Malignant spindle cell tumors of the posterior fossa in children: case series and review of management.

OBJECTIVE: The WHO Classification of Tumours of the Central Nervous System (2016) classifies nonmeningothelial malignant spindle cell tumors involving the extraaxial tissues of the posterior fossa as melanocytic tumors and malignant mesenchymal tumors (sarcomas). The objective of this study was to conduct a review of the literature pertaining to the management strategies of posterior fossa malignant spindle cell tumors in the pediatric population. METHODS: The authors performed an institutional search of their pathology database for patients younger than 18 years of age who presented with posterior fossa malignant spindle cell tumors. A literature review was also performed using the PubMed database, with "posterior fossa" or "spindle cell tumors" or "Ewing sarcoma" or "high-grade" or "spindle cell sarcoma" or "leptomeningeal melanocytoma" as keywords. The database search was restricted to pediatric patients (age ≤ 18 years). Parameters reported from the literature review included patient age, tumor location, presenting symptoms, treatment modalities (resection, chemotherapy, and/or radiotherapy), leptomeningeal spread at or after the time of treatment, and follow-up length and resulting outcome. RESULTS: The authors report 3 rare cases of posterior fossa malignant spindle cell tumors, including Ewing sarcoma in a 13-year-old male; high-grade spindle cell sarcoma, not otherwise specified in a 10-year-old male; and primary leptomeningeal melanocytoma in a 16-year-old female. All 3 patients underwent resection and radiotherapy and either chemotherapy or targeted immunotherapy. At the last follow-up, all patients were alive with either resolution or stable disease. CONCLUSIONS: A review of these 3 cases and the existing literature support managing patients with intracranial malignant spindle cell tumors with multimodal therapy that can include a combination of resection, radiotherapy, and chemotherapy or immunotherapy to prolong progression-free and overall survival.

Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer.

BACKGROUND: Distal pancreatic carcinoma is one of the most lethal cancers largely due to its high incidence of distant metastasis. This study aims to assess the prognostic value of splenic-vasculature involvement in resected distal pancreatic carcinoma. METHODS: In this retrospective study, we collected the clinicopathologic information of 454 patients with pancreatic cancer and performed univariate and multivariate analyses to identify factors associated with progression-free survival (PFS) and overall survival (OS), with an emphasis on the prognostic value of splenic-artery and -vein involvement. RESULTS: Univariate analysis revealed that larger tumor size, non-intraductal papillary mucinous neoplasm (non-IPMN)-associated adenocarcinoma, poor differentiation, stage pT3, nodal metastasis, lymphovascular invasion, perineural invasion, and pathologic and radiographic evidence of splenic-vein invasion were significantly associated with shorter PFS and OS (all P < 0.05). Multivariate analysis confirmed non-IPMN-associated adenocarcinoma, stage pT3, stage pN1-2, and post-operative adjuvant chemotherapy as independent risk factors for both PFS and OS, and larger tumor size and radiographic evidence of splenic-artery invasion as predictors of PFS only. CONCLUSION: Guidelines should be developed for a uniform approach with regard to the examination and reporting of the status of the splenic vasculature when dealing with distal-pancreatic-cancer specimens.

Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression.

Tumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved cell death remain obscure. Here, we show that necrosis in glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse brain tumors kill cocultured tumor cells. Mechanistically, neutrophils induce iron-dependent accumulation of lipid peroxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibition or depletion of myeloperoxidase suppresses neutrophil-induced tumor cell cytotoxicity. Intratumoral glutathione peroxidase 4 overexpression or acyl-CoA synthetase long chain family member 4 depletion diminishes necrosis and aggressiveness of tumors. Furthermore, analyses of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poor survival. Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs and reveals a pro-tumorigenic role of ferroptosis. Together, we propose that certain tumor damage(s) occurring during early tumor progression (i.e. ischemia) recruits neutrophils to the site of tissue damage and thereby results in a positive feedback loop, amplifying GBM necrosis development to its fullest extent.

Validation of American Joint Committee on Cancer 8th edition of TNM staging in resected distal pancreatic cancer.

BACKGROUND: In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma (PDAC), the American Joint Committee on Cancer (AJCC) has published its eighth edition staging manual. Some major changes have been introduced in the new staging system for both T and N categories. Given the rarity of resectable disease, distal pancreatic cancer is likely underrepresented in the published clinical studies, and how the impact of the staging system actually reflects on to clinical outcomes remain unclear. AIM: To validate the AJCC 8th edition of TNM staging in distal PDAC. METHODS: A retrospective cohort study was performed in seven academic medical centers in the United States. Clinicopathological prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated through univariate and multivariate analyses. RESULTS: Overall, 454 patients were enrolled in the study, and were divided into 2 subgroups: Invasive intraductal papillary mucinous neoplasms (IPMN) (115 cases) and non-IPMN associated adenocarcinoma (339 cases). Compared to invasive IPMN, non-IPMN associated adenocarcinomas are more common in relatively younger patients, have larger tumor size, are more likely to have positive lymph nodes, and are associated with a higher tumor (T) stage and nodal (N) stage, lymphovascular invasion, perineural invasion, tumor recurrence, and a worse PFS and OS. The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual, and it's more evenly distributed based on 8th edition staging manual. T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort, although dividing into N1 and N2 according to the 8th edition does not show additional stratification. For PDAC arising in IPMN, T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS. For PDAC without an IPMN component, T staging from both versions fails to stratify PFS and OS. CONCLUSION: The AJCC 8th edition TNM staging system provides even distribution for the T staging, however, it does not provide better risk stratification than previous staging system for distal pancreatic cancer.