MDM2 analysis in the management of benign lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas: A useful prognostication tool?

INTRODUCTION: Well-differentiated liposarcomas (WDLS) are low-grade lipomatous tumors with low malignant potential. Previous review identified controversy on whether upfront wide resection is necessary when they occur on the trunk or the extremities. MDM2 amplification is a genetic mutation typically present in WDLS and absent in benign lipomas (BL). We aimed to study the influence of MDM2 status on the management/recurrences of lipomatous tumors in the trunk or the extremities. METHODS: All patients with lipomatous tumors with MDM2 testing in the Province of Alberta between 2015 and 2020 were identified from the Cancer Cytogenetics Laboratory dataset. High grade sarcomas, retroperitoneal, head/neck, or groin tumors were excluded. Primary outcome measures including MDM2 status, surgical margin, local recurrence, reoperation rate, dedifferentiation, and metastasis were abstracted from chart review. Descriptive statistics were used to analyse treatment patterns and recurrence rates according to MDM2 status. RESULTS: Total of 764 charts were retrieved, and 282 were included for analysis. 33 showed MDM2 amplification (11.7%), and 2 of them had local recurrence (6.1%). Two patients with recurrent tumors underwent limb-salvaging reoperation (6.1%), but no dedifferentiation or metastasis was seen. CONCLUSION: Findings in this study confirmed the benign behaviour of truncal/extremities lipomas with no MDM2 amplification. Given we found a 6.1% recurrence rate in MDM2 amplified tumors, a prolong follow up of this subset of patients is warranted. Overall, regardless of the MDM2 status, we believe an initial marginal excision is a reasonable surgical approach as recurrences are rare, and they can be managed with re-excision when they occur.

Adipocyte-rich CTNNB1-mutated Intramuscular Gardner Fibroma Progressing to Desmoid Fibromatosis.

Gardner fibroma (GF) is a benign soft-tissue tumor that is associated with Gardner syndrome and can progress to, or co-occur with, desmoid fibromatosis (DF). Herein, we report a unique case of an 11-year-old boy who presented with a rapidly growing soft-tissue mass after biopsy of a stable fat-rich lesion present in the calf muscles since infancy, with Magnetic resonance imaging findings suggesting an intramuscular adipocytic tumor. The resection showed GF and DF. DF arising from a preexisting GF (the so-called "GF-DF sequence") is a well-documented phenomenon. Although immunohistochemistry was negative for nuclear ß-catenin expression, a CTTNB1 S45F mutation, which has been associated with aggressive behavior in DF, was identified in both components using a next-generation sequencing-based molecular assay. This is the first time a mutation in CTNNB1 has been identified in GF and the GF-DF sequence, thus expanding our knowledge of the molecular pathogenesis of the GF-DF sequence and highlighting the role of molecular testing in pediatric soft-tissue tumors. The histologic findings of an adipocyte-rich intramuscular GF also are unique, expanding the morphological spectrum of GF and adding GF to the differential diagnosis of intramuscular lesions with an adipocytic component.

Invasive Candida albicans fungal infection requiring explantation of a noncrosslinked porcine derived biologic mesh: a rare but catastrophic complication in abdominal wall reconstruction.

SUMMARY: Biologic mesh is preferred over synthetic mesh for complex and contaminated abdominal wall repairs; however, there are very little data on the risks and complications associated with its use. We report the case of a 67-year-old man with failed synthetic mesh repair for recurrent ventral hernia, who subsequently required an abdominal wall reconstruction (AWR), including the intraperitoneal sublay of noncrosslinked biologic mesh. His postoperative course was complicated with catastrophic sepsis and sustained hemodynamic instability, responding only to mesh explantation. The biologic mesh was subsequently noted to be histologically infected with invasive Candida albicans. Although noncrosslinked biologic mesh is a valuable adjunct to AWR, it is not infection-resistant. Although it is rare, infection of any foreign tissue, including biologic mesh, can occur in the setting of complex ventral abdominal wall repairs. Clinicians should be watchful for such infections in complex repairs as they may require biologic mesh explantation for clinical recovery.

Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma.

ERG gene encodes for an Ets family regulatory transcription factor and is involved in recurrent chromosomal translocations found in a subset of acute myeloid leukemias, prostate carcinomas and Ewing sarcomas. The purpose of this study was to examine the utility of an ERG antibody to detect EWSR1-ERG rearranged Ewing sarcomas. A formalin-fixed paraffin-embedded tissue microarray and whole-tissue sections from 32 genetically characterized Ewing sarcomas were examined: 22 with EWSR1-FLI1, 8 with EWSR1-ERG and 2 with EWSR1-NFATC2. Immunohistochemistry was performed using a rabbit anti-ERG monoclonal antibody directed against the C-terminus of the protein and a mouse anti-FLI1 monoclonal antibody against a FLI1 Ets domain (C-terminus) fusion protein. Immunoreactivity was graded for extent and intensity of positive tumor cell nuclei. ERG labeling was seen in 7/8 EWSR1-ERG cases (predominantly diffuse (5+), moderate to strong), while only 3/24 non-EWR1-ERG cases showed labeling (very weak). FLI1 labeling was observed in 29/31 cases regardless of fusion variant; 23 displayed diffuse (5+) strong/moderate labeling (5/7 EWSR1-ERG, 18/22 EWSR1-FLI1). Both EWSR1-NFATC2 cases had weak reactivity with FLI1 and weak or no reactivity for ERG. In conclusion, strong nuclear ERG immunoreactivity is specific for Ewing sarcomas with EWSR1-ERG rearrangement. In contrast, FLI1 was not specific to rearrangement type, likely because of cross reactivity with the highly homologous Ets DNA-binding domain present in the C-terminus of both ERG and FLI1.