p16 Immunohistochemistry as an Alternative Marker to Distinguish Atypical Lipomatous Tumor From Deep-seated Lipoma
Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) is a locally aggressive malignant mesenchymal neoplasm, resembling ordinary lipoma in many clinical aspects. This study investigates the value of expression of p16, an important cell cycle regulator, alone or in combination with MDM2, to distinguish the 2 entities. Fifty cases of lipomatous neoplasms, with cytogenetic results, from 45 patients were collected from the archives in Department of Pathology, University of Medicine and Dentistry of New Jersey/New Jersey Medical School during 1998 to 2006. These include 18 cases of deep-seated lipoma, 1 hibernoma, 1 lipoblastoma, and 30 cases of ALT/WDLPS. p16 was detected in 25/30 (83.3%) of ALT/WDLPS, and none (0/18) of the deep-seated lipomas (P<0.0000001, Fisher exact test). MDM2 was detected in 18/30 (60%) of ALT/WDLPS, and was negative in 0/18 of the deep-seated lipomas (P<0.0001, Fisher exact test). Combined together, 27/30 (90%) of ALT/WDLPS showed positive staining of either p16, MDM2, or both, whereas no staining was observed in all the deep-seated lipomas (P<0.0000001, Fisher exact test). The single case of hibernoma and lipoblastoma revealed p16+MDM2- phenotype. These results indicated that p16 is yet another marker which seems to be a valuable marker to differentiate ALT/WDLPS from deep-seated lipomas.
Available from: Jayson Wang
- "Most recent studies have utilized FISH, using commercial probes for MDM2  . While immunohistochemistry for MDM2 has high levels of accuracy , especially when coupled with that for CDK4 and p16       , the MDM2 antibody can be technically inconsistent  and p16 is nonspecific as it is expressed in a variety of nonadipocytic neoplasms. To this end, as FISH is shown to be a robust ancillary molecular cytogenetic technique  and its use becomes more widespread routinely; it seems reasonable to use it to assess for MDM2 amplification in the first instance. "
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ABSTRACT: Background. The assessment of MDM2 gene amplification by fluorescence in situ hybridization (FISH) has become a routine ancillary tool for diagnosing atypical lipomatous tumor (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma (WDL/DDL) in specialist sarcoma units. We describe our experience of its utility at our tertiary institute. Methods. All routine histology samples in which MDM2 amplification was assessed with FISH over a 2-year period were included, and FISH results were correlated with clinical and histologic findings. Results. 365 samples from 347 patients had FISH for MDM2 gene amplification. 170 were positive (i.e., showed MDM2 gene amplification), 192 were negative, and 3 were technically unsatisfactory. There were 122 histologically benign cases showing a histology:FISH concordance rate of 92.6%, 142 WDL/DDL (concordance 96.5%), and 34 cases histologically equivocal for WDL (concordance 50%). Of 64 spindle cell/pleomorphic neoplasms (in which DDL was a differential diagnosis), 21.9% showed MDM2 amplification. Of the cases with discrepant histology and FISH, all but 3 had diagnoses amended following FISH results. For discrepancies of benign histology but positive FISH, lesions were on average larger, more frequently in "classical" (intra-abdominal or inguinal) sites for WDL/DDL and more frequently core biopsies. Discrepancies of malignant histology but negative FISH were smaller, less frequently in "classical" sites but again more frequently core biopsies. Conclusions. FISH has a high correlation rate with histology for cases with firm histologic diagnoses of lipoma or WDL/DDL. It is a useful ancillary diagnostic tool in histologically equivocal cases, particularly in WDL lacking significant histologic atypia or DDL without corresponding WDL component, especially in larger tumors, those from intra-abdominal or inguinal sites or core biopsies. There is a significant group of well-differentiated adipocytic neoplasms which are difficult to diagnose on morphology alone, in which FISH for MDM2 amplification is diagnostically contributory.
Available from: Dorota Jesionek-Kupnicka
- "Immunohistochemical expression of MDM2 and CDK4     had a diagnostic value in confirmation of diagnosis. He et al.   recommended p16 protein as a highly specific marker for ALT/WDLPS, alternative to MDM2, that allows to distinguish it from deep-seated lipoma. [ "
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ABSTRACT: Liposarcoma is the most common soft tissue malignant tumor. It mostly arises in the subcutaneous tissue of shoulders, limbs and neck, and retroperitoneal space, but head occurrence is very rare. Atypical lipomatous tumor (ALT) is a well-differentiated liposarcoma (WDLPS) and constitutes 40-45% of all liposarcoma cases. A case of 57-year-old woman with a tumor of the left cheek, causing a discreet face asymmetry is presented. The tumor was soft and caused no tenderness. The patient reported no previous injury of the region. Fine-needle aspiration biopsy (FNAB) revealed atypical cells suspected of liposarcoma. MR examination showed fascicles of adipose tissue, which made the left cheek prominent. The patient was operated under general anaesthesia. Adipose tissue of the left cheek was removed. Postoperative course was uneventful. The final histopathological diagnosis - was atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS). The patient remains under laryngological care. No recurrence of the disease has been observed during the 5 years follow-up.
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ABSTRACT: Atypical lipomatous tumors (ALTs) are characterized primarily by their location, which provides the most valuable insight towards the likelihood of complete surgical excision. MRI or CT, are invaluable tools that not only aid in a radiologic diagnosis, but are also able to precisely define location and extent of these tumors. This further aids in surgical decision-making and postoperative surveillance.
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