Liposarcoma pathophysiology: Difference between revisions
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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> | 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> | ||
Spindle cell lipocarcinoma, a rare adult type of well-differentiated liposarcoma<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> | |||
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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. | |||
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 | 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 | ||
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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
Pathogenesis
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.[1]
According to the WHO classification described previously, well differentiated liposarcomas may be sub-classified into 3 types: sclerosing; adipocytic; and inflammatory.
Sclerosing Liposarcoma
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.[1]
Adipocytic Liposarcoma
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.[1]
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.[1]
Inflammatory Liposarcoma
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.[1][2][3] For the diagnosis of inflammatory liposarcoma a large sample is required to avoid missing the adipocitic component of the neoplasm.[1]
Spindle cell lipocarcinoma, a rare adult type of well-differentiated liposarcoma[4][5]
Dedifferentiated Liposarcoma
Myxoid Liposarcoma
Round Cell Liposarcoma
Pleomorphic Liposarcoma
Genetics
Associated Conditions
Gross Pathology
Microscopic Pathology
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.