Liposarcoma pathophysiology: Difference between revisions

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__NOTOC__
__NOTOC__
{{Liposarcoma}}
{{Liposarcoma}}
{{CMG}} {{AE}} {{JS}}
{{CMG}} {{AE}} {{JS}}{{Sab}}


==Overview==
==Overview==
Liposarcoma is the most common [[sarcoma]] of [[soft tissue]]. The [[pathogenesis]] of liposarcoma depends on the [[Histology|histological]] sub-type. The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas. The majority of well differentiated liposarcomas arise in the [[retroperitoneum]]. The [[chromosome]] region 12q13-15, is rich in [[protooncogene]]s, including the ''[[CHOP]]'', ''[[Cyclin-dependent kinase 4|CDK4]]'', ''[[MDM2]]'', ''HMGI-C'', ''GLI'', ''SAS'', ''OS1'', and the ''[[OS9 (gene)|OS9]]'', all of which play an important role in the [[pathogenesis]] of many [[neoplasms]]. Liposarcoma is associated with [[Genetic disorder|genetic conditions]] like [[Li-Fraumeni syndrome]]. Liposarcoma usually presents as a mass which often resembles [[lipoma]] and is [[Nodular|multinodular]]. [[Microscopic]] [[pathological]] findings of liposarcoma depend on the sub-type.


==Pathogenesis==
==Pathophysiology==
According to their class, each liposarcoma will have specific characteristics and pathogenesis:
===Well Differentiated Liposarcoma===
This type of liposarcoma occurs both at the [[limbs]] and [[retroperitoneum]] in equal frequency, and occasionally at the [[mediastinum]] and [[spermatic cord]], representing about 45% of liposarcomas.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref>


According to the WHO classification described previously, well differentiated liposarcomas may be sub-classified into 3 types: ''sclerosing''; ''adipocytic''; and ''inflammatory''.
=== Pathogenesis ===
====Sclerosing Liposarcoma====
*Liposarcoma is the most common [[sarcoma]] of [[soft tissue]].<ref>{{Cite journal
Occurs most frequently at the retroperitoneum and paratesticular regions.  The particular [[histological]] finding in this type of well differentiated liposarcoma is the identification of distinctive [[stromal]] cells distributed across the tissue, and associated with lipoblasts filled with multiple [[vacuoles]]. This association forms a [[collagenous]] background of fibrillary appearance. In certain cases the fibrous component of the [[neoplasm]] may occupy most of its mass.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304 }} </ref>
  | author = [[Kate Lynn J. Bill]], [[Lucia Casadei]], [[Bethany C. Prudner]], [[Hans Iwenofu]], [[Anne M. Strohecker]] & [[Raphael E. Pollock]]
====Adipocytic Liposarcoma====
| title = Liposarcoma: molecular targets and therapeutic implications
Frequently composed by [[adipocytes]] with different cell sizes, hyperchromasia and nuclear atypia.  [[Fibrous]] septa may be identified among [[adipocytes]], containing hyperchromatic [[stromal cells]].  Besides these two types of cells, mono or multivacuolated lipoblasts may also be identified.  These last are characterized by the presence of single (mono) or multiple (multi) peripheral cytoplasmic vacuoles that press on the hyperchromatic nucleus.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref>
  | journal = [[Cellular and molecular life sciences : CMLS]]
| volume = 73
| issue = 19
| pages = 3711–3718
| year = 2016
| month = October
| doi = 10.1007/s00018-016-2266-2
| pmid = 27173057
}}</ref>
*The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas.<ref>{{Cite journal
| author = [[Kate Lynn J. Bill]], [[Lucia Casadei]], [[Bethany C. Prudner]], [[Hans Iwenofu]], [[Anne M. Strohecker]] & [[Raphael E. Pollock]]
| title = Liposarcoma: molecular targets and therapeutic implications
| journal = [[Cellular and molecular life sciences : CMLS]]
| volume = 73
| issue = 19
| pages = 3711–3718
| year = 2016
| month = October
| doi = 10.1007/s00018-016-2266-2
| pmid = 27173057
}}</ref>
*The majority of well differentiated liposarcomas arise in the [[retroperitoneum]].<ref>{{Cite journal
| author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
| title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
| journal = [[The American journal of surgical pathology]]
| volume = 11
| issue = 3
| pages = 161–183
| year = 1987
| month = March
  | pmid = 3826477
}}</ref><ref>{{Cite journal
| author = [[Emily Z. Keung]], [[Jason L. Hornick]], [[Monica M. Bertagnolli]], [[Elizabeth H. Baldini]] & [[Chandrajit P. Raut]]
  | title = Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery
| journal = [[Journal of the American College of Surgeons]]
| volume = 218
| issue = 2
| pages = 206–217
| year = 2014
| month = February
| doi = 10.1016/j.jamcollsurg.2013.10.009
| pmid = 24315890
}}</ref>


In general, adipocytic [[neoplasms]] are often identified by the presence of these lipoblasts, however, its presence is not synonym, since multiple benign lesions may contain lipoblasts; nor are they identified in every [[liposarcoma]], as its absence does not prevent the diagnosis of the condition, if remaining criteria are met.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref>
*The [[tumor]] can also arise in the deep [[soft tissue]] of the [[thigh]], [[mediastinum]], and paratesticular area.<ref>{{Cite journal
====Inflammatory Liposarcoma====
| author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
Its adipocitic nature may be misidentified due to the heavy chronic inflammatory infiltrate.  The inflammatory component is frequently composed of different lympho-plasmacytic aggregates. These tend to be predominantly formed by a specific type of B-cell yet, T-cells may in some cases populate the inflammatory aggregate.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref><ref name="pmid9158675">{{cite journal| author=Kraus MD, Guillou L, Fletcher CD| title=Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked variant of a common sarcoma. | journal=Am J Surg Pathol | year= 1997 | volume= 21 | issue= 5 | pages= 518-27 | pmid=9158675 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9158675 }} </ref><ref name="pmid9255251">{{cite journal| author=Argani P, Facchetti F, Inghirami G, Rosai J| title=Lymphocyte-rich well-differentiated liposarcoma: report of nine cases. | journal=Am J Surg Pathol | year= 1997 | volume= 21 | issue= 8 | pages= 884-95 | pmid=9255251 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9255251  }} </ref> For the diagnosis of inflammatory liposarcoma a large sample is required to avoid missing the adipocitic component of the neoplasm.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref>
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
| journal = [[The American journal of surgical pathology]]
| volume = 11
| issue = 3
| pages = 161–183
| year = 1987
| month = March
| pmid = 3826477
}}</ref><ref>{{Cite journal
| author = [[Emily Z. Keung]], [[Jason L. Hornick]], [[Monica M. Bertagnolli]], [[Elizabeth H. Baldini]] & [[Chandrajit P. Raut]]
  | title = Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery
| journal = [[Journal of the American College of Surgeons]]
| volume = 218
| issue = 2
| pages = 206–217
  | year = 2014
| month = February
| doi = 10.1016/j.jamcollsurg.2013.10.009
| pmid = 24315890
}}</ref>


'''Spindle cell lipocarcinoma''' is a rare adult type of well-differentiated liposarcoma.  It results from the proliferation of neural-like spindle cells, organized in a fibrous structure, containing lipoblasts.<ref name="pmid8067512">{{cite journal| author=Dei Tos AP, Mentzel T, Newman PL, Fletcher CD| title=Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases. | journal=Am J Surg Pathol | year= 1994 | volume= 18 | issue= 9 | pages= 913-21 | pmid=8067512 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8067512 }} </ref><ref name="pmid5">{{cite journal| author=Hendrickson WA, Ward KB| title=Atomic models for the polypeptide backbones of myohemerythrin and hemerythrin. | journal=Biochem Biophys Res Commun | year= 1975 | volume= 66 | issue= 4 | pages= 1349-56 | pmid=5 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5 }} </ref>
*[[Retroperitoneum|Retroperitoneal]] [[Tumor|tumors]] are more likely to recur.<ref>{{Cite journal
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
| title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
| journal = [[The American journal of surgical pathology]]
| volume = 11
| issue = 3
| pages = 161–183
| year = 1987
| month = March
| pmid = 3826477
}}</ref><ref>{{Cite journal
| author = [[Elizabeth Fabre-Guillevin]], [[Jean-Michel Coindre]], [[Nicolas de Saint Aubain Somerhausen]], [[Francoise Bonichon]], [[Eberhard Stoeckle]] & [[Nguyen Binh Bui]]
| title = Retroperitoneal liposarcomas: follow-up analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas
| journal = [[Cancer]]
| volume = 106
| issue = 12
| pages = 2725–2733
| year = 2006
| month = June
| doi = 10.1002/cncr.21933
| pmid = 16688768
}}</ref>
*The dedifferentiated sub-type arises as a primary or [[de novo]] [[lesion]] in majority of the cases.<ref name="GhadimiAl-Zaid2011">{{cite journal|last1=Ghadimi|first1=Markus P.|last2=Al-Zaid|first2=Tariq|last3=Madewell|first3=John|last4=Peng|first4=Tingsheng|last5=Colombo|first5=Chiara|last6=Hoffman|first6=Aviad|last7=Creighton|first7=Chad J.|last8=Zhang|first8=Yiqun|last9=Zhang|first9=Anna|last10=Lazar|first10=Alexander J.|last11=Pollock|first11=Raphael E.|last12=Lev|first12=Dina|title=Diagnosis, Management, and Outcome of Patients with Dedifferentiated Liposarcoma Systemic Metastasis|journal=Annals of Surgical Oncology|volume=18|issue=13|year=2011|pages=3762–3770|issn=1068-9265|doi=10.1245/s10434-011-1794-0}}</ref><ref>{{Cite journal
| author = [[G. Lahat]], [[D. A. Anaya]], [[X. Wang]], [[D. Tuvin]], [[D. Lev]] & [[R. E. Pollock]]
| title = Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches
| journal = [[Annals of surgical oncology]]
| volume = 15
| issue = 6
| pages = 1585–1593
| year = 2008
| month = June
| doi = 10.1245/s10434-007-9805-x
  | pmid = 18398663
}}</ref><ref>{{Cite journal
| author = [[H. L. Evans]], [[K. K. Khurana]], [[B. L. Kemp]] & [[A. G. Ayala]]
| title = Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma
| journal = [[The American journal of surgical pathology]]
| volume = 18
| issue = 11
| pages = 1150–1157
| year = 1994
| month = November
| pmid = 7943536
}}</ref><ref>{{Cite journal
| author = [[W. H. Henricks]], [[Y. C. Chu]], [[J. R. Goldblum]] & [[S. W. Weiss]]
| title = Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation
| journal = [[The American journal of surgical pathology]]
| volume = 21
| issue = 3
| pages = 271–281
| year = 1997
| month = March
  | pmid = 9060596
}}</ref>


Because well-differentiated lipomas are characterized by having approximately 30% risk of '''recurrence''' and '''no potential to metastasize''', unless dedifferentiation occurs, two terms have emerged: atypical lipoma and atypical lipomatous tumor. However, there is still no consensus on when to use each term.<ref name="pmid421182">{{cite journal| author=Evans HL, Soule EH, Winkelmann RK| title=Atypical lipoma, atypical intramuscular lipoma, and well differentiated retroperitoneal liposarcoma: a reappraisal of 30 cases formerly classified as well differentiated liposarcoma. | journal=Cancer | year= 1979 | volume= 43 | issue= 2 | pages= 574-84 | pmid=421182 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=421182 }} </ref>
*The dedifferentiated sub-type is clinically more aggressive than the well differentiated liposarcoma.<ref name="SingerAntonescu2003">{{cite journal|last1=Singer|first1=Samuel|last2=Antonescu|first2=Cristina R.|last3=Riedel|first3=Elyn|last4=Brennan|first4=Murray F.|title=Histologic Subtype and Margin of Resection Predict Pattern of Recurrence and Survival for Retroperitoneal Liposarcoma|journal=Transactions of the ... Meeting of the American Surgical Association|volume=121|year=2003|pages=52–65|issn=0066-0833|doi=10.1097/01.sla.0000086542.11899.38}}</ref><ref>{{Cite journal
| author = [[G. Lahat]], [[D. A. Anaya]], [[X. Wang]], [[D. Tuvin]], [[D. Lev]] & [[R. E. Pollock]]
| title = Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches
| journal = [[Annals of surgical oncology]]
| volume = 15
| issue = 6
| pages = 1585–1593
| year = 2008
| month = June
| doi = 10.1245/s10434-007-9805-x
| pmid = 18398663
}}</ref><ref>{{Cite journal
| author = [[Emily Z. Keung]], [[Jason L. Hornick]], [[Monica M. Bertagnolli]], [[Elizabeth H. Baldini]] & [[Chandrajit P. Raut]]
| title = Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery
| journal = [[Journal of the American College of Surgeons]]
| volume = 218
| issue = 2
| pages = 206–217
| year = 2014
| month = February
| doi = 10.1016/j.jamcollsurg.2013.10.009
| pmid = 24315890
}}</ref><ref>{{Cite journal
| author = [[Khin Thway]], [[Robin L. Jones]], [[Jonathan Noujaim]], [[Shane Zaidi]], [[Aisha B. Miah]] & [[Cyril Fisher]]
| title = Dedifferentiated Liposarcoma: Updates on Morphology, Genetics, and Therapeutic Strategies
| journal = [[Advances in anatomic pathology]]
| volume = 23
| issue = 1
| pages = 30–40
| year = 2016
| month = January
| doi = 10.1097/PAP.0000000000000101
| pmid = 26645460
}}</ref>
==Genetics==
====Well-Differentiated Liposarcoma====
* The [[chromosome]] region 12q13-15, is rich in [[protooncogene]]s, including the ''[[CHOP]]'', ''[[Cyclin-dependent kinase 4|CDK4]]'', ''[[MDM2]]'', ''HMGI-C'', ''GLI'', ''SAS'', ''OS1'', and the ''[[OS9 (gene)|OS9]]'', all of which play an important role in the [[pathogenesis]] of many [[neoplasms]]. 
* [[Amplification]] of some of these regions, with concomitant [[amplification]] of their [[Protein|proteins]], has clearly been demonstrated in liposarcoma.<ref name="pmid10727978">{{cite journal| author=Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M et al.| title=Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. | journal=J Pathol | year= 2000 | volume= 190 | issue= 5 | pages= 531-6 | pmid=10727978 | doi=10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10727978  }} </ref> 
* The difference between [[malignant]] and [[benign]] masses resides in the amount of rearranged [[gene]] present in each [[Tissue (biology)|tissue]].<ref name="pmid10727978">{{cite journal| author=Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M et al.| title=Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. | journal=J Pathol | year= 2000 | volume= 190 | issue= 5 | pages= 531-6 | pmid=10727978 | doi=10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10727978 }} </ref>


===Dedifferentiated Liposarcoma===
==Associated Conditions==
In this form of liposarcoma there is a transition from a low-grade differentiation, to a high-grade differentiation within the same mass of well-differentiated liposarcoma.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref><ref name="pmid534388">{{cite journal| author=Evans HL| title=Liposarcoma: a study of 55 cases with a reassessment of its classification. | journal=Am J Surg Pathol | year= 1979 | volume= 3 | issue= 6 | pages= 507-23 | pmid=534388 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=534388  }} </ref><ref name="pmid192432">{{cite journal| author=Dahlin DC, Unni KK, Matsuno T| title=Malignant (fibrous) histiocytoma of bone--fact or fancy?. | journal=Cancer | year= 1977 | volume= 39 | issue= 4 | pages= 1508-16 | pmid=192432 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=192432  }} </ref>  Dedifferentiation from well-differented liposarcomas occurs in 90% of the cases in the primary tumor, and in the remaining in recurrent neoplasms.
* Liposarcoma is associated with [[Genetic disorder|genetic conditions]] like [[Li-Fraumeni syndrome]].


<!--
==Gross Pathology==
The transition usually occurs in an abrupt fashion (Fig 8); however, in some cases this can be more gradual and exceptionally low- grade and high-grade areas appear to be intermingled. Dedifferentiated areas exhibit a variable histologic pic- ture but most frequently it overlaps with storiform and pleomorphic malignant fibrous histiocytoma (Fig 9) as well as myxofibrosarcoma. Recently, it also has been proposed that dedifferentiated liposarcoma should be further classified into low-grade and high-grade sub- types.18,24 Low-grade dedifferentiation was defined by the presence of bland spindle cells organized in a fascicular pattern and exhibiting a cellularity intermedi- ate between well-differentiated sclerosing liposarcoma and usual high-grade areas. The very existence of low-grade dedifferentiation raises the question of the differential diagnosis with spindle cell liposarcoma. However, it should be noted that spindle cell liposar- coma represents a lipogenic lesion (eg, it contains atypical adipocytes or lipoblasts) whereas dedifferenti- ated areas, both low- and high-grade, are generally nonlipogenic.
*Liposarcoma usually presents as a mass which often resembles [[lipoma]] and is [[Nodular|multinodular]].
*Cut surface may be soft or firm and is yellow in color.
*Focal mucinous area may be seen.
*Areas of [[necrosis]] may be noted.


Dedifferentiated liposarcoma may exhibit heterolo- gous differentiation in approximately 5% to 10% of cases, which apparently does not affect the clinical outcome. Most often the line of heterologous differentia- tion is myogenic (Figs 10-12) or osteo/chondrosarcoma- tous, but angiosarcomatous elements also have been reported. Recently, a peculiar ‘‘neural-like’’ or ‘‘meningo- thelial-like whorling pattern of dedifferentiation has been described but both immunohistochemistry and electron microscopy failed to elucidate the line of differ- entiation in these lesions25,26 (Fig 13). This pattern is often associated with ossification (Fig 14).  Surprisingly, the biological behavior of dedifferenti- ated liposarcoma tends to be less aggressive than that of other types of high-grade pleomorphic sarcomas.17,18 At variance with well-differentiated liposarcoma, dediffer- entiation is associated with a 15% to 20% metastatic rate. However, long-term survival rates for retroperito- neal dedifferentiated liposarcoma is not significantly worse than that observed in ordinary well-differentiated liposarcoma occurring at the same site, mortality being more related to repeated destructive local recurrences than to metastatic spread. The fact that dedifferenti- ated liposarcoma can recur as an entirely well-differenti- ated liposarcoma also represents a morphologic indica- tor of the unique biologic behavior of this liposarcoma subtype.
==Microscopic Pathology==
Each liposarcoma sub-type has specific characteristics:
===Well-Differentiated Liposarcoma===
====Sclerosing Liposarcoma====
* The particular [[histological]] finding in this type of well differentiated liposarcoma is the identification of distinctive [[stromal]] [[Cell (biology)|cells]] distributed across the [[Tissue (biology)|tissue]], which are associated with lipoblasts filled with multiple [[vacuoles]]. 
* This association forms a [[collagenous]] background of fibrillary appearance. 
* In certain cases, the [[Fiber|fibrous]] component of the [[neoplasm]] may occupy most of its mass.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref>
 
====Adipocytic Liposarcoma====
* Frequently composed by [[adipocytes]] with different [[Cell (biology)|cell]] sizes, [[Hyperchromicity|hyperchromasia]], and [[Cell nucleus|nuclear]] atypia.
* [[Fibrous]] [[Septum|septa]] may be identified surrounding [[adipocytes]], containing [[Hyperchromicity|hyperchromatic]] [[stromal cells]].
* Besides these two types of [[Cell (biology)|cells]], mono- or multi-[[Vacuole|vacuolated]] lipoblasts may also be identified.
* Lipoblasts are characterized by the presence of single (mono) or multiple (multi) [[Periphery|peripheral]] [[Cytoplasm|cytoplasmic]] [[Vacuole|vacuoles]] that press on the [[Hyperchromicity|hyperchromatic]] [[Cell nucleus|nucleus]].<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304 }} </ref>
* In general, [[Adipocyte|adipocytic]] [[neoplasms]] are often identified by the presence of these lipoblasts. 
* Additionally, lipoblasts may infrequently be absent, which makes the [[diagnosis]] of [[Adipocyte|adipocytic]] [[neoplasm]] more difficult but possible with the help of other [[Histology|histological]] features.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref>


Genetics as well as molecular pathology have recently provided data that, at least in part, may account for the discrepancy observed between morphology and biologic aggressiveness. Interestingly, in stark contrast with the complex karyotypic aberrations observed in pleomor- phic sarcomas, dedifferentiated liposarcoma usually retains the same basic cytogenetic anomalies as well- differentiated liposarcoma represented by the presence of ring and/or giant marker chromosomes,27 although there may be superimposed additional aberrations.28 A significant increase in the level of both MDM2 overex- pression and amplification in the high-grade areas has been observed that may account for the tumor progres- sion in this subset of sarcomas.29,30 However, at variance with high-grade pleomorphic sarcomas, in which con- comitant MDM2 amplification and TP53 mutation are detected31 and that are significantly related to poor clinical outcome, retention of TP53 integrity is almost always observed in dedifferentiated liposarcoma.29 There- fore, dedifferentiated liposarcoma appears to be just one more step along the spectrum of well-differentiated adipocytic neoplasms, showing only an increased dosage of the same molecular targets involved in the molecular pathogenesis of well-differentiated liposarcoma.
====Inflammatory Liposarcoma====
* Its [[Adipocyte|adipocytic]] nature may be misidentified due to the heavy [[Chronic inflammation|chronic inflammatory]] infiltrate.  
* The [[Inflammation|inflammatory]] component is frequently composed of different [[Lymphocyte|lympho]]-[[Plasma cell|plasmacytic]] aggregates. These tend to be predominantly formed by a specific type of [[B-cell]], or less commonly [[T-cells]] may populate the [[Inflammation|inflammatory]] aggregate.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref><ref name="pmid9158675">{{cite journal| author=Kraus MD, Guillou L, Fletcher CD| title=Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked variant of a common sarcoma. | journal=Am J Surg Pathol | year= 1997 | volume= 21 | issue= 5 | pages= 518-27 | pmid=9158675 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9158675  }} </ref><ref name="pmid9255251">{{cite journal| author=Argani P, Facchetti F, Inghirami G, Rosai J| title=Lymphocyte-rich well-differentiated liposarcoma: report of nine cases. | journal=Am J Surg Pathol | year= 1997 | volume= 21 | issue= 8 | pages= 884-95 | pmid=9255251 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9255251  }} </ref> 


-->
==== '''Spindle Cell Lipocarcinoma''' ====
* This is a rare [[adult]]-type of well-differentiated liposarcoma. 
* It results from the [[Cell growth|proliferation]] of [[neural]]-like [[spindle cells]], which are organized in a [[fibrous]] structure, that contains lipoblasts.<ref name="pmid8067512">{{cite journal| author=Dei Tos AP, Mentzel T, Newman PL, Fletcher CD| title=Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases. | journal=Am J Surg Pathol | year= 1994 | volume= 18 | issue= 9 | pages= 913-21 | pmid=8067512 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8067512  }} </ref><ref name="pmid5">{{cite journal| author=Hendrickson WA, Ward KB| title=Atomic models for the polypeptide backbones of myohemerythrin and hemerythrin. | journal=Biochem Biophys Res Commun | year= 1975 | volume= 66 | issue= 4 | pages= 1349-56 | pmid=5 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5  }} </ref>
 
===De-differentiated Liposarcoma===
* In this form of liposarcoma, there is a transition from a low-grade differentiation to a high-grade differentiation within the same mass of well-differentiated liposarcoma.<ref name="pmid10982304">{{cite journal| author=Dei Tos AP| title=Liposarcoma: new entities and evolving concepts. | journal=Ann Diagn Pathol | year= 2000 | volume= 4 | issue= 4 | pages= 252-66 | pmid=10982304 | doi=10.1053/adpa.2000.8133 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10982304  }} </ref><ref name="pmid534388">{{cite journal| author=Evans HL| title=Liposarcoma: a study of 55 cases with a reassessment of its classification. | journal=Am J Surg Pathol | year= 1979 | volume= 3 | issue= 6 | pages= 507-23 | pmid=534388 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=534388  }} </ref><ref name="pmid192432">{{cite journal| author=Dahlin DC, Unni KK, Matsuno T| title=Malignant (fibrous) histiocytoma of bone--fact or fancy?. | journal=Cancer | year= 1977 | volume= 39 | issue= 4 | pages= 1508-16 | pmid=192432 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=192432  }} </ref> 
* 90% of dedifferentiation from well-differentiated liposarcomas occur in [[Primary tumor|primary tumors]], while the remaining 10% occur in recurrent [[Neoplasm|neoplasms]].<ref name="GhadimiAl-Zaid20112">{{cite journal|last1=Ghadimi|first1=Markus P.|last2=Al-Zaid|first2=Tariq|last3=Madewell|first3=John|last4=Peng|first4=Tingsheng|last5=Colombo|first5=Chiara|last6=Hoffman|first6=Aviad|last7=Creighton|first7=Chad J.|last8=Zhang|first8=Yiqun|last9=Zhang|first9=Anna|last10=Lazar|first10=Alexander J.|last11=Pollock|first11=Raphael E.|last12=Lev|first12=Dina|title=Diagnosis, Management, and Outcome of Patients with Dedifferentiated Liposarcoma Systemic Metastasis|journal=Annals of Surgical Oncology|volume=18|issue=13|year=2011|pages=3762–3770|issn=1068-9265|doi=10.1245/s10434-011-1794-0}}</ref><ref>{{Cite journal
| author = [[G. Lahat]], [[D. A. Anaya]], [[X. Wang]], [[D. Tuvin]], [[D. Lev]] & [[R. E. Pollock]]
| title = Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches
| journal = [[Annals of surgical oncology]]
| volume = 15
| issue = 6
| pages = 1585–1593
| year = 2008
| month = June
| doi = 10.1245/s10434-007-9805-x
| pmid = 18398663
}}</ref><ref>{{Cite journal
| author = [[H. L. Evans]], [[K. K. Khurana]], [[B. L. Kemp]] & [[A. G. Ayala]]
| title = Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma
| journal = [[The American journal of surgical pathology]]
| volume = 18
| issue = 11
| pages = 1150–1157
| year = 1994
| month = November
| pmid = 7943536
}}</ref><ref>{{Cite journal
| author = [[W. H. Henricks]], [[Y. C. Chu]], [[J. R. Goldblum]] & [[S. W. Weiss]]
| title = Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation
| journal = [[The American journal of surgical pathology]]
| volume = 21
| issue = 3
| pages = 271–281
| year = 1997
| month = March
| pmid = 9060596
}}</ref>


===Myxoid Liposarcoma===
===Myxoid Liposarcoma===
* They have a non-[[Homogeneity|homogenous]] appearance with [[Cyst|cystic]] and solid components.


===Round Cell Liposarcoma===
===Round Cell Liposarcoma===
* It is a high-grade liposarcoma which is a poorly differentiated form of myxoid sarcoma.
* It has a very poor [[prognosis]] and often [[Metastasis|metastasizes]] to the [[retroperitoneum]], [[pleural cavity]], [[soft tissue]], or [[pelvis]] and very rarely to the [[Lung|lungs]]. 
* [[Microscopic|Microscopically]], it consists of small, round, or [[spindle cells]] with sparse [[eosinophilic]] and [[Granule (cell biology)|granular]] [[cytoplasm]] and large [[Cell nucleus|nuclei]]. 
* It may have scattered lipoblasts and areas of [[necrosis]].


===Pleomorphic Liposarcoma===
===Pleiomorphic Liposarcoma===
 
* [[Pleomorphism|Pleomorphic]] [[Cell (biology)|cells]] may be identified with enlarged round to bizarre [[Cell nucleus|nuclei]].
==Genetics==
==Images==
===Well-Differentiated Liposarcoma===
{|
Specific diagnostic techniques, such as karyotipic analysis, have showed a specific characteristic of these cells, namely the presence of a large marker chromosome and/or of an extra ring.<ref name="pmid8827023">{{cite journal| author=Rosai J, Akerman M, Dal Cin P, DeWever I, Fletcher CD, Mandahl N et al.| title=Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group). | journal=Am J Surg Pathol | year= 1996 | volume= 20 | issue= 10 | pages= 1182-9 | pmid=8827023 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8827023  }} </ref> With the help of in situ hybridization, these rings and/or large markers were noted to accommodate amplified genetic sequences of the 12q13-15 chromosome region.<ref name="pmid8353809">{{cite journal| author=Dal Cin P, Kools P, Sciot R, De Wever I, Van Damme B, Van de Ven W et al.| title=Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors. | journal=Cancer Genet Cytogenet | year= 1993 | volume= 68 | issue= 2 | pages= 85-90 | pmid=8353809 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8353809 }} </ref>  This chromosome region is rich in [[protooncogene]]s, including the CHOP, CDK4, MDM2, HMGI-C, GLI, SAS, OS1, and the OS9, which play an important role in the [[pathogenesis]] of many [[neoplasms]].  Amplification of some of these regions, with concomitant amplification of their proteins has been demonstrated in this type of [[soft tissue sarcoma]].<ref name="pmid10727978">{{cite journal| author=Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M et al.| title=Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. | journal=J Pathol | year= 2000 | volume= 190 | issue= 5 | pages= 531-6 | pmid=10727978 | doi=10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10727978 }} </ref>  Because this same region is rearranged in benign lipomas as well, this last may integrate a well-defferentiated liposarcoma mass.  The difference between these malignant and benign tissues resides in the amount of rearranged gene present in each one.<ref name="pmid10727978">{{cite journal| author=Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M et al.| title=Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. | journal=J Pathol | year= 2000 | volume= 190 | issue= 5 | pages= 531-6 | pmid=10727978 | doi=10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10727978  }} </ref>
|[[File:Well Differentiated Liposarcoma.jpg|left|thumb|250px|Well Differentiated Liposarcoma.  Image courtesy of Wikimedia Commons]]
 
|[[File:Dedifferentiated Liposarcoma.jpg|center|thumb|250px|Dedifferentiated Liposarcoma.  Image courtesy of Wikimedia Commons]]
==Associated Conditions==
|[[File:Dedifferentiated Liposarcoma 2.jpg|right|thumb|250px|Dedifferentiated Liposarcoma.  Image courtesy of Wikimedia Commons]]
 
|-
==Gross Pathology==
|[[File:Dedifferentiated Liposarcoma 3.jpg|left|thumb|250px|Dedifferentiated Liposarcoma.  Image courtesy of Wikimedia Commons]]
 
|[[File:Dedifferentiated Liposarcoma 4.jpg|center|thumb|250px|Dedifferentiated Liposarcoma. Image courtesy of Wikimedia Commons]]
==Microscopic Pathology==
|}


==References==
==References==
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Latest revision as of 16:48, 27 May 2019

Liposarcoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]Sabawoon Mirwais, M.B.B.S, M.D.[3]

Overview

Liposarcoma is the most common sarcoma of soft tissue. The pathogenesis of liposarcoma depends on the histological sub-type. The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas. The majority of well differentiated liposarcomas arise in the retroperitoneum. The chromosome region 12q13-15, is rich in protooncogenes, including the CHOP, CDK4, MDM2, HMGI-C, GLI, SAS, OS1, and the OS9, all of which play an important role in the pathogenesis of many neoplasms. Liposarcoma is associated with genetic conditions like Li-Fraumeni syndrome. Liposarcoma usually presents as a mass which often resembles lipoma and is multinodular. Microscopic pathological findings of liposarcoma depend on the sub-type.

Pathophysiology

Pathogenesis

  • Liposarcoma is the most common sarcoma of soft tissue.[1]
  • The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas.[2]
  • The majority of well differentiated liposarcomas arise in the retroperitoneum.[3][4]
  • The dedifferentiated sub-type is clinically more aggressive than the well differentiated liposarcoma.[13][14][15][16]

Genetics

Well-Differentiated Liposarcoma

Associated Conditions

Gross Pathology

  • Liposarcoma usually presents as a mass which often resembles lipoma and is multinodular.
  • Cut surface may be soft or firm and is yellow in color.
  • Focal mucinous area may be seen.
  • Areas of necrosis may be noted.

Microscopic Pathology

Each liposarcoma sub-type has specific characteristics:

Well-Differentiated Liposarcoma

Sclerosing Liposarcoma

  • The particular histological finding in this type of well differentiated liposarcoma is the identification of distinctive stromal cells distributed across the tissue, which are associated with lipoblasts filled with multiple vacuoles.
  • This association forms a collagenous background of fibrillary appearance.
  • In certain cases, the fibrous component of the neoplasm may occupy most of its mass.[18]

Adipocytic Liposarcoma

Inflammatory Liposarcoma

Spindle Cell Lipocarcinoma

De-differentiated Liposarcoma

  • In this form of liposarcoma, there is a transition from a low-grade differentiation to a high-grade differentiation within the same mass of well-differentiated liposarcoma.[18][23][24]
  • 90% of dedifferentiation from well-differentiated liposarcomas occur in primary tumors, while the remaining 10% occur in recurrent neoplasms.[25][26][27][28]

Myxoid Liposarcoma

Round Cell Liposarcoma

Pleiomorphic Liposarcoma

Images

Well Differentiated Liposarcoma. Image courtesy of Wikimedia Commons
Dedifferentiated Liposarcoma. Image courtesy of Wikimedia Commons
Dedifferentiated Liposarcoma. Image courtesy of Wikimedia Commons
Dedifferentiated Liposarcoma. Image courtesy of Wikimedia Commons
Dedifferentiated Liposarcoma. Image courtesy of Wikimedia Commons

References

  1. ↑ Kate Lynn J. Bill, Lucia Casadei, Bethany C. Prudner, Hans Iwenofu, Anne M. Strohecker & Raphael E. Pollock (2016). "Liposarcoma: molecular targets and therapeutic implications". Cellular and molecular life sciences : CMLS. 73 (19): 3711–3718. doi:10.1007/s00018-016-2266-2. PMID 27173057. Unknown parameter |month= ignored (help)
  2. ↑ Kate Lynn J. Bill, Lucia Casadei, Bethany C. Prudner, Hans Iwenofu, Anne M. Strohecker & Raphael E. Pollock (2016). "Liposarcoma: molecular targets and therapeutic implications". Cellular and molecular life sciences : CMLS. 73 (19): 3711–3718. doi:10.1007/s00018-016-2266-2. PMID 27173057. Unknown parameter |month= ignored (help)
  3. ↑ N. Azumi, J. Curtis, R. L. Kempson & M. R. Hendrickson (1987). "Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases". The American journal of surgical pathology. 11 (3): 161–183. PMID 3826477. Unknown parameter |month= ignored (help)
  4. ↑ Emily Z. Keung, Jason L. Hornick, Monica M. Bertagnolli, Elizabeth H. Baldini & Chandrajit P. Raut (2014). "Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery". Journal of the American College of Surgeons. 218 (2): 206–217. doi:10.1016/j.jamcollsurg.2013.10.009. PMID 24315890. Unknown parameter |month= ignored (help)
  5. ↑ N. Azumi, J. Curtis, R. L. Kempson & M. R. Hendrickson (1987). "Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases". The American journal of surgical pathology. 11 (3): 161–183. PMID 3826477. Unknown parameter |month= ignored (help)
  6. ↑ Emily Z. Keung, Jason L. Hornick, Monica M. Bertagnolli, Elizabeth H. Baldini & Chandrajit P. Raut (2014). "Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery". Journal of the American College of Surgeons. 218 (2): 206–217. doi:10.1016/j.jamcollsurg.2013.10.009. PMID 24315890. Unknown parameter |month= ignored (help)
  7. ↑ N. Azumi, J. Curtis, R. L. Kempson & M. R. Hendrickson (1987). "Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases". The American journal of surgical pathology. 11 (3): 161–183. PMID 3826477. Unknown parameter |month= ignored (help)
  8. ↑ Elizabeth Fabre-Guillevin, Jean-Michel Coindre, Nicolas de Saint Aubain Somerhausen, Francoise Bonichon, Eberhard Stoeckle & Nguyen Binh Bui (2006). "Retroperitoneal liposarcomas: follow-up analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas". Cancer. 106 (12): 2725–2733. doi:10.1002/cncr.21933. PMID 16688768. Unknown parameter |month= ignored (help)
  9. ↑ Ghadimi, Markus P.; Al-Zaid, Tariq; Madewell, John; Peng, Tingsheng; Colombo, Chiara; Hoffman, Aviad; Creighton, Chad J.; Zhang, Yiqun; Zhang, Anna; Lazar, Alexander J.; Pollock, Raphael E.; Lev, Dina (2011). "Diagnosis, Management, and Outcome of Patients with Dedifferentiated Liposarcoma Systemic Metastasis". Annals of Surgical Oncology. 18 (13): 3762–3770. doi:10.1245/s10434-011-1794-0. ISSN 1068-9265.
  10. ↑ G. Lahat, D. A. Anaya, X. Wang, D. Tuvin, D. Lev & R. E. Pollock (2008). "Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches". Annals of surgical oncology. 15 (6): 1585–1593. doi:10.1245/s10434-007-9805-x. PMID 18398663. Unknown parameter |month= ignored (help)
  11. ↑ H. L. Evans, K. K. Khurana, B. L. Kemp & A. G. Ayala (1994). "Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma". The American journal of surgical pathology. 18 (11): 1150–1157. PMID 7943536. Unknown parameter |month= ignored (help)
  12. ↑ W. H. Henricks, Y. C. Chu, J. R. Goldblum & S. W. Weiss (1997). "Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation". The American journal of surgical pathology. 21 (3): 271–281. PMID 9060596. Unknown parameter |month= ignored (help)
  13. ↑ Singer, Samuel; Antonescu, Cristina R.; Riedel, Elyn; Brennan, Murray F. (2003). "Histologic Subtype and Margin of Resection Predict Pattern of Recurrence and Survival for Retroperitoneal Liposarcoma". Transactions of the ... Meeting of the American Surgical Association. 121: 52–65. doi:10.1097/01.sla.0000086542.11899.38. ISSN 0066-0833.
  14. ↑ G. Lahat, D. A. Anaya, X. Wang, D. Tuvin, D. Lev & R. E. Pollock (2008). "Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches". Annals of surgical oncology. 15 (6): 1585–1593. doi:10.1245/s10434-007-9805-x. PMID 18398663. Unknown parameter |month= ignored (help)
  15. ↑ Emily Z. Keung, Jason L. Hornick, Monica M. Bertagnolli, Elizabeth H. Baldini & Chandrajit P. Raut (2014). "Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery". Journal of the American College of Surgeons. 218 (2): 206–217. doi:10.1016/j.jamcollsurg.2013.10.009. PMID 24315890. Unknown parameter |month= ignored (help)
  16. ↑ Khin Thway, Robin L. Jones, Jonathan Noujaim, Shane Zaidi, Aisha B. Miah & Cyril Fisher (2016). "Dedifferentiated Liposarcoma: Updates on Morphology, Genetics, and Therapeutic Strategies". Advances in anatomic pathology. 23 (1): 30–40. doi:10.1097/PAP.0000000000000101. PMID 26645460. Unknown parameter |month= ignored (help)
  17. ↑ 17.0 17.1 Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M; et al. (2000). "Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours". J Pathol. 190 (5): 531–6. doi:10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W. PMID 10727978.
  18. ↑ 18.0 18.1 18.2 18.3 18.4 Dei Tos AP (2000). "Liposarcoma: new entities and evolving concepts". Ann Diagn Pathol. 4 (4): 252–66. doi:10.1053/adpa.2000.8133. PMID 10982304.
  19. ↑ Kraus MD, Guillou L, Fletcher CD (1997). "Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked variant of a common sarcoma". Am J Surg Pathol. 21 (5): 518–27. PMID 9158675.
  20. ↑ Argani P, Facchetti F, Inghirami G, Rosai J (1997). "Lymphocyte-rich well-differentiated liposarcoma: report of nine cases". Am J Surg Pathol. 21 (8): 884–95. PMID 9255251.
  21. ↑ Dei Tos AP, Mentzel T, Newman PL, Fletcher CD (1994). "Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases". Am J Surg Pathol. 18 (9): 913–21. PMID 8067512.
  22. ↑ Hendrickson WA, Ward KB (1975). "Atomic models for the polypeptide backbones of myohemerythrin and hemerythrin". Biochem Biophys Res Commun. 66 (4): 1349–56. PMID 5.
  23. ↑ Evans HL (1979). "Liposarcoma: a study of 55 cases with a reassessment of its classification". Am J Surg Pathol. 3 (6): 507–23. PMID 534388.
  24. ↑ Dahlin DC, Unni KK, Matsuno T (1977). "Malignant (fibrous) histiocytoma of bone--fact or fancy?". Cancer. 39 (4): 1508–16. PMID 192432.
  25. ↑ Ghadimi, Markus P.; Al-Zaid, Tariq; Madewell, John; Peng, Tingsheng; Colombo, Chiara; Hoffman, Aviad; Creighton, Chad J.; Zhang, Yiqun; Zhang, Anna; Lazar, Alexander J.; Pollock, Raphael E.; Lev, Dina (2011). "Diagnosis, Management, and Outcome of Patients with Dedifferentiated Liposarcoma Systemic Metastasis". Annals of Surgical Oncology. 18 (13): 3762–3770. doi:10.1245/s10434-011-1794-0. ISSN 1068-9265.
  26. ↑ G. Lahat, D. A. Anaya, X. Wang, D. Tuvin, D. Lev & R. E. Pollock (2008). "Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches". Annals of surgical oncology. 15 (6): 1585–1593. doi:10.1245/s10434-007-9805-x. PMID 18398663. Unknown parameter |month= ignored (help)
  27. ↑ H. L. Evans, K. K. Khurana, B. L. Kemp & A. G. Ayala (1994). "Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma". The American journal of surgical pathology. 18 (11): 1150–1157. PMID 7943536. Unknown parameter |month= ignored (help)
  28. ↑ W. H. Henricks, Y. C. Chu, J. R. Goldblum & S. W. Weiss (1997). "Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation". The American journal of surgical pathology. 21 (3): 271–281. PMID 9060596. Unknown parameter |month= ignored (help)


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