Liposarcoma pathophysiology: Difference between revisions
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According to their class, each liposarcoma will have specific characteristics and pathogenesis: | According to their class, each liposarcoma will have specific characteristics and pathogenesis: | ||
===Well Differentiated Liposarcoma=== | ===Well Differentiated Liposarcoma=== | ||
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Well-differentiated liposarcoma represents approxi- mately 40% to 45% of all liposarcomas and tends to occur equally in the retroperitoneum or the limbs. Spermatic cord and mediastinum represent less-fre- quent but well-known anatomic locations. Morphologi- cally, the WHO classification recognizes three subtypes of well-differentiated liposarcoma: adipocytic (or lipoma- like), sclerosing, and inflammatory. Adipocytic liposar- coma is mostly composed of mature adipocytes exhibit- ing striking variation in cell size and at least focal nuclear atypia and hyperchromasia (Fig 1). Scattered hyperchromatic stromal cells may be encountered within fibrous septa. Of course, a varying number (from many to none) of monovacuolated or multivacuolated lipo- blasts (defined by the presence of single or multiple sharply marginated cytoplasmic vacuoles that indent an enlarged hyperchromatic nucleus) may be found (Fig 2). It is a commonly held opinion that lipoblasts represent the hallmark for any type of malignant adipocytic lesion. | |||
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. | |||
Sclerosing liposarcoma is characterized clinically by the tendency to occur most frequently in the retroperito- neum and in the paratesticular region. Microscopically, the main histologic finding is the presence of scattered, distinctive, bizarre stromal cells associated with rare multivacuolated lipoblasts set in a fibrillary collagenous background (Fig 3). Occasionally the fibrous component represents the vast majority of the neoplasm to the extent that lipogenic areas can be easily overlooked or even missed in a small tissue sample (Fig 4). | |||
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. | |||
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. | |||
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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===Dedifferentiated Liposarcoma=== | ===Dedifferentiated Liposarcoma=== | ||
Revision as of 14:55, 19 September 2014
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Liposarcoma Microchapters |
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Liposarcoma pathophysiology On the Web |
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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
Dedifferentiated Liposarcoma
Myxoid Liposarcoma
Round Cell Liposarcoma
Pleomorphic Liposarcoma
Genetics
Associated Conditions
Gross Pathology
Microscopic Pathology
References