ABSTRACT
Ancillary molecular testing has been advocated for diagnostic accuracy in the differentiation of lipomas from atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL); however, the implications and specific indications for use are not well-established in the current literature. Herein, we extend previous findings by quantitatively evaluating the impact of molecular testing of lipomatous neoplasms in our routine clinical practice, how it modifies the historical perspective of their clinical course, and the effect of distinct surgical procedures in modulating the risk of local recurrence for these tumors after molecular classification. On the basis of these analyses, we suggest a specific set of basic recommendations for complementary molecular assessment in the diagnosis of lipomatous tumors. Four hundred and five lipomatous neoplasms located in the trunk and extremities were analyzed histologically and for the presence of 12q13-15 amplification on paraffin-embedded tissues by assessing MDM2/CPM amplification. Survival analyses were calculated with Kaplan-Meier and compared with the log-rank. Multivariate analysis was evaluated by the Cox regression method. The 405 tumors were histologically classified as ordinary lipoma (n=324), intramuscular lipoma (n=29), and ALT/WDL (n=52). The level of agreement between the histologic diagnosis and the molecular diagnosis was high (96%) but pathologists showed a tendency to overestimate cytologic atypia and the diagnosis of ALT/WDL (precision, 79%; accuracy, 88%). Molecular assessment led to a major diagnostic reclassification in 18 tumors (4%). Eleven of the tumors histologically classified as ALT/WDL were reclassified as ordinary lipoma (n=5) and intramuscular lipoma (n=6); none of which recurred. Seven ordinary lipomas were reclassified as ALT/WDL, 6 of which were larger than 15 cm and deeply located; 2 recurred locally. After molecular data, the 5-year local recurrence rates for ordinary lipoma, intramuscular lipoma, and ALT/WDL were 1%, 12%, and 44%, respectively. Multivariate analyses after molecular assessment showed tumor type and type of resection to be associated with the risk of local recurrence. Complementary molecular testing refines the histologic classification of lipomatous tumors and better estimates the impact of surgical procedures on the risk of local recurrence. Pathologists tend to overestimate the degree of cytologic atypia and the indiscriminate use of molecular testing should be avoided, especially for extremity-based tumors. Molecular testing should be considered for "relapsing lipomas," tumors with questionable cytologic atypia (even if widely excised), or for large lipomatous tumors (>15 cm) without diagnostic cytologic atypia.
Subject(s)
Lipoma/genetics , Liposarcoma/genetics , Molecular Diagnostic Techniques , Soft Tissue Neoplasms/genetics , Chromosomes, Human, Pair 12 , DNA, Neoplasm/analysis , Disease-Free Survival , Extremities , Female , GPI-Linked Proteins , Gene Amplification , Humans , In Situ Hybridization, Fluorescence , Lipoma/diagnosis , Lipoma/mortality , Liposarcoma/diagnosis , Liposarcoma/mortality , Male , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Middle Aged , Neoplasm Recurrence, Local , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/mortality , Treatment OutcomeABSTRACT
Ordinary lipoma frequently harbors rearrangement of HMGA2. LPP is the most common partner gene to HMGA2, but has not been seen fused to HMGA1. We report the fusion of HMGA1 to the intergenic region between LPP and TPRG1 in a lipoma. Conventional cytogenetic analysis of an abdominal-wall lipoma diagnosed in a 60-year-old woman showed a t(3;6)(q27;p21). Molecular cytogenetic mapping of available paraffin-embedded tissues revealed the fusion of HMGA1 to a 139-kb genomic region between the LPP and TPRG1 loci. No rearrangement of HMGA2 was found. The biological function of this novel fusion could be similar to the role of HMGA2-LPP in tumorigenesis.
Subject(s)
Cytoskeletal Proteins/genetics , Gene Fusion , HMGA1a Protein/genetics , Lipoma/genetics , Proteins/genetics , Female , Humans , LIM Domain Proteins , Middle Aged , Paraffin EmbeddingABSTRACT
Intraabdominal myositis ossificans (IMO) is a rare benign disorder characterized by reactive bone formation in intraabdominal soft tissue that should be distinguished from a malignant condition. We retrospectively searched our patient records and report 9 new cases of IMO. The lesions occurred in 7 men and 2 women with a mean age of 50 years (range, 24--76 years), 5 of whom had previous abdominal surgery. Histologically, all the cases were similar, consisting of a reactive mesenchymal process in adipose tissue. Mitosis was observed, but with no atypical forms, and the lesions lacked malignant cytologic features. IMO is an uncommon benign lesion that develops relatively rapidly. The pathogenesis is related to intraabdominal surgical procedures, but the exact mechanism remains to be determined.
