Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell-T-cell interactions at single-cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: p = 0.07; validation cohort: p = 0.19). We next utilised our region-based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (discovery cohort: p = 0.01; validation cohort: p = 0.003). © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Spatial Effects of Infiltrating T cells on Neighbouring Cancer Cells and Prognosis in Stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks, as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil-based chemotherapy. Images underwent segmentation for tumour, stroma and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell - T cell interactions at single-cell level. In our discovery cohort (MSK), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (HV) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (Discovery cohort: p = 0.07, Validation cohort: p = 0.19). We next utilized our region-based nearest neighbourhood approach to determine the spatial relationships between cytotoxic T cells, helper T cells and cancer cell clusters. In the both cohorts, we found that lower distance between cytotoxic T cells, T helper cells and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (Discovery cohort: p = 0.01, Validation cohort: p = 0.003).

The relationship between DNA mismatch repair gene and other prognostic parameters in pancreatic adenocarcinoma.

The aim of the study was to determine DNA mismatch repair (MMR) proteins by immunohistochemically using MLH1, MSH2, MSH6, and PMS2 antibodies in patients diagnosed as pancreatic ductal adenocarcinoma and to assess its relationship with histopathological and clinical prognostic parameters. Fifty cases with a diagnosis of pancreatic ductal adenocarcinoma who underwent surgical resection, were included in the study. Demographic and histopathological features of the patients were collected from the medical records. The relationships between microsatellite status and prognostic parameters were determined. The mean age of the patients was 66.5 ± 9.5 years (range: 47-87) and male/female ratio was 1.63 (31/19). No errors were detected in DNA MMR proteins in any of the cases, and were classified as microsatellite stable. The mean tumor diameter was 4.01 ± 1.77 cm and 74% of the tumors were localized in the pancreatic head. All of the cases had lymphatic invasion, whereas vascular invasion was detected in only 78% and perineural invasion in 98% of the patients. When the relationship between prognostic parameters and survival was evaluated, statistically significant correlation was observed in patient age and histopathological parameters such as tumor diameter, status of surgical margins, and vascular invasion (p < 0.05). Age, tumor size, presence of tumor at surgical margins, vascular invasion, and adjuvant treatment were correlated with survival. Although microsatellite instability was not detected in our cases, it is important to determine the microsatellite status by immunohistochemistry for predicting the chemotherapy response and determining the immunotherapy option in pancreatic adenocarcinomas.

Imaging findings of intraventricular pilocytic astrocytoma.

OBJECTIVE: The aim of this study is to present the clinical and imaging findings of 16 patients with intraventricular pilocytic astrocytomas (PAs). METHODS: 16 patients with histopathological diagnosis of intraventricular PA between February 2016 and January 2022 were evaluated retrospectively. Imaging and clinical findings of the patients, as well as apparent diffusion coefficient (ADC) measurements were analyzed. RESULTS: Of 16 patients, 8 (%50) were male and 8 (%50) were female. The mean age of the patients was 20.8 years (2-44 years range). The most common symptoms in the patients were headache and ataxia. The mean long-axis size of lesions was found to be 48.19 ± 21.59 (range, 15-92 mm). 9 out of 16 lesions (56.2%) were located in the fourth ventricle. The majority of the lesions were iso-hypointense in T1W and hyperintense in T2W images. The mean ADC value of PAs was 1.57 × 10-3 ± 0.2 mm2/s, while the mean thalamic ADC and white matter ADC values were found to be 0.78 × 10-3 ± 0.04 and 0.76 × 10-3 ± 0.06 mm2/s, respectively. There was a statistically significant difference between the ADC values obtained from the solid components of the lesions and the thalami/white matter (p < 0.001). CONCLUSION: PAs often originate from midline structures, however, they can also be located intraventricularly. Although intraventricular PAs are frequently seen in pediatric population, it should be kept in mind that they can also be seen in adults, albeit rarely. ADVANCES IN KNOWLEDGE: PA should be considered in the differential diagnosis of intraventricular neoplasms in case of high ADC values.

Case report: Spinal drop metastasis of IDH-mutant, 1p/19q-codeleted oligodendroglioma.

Background: Symptomatic spinal metastases of oligodendroglioma are rare. Moreover, none of the previously published cases demonstrated the typical IDH mutation and 1p/19q-codeletion for this glial tumor. This case presents an IDH mutant, 1p/19q-codeleted oligodendroglioma with multiple spinal drop metastases. Case description: We report a case of a 55-year-old woman with left frontal grade 3 oligodendroglioma diagnosed 3 years ago. No tumor recurrence was observed in post-operative follow-up MRI examinations. However, she was admitted to our institution again with severe low back pain. Gadolinium enhanced MRI of the spine revealed an intradural, extramedullary metastatic lesion between T11-L1 levels and multiple enhancing metastatic tumor deposits around cauda equine roots between L4-S1. T11-T12 midline laminectomy was performed and gross total resection of metastatic lesions was achieved. Final histological diagnosis of the spinal lesions was WHO Grade 3 Oligodendroglioma, IDH-mutant, 1p/19q-codeleted. Conclusion: This case is the first molecularly-defined spinal metastatic oligodendroglioma. The possibility of drop metastasis should be kept in mind in oligodendroglioma patients with spinal cord-related symptoms. There is no standard approach for the diagnosis and treatment of spinal metastases of this type of glial tumor.

Multinodular and vacuolating neuronal tumor of the cerebrum: Two cases and review of the literature.

BACKGROUND: Multinodular and vacuolating neuronal tumor (MVNT) recently described as a purely neuronal tumor. Although its nature as a genuine tumor is controversial, this new entity assumed benign lesion and mostly affecting adults. Herein, we introduce two cases of MVNT presumed low grade glial tumor (LGG) and focal cortical dyplasia (FCD) as a differential diagnosis. CASE DESCRIPTION: Case 1 has admitted to our hospital with headache which frequency and severity has increased within two months. Radiological examination revealed hyperintensity on T2-WI and T2 FLAIR images. Microsurgical resection was performed and histopathological findings were compatible with MVNT instead of low grade glial tumor as we thought. Case 2, who presented at our hospital with one episode seizure. MRI showed T2 hyperintensity and T1 hypointensity without contrast enhancement. We suspected FCD, thus performed microsurgical gross total resection with frontal craniotomy. Pathological findings confirmed MVNT as a diagnosis. Both cases were discharged on the 3rd day after surgery without any complications and with no regrowth of tumor at the 9-months and 3-months follow-up respectively. CONCLUSIONS: Radiological hallmarks may be helpful to prevent from aggressive treatment in case of patient is asemptomatic. Nevertheless further studies are necessary for the adoption of 'wait and see' philosophy and give a verdict about benign nature of these tumors.