Exploratory analysis of immunomodulatory factors identifies L1CAM as a prognostic marker in alveolar soft-part sarcoma.

Background: Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response. Objectives: To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes. Design: A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators. Methods: Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan-Meier. Results: PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. L1CAM was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS. Conclusion: High L1CAM expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS.

Understanding immune response in a rare cancer: exploring avenues for alveolar soft-part sarcoma Why was the study done? Alveolar soft-part sarcoma (ASPS) is a rare cancer with limited treatment options. Our study aimed to understand how the immune system responds to ASPS and explore potential treatments, as current therapies are often ineffective. What did the researchers do? We analyzed data from 19 ASPS patients to investigate immune response and potential treatment targets. We examined the expression of immune markers and genes related to immune response to identify factors influencing patient outcomes. What did the researchers find? We found that most tumors showed signs of an active immune response, with a protein called PD-L1 being present. We also noticed that many tumors had a type of immune cell called CD8+ lymphocytes. Although having more of these CD8+ cells seemed to be linked to better survival, this connection wasn't strong enough to be certain. We didn't find any clear links with other immune markers we looked at. However, we did find that a protein called L1CAM was more common in patients who had fewer CD8+ cells in their tumors, and this was linked to poorer overall survival. What do the findings mean? Our study sheds light on the immune response in ASPS and identifies potential targets for therapy. By understanding these mechanisms, we hope to pave the way for more effective treatments and improve outcomes for ASPS patients in the future.

Spontaneous remission of a pulmonary sclerosing epithelioid fibrosarcoma: a case report of a possible abscopal effect.

Background: Spontaneous remission (SR) is defined as the complete or partial disappearance of a diagnosed malignant disease in the absence of known active medical treatment. The role of the immune system is thought to be important, but has not yet been elucidated. On this matter, there are studies that suggest that the abscopal effect (AE), which is defined as the remission of untreated lesions beyond the irradiated area, may be explained by the activation of a systemic immune response against the tumor. Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of soft tissue sarcoma that is characterized by a slow evolution, with local recurrences and late metastases. The treatment is based on surgery, leaving a minimal role to chemotherapy (ChT) and radiotherapy (RT) for metastatic unresectable disease, and no cases of SR have been reported in the literature so far. Case Description: We present the case of a patient with a lung metastatic recurrence of SEF, diagnosed and treated with surgery 8 years before. After progression to pazopanib and other ChT drugs, because of the chest pain associated with a pleural mass invading the second costal arch, the patient received antalgic local RT treatment. Months later, and without any further treatment, a partial remission of all the tumoral lesions was presented, and she is alive 25 years after the first diagnosis. Conclusions: As far as reported in the literature, this is the first case of SR in SEF. Among the possible causes of this SR, we think that the most plausible is that palliative treatment with RT of the pleural mass induced an AE, leading to a reduction of all tumoral lesions, even those outside the irradiated region.

Low-grade extrauterine endometrial stromal sarcoma of the peritoneum: A case report and literature review.

Endometrial stromal sarcoma (ESS) is an uncommon mesenchymal tumor that accounts for less than 1% of all primary uterine malignancies and extrauterine endometrial stromal sarcoma (EESS) is even rarer. We report the case of a 75-year-old woman with an abdominal tumor and multiple peritoneal implants. Histological analysis of the surgical specimens showed bland cellularity resembling normal endometrial stroma. The diagnosis of a low-grade EESS was confirmed by immunophenotypic findings and demonstration of JAZF1 translocation. After extensive sampling, no evidence of endometriosis was found. Our case showed atypical aggressive behavior and we discuss the possible influence of the high mitotic count (8/10 HPFs) in some areas of the tumor, the multifocality of the abdominal implants and the postmenopausal status of the patient. The unusual clinical presentation and extrauterine location of such a rare tumor were challenging implying a wide range of differential diagnosis. The correlation of morphological, immunohistochemical and molecular findings was necessary to arrive at the correct diagnosis.

Borderline resectable pancreatic cancer. Challenges and controversies.

Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by surgery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic cancer, the complexity of its management and controversies and point out where further research and international cooperation for a consensus strategy is urgently needed.