Liposarcoma pathophysiology: Difference between revisions

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==Overview==
==Overview==
The pathogenesis of liposarcoma depends on the histological subtype. The role of proto-oncogenes has been implicated in the disease development.
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]].


==Pathophysiology==
==Pathophysiology==


=== Pathogenesis ===
=== Pathogenesis ===
*Liposarcoma is the most common sarcoma of soft tissue.<ref>{{Cite journal
*Liposarcoma is the most common [[sarcoma]] of [[soft tissue]].<ref>{{Cite journal
  | author = [[Kate Lynn J. Bill]], [[Lucia Casadei]], [[Bethany C. Prudner]], [[Hans Iwenofu]], [[Anne M. Strohecker]] & [[Raphael E. Pollock]]
  | 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
  | title = Liposarcoma: molecular targets and therapeutic implications
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  | pmid = 27173057
  | pmid = 27173057
}}</ref>
}}</ref>
*The two sub-types, well differentiated and dedifferentiated are the two most commonly occurring liposarcomas.<ref>{{Cite journal
*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]]
  | 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
  | title = Liposarcoma: molecular targets and therapeutic implications
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  | pmid = 27173057
  | pmid = 27173057
}}</ref>
}}</ref>
*The majority of well differentiated liposarcomas arise in the retroperitoneum.<ref>{{Cite journal
*The majority of well differentiated liposarcomas arise in the [[retroperitoneum]].<ref>{{Cite journal
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
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  | month = March
  | month = March
  | pmid = 3826477
  | pmid = 3826477
}}</ref>
}}</ref><ref>{{Cite journal
<ref>{{Cite journal
  | author = [[Emily Z. Keung]], [[Jason L. Hornick]], [[Monica M. Bertagnolli]], [[Elizabeth H. Baldini]] & [[Chandrajit P. Raut]]
  | 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
  | title = Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery
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  | pmid = 24315890
  | pmid = 24315890
}}</ref>
}}</ref>
*The tumor can also arise in the deep soft tissue of the thigh, mediastinum, and paratesticular area.<ref>{{Cite journal
 
*The [[tumor]] can also arise in the deep [[soft tissue]] of the [[thigh]], [[mediastinum]], and paratesticular area.<ref>{{Cite journal
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
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  | month = March
  | month = March
  | pmid = 3826477
  | pmid = 3826477
}}</ref>
}}</ref><ref>{{Cite journal
<ref>{{Cite journal
  | author = [[Emily Z. Keung]], [[Jason L. Hornick]], [[Monica M. Bertagnolli]], [[Elizabeth H. Baldini]] & [[Chandrajit P. Raut]]
  | 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
  | title = Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery
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  | pmid = 24315890
  | pmid = 24315890
}}</ref>
}}</ref>
*Retroperitoneal tumors are more likely to recur.<ref>{{Cite journal
 
*[[Retroperitoneum|Retroperitoneal]] [[Tumor|tumors]] are more likely to recur.<ref>{{Cite journal
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
  | author = [[N. Azumi]], [[J. Curtis]], [[R. L. Kempson]] & [[M. R. Hendrickson]]
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
  | title = Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases
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  | pmid = 16688768
  | pmid = 16688768
}}</ref>
}}</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
*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]]
  | 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
  | title = Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches
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  | doi = 10.1245/s10434-007-9805-x
  | doi = 10.1245/s10434-007-9805-x
  | pmid = 18398663
  | pmid = 18398663
}}</ref>
}}</ref><ref>{{Cite journal
<ref>{{Cite journal
  | author = [[H. L. Evans]], [[K. K. Khurana]], [[B. L. Kemp]] & [[A. G. Ayala]]
  | author = [[H. L. Evans]], [[K. K. Khurana]], [[B. L. Kemp]] & [[A. G. Ayala]]
  | title = Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma
  | title = Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma
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  | pmid = 9060596
  | pmid = 9060596
}}</ref>
}}</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
*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]]
  | 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
  | title = Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches
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  | pmid = 26645460
  | pmid = 26645460
}}</ref>
}}</ref>
==Genetics==
==Genetics==
====Well-Differentiated Liposarcoma====
====Well-Differentiated Liposarcoma====
Specific diagnostic techniques, such as karyotyping, 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 fluorescence in-situ hybridization (FISH) technique, 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'', all of which play an important role in the [[pathogenesis]] of many [[neoplasms]].  Amplification of some of these regions, with concomitant amplification of their proteins, was clearly 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>  Because this same region is rearranged in benign lipomas as well, benign lesions may develop to become well-defferentiated liposarcoma masses.  The difference between malignant and benign masses resides in the amount of rearranged gene present in each 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>
* This [[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>


==Associated Conditions==
==Associated Conditions==
Liposarcoma is associated with genetic conditions like [[Li-Fraumeni syndrome]].
Liposarcoma is associated with [[Genetic disorder|genetic conditions]] like [[Li-Fraumeni syndrome]].


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


==Microscopic Pathology==
==Microscopic Pathology==
Each liposarcoma subtype has specific characteristics:
Each liposarcoma sub-type has specific characteristics:
===Well-Differentiated Liposarcoma===
===Well-Differentiated Liposarcoma===
====Sclerosing 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.<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 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====
====Adipocytic Liposarcoma====
Frequently composed by [[adipocytes]] with different cell sizes, hyperchromasia, and nuclear atypia. [[Fibrous]] septa may be identified surrounding [[adipocytes]], containing hyperchromatic [[stromal cells]].  Besides these two types of cells, mono- or multi-vacuolated lipoblasts may also be identified. Lipoblasts 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> In general, adipocytic [[neoplasms]] are often identified by the presence of these lipoblasts.  However, the presence of lipoblasts is not specific, since multiple benign lesions may contain lipoblasts. Additionally, lipoblasts may infrequently be absent, which makes the diagnosis of adipocytic neoplasm more difficult but possible with the help of other 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>
* 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>
 
====Inflammatory Liposarcoma====
====Inflammatory Liposarcoma====
Its adipocytic 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]], or less commonly [[T-cells]] may 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>   
* Its [[Adipocyte|adipocytic]] nature may be misidentified due to the heavy [[Chronic inflammation|chronic inflammatory]] infiltrate.  
'''Spindle cell lipocarcinoma''' is a rare adult-type of well-differentiated liposarcoma.  It results from the 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>
* 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===
===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 tumors, while the remaining 10% occur in recurrent neoplasms.  
* 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>


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

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.

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

Liposarcoma is associated with genetic conditions like Li-Fraumeni syndrome.

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]

Myxoid Liposarcoma

Micrograph of myxoid 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 metastasize to the retroperitoneum, pleural cavity, soft tissue, or pelvis and very rarely to the lungs. Microscopically it consists of small, round, or spindle cells with sparse eosinophilic and granular cytoplasm and large nuclei. It may have scattered lipoblasts and areas of necrosis.

Pleiomorphic Liposarcoma

Pleomorphic cells may be identified with enlarged round to bizarre nuclei.

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.


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