Raman Spectroscopy and Oncology: Multivariate Statistics Methods for Cancer Grading

Over the last decade, Raman spectroscopy was demonstrated as a label-free and destructive optical spectroscopy that was able to improve diagnostic accuracy in cancer diagnosis. This ability is principally based on the great amount of biochemical information produced by the Raman scattering while investigating biological tissues. However, to achieve the relevant clinical requirements, the spectroscopic analysis and its ability to grade cancer tissues require sophisticated multivariate statistics. In this paper, we critically review multivariate statistics methods analyzed in light of their ability to process datasets generated by Raman spectroscopy in chondrogenic tumors, where distinguishing between enchondroma and the first grade of malignancy is a critical problem for pathologists.

Diffusion-Weighted Magnetic Resonance Imaging in the Evaluation of Wilms Tumors: Correlation with Histological Data. Pilot Study

The aim of the study is to assess the difference in apparent diffusion coefficient (ADC) values depending on the degrees of malignancy of Wilms’ tumor. The study includes 64 patients with verified Wilms tumor after a course of chemotherapy, before undergoing surgical treatment. The patients were examined using scanners with magnetic field induction of 3.0 and 1,5 T. ADC data collection (mm2/s) was carried out using specialized software. Statistical analysis was performed using the Graphpad Prism software package. Based on the results of this study, average ADC values were obtained for histological types of Wilms’ tumors distributed by clinical risk groups: 0.4 × 10-3 mm2/s — for the low grade of malignancy, 1.1 × 10-3 mm2/s — for the average grade of malignancy and 0.6 × 10-3 mm2/s — for the high grade. In addition, for the average grade of malignancy, the ADC values were divided into groups depending on the cellular composition — 1 ± 0.2 × 10-3 mm2/s — for the regressive and mixed type; 0.9 ± 0.2 × 10-3 mm2/s — for the epithelial type; 1.3 ± 0.4 × 10-3 mm2/s — for the stromal type. Thus, diffusion-weighted MRI can be a useful tool in the initial assessment and differential diagnosis of patients with Wilms tumor.

Dynamic Interplay between Lower-Grade Glioma Instability and Brain Metaplasticity: Proposal of an Original Model to Guide the Therapeutic Strategy

The behavior of lower-grade glioma (LGG) is changing over time, spontaneously, and in reaction to treatments. First, due to genomic instability and clonal expansion, although LGG progresses slowly during the early period of the disease, its growth velocity will accelerate when this tumor will transform to a higher grade of malignancy. Furthermore, its pattern of progression may change following therapy, e.g., by switching from a proliferative towards a more diffuse profile, in particular after surgical resection. In parallel to this plasticity of the neoplasm, the brain itself is constantly adapting to the tumor and possible treatment(s) thanks to reconfiguration within and between neural networks. Furthermore, the pattern of reallocation can also change, especially by switching from a perilesional to a contrahemispheric functional reorganization. Such a reorientation of mechanisms of cerebral reshaping, related to metaplasticity, consists of optimizing the efficiency of neural delocalization in order to allow functional compensation by adapting over time the profile of circuits redistribution to the behavioral modifications of the glioma. This interplay between LGG mutations and reactional connectomal instability leads to perpetual modulations in the glioma–neural equilibrium, both at ultrastructural and macroscopic levels, explaining the possible preservation of quality of life despite tumor progression. Here, an original model of these dynamic interactions across LGG plasticity and the brain metanetwork is proposed to guide a tailored step-by-step individualized therapeutic strategy over years. Integration of these new parameters, not yet considered in the current guidelines, might improve management of LGG patients.

MODERN METHODS OF DIAGNOSIS AND TREATMENT OF ATYPICAL TERATOID RHABDOID TUMORS CNS IN CHILDREN

Atypical teratoid rhabdoid tumors (ATRT) of the CNS in children are a group of aggressive malignant neoplasms with extremely poor prognosis, and therefore these tumors are classified as IV (highest) grade of malignancy. At the time of diagnosis, 20% of patients are found to have metastasized to the brain and spinal cord. The pathogenesis of ATRT is based on the biallelic mutation of the SMARCB1 gene, more rarely SMARCA4 genes. Despite the use of intensive multimodal therapy, the survival rate of patients with ATRT remains low. Recently, several groups of scientists, based on epigenetic and transcriptional studies, have identified 3 molecular groups of ATRT with different therapeutic sensitivity to chemoradiation therapy and, accordingly, have a different prognosis of the disease. This article presents the current literature data on epidemiology, pathogenesis, clinic, diagnosis and therapy of patients with ATRT, and describes the directions of treatment.

Neutrophil-to-Lymphocyte Ratio Is a Useful Marker for Predicting Histological Types of Early Gastric Cancer

Background: The indications for endoscopic submucosal dissection (ESD) for gastric cancer are based on preoperative histological assessment; however, examination of tissue biopsy is not always reliable as only a limited portion of the lesion can be obtained. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of inflammatory response and are potentially associated with the grade of malignancy in gastric cancer. We aimed to investigate the association between NLR and PLR and the histology of gastric cancer. Methods: This study included 218 patients who underwent ESD for gastric cancer. The relationship between NLR/PLR and histological diagnosis was investigated. Results: Patients with adenocarcinomas showed significantly higher NLR and PLR than those with adenomas (p < 0.001 and p < 0.05, respectively). Further, patients with undifferentiated adenocarcinoma showed a significantly higher NLR (p < 0.05) than those with differentiated adenocarcinoma. Conclusion: This study suggests that NLR could be a useful marker for assessing early gastric cancer.

Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms

Although pancreatic neuroendocrine neoplasms (PNENs) are relatively rare tumors, their number is increasing with advances in diagnostic imaging modalities. Even small lesions that are difficult to detect using computed tomography or magnetic resonance imaging can now be detected with endoscopic ultrasound (EUS). Contrast-enhanced EUS is useful, and not only diagnosis but also malignancy detection has become possible by evaluating the vascularity of tumors. Pathological diagnosis using EUS with fine-needle aspiration (EUS-FNA) is useful when diagnostic imaging is difficult. EUS-FNA can also be used to evaluate the grade of malignancy. Pooling the data of the studies that compared the PNENs grading between EUS-FNA samples and surgical specimens showed a concordance rate of 77.5% (κ-statistic = 0.65, 95% confidence interval = 0.59–0.71, p < 0.01). Stratified analysis for small tumor size (2 cm) showed that the concordance rate was 84.5% and the kappa correlation index was 0.59 (95% confidence interval = 0.43–0.74, p < 0.01). The evolution of ultrasound imaging technologies such as contrast-enhanced and elastography and the artificial intelligence that analyzes them, the evolution of needles, and genetic analysis, will further develop the diagnosis and treatment of PNENs in the future.

Configuration of soft-tissue sarcoma on MRI correlates with grade of malignancy

Background The aim of the study was to assess whether the configuration of primary soft-tissue sarcoma (STS) on MRI correlates with the grade of malignancy. Patients and methods 71 patients with histologically proven STS were included. Primary STS were examined for configuration, borders, and volume on MRI. The tumors were divided into high-grade (G3), intermediate-grade (G2) and low-grade (G1) STS according to the grading system of the French Federation of Cancer Centers Sarcoma Group (FNCLCC). Results 30 high-grade, 22 intermediate-grade and 19 low-grade primary STS lesions were identified. High- and intermediate-grade (G3/2) STS significantly most often appeared as polycyclic/multilobulated tumors (p < 0.001 and p = 0.002, respectively). Low-grade (G1) STS mainly showed an ovoid/nodular or streaky configuration (p = 0.008), and well-defined borders. The appearance of high-, intermediate- and low-grade STS with an ovoid/nodular configuration were mainly the same on MRI. All streaky G3/2 sarcoma and 17 of 20 patients with polycyclic/multilobulated G3 sarcoma showed infiltrative borders. High-grade streaky and polycyclic/multilobulated STS are larger in volume, compared to intermediate- and low-grade STS. Conclusions Configuration of STS on MRI can indicate the grade of malignancy. Higher-grade (G2/3) STS most often show a polycyclic/multilobulated configuration, while low-grade STS are mainly ovoid/nodular or streaky. Infiltrative behavior might suggest higher-grade STS in streaky and polycyclic/multilobulated STS.

Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms

Although pancreatic neuroendocrine neoplasms (PNENs) are relatively rare tumors, their number is increasing with advances in diagnostic imaging modalities. Even small lesions that are difficult to detect using computed tomography or magnetic resonance imaging can be detected with endoscopic ultrasound (EUS). Contrast-enhanced EUS is useful, and not only diagnosis but also malignancy detection have become possible by evaluating the vascularity of tumors. Pathological diagnosis using EUS with fine-needle aspiration (EUS-FNA) is useful when diagnostic imaging is difficult. EUS-FNA can also evaluate the grade of malignancy. Pooling the data of the studies which compared the PNENs grading between EUS-FNA samples and surgical specimen, the concordance rate was 77.5% (&kappa;-statistic: 0.65, 95% confidence interval = 0.59 - 0.71, P&lt; 0.01). EUS is a particularly important modality for the treatment of PNENs.

A novel clinically-oriented classification of fine-needle aspiration cytology for salivary gland tumors: a 20-year retrospective analysis of 1175 patients

Background When determining treatment strategy for a salivary gland tumor, assessing histology and malignancy grade before surgery is essential. Several new diagnostic classification systems for salivary gland cytology have recently been proposed. However, none incorporate histology and grade of malignancy. Methods We developed a new cytology classification system that incorporates histology and grade of malignancy of salivary gland tumors (OMC classification), consisting of 11 categories. Our OMC classification was applied to 1175 patients who had preoperative cytology and confirmed final pathological diagnosis available from the past 20 years at our hospital (benign tumor: 981 patients, malignant tumor: 194 patients). Results Based on the cytology, 729 patients (62.0%) had benign histology (Category 4–1), and 87 patients (7.4%) were diagnosed with grade of malignancy (Category 6–3 + 6–4). Based on the final pathological diagnosis, the accuracy rate of Category 4–1 and Category 6–3 + 6–4 of our classification system was 93.4% and 88.5%, respectively. Conclusion Based on the correct diagnosis rate, the inclusion of histology and grade of malignancy in the salivary gland cytology classification was considered feasible. Thus, the OMC classification system is considered a useful tool when determining the treatment strategy for a salivary gland tumor.