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>


*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]]
| 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.<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>
*[[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>


*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>


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


<!--
==Gross Pathology==
However, it is important to emphasize that the mere presence of lipoblasts does not make (or is required for) a diagnosis of liposarcoma. As a matter of fact, there exist a number of entirely benign adipocytic lesions (eg, lipoblastoma, pleomorphic lipoma, chondroid lipoma) that may contain numerous lipoblasts. By contrast, the absence of lipoblasts within an adipocytic neoplasm fulfilling all the remaining diagnostic criteria for liposar- coma does not prevent such a diagnosis.
*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.


Another morphologic variation that represents a potential diagnostic pitfall is the presence of a chronic inflammatory infiltrate to the extent that the adipocytic nature of the neoplasm can be obscured (Fig 5). The existence of examples of liposarcoma characterized by the presence of prominent mononuclear inflammatory infiltrates has been acknowledged since the publication of Stout’s5 classification of liposarcoma. Nonetheless, reports dealing specifically with this subtype have not been available until very recently.6,7 The inflammatory infiltrate is usually composed of polyphenotypic lympho- plasmacytic aggregates in which a B-cell phenotype tends to predominate. However, cases exist in which a T-cell population represents the main inflammatory component. Differential diagnosis includes nonadipo- cytic lesions such as inflammatory myofibroblastic tu- mor and Castleman’s disease. Careful as well as exten- sive sampling is mandatory to permit recognition of the adipocytic component that otherwise could be easily missed. The presence of bizarre multinucleate stromal cells represents a useful diagnostic clue.
==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>


In 1994, a rare variant of well-differentiated liposar- coma was described under the term spindle cell liposar- coma,8,9 which occurs in adults and, at least in the first series, appeared to relatively often involve subcutaneous soft tissue. However, through observation of a larger number of cases, the anatomic distribution of spindle cell liposarcoma seems to be comparable to that of the other well-differentiated liposarcoma subtypes. Morpho- logically, spindle cell liposarcoma is composed of a fairly bland neural-like spindle cell proliferation set in a fibrous and/or myxoid background (Fig 6) and is associ- ated with an atypical lipomatous component that usu- ally includes lipoblasts (Fig 7). Main differential diag- noses include spindle cell lipoma (composed of bland, sometimes palisading, CD34-positive spindle cells, ad- mixed with eosinophilic refractile collagen bundles), neurofibroma (characterized by a less cellular S-100– positive spindle cell proliferation with wavy nuclei), dermatofibrosarcoma protuberans (cytologically bland, monomorphic CD34-positive spindle cell proliferation organized in a distinctive storiform growth pattern and characterized by tendency to infiltrate the surrounding fat in a peculiar ‘‘honeycomb’’ pattern), malignant peripheral nerve sheath tumor (generally highly cellular tumors composed of tapering or wavy spindle cells featuring perivascular accentuation and focal S-100– positive immunoreactivity in approximately 50% of cases), and well-differentiated sclerosing liposarcoma (characterized by the presence of bizarre hyperchro- matic stromal cells set in fibrillary collagen). The pres- ence of an atypical lipomatous component also permits distinction from low-grade fibromyxoid sarcoma (Evans’ tumor). Interestingly, spindle cell liposarcoma exhibits chromosome changes (ring chromosomes and giant marker chromosomes) identical to those observed in other members of the well-differentiated liposarcoma group, thus validating its classification.
====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>


As previously mentioned, the integration between morphologic and cytogenetic observations has proved extremely useful, and adipocytic neoplasms represent one of the fields of surgical pathology wherein such a synergy has been most fruitful (Table 2). Karyotypic analysis of well-differentiated liposarcoma has shown that this group of mesenchymal neoplasms is marked by the presence of extra ring and/or giant marker chromo- somes.10 Fluorescence in situ hybridization studies have demonstrated that these rings and giant markers con- tain amplified sequences derived from the 12q13-15 chromosome region.11 The 12q13-15 chromosome re- gion is very complex and contains several important protooncogenes, such as MDM2, CDK4, HMGI-C, SAS, GLI, CHOP, OS1, and OS9, known to play an important role in the molecular pathogenesis of many neoplastic processes. Interestingly, concomitant amplification of HMGI-C (a gene encoding for an architectural transcrip- tion factor involved in adipocytic differentiation), MDM2, and CDK4 (both acting as positive regulators of cell cycle progression at the G1-S checkpoint), as well as overexpression of the proteins thereof has been recently demonstrated in well-differentiated liposarcomas.12 The fact that the 12q13-15 region is also rearranged in ordinary benign lipomas (leading to HMGI-C activa- tion) and the observation of 12q15 duplication in adipo- cytic neoplasms exhibiting minimal atypical changes (C.D.M. Fletcher, unpublished observation) have led to the postulation that ordinary lipomas may form a morphologic and genetic continuum with well-differenti- ated liposarcoma, with the degree of atypia being a gene dosage effect.12
====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>


===Dedifferentiated 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 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==
 
{|
==Associated Conditions==
|[[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]]
==Gross Pathology==
|[[File:Dedifferentiated Liposarcoma 2.jpg|right|thumb|250px|Dedifferentiated Liposarcoma.  Image courtesy of Wikimedia Commons]]
 
|-
==Microscopic 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]]
|}


==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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