734 mm^2.
    • Most resident microscopes have a field of view = 0.2376 mm^2.
      • Thus, ~7.3 HPFs on a resident microscope corresponds to 10 US-CAP HPFs.
Necrosis
  • None = score 0.
  • <=50% of tumour = score 1.
  • >50% of tumour = score 2.

System used by some at MSH

Some pathologists at MSH use the system advocated by Costa et al..[9]

Scoring

  • Grade 1 = 1 point.
  • Grade 2 = 2 points.
  • Grade 3 = 3-4 points.

Components

Points for each of the following:

  • Mitotic activity >= 6 / 10 HPF @ 40X - definition suffers from HPFitis.
  • Pleomorphism present.
  • Cellularity (cells/matrix) > 50%.
  • Necrosis >15% - microscopic (without targeting necrosis grossly) or grossly.

Stage

Main article: Cancer staging systems

Lymph node metastases in sarcomas

Main article: Lymph node metastasis

Sarcomas more likely to be found in the lymph nodes - mnemonic RACE For MS:[12]

DDx by history/site

Retroperiteum

  1. Liposarcoma.
  2. Undifferentiated pleomorphic sarcoma.
  3. Leiomyosarcoma.
  4. MPNST.

Note: Synovial sarcoma and fibrosarcoma are very rare in the retroperitoneum.

Young person - extremity sarcoma

  1. Epithelioid sarcoma.
  2. Synovial sarcoma.

Gross characteristics

  • Usually non-specific.
  • Most sarcomas have a pushing border.
    • If there is an infiltrative border think: (1) fibromatosis, (2) carcinoma.

Adipocytic tumours

Main article: Adipocytic tumours

This category includes:

  • Lipoma.
  • Liposarcoma.
  • Hibernoma.

Smooth muscle tumours

Main article: Smooth muscle tumours

IHC markers: desmin, SMA, H-caldemsin (most specific).

Leiomyosarcoma

Main article: Leiomyosarcoma

Microscopic

Features (summary):

  • Fasicular cellular spindle cell lesion with:
    • Nuclear atypia.
    • Necrosis.
    • High mitotic rate.

Fibrohistiocytic tumours

Fibrohistiocytic refers (only) to the histomorphologic appearance and therefore may be written in quotation marks; these tumours are not derived from histiocytes (or tissue macrophages), as the name implies.[13]

Pleomorphic undifferentiated sarcoma

  • Abbreviated PUS.
  • AKA Undifferentiated pleomorphic sarcoma, abbreviated UPS.
  • Previously known as malignant fibrous histiocytoma, abbreviated MFH.[14]
Main article: Pleomorphic undifferentiated sarcoma

Fibroblastic/myofibroblastic tumours

Main article: Fibroblastic/myofibroblastic tumours

This is a very large and important group of soft tissue lesions. It is covered in a separate article.

The grouping includes:

Perivascular tumours

This grouping includes only two:[15]

Vascular lesions

Main article: Vascular lesions

Vascular lesions are "too red"; they have too many RBCs.

They include:

Skeletal muscle tumours

Rhabdomyoma

Main article: Rhabdomyoma

Rhabdomyosarcoma

  • Abbreviated RMS.
Main article: Rhabdomyosarcoma

Comes it two main flavours:

  • Alveolar rhabdomyosarcoma.
  • Embryonal rhabdomyosarcoma.

The histology may be that of a small round cell tumour.

Chondro-osseous tumours

Main article: Chondro-osseous tumours

This grouping includes tumours derived from cartilage and bone.

Tumours of uncertain differentiation

Angiomatoid fibrous histiocytoma

Main article: Angiomatoid fibrous histiocytoma

Aggressive angiomyxoma

  • AKA deep aggressive angiomyxoma.
Main article: Aggressive angiomyxoma

Angiomyofibroblastoma

Main article: Angiomyofibroblastoma

Extrarenal malignant rhabdoid tumour

Main article: Extrarenal malignant rhabdoid tumour

Ewing sarcoma/PNET

Main article: Ewing sarcoma

Epithelioid sarcoma

Sarcomas with an epithelioid morphology are covered in epithelioid sarcomas.
Main article: Epithelioid sarcoma

Alveolar soft part sarcoma

Main article: Alveolar soft part sarcoma

Desmoplastic small round cell tumour

Main article: Desmoplastic small round cell tumour

Clear cell sarcoma

Main article: Clear cell sarcoma

Synovial sarcoma

Main article: Synovial sarcoma

Other

Granulocytic sarcoma

  • Common alternate terms: extramedullary leukemia,[17] myeloid sarcoma, chloroma.
  • Other terms:[18] myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, or myelosarcoma.
Main article: Granulocytic sarcoma

See also

References

  1. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 601-3. ISBN 978-0781765275.
  2. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 598-604. ISBN 978-0781765275.
  3. ↑ 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.
  4. ↑ Fletcher CD, Fletcher JA, Dal Cin P, Ladanyi M, Woodruff JM (July 2001). "Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics?". Histopathology 39 (1): 100–3. PMID 11454050.
  5. ↑ Mangano WE, Cagle PT, Churg A, Vollmer RT, Roggli VL (August 1998). "The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining". Am. J. Clin. Pathol. 110 (2): 191–9. PMID 9704618.
  6. ↑ Meister P, Höhne N, Konrad E, Eder M (July 1979). "Fibrous histiocytoma: an analysis of the storiform pattern". Virchows Arch A Pathol Anat Histol 383 (1): 31–41. PMID 224569.
  7. ↑ 7.0 7.1 Guillou L, Coindre JM, Bonichon F, et al. (January 1997). "Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma". J. Clin. Oncol. 15 (1): 350–62. PMID 8996162.
  8. ↑ 8.0 8.1 8.2 URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf. Accessed on: 12 April 2011.
  9. ↑ Costa J, Wesley RA, Glatstein E, Rosenberg SA (February 1984). "The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases". Cancer 53 (3): 530–41. PMID 6692258.
  10. ↑ 10.0 10.1 Fong, Y.; Coit, DG.; Woodruff, JM.; Brennan, MF. (Jan 1993). "Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.". Ann Surg 217 (1): 72-7. PMC 1242736. PMID 8424704. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242736/.
  11. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf. Accessed on: 28 March 2012.
  12. ↑ URL: http://www.aippg.net/forum/f21/surgery-mnemonics-79897/. Accessed on: 23 March 2012.
  13. ↑ Luzar, B.; Calonje, E. (Jan 2010). "Cutaneous fibrohistiocytic tumours - an update.". Histopathology 56 (1): 148-65. doi:10.1111/j.1365-2559.2009.03447.x. PMID 20055912.
  14. ↑ URL: http://sarcomahelp.org/learning_center/mfh.html. Accessed on: 8 April 2011.
  15. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 602. ISBN 978-0781765275.
  16. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 627. ISBN 978-0781765275.
  17. ↑ Bakst, RL.; Tallman, MS.; Douer, D.; Yahalom, J. (Oct 2011). "How I treat extramedullary acute myeloid leukemia.". Blood 118 (14): 3785-93. doi:10.1182/blood-2011-04-347229. PMID 21795742.
  18. ↑ Eom, KS.; Kim, TY. (Mar 2011). "Intraparenchymal myeloid sarcoma and subsequent spinal myeloid sarcoma for acute myeloblastic leukemia.". J Korean Neurosurg Soc 49 (3): 171-4. doi:10.3340/jkns.2011.49.3.171. PMC 3085814. PMID 21556238. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085814/.
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