Thursday 9 October 2008
Adipose tissue tumors of the retroperitoneum showing no identifiable cytologic atypia are usually classified as lipomalike well-differentiated liposarcoma.
Whether a subset of these tumors represents true examples of retroperitoneal lipoma remains a controversial subject, because the diagnostic liposarcoma cells may be of difficult identification, even after extensive sampling.
The discrimination between ordinary lipoma and atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) is a common diagnostic challenge in diagnostic soft tissue pathology.
Histologic, cytogenetic, and molecular genetic data support the idea that these two major groups of adipose tissue tumors are distinct biologic entities in spite of overlapping histologic features. Careful tissue sampling and histologic examination are the major and simplest steps for the correct discrimination between a lipoma and an ALT/WDL.
Lipomas can be superficial or deep seated and are histologically characterized by mature fat cells with no cytologic atypia/hyperchromasia/pleomorphism. Occasionally, lipoblasts can be seen in lipomas, especially near blood vessels. However, they do not exhibit cytologic atypia/hyperchromasia/pleomorphism.
ALT/WDL are histologically characterized by the presence of mixed population of lipoblasts and lipocytes but more importantly by atypical hyperchromatic pleomorphic cells. These tend to be more commonly found near blood vessels and within fibrous septa. It is also important to note that the identification of lipoblasts is not a necessary criterion for the diagnosis of an ALT/WDL.
The discrimination between lipoma and ALT/WDL becomes challenging when the diagnostic atypical hyperchromatic pleomorphic cells are rare or have subtle atypical cytologic features.
Many cell types or tissue artifacts can simulate these cells, including lockhern artifact (intranuclear holes), activated fibroblasts/myofibroblasts, multinucleated giant cells, and degenerated skeletal muscle fibers. However, in most instances these cells can be correctly identified by careful examination. However, ALT/WDL cells with subtle cytologic features can be very difficult to recognize by histologic exam.
Lipoma and ALT/WDL have very distinct cytogenetic and molecular genetic characteristics:
Lipomas are mainly characterized by rearrangements of chromosome 12q13q15 with several partner chromosomes in approximately 50-60% of cases, especially chromosome 3. Lipomas without 12q13q15 rearrangements frequently show rearrangements of chromosome 6p21. Several lipoma fusion genes have been identified and the most common is LPP-HMGA2, product of the t(3;12)(q27-q28;q14-a15). Interestingly, lipomas grow relatively well in culture and, in our experience, 60-70% of them show abnormal karyotypes.
ALT/WDL usually exhibit supernumerary ring or giant maker chromosomes by standard cytogenetic analysis. These abnormal chromosomes are composed by amplified genomic material mainly derived from chromosome bands 12q13q15. These bands contain several cancer genes, including MDM2, SAS, CDK4 and HMGA2. MDM2 seems to be the most consistently amplified gene in ALT/WDL (>99% of cases). Amplification of these genes is not observed in lipoma.
no evidence of cytologic atypia.
Ida CM, Wang X, Erickson-Johnson MR, Wenger DE, Blute ML, Nascimento AG, Oliveira AM. Primary retroperitoneal lipoma: a soft tissue pathology heresy?: report of a case with classic histologic, cytogenetics, and molecular genetic features. Am J Surg Pathol. 2008 Jun;32(6):951-4. PMID: 18551755
Weiss SW, Rao VK. Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum, and miscellaneous sites. A follow-up study of 92 cases with analysis of the incidence of "dedifferentiation". Am J Surg Pathol 1992;16(11):1051-8.
Sandberg AA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: lipoma. Cancer Genet Cytogenet 2004;150(2):93-115.
Rosai J, Akerman M, Dal CP, DeWever I, Fletcher CD, Mandahl N, et al. 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). Am J Surg Pathol 1996;20(10):1182-9.
Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF, et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 1999;24(1):30-41.
Nilbert M, Rydholm A, Mitelman F, Meltzer PS, Mandahl N. Characterization of the 12q13-15 amplicon in soft tissue tumors. Cancer Genet Cytogenet 1995;83(1):32-6.
Mandahl N, Akerman M, Aman P, Dal CP, De W, I, Fletcher CD, et al. Duplication of chromosome segment 12q15-24 is associated with atypical lipomatous tumors: a report of the CHAMP collaborative study group. CHromosomes And MorPhology. Int J Cancer 1996;67(5):632-5.
Fletcher CD, Akerman M, Dal CP, De W, I, Mandahl N, Mertens F, et al. Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. Am J Pathol 1996;148(2):623-30.
Evans HL, Soule EH, Winkelmann RK. Atypical lipoma, atypical intramuscular lipoma, and well differentiated retroperitoneal liposarcoma: a reappraisal of 30 cases formerly classified as well differentiated liposarcoma. Cancer 1979;43(2):574-84.
Dei Tos A, Pedeutour F. Atypical lipomatous tumour/well differentiated liposarcoma. In: Fletcher CD, Unni KK, Mertens F, eds. Tumours of Soft Tissue and Bone. 2nd ed. Lyon: IARCPress World Health Organization, 2002.
Bassett MD, Schuetze SM, Disteche C, Norwood TH, Swisshelm K, Chen X, et al. Deep-seated, well differentiated lipomatous tumors of the chest wall and extremities: the role of cytogenetics in classification and prognostication. Cancer 2005;103(2):409-16.
Arlotta P, Tai AK, Manfioletti G, Clifford C, Jay G, Ono SJ. Transgenic mice expressing a truncated form of the high mobility group I-C protein develop adiposity and an abnormally high prevalence of lipomas. J Biol Chem 2000;275(19):1439-400.
Sandberg AA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma. Cancer Genet Cytogenet 2004;155(1):1-24.
Pedeutour F, Suijkerbuijk RF, Forus A, Van GJ, Van de KW, Coindre JM, et al. Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma. Genes Chromosomes Cancer 1994;10(2):85-94.
Coindre JM, Hostein I, Maire G, Derre J, Guillou L, Leroux A, et al. Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity. J Pathol 2004;203(3):822-30.
Trahan S, Erickson-Johnson MR, Rodriguez F, Aubry MC, Cheville JC, Myers JL, Oliveira AM. Formation of the 12q14-q15 amplicon precedes the development of a well-differentiated liposarcoma arising from a nonchondroid pulmonary hamartoma. Am J Surg Pathol 2006;30(10):1326-9.
Shimada S, Ishizawa T, Ishizawa K, Matsumura T, Hasegawa T, Hirose T. The value of MDM2 and CDK4 amplification levels using real-time polymerase chain reaction for the differential diagnosis of liposarcomas and their histologic mimickers. Hum Pathol 2006;37(9):1123-9.
Hostein I, Pelmus M, Aurias A, Pedeutour F, Mathoulin-Pelissier S, Coindre JM. Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax-embedded material: a potential tool for the diagnosis of atypical lipomatous tumours/well-differentiated liposarcomas. J Pathol 2004;202(1):95-102.
Binh MB, Garau XS, Guillou L, Aurias A, Coindre JM. Reproducibility of MDM2 and CDK4 staining in soft tissue tumors. Am J Clin Pathol 2006;125(5):693-7.
Binh MB, Sastre-Garau X, Guillou L, de PG, Terrier P, Lagace R, et al. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol 2005;29(10):1340-7.
Adachi T, Oda Y, Sakamoto A, Saito T, Tamiya S, Masuda K, et al. Immunoreactivity of p53, mdm2, and p21WAF1 in dedifferentiated liposarcoma: special emphasis on the distinct immunophenotype of the well-differentiated component. Int J Surg Pathol 2001;9(2):99-109.
Jacob E, Erickson-Johnson M, Wang X, Nascimento A, Oliveira A. Assessment of MDM2 amplification using fluorescence in situ hybridization on paraffin-embedded tissues discriminates atypical lipomatous tumors from lipomas. Lab Invest 2006; 86: 13A.