title: Cutaneous and subcutaneous pleomorphic liposarcoma: a clinicopathologic study of 29 cases with evaluation of MDM2 gene amplification in 26.
abstract: Pleomorphic liposarcoma (PL) is an uncommon form of liposarcoma that rarely occurs in the skin and subcutis. As its behavior in this setting is incompletely characterized, we undertook a study of a series of superficial PLs, defined as those arising or based primarily in the dermis and/or subcutis without involvement of deep structures. In addition, MDM2 gene amplification, a diagnostic signature of well-differentiated/dedifferentiated liposarcoma (WDL/DL), was evaluated to address the recent observation that this gene is amplified within PL-like areas in DL. PLs were obtained from institutional and consultation files (n=29). Cases were evaluated with respect to age, sex, location (dermis, dermis and subcutis, subcutis), size, predominant pattern (pleomorphic spindled or epithelioid), extent of lipogenic differentiation, and tumor necrosis. MDM2 amplification was analyzed using FISH on formalin-fixed, paraffin-embedded material in 26 cases. Patients ranged in age from 5 to 93 years (M:F=1.4:1). Tumors were located on the extremity (n=15), trunk (n=7), and head and neck (n=7) and involved the dermis (n=4), dermis and subcutis (n=10), and subcutis (n=15). Tumor size ranged from 0.8 to 15 cm (median=2 cm). All were mitotically active high-grade sarcomas [FNCLCC grade 2 (n=23) or 3 (n=6)] with either a pleomorphic spindled (n=24) or an epithelioid pattern (n=5) with variable extent of lipogenic differentiation [<25% (n=15), 25% to 50% (n=9), >50% (n=5)]. Necrosis was present in 3 cases. MDM2 gene amplification was present in 3 of 26 cases. Follow-up information in 24 cases (range=1 to 192 mo; median=48 mo; mean=59 mo) revealed local recurrences (4/24) but no metastasis or death from disease. We conclude that cutaneous and subcutaneous PLs, despite their high grade, have a much more favorable outcome compared with their deep-seated counterparts, most likely attributed to their small size and superficial location. The low incidence of MDM2 gene amplification in our series indicates that most superficial PLs are unrelated to WDL/DL. PL likely evolves by way of more than 1 molecular pathway.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Jerad M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Monisha
authors.initials: M
authors.lastname: Dandekar
authors.forename: Dafydd
authors.initials: D
authors.lastname: Thomas
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Sharon W
authors.initials: SW
authors.lastname: Weiss
authors.forename: Steven D
authors.initials: SD
authors.lastname: Billings
authors.forename: David R
authors.initials: DR
authors.lastname: Lucas
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.forename: Rajiv M
authors.initials: RM
authors.lastname: Patel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009336:Necrosis; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013997:Time Factors; D014481:United States; D055815:Young Adult
chemical_list: D051736:Proto-Oncogene Proteins c-mdm2