Dysplastic Lipoma
| Autor: | Michael Michal, Dmitry V. Kazakov, Petr Grossmann, Zoltan Szep, Peter Švajdler, Marián Švajdler, Petr Steiner, Michal Michal, John F. Fetsch, Kvetoslava Michalova, Ladislav Hadravsky, Petr Martinek, Alejandro Luiña Contreras, Abbas Agaimy |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Pathology DNA Mutational Analysis Atypical Lipomatous Tumor Neoplasms Multiple Primary 0302 clinical medicine Adipocytes Atypia Fat Necrosis Nuclear atypia skin and connective tissue diseases In Situ Hybridization Fluorescence Aged 80 and over integumentary system Retinoblastoma Proto-Oncogene Proteins c-mdm2 Liposarcoma Middle Aged Lipoma Immunohistochemistry Up-Regulation Europe Retinoblastoma Binding Proteins 030220 oncology & carcinogenesis Female Anatomy Adult medicine.medical_specialty Ubiquitin-Protein Ligases Pathology and Forensic Medicine Diagnosis Differential Young Adult 03 medical and health sciences Predictive Value of Tests Biomarkers Tumor medicine Humans Genetic Predisposition to Disease Fat necrosis Aged Retrospective Studies business.industry Gene Amplification medicine.disease body regions 030104 developmental biology Mutation Anisocytosis Surgery Lipomatous Neoplasm Tumor Suppressor Protein p53 business |
| Zdroj: | American Journal of Surgical Pathology. 42:1530-1540 |
| ISSN: | 0147-5185 |
| DOI: | 10.1097/pas.0000000000001129 |
| Popis: | 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 in1% 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 in45% 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. |
| Databáze: | OpenAIRE |
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