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. 


=Introduction=
==WHO classification of soft tissue lesions/tumours==
==WHO classification of soft tissue lesions/tumours==
===Morphologic grouping<ref name=Ref_WMSP601-3>{{Ref WMSP|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>{{Ref WMSP|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>
Line 35: Line 39:
**May directly affect treatment.
**May directly affect treatment.


=Adipocytic tumours=
===Translocations===
{{Main|Adipocytic tumours}}
{{Main|Chromosomal translocations}}
*Many tumours in soft tissue pathology are diagnosed inconjunction with the finding of [[chromosomal translocations]].


This category includes:
==Morphohistologic patterns==
*Lipoma.
{{Main|Morphologic patterns}}
*Liposarcoma.
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Hibernoma.
! Name
! Description
! DDx
! Image(s)
|-
| 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 ? -->
|}


=Smooth muscle tumours=
Notes:
==Leiomyosarcoma==
*Memory device: herring bone DDx ''MSF'' = MPNST, Synovial sarcoma, Fibrosarcoma.
See gyne notes.


===Microscopy===
==Grading==
Features:
*Several systems exist.
*Nuclear atypia.
*The US-CAP advocates the use of the French system over the NCI system.
*[[Necrosis]].
**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>
*Mitoses.


=Fibroblastic/myofibroblastic tumours=
===French system===
*Formally known as the grading system from the ''French Federation of Cancer Centres Sarcoma Group'' (FNCLCC).


==Proliferative fasciitis==
====Overview====
*Need to write something here.
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>
#Differentiation (score 1-3).
#*De facto, this is mostly the ''histologic type''.
#Mitotic rate (score 1-3).
#Necrosis (score 0-2)


==Solitary fibrous tumour==
Obtaining a score:
===General===
*Add all the points from the three components.
*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>


===Microscopic===
Scoring:
Features:
*Grade 1 = 2-3.
*Well-circumscribed.
*Grade 2 = 4-5.
*Fibroblast-like cells (spindle cells).
*Grade 3 = 6-8.
*Hemangiopericytoma-like area (staghorn vessels) - not seen on image.
*Keloid-like collagen bundles.


Images:
=====Differentiation=====
*[http://commons.wikimedia.org/wiki/File:Solitary_fibrous_tumour_low_mag.jpg SFT - low mag. (WC)].
*Standardized for histologic types.
*[http://commons.wikimedia.org/wiki/File:Solitary_fibrous_tumour_intermed_mag.jpg SFT - intermed. mag. (WC)].
*Most tumours = 3/3.
*[http://commons.wikimedia.org/wiki/File:Solitary_fibrous_tumour_high_mag.jpg SFT - high mag. (WC)].


==Hemangiopericytoma==
Exceptions:<ref name=uscap_stp/>
===General===
*Well-differentiated liposarcoma = 1.
*Grouped with ''solitary fibrous tumour'' in the WHO classification; possibly the same tumour (?).<ref name=Ref_WMSP609>{{Ref WMSP|609}}</ref>
*Myxoid liposarcoma = 2.
*Arises from the ''pericyte'', a connective tissue cell of small vessels that is thought to be involved in flow regulation.
*Conventional [[liposarcoma]] = 2.
*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>
*Fibrosarcoma = 2.
*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>
*[[Myxofibrosarcoma]] =2.


===Presentation===
A group of tumours is not graded:<ref name=uscap_stp/>
*Usually painless mass, slow enlargement.
*[[MPNST]].
*[[Rhabdomyosarcoma]].
*[[Alveolar soft part sarcoma]].
*[[Clear cell sarcoma]].
*[[Extraskeletal myxoid chondrosarcoma]].


====Radiology====
=====Mitotic rate=====
*Intramedullary lytic mass.
*0-9 mitoses/10 HPF.
*May be well-circumscribed.
*10-19 mitoses/10 HPF.
*+/-Periosteal reaction.
*>=20 mitoses/10 HPF.
*+/-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>
Notes:
===Location===
*1 HPF = 0.1734 mm^2.
*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>
**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.


===Histology===
=====Necrosis=====
Features:<ref>URL: [http://emedicine.medscape.com/article/1255879-diagnosis http://emedicine.medscape.com/article/1255879-diagnosis]. Accessed on: 2 May 2010.</ref>
*None = score 0.
*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>
*<=50% of tumour = score 1.
**Abundant thin-walled branching small vessels of variable size.
*>50% of tumour = score 2.
***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===
===System used by some at MSH===
Features:<ref name=Ref_WMSP609>{{Ref WMSP|609}}</ref><ref name=enzinger/>
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>
*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.


May be in the DDx for [[meningioma]]:<ref>Croul, SE. 8 November 2010.</ref>
====Scoring====
*EMA -ve.
*Grade 1 = 1 point.
*S100 -ve.
*Grade 2 = 2 points.
*Grade 3 = 3-4 points.


===DDx===
====Components====
*Other vascular tumours.
Points for each of the following:
*Vascular malformations.
*Mitotic activity >= 6 / 10 HPF @ 40X - definition suffers from [[HPFitis]].
*Synovial sarcoma.
*Pleomorphism present.
*Cellularity (cells/matrix) > 50%.
*Necrosis >15% - microscopic (without targeting necrosis grossly) ''or'' grossly.


==Desmoplastic fibroblastoma==
==Stage==
*AKA ''collagenous fibroma''.<ref name=pmid18271804>{{Cite journal  | last1 = Watanabe | first1 = H. | last2 = Ishida | first2 = Y. | last3 = Nagashima | first3 = K. | last4 = Makino | first4 = T. | last5 = Norisugi | first5 = O. | last6 = Shimizu | first6 = T. | title = Desmoplastic fibroblastoma (collagenous fibroma). | journal = J Dermatol | volume = 35 | issue = 2 | pages = 93-7 | month = Feb | year = 2008 | doi = 10.1111/j.1346-8138.2008.00421.x | PMID = 18271804 }}</ref>
{{Main|Cancer staging systems}}
*Benign lesion.
===Lymph node metastases in sarcomas===
*Classically found in shoulder region.
{{Main|Lymph node metastasis}}
*[[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.


===IHC===
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>
*Beta-catenin -ve.<ref name=pmid18544056>{{Cite journal  | last1 = Takahara | first1 = M. | last2 = Ichikawa | first2 = R. | last3 = Oda | first3 = Y. | last4 = Uchi | first4 = H. | last5 = Takeuchi | first5 = S. | last6 = Moroi | first6 = Y. | last7 = Kiryu | first7 = H. | last8 = Furue | first8 = M. | title = Desmoplastic fibroblastoma: a case presenting as a protruding nodule in the dermis. | journal = J Cutan Pathol | volume = 35 Suppl 1 | issue =  | pages = 70-3 | month = Oct | year = 2008 | doi = 10.1111/j.1600-0560.2007.00964.x | PMID = 18544056 }}
*[[rhabdomyosarcoma|'''R'''habdomyosarcoma]]
</ref>
*[[Angiosarcoma|'''A'''ngiosarcoma]].
**Significance ???
*[[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]].


=Vascular lesions=
==DDx by history/site==
Vascular lesions are "too red"; they have too many RBCs.
===Retroperiteum===
#[[Liposarcoma]].
#[[Undifferentiated pleomorphic sarcoma]].
#[[Leiomyosarcoma]].
#[[MPNST]].


==Hemangioma==
Note:
===General===
[[Synovial sarcoma]] and [[fibrosarcoma]] are very rare in the retroperitoneum.
Comes is various flavours:<ref name=pmid10410855>{{cite journal |author=Prieto VG, Shea CR |title=Selected cutaneous vascular neoplasms. A review |journal=Dermatol Clin |volume=17 |issue=3 |pages=507–20, viii |year=1999 |month=July |pmid=10410855 |doi= |url=}}</ref>
*Tufted.
**Small clusters of blood vessels.
*Microvenular hemangioma.
*Glomeruloid hemangioma.
*Epithelioid hemangioma.
*Targetoid hemosideric hemangioma.


===Microscopic===
===Young person - extremity sarcoma===
Features:
#[[Epithelioid sarcoma]].
*Abundance of benign small blood vessels. (???)
#[[Synovial sarcoma]].


==Kaposi sarcoma==
==Gross characteristics==
===General===
*Usually non-specific.
*Not really a sarcoma.
*Most sarcomas have a pushing border.
*Caused by HHV-8.
**If there is an infiltrative border think: (1) fibromatosis, (2) carcinoma.
*Associated with immunodeficiency, e.g. [[HIV]]/AIDS.


===Stages===
=Adipocytic tumours=
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>
{{Main|Adipocytic tumours}}
#Patch stage.
#Plaque stage.
#Nodular stage.
#Lymphangioma-like. (???)


===Microscopic===
This category includes:
Features:<ref name=Ref_Klatt23>{{Ref Klatt|23}}</ref>- '''key feature'''.
*Lipoma.
*+/-Nuclear atypia.
*Liposarcoma.
*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'''.
*Hibernoma.
*+/-Hemosiderin deposits.


DDx:
=Smooth muscle tumours=
*Angiosarcoma (have many mitoses, nuclear atypia).
{{Main|Smooth muscle tumours}}
*Masson's hemangioma (Intravascular papillary endothelial hyperplasia).
IHC markers: desmin, SMA, H-caldemsin (most specific).


Notes:
==Leiomyosarcoma==
*Hyaline globules have a DDx ([[hepatocellular carcinoma]], lung adenocarcinoma, [[chondrosarcoma]]s + others).<ref name=pmid7528163/>
{{Main|Leiomyosarcoma}}
*Promontory sign - small vessel protruding into an abnormal vascular space.<ref name=pmid19318797>{{cite journal |author=Lazova R, McNiff JM, Glusac EJ, Godic A |title=Promontory sign--present in patch and plaque stage of angiosarcoma! |journal=Am J Dermatopathol |volume=31 |issue=2 |pages=132–6 |year=2009 |month=April |pmid=19318797 |doi=10.1097/DAD.0b013e3181951045 |url=}}</ref>
**Not pathognomonic for KS.<ref name=pmid20577080>{{cite journal |author=Fernandez-Flores A, Rodriguez R |title=Promontory Sign in a Reactive Benign Vascular Proliferation |journal=Am J Dermatopathol |volume= |issue= |pages= |year=2010 |month=June |pmid=20577080 |doi=10.1097/DAD.0b013e3181cf0ae5 |url=}}</ref>
**Image: [http://www.diagnosticpathology.org/content/3/1/31/figure/F1 Promontory sign (diagnosticpathology.org)].


Images:
*[http://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_high_mag.jpg Kaposi sacoma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Kaposi_sarcoma_low_intermed_mag.jpg Kaposi sarcoma - intermed. mag. (WC)].
===IHC===
*CD31 +ve.
*CD34 +ve.
*HHV-8 +ve.
==Masson hemangioma==
===General===
*Benign non-neoplastic lesion - a vessel that has thrombosed and recanalized.
*[[AKA]] ''intravascular papillary endothelial hyperplasia''.<ref name=pmid15865098>{{cite journal |author=Korkolis DP, Papaevangelou M, Koulaxouzidis G, Zirganos N, Psichogiou H, Vassilopoulos PP |title=Intravascular papillary endothelial hyperplasia (Masson's hemangioma) presenting as a soft-tissue sarcoma |journal=Anticancer Res. |volume=25 |issue=2B |pages=1409–12 |year=2005 |pmid=15865098 |doi= |url=}}</ref>
*Histomorphologically may be confused with low-grade angiosarcoma or other soft tissue sarcomas.<ref name=pmid15865098/>
===Microscopic===
===Microscopic===
Features:
Features (summary):
*Well-circumscribed - '''key (low power) feature'''.  
*Fasicular cellular spindle cell lesion with:
*Abundant small vascular channels with benign endothelium.
**Nuclear atypia.
**[[Necrosis]].
**High mitotic rate.


Notes:
=Fibrohistiocytic tumours=
*Looks like Kaposi sarcoma at high power.
''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>


==Angiosarcoma==
==Pleomorphic undifferentiated sarcoma==
===General===
*Abbreviated ''PUS''.
*Malignant tumour - with a horrible prognosis.<ref name=pmid20537949>{{cite journal |author=Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ |title=Angiosarcoma |journal=Lancet Oncol |volume= |issue= |pages= |year=2010 |month=May |pmid=20537949 |doi=10.1016/S1470-2045(10)70023-1 |url=}}</ref>
*[[AKA]] ''Undifferentiated pleomorphic sarcoma'', abbreviated ''UPS''.
*Classically on the scalp or head & neck.
*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>
*May arise secondary to therapeutic radiation or chronic lymphoedema related to breast carcinoma.
{{Main|Pleomorphic undifferentiated sarcoma}}


===Microscopic===
=Fibroblastic/myofibroblastic tumours=
Features:
{{Main|Fibroblastic/myofibroblastic tumours}}
*Very many small capillaries of irregular shape lined with:
**Pleomorphic nuclei.
***May have hobnail morphology.
*Mitoses.
*Cytoplasmic vacuoles.
**Cells trying to form lumina - embryologic.


Notes:
This is a very large and important group of soft tissue lesions.  It is covered in a separate article.
*Epithelioid variant (with abundant cytoplasm & sheeting architecture) may resemble ''[[melanoma]]'' or ''[[hepatocellular carcinoma]]''.


===IHC===
The grouping includes:
*CD34 +ve.
*[[Inflammatory myofibroblastic tumour]].
*D2-40 +ve. (???)
*[[Nodular fasciitis]].
*CD31 +ve.
*[[Desmoid-type fibromatosis]] (Desmoid tumour).
*[[Proliferative fasciitis]].
*[[Solitary fibrous tumour]] ([[Hemangiopericytoma]]).
*[[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 name=Ref_Klatt23>{{Ref Klatt|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=
Line 258: Line 270:


=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.
*BCL2 +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==
===General===
{{Main|Desmoplastic small round cell tumour}}
*May arise from an ''enchondroma''.
*Usually a good prognosis.


===Microscopic===
==Clear cell sarcoma==
Features:
{{Main|Clear cell sarcoma}}
*Resembles cartilage at low power.<ref name=Ref_Klatt417>{{Ref Klatt|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)].
 
DDx:
*[[Chordoma]].
 
====Grading====
Features:<ref name=Ref_WMSP643>{{Ref WMSP|643}}</ref>
*Grade I: moderate cellularity +/- binucleated cells.
*Grade III: nuclear pleomorphism, mitoses common.
*Grade II: between Grade I and Grade III.
 
===IHC===
*S-100 -ve. (???)
 
==Mesenchymal 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)].


==Synovial sarcoma==
==Synovial sarcoma==
===General===
{{Main|Synovial sarcoma}}
*Does not arise from cartilage.<ref name=Ref_WMSP627>{{Ref WMSP|627}}</ref>
*Young adults or adolescents.
 
===Microscopic===
Comes in three flavours:<ref name=Ref_WMSP627>{{Ref WMSP|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>
#Spindle cell sarcoma with features of hemangiopericytoma, i.e. staghorn vessels.
#Biphasic synovial sarcoma:
##Spindle cells with features of hemangiopericytoma.
##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 name=Ref_WMSP627>{{Ref WMSP|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===
=Other=
Unique translocation:
==Granulocytic sarcoma==
*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>
*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.
*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.
{{Main|Granulocytic sarcoma}}


=See also=
=See also=

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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