Genes, Chromosomes & Cancer最新文献

Various cutaneous adnexal neoplasms have been associated with gene fusions as the main driver of their histogenesis, most of which showed poroid or hidradenomatous differentiation or represented other tumors of sweat glands. Recently, we encountered two cases of primitive basaloid neoplasms of predominantly folliculogenic/pilosebaceous origin, both surprisingly harboring recurrent EWSR1 rearrangements. Both tumors presented in young patients of either sex (1 F; 17 years; 1 M; 37 years) and involved the dermis and subcutaneous tissue of the abdominal wall (case 1) and the buttock (case 2). Histologically, the tumors were composed of primitive, basaloid cells with areas of keratinization (case 1) or foci of sebaceous differentiation (case 2) and stained strongly with keratins, p40 (case 1) or p63 (case 2), while lacking significant CD99 expression in both cases. Case 1 harbored an EWSR1::FLI1 fusion while case 2 harbored an EWSR1::PBX3 fusion. Clinical follow-up was available for case 2 and showed no evidence of disease at 15 months of follow-up. Methylation profiling showed case 1 to cluster with cutaneous squamous cell carcinoma, while case 2 was independent but positioned close to salivary gland epithelial-myoepithelial carcinoma. These findings expand on the histopathologic and molecular genetic features of basaloid tumors with apparent adnexal differentiation and raise awareness to carefully interpret and correlate molecular findings with morphology and immunophenotype to avoid misinterpretation as a mesenchymal neoplasm.

Endometrial stromal sarcoma-like (ESS-like) sarcomas have rarely been described in male patients and represent a subset of “Mullerian analog” tumors. These ESS-like sarcomas most commonly arise in the paratesticular or pelvic regions and often harbor the same signature molecular fusion events that are typical of endometrial stromal sarcoma (ESS) of the uterine corpus. Here we report and describe an ESS-like sarcoma of the paratesticular soft tissue in an 85-year-old man with an EPC1-SUZ12 t(10;17)(p11.22;q12) fusion. This fusion event has been described in a high-grade uterine ESS one time previously where it displayed an aggressive clinical course. However, our patient showed no evidence of metastatic disease prior to surgery or in a short follow-up period after resection.

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) share overlapping etiological factors but differ molecularly. In the study, 4 patients with prostate cancer and 3 patients with BPH were included. All patients with prostate cancer and BPH had a histologically confirmed diagnosis. Among the prostate cancer group were 3 patients with acinar prostate adenocarcinoma and 1 patient with small-acinar prostate adenocarcinoma. Using single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from PCa and BPH patients, we identified 16 immune cell clusters, with elevated CD14+ monocytes, NK cells, and γδ T cells in PCa. Differential gene expression analysis revealed 40 overexpressed genes in PCa monocytes, including CSMD1, ZBTB16, ZNF217, and SERPINI2, linked to tumor progression, cell cycle regulation, EMT, androgen signaling, and metabolism. SCN2A was highly expressed in PCa B cells, while ABO, FMN1, and TXNIP in CD4+ T cells modulated immune evasion, cytoskeletal regulation, and oxidative stress. Pathway analysis showed PCa monocytes had heightened interleukin-27 signaling, whereas BPH monocytes exhibited increased cholesterol storage and Notch signaling. CellChat analysis highlighted monocytes' central role in immune regulation, with distinct interactions via MIF, galectin, and TGF-β pathways in PCa and BPH. These findings reveal unique immune microenvironments and transcriptional heterogeneity between PCa and BPH, offering potential biomarkers for differentiation and insights into prostate pathology mechanisms.

Uterine sarcomas are uncommon mesenchymal neoplasms ranging from low- to high-grade or undifferentiated. High-grade sarcomas are characterized by various morphologic, immunohistochemical, and molecular alterations. Here, we report the first description of a patient with uterine sarcoma with a MEIS2::FOXO4 fusion. This tumor showed alternating fascicular and diffuse architecture with a prominent nodular growth displaying striking hyalinization and less prominent myxoid background admixed with more cellular internodular areas. The neoplastic cells ranged from spindled to stellate to epithelioid and exhibited variable cytologic atypia and mitotic activity. Immunohistochemical stains showed diffuse expression of smooth muscle actin, preserved expression of PTEN, ATRX, and Rb1, wild-type expression of p53, weak expression of PLAG1, multifocal expression of MDM2, and no reactivity for desmin. RNA sequencing detected a MEIS2::FOXO4 gene fusion with breakpoints at MEIS2 exon 6 and FOXO4 exon 2. Although this gene fusion has been described in other soft tissue neoplasms, it has not been previously reported in uterine sarcomas and highlights the significance of performing molecular analysis in uterine mesenchymal tumors with unusual morphology and/or immunophenotype.

NR1D1-rearranged tumors are distinct mesenchymal neoplasms with epithelioid morphology and aggressive potential. This report presents an 85-year-old male with a slow-growing sternal mass identified as a pseudo-cyst, characterized by a dense proliferation of epithelioid tumor cells. These cells exhibited pale cytoplasm and uniform oval nuclei, with some areas of spindle cells and extensive necrosis. The mitotic count was 12 per 1.7 mm². Immunohistochemical analysis showed positivity for EMA, ERG, AE1AE3, and CK7, but negativity for SMA, desmin, CD117, CD31, SOX10, MelanA, synaptophysin, INSM1, CK20, CD34, TTF1, WT1, caldesmon, myogenin, and collagen IV. INI1 expression was preserved. The Ki67 index was high. Whole-transcriptome sequencing revealed an in-frame NR1D1::MAML3 fusion, retaining two key protein domains of NR1D1. Nine months post-diagnosis, the patient developed pleural, bilateral lung, and bone metastases. This case underscores the necessity of molecular analysis for precise tumor classification, given the tumor's varied morphological features and poor prognosis.