Myxoinflammatory fibroblastic sarcoma: ultrastructural study of 7 cases.

Since first described, several studies about Myxoinflammatory fibroblastic sarcomas (MIFS) have been published stating the clinicopathological, morphological and immunohistochemical features. However, the ultrastructural findings of these MIFS are limited. Thus, the objective of the present paper is to describe the ultrastructural characteristics of these type of tumors by utilizing tissue that was embedded in paraffin and submitted for immunohistochemistry.The tissue of seven different cases was obtained for ultrastructural study with automatized staining devices, that were later observed by using transmission electron microscopy. Histologically all cases displayed conventional structures of Myxoinflammatory fibroblastic sarcoma (Reed-Sternberg like cells, pseudolipoblasts and emperipolesis). Conversely, two of them exhibited high-grade components, one rich in osteoclastic type giant cells and hypercellular areas, and another one rich in inflammation (Hodgkin-like).After immunohistochemistry, all the samples revealed positivity for CD68 with six cases CD163 and five being positive to CD34, Cyclin-D1, and D2-40. Ultrastructural findings indicated rough endoplasmic reticulum with dilatation of the cisterns that indented the nuclei ("soccer ball" cells), abundant lysosomes, phagolysosomes, and intermediate filaments evidencing this entity as a morphologic continuum that exhibited modified fibroblastic phenotype and variable proportion of macrophagic differentiation.

Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.

Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer. Whole RNA sequencing of 12 patient biopsies revealed 269 differentially expressed genes in chemoresistant patients. We further validated eight highly correlated genes associated with resistance. Among these, solute carrier family 12 member 1 (SLC12A1) and glutamate ionotropic AMPA type subunit 4 (GRIA4), both implicated in ion transport, showed the strongest association with chemoresistance. Notably, SLC12A1 expression was downregulated, while protein levels of glutamate receptor 4 (GLUR4), encoded by GRIA4, were elevated in patients with a worse prognosis. Our results suggest a potential link between SLC12A1 gene expression and GLUR4 protein levels with chemoresistance in luminal breast cancer. In particular, GLUR4 protein could serve as a potential target for drug intervention to overcome chemoresistance.

Does compartmental resection really impact retroperitoneal soft tissue sarcomas? A retrospective analysis from a Single Referral Center.

BACKGROUND: The treatment of choice for retroperitoneal soft tissue sarcomas (RPS) is surgical resection; the outcomes with more radical surgeries, notably compartmental resection, remains a subject of debate. Arguments against it, include the complexity of the technique and high morbidity. MATERIALS AND METHODS: A retrospective analysis of cases treated in a single center from January 2010 to December 2019 is presented. Two time periods were evaluated: 2010-2015 and 2016-2019, corresponding to before and after the implementation of routine compartmentectomy. We evaluated the short- and long-term outcomes of compartmental resection compared to limited surgeries through a multivariate analysis of prognostic factors. RESULTS: A total of 176 cases were included, of which 102 met the inclusion criteria. The sex distribution was similar. The average age was 52.9 years, and the average tumor size was 24.5 cm. The most frequent histology was liposarcoma (65.7%), followed by leiomyosarcoma (12.7%), and malignant peripheral nerve sheath tumor (8.8%). The median follow-up period was 40 months. We found a lower local recurrence in the group treated in the recent period (compartmentectomy) 42.3% vs 20% p = 0.007. The median overall survival (OS) was 38.7 months, and there was no difference in distant recurrence between the two time periods. Postoperative morbidity was higher in the recent period (25% vs 10% p 0.041), with no difference in 30-day mortality. CONCLUSIONS: The implementation of extensive surgery, specifically compartmentectomy, for retroperitoneal sarcomas has been linked to reduced local recurrence. We recommend considering this surgical approach for RPS in alignment with current expert consensus guidelines, as highlighted by the updated TARPSWG consensus.

Epidemiological profile of soft tissue sarcomas of the extremities: Incidence, histological subtypes, and primary sites.

BACKGROUND: Soft tissue sarcomas (STS) are a heterogeneous group of rare tumours that represent less than 1% of all malignant, solid tumours in adults. There is limited epidemiological information regarding STS in Latin America. Therefore, the objective of this study is to present an epidemiological profile of these tumours observed at a single reference centre. METHODS: A retrospective study was carried out based on hospital records obtained from a registry of 879 patients with STS of the extremities who were treated at the National Cancer Institute of Mexico from January 1, 1994 to December 31, 2017. Epidemiological variables and relevant clinical data were collected. Five-year survival rates were analysed using Kaplan-Meier estimates, and a multivariate Cox proportional-hazards model measured associations. RESULTS: A total of 879 records were collected. The median age was 45 years (15-95 years), and the ratio of men to women was 1:1, with 433 men (49.3%), and 446 women (50.7%). The median tumour size was 11.4 cm (2-49 cm). The most prevalent histological variants were liposarcomas and synovial sarcomas. The lower limb was the most frequently affected extremity, with the thigh being the most common site followed by the leg. A majority of the patients were diagnosed at clinical stages IIIA-IV. CONCLUSIONS: The data collected from the present cohort provides an overview of the epidemiological profile of STS at a single reference centre in Latin America, and allow comparison with global data.

Should metastatic lymph nodes be considered at the same clinical stage as distant metastasis in soft tissue sarcomas?

INTRODUCTION: Lymph node metastasis (LNM) in soft tissue sarcomas (STS) are uncommon, occurring in only 3% - 5% of all sarcomas, and are classified as Stage IV, along with distant metastasis (DM). This paper compares the prognosis of patients with lymphatic and DM, in extremity STS (eSTS). METHODS: A retrospective study was carried out in a high-volume sarcoma center; 853 patients with eSTS sarcomas were identified and classified from January 1, 1997 to December 31, 2017. Cases with pathological confirmation of LNM were included. Five-year survival rates were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: LNM was present in 46 of the cases (5.4%), with an overall survival of 21 months (95% confidence interval [CI], 16.7 - 25.2), compared to 18 months (95% confidence interval [CI], 14.2 - 21.7) in those with only DM. Median recurrence-free survival was 21 months (95% confidence interval [CI], 19.7 - 22.4), vs. 20 months (95% confidence interval [CI], 16.2- 23.7), respectively. LNM only and DM only had also a similar OS of 21 months (95% CI 16.7-25.2) vs 18 months (95% CI 14.2-21.7. N1M1 cases had the worse median OS with 15 months (95% confidence interval [CI], 10.9-19.7) CONCLUSIONS: Overall survival and recurrence free survival in patients with lymph node disease and metastatic disease are similar. However prognosis is worse in N1M1. Use of systemic treatment in patients with LNM is not as common as in metastatic cases, this difference in treatment and the fact that prognosis is similar suggests that both biological behavior and effect of treatment have been underestimated. A subclassification of clinical stage IV might be the next step.

An Overview of Vasculogenic Mimicry in Breast Cancer.

Vasculogenic mimicry (VM) is the formation of vascular channels lacking endothelial cells. These channels are lined by tumor cells with cancer stem cell features, positive for periodic acid-Schiff, and negative for CD31 staining. The term VM was introduced by Maniotis et al. (1), who reported this phenomenon in highly aggressive uveal melanomas; since then, VM has been associated with poor prognosis, tumor aggressiveness, metastasis, and drug resistance in several tumors, including breast cancer. It is proposed that VM and angiogenesis (the de novo formation of blood vessels from the established vasculature by endothelial cells, which is observed in several tumors) rely on some common mechanisms. Furthermore, it is also suggested that VM could constitute a means to circumvent anti-angiogenic treatment in cancer. Therefore, it is important to determinant the factors that dictate the onset of VM. In this review, we describe the current understanding of VM formation in breast cancer, including specific signaling pathways, and cancer stem cells. In addition, we discuss the clinical significance of VM in prognosis and new opportunities of VM as a target for breast cancer therapy.

Multiple Molecular Targets Associated with Genomic Instability in Lung Cancer.

Lung cancer (LC) is the first cause of cancer-related deaths worldwide. Elucidating the pathogenesis of LC will give information on key elements of tumor initiation and development while helping to design novel targeted therapies. LC is an heterogeneous disease that has the second highest mutation rate surpassed only by melanoma, since 90% of LC occurs in tobacco smokers. However, only a small percent of smokers develops LC, indicating an inherent genomic instability. Additionally, LC in never smokers suggests other molecular mechanisms not causally linked to tobacco carcinogens. This review presents a current outlook of the connection between LC and genomic instability at the molecular and clinical level summarizing its implications for diagnosis, therapy, and prognosis. The genomic landscape of LC shows widespread alterations such as DNA methylation, point mutations, copy number variation, chromosomal translocations, and aneuploidy. Genome maintenance mechanisms including cell cycle control, DNA repair, and mitotic checkpoints open a window to translational research for finding novel diagnostic biomarkers and targeted therapies in LC.

Carcinoma de células acinares de glándula lacrimal metastásico en columna torácica. Reporte de un caso y revisión de la literatura / Acinar cell carcinoma of lacrimal gland metastatic a thoracic spine. Case report and literature review

Resumen El carcinoma de células acinares es una neoplasia poco frecuente que se presenta principalmente en las glándulas salivales. Presentamos el caso de un paciente femenino de 48 años con dolor, paresia palpebral derecha y aumento de volumen. Biopsia que confirma diagnóstico, manejada con exenteración orbitaria derecha más RT. Durante seguimiento seis años después se presenta dolor columna dorsal, RMN con lesión osteoblástica en T2 biopsia con metástasis de carcinoma de células acinares. Debido a su baja incidencia el comportamiento del carcinoma de células acinares de la glán dula lacrimal es incierto, no hay reportes en la literatura de lesiones metastásicas únicas en columna.

Abstract Acinar cell carcinoma is a rare neoplasm occurs primarily in the salivary glands. We report the case of a female patient of 48 years with pain, right palpebral paresis, and increased volume. Biopsy confirmed diagnosis, handled right exenteration more RT. During follow-up six years after dorsal spine pain, MRI with T2 lesion biopsy osteoblastic metastatic carcinoma of acinar cells. Because of its low incidence behavior acinar cell carcinoma of the lacrimal gland is uncertain, there are no reports in the literature of metastatic lesions unique column.