PMID- 30001242 OWN - NLM STAT- MEDLINE DCOM- 20190903 LR - 20190903 IS - 1532-0979 (Electronic) IS - 0147-5185 (Linking) VI - 42 IP - 11 DP - 2018 Nov TI - Dysplastic Lipoma: A Distinctive Atypical Lipomatous Neoplasm With Anisocytosis, Focal Nuclear Atypia, p53 Overexpression, and a Lack of MDM2 Gene Amplification by FISH; A Report of 66 Cases Demonstrating Occasional Multifocality and a Rare Association With Retinoblastoma. PG - 1530-1540 LID - 10.1097/PAS.0000000000001129 [doi] AB - In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification. FAU - Michal, Michael AU - Michal M AD - Department of Pathology. AD - Biomedical Center, Faculty of Medicine in Pilsen, Charles University. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Agaimy, Abbas AU - Agaimy A AD - Institute of Pathology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital, Erlangen, Germany. FAU - Contreras, Alejandro Luina AU - Contreras AL AD - The Joint Pathology Center, Silver Spring, MD. FAU - Svajdler, Marian AU - Svajdler M AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Kazakov, Dmitry V AU - Kazakov DV AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Steiner, Petr AU - Steiner P AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Grossmann, Petr AU - Grossmann P AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Martinek, Petr AU - Martinek P AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Hadravsky, Ladislav AU - Hadravsky L AD - Department of Pathology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. FAU - Michalova, Kvetoslava AU - Michalova K AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Svajdler, Peter AU - Svajdler P AD - Department of Pathology, Louis Pasteur University Hospital, Kosice. FAU - Szep, Zoltan AU - Szep Z AD - Cytopathos Ltd, Bratislava, Slovakia. FAU - Michal, Michal AU - Michal M AD - Department of Pathology. AD - Bioptical Laboratory Ltd, Pilsen. FAU - Fetsch, John F AU - Fetsch JF AD - The Joint Pathology Center, Silver Spring, MD. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (Biomarkers, Tumor) RN - 0 (RB1 protein, human) RN - 0 (Retinoblastoma Binding Proteins) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM CIN - Am J Surg Pathol. 2019 Feb;43(2):288-289. PMID: 30211727 CIN - Am J Surg Pathol. 2019 Feb;43(2):289-290. PMID: 30418185 MH - *Adipocytes/chemistry/pathology MH - Adult MH - Aged MH - Aged, 80 and over MH - *Biomarkers, Tumor/analysis/genetics MH - DNA Mutational Analysis MH - Diagnosis, Differential MH - Europe MH - Fat Necrosis MH - Female MH - *Gene Amplification MH - Genetic Predisposition to Disease MH - Humans MH - Immunohistochemistry MH - *In Situ Hybridization, Fluorescence MH - *Liposarcoma/chemistry/genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - *Neoplasms, Multiple Primary/chemistry/genetics/pathology MH - Predictive Value of Tests MH - Proto-Oncogene Proteins c-mdm2/*genetics MH - *Retinoblastoma/chemistry/genetics/pathology MH - Retinoblastoma Binding Proteins/genetics MH - Retrospective Studies MH - *Tumor Suppressor Protein p53/analysis/genetics MH - Ubiquitin-Protein Ligases/genetics MH - Up-Regulation MH - Young Adult EDAT- 2018/07/13 06:00 MHDA- 2019/09/04 06:00 CRDT- 2018/07/13 06:00 PHST- 2018/07/13 06:00 [pubmed] PHST- 2019/09/04 06:00 [medline] PHST- 2018/07/13 06:00 [entrez] AID - 10.1097/PAS.0000000000001129 [doi] PST - ppublish SO - Am J Surg Pathol. 2018 Nov;42(11):1530-1540. doi: 10.1097/PAS.0000000000001129.