Small Tumors Research Articles

Molecular Differences in Mitochondrial Genomes (Mitogenomes) of Dogs with Recurrent and Multiple Tumours and Their Reference to the Human Mitochondrial Genome

Abstract The aim of this study was to identify molecular defects caused by mutations in mitochondrial DNA in cases of recurrent and multiple canine tumours. We presented molecular differences in the mtDNA genome for two tumours observed in different body parts of five dogs and throughout time in the case of the recurrence. Mitochondrial DNA was sequenced on an Illumina MiSeq sequencer using a 600-cycle kit in a paired-end mode targeting at least 100x coverage. The sequences obtained were subjected to bioinformatic analyses in order to determine mutation and polymorphic sites within the analysed mtdna genome in the tumour tissue. The total amount of changes: single nucleotide polymorphisms (SNPs), indels, mutations, and heteroplasmy detected in this study was 329. Ten polymorphisms were found in all analysed samples: ins.2679_2680g (tRNA-Leu (UUR)), m.5367c>t (COX1), m.5444t>C (COX1), m.6065a>G (COX1), m.8368c>T (ATP6), m.8807g>A (COX3), ins.9913_9914tg (ND4L), m.13299t>A (ND5), m.15814c>T, and m.16418A>G (control region). Interestingly, the highest number of differences in the mtdna genome was observed between non-cancerous pyogranuloma tissue and epithelioma glandulae sebacei. The mutations in the non-cancerous tissue were mainly found in positions where polymorphisms were observed in blood and tumour tissue. The lowest number of changes was observed for the youngest analysed dog, which may indicate that some changes appeared in the mitogenomes with age. There were fewer heteroplasmic alterations in the larger than smaller tumour, which may suggest that the tumour growth is enhanced by genomic instability. The changes in the protein-coding genes were mostly synonymous, and nonsynonymous changes did not lead to alterations in protein properties. New mutations were observed in the post-recurrence tumours in comparison with the pre-recurrent tissue and blood.

Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian women.

Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.

Desmoplastic Small Round Cell Tumors: Clinical Presentation, Molecular Characterization, and Therapeutic Approach of Seven Patients

Desmoplastic small round blue cell tumor (DSRCT) is a highly aggressive fatal sarcoma without evidence‐based therapeutic guidelines. We present here seven patients with DSRCT including immunohistochemistry combined with fluorescence in situ hybridization (FISH), next generation sequencing (NGS, n = 6) as well as OncoScan array (n = 3) analyses and show consecutive therapeutic approaches. All seven DSRCT patients presented with an extended abdominal mass; median age at diagnosis was 24.8 years. NGS analyses revealed five class 4 or 5 sequence variants. Remarkably, OncoScan and targeted analyses by FISH identified genomic gains of CCND1 in two cases. Cyclin D1 expression was present in all seven tumors as shown by immunohistochemical staining. Multimodal therapeutic concepts included systemic therapies, resection, and radiation. Six patients were treated as first‐line therapy with conventional chemotherapy. All except one patient had a dismal therapy response. Subsequent therapy lines consisted of chemotherapeutic combinations followed by targeted therapies. Due to Cyclin D1 expression, the CDK4/6 inhibitor palbociclib was applied to four patients. The median therapy duration until disease progression in these patients was 4.5 months (range, 1.5–5 months). So, CCND1 genomic gain and Cyclin D1 expression are common features pointing to cell‐cycle deregulation as a possible therapeutic target.

Identification of TIMP1-induced dysregulation of epithelial-mesenchymal transition as a key pathway in inflammatory bowel disease and small intestinal neuroendocrine tumors shared pathogenesis.

Inflammatory Bowel Disease (IBD) is believed to be a risk factor for Small Intestinal Neuroendocrine Tumors (SI-NET) development; however, the molecular relationship between IBD and SI-NET has yet to be elucidated. In this study, we use a systems biology approach to uncover such relationships. We identified a more similar transcriptomic-wide expression pattern between Crohn's Disease (CD) and SI-NET whereas a higher proportion of overlapping dysregulated genes between Ulcerative Colitis (UC) and SI-NET. Enrichment analysis indicates that extracellular matrix remodeling, particularly in epithelial-mesenchymal transition and intestinal fibrosis mediated by TIMP1, is the most significantly dysregulated pathway among upregulated genes shared between both IBD subtypes and SI-NET. However, this remodeling occurs through distinct regulatory molecular mechanisms unique to each IBD subtype. Specifically, myofibroblast activation in CD and SI-NET is mediated through IL-6 and ciliary-dependent signaling pathways. Contrarily, in UC and SI-NET, this phenomenon is mainly regulated through immune cells like macrophages and the NCAM signaling pathway, a potential gut-brain axis in the context of these two diseases. In both IBD and SI-NET, intestinal fibrosis resulted in significant metabolic reprogramming of fatty acid and glucose to an inflammatory- and cancer-inducing state. This altered metabolic state, revealed through enrichment analysis of downregulated genes, showed dysfunctions in oxidative phosphorylation, gluconeogenesis, and glycogenesis, indicating a shift towards glycolysis. Also known as the Warburg effect, this glycolytic switch, in return, exacerbates fibrosis. Corresponding to enrichment analysis results, network construction and subsequent topological analysis pinpointed 7 protein complexes, 17 hub genes, 11 microRNA, and 1 transcription factor related to extracellular matrix accumulation and metabolic reprogramming that are candidate biomarkers in both IBD and SI-NET. Together, these biological pathways and candidate biomarkers may serve as potential therapeutic targets for these diseases.

Development of thiacrown ligands for encapsulation of mercury-197m/g into radiopharmaceuticals.

The theranostic pair mercury-197m and mercury-197g (197m/gHg, t1/2 = 23.8 h/64.14 h), through their γ rays and Meitner-Auger electron emissions, have potential use as constituents in radiopharmaceuticals to treat small metastatic tumours. However, the use of this pair of nuclear isomers in radiopharmaceuticals requires the development of suitable [197m/gHg]Hg2+ chelators as currently there is a lack of established ligands for radiometals in the field. Herein, this work studies the natHg/197m/gHg coordination of three thiacrown 18-membered N2S4 macrocycles with pendant arms of varying chemical "softness". Following the synthesis and characterization of the N2S4 ligand series (6,6'-((1,4,10,13-tetrathia-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid (N2S4-Pa), 7,16-bis(pyridin-2-ylmethyl)-1,4,10,13-tetrathia-7,16-diazacyclooctadecane (N2S4-Py) and 7,16-bis(2-(methylthio)ethyl)-1,4,10,13-tetrathia-7,16-diazacyclooctadecane (N2S4-Thio)), Hg2+ complexes were studied through mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, and density functional theory (DFT) calculations, revealing successful complexation of all ligands with the Hg2+ ion. Radiolabeling studies demonstrated the effect of the pendant arm on [197m/gHg]Hg2+ coordination, as N2S4-Thio and N2S4-Py had the highest radiochemical yield, similar to that of previously reported N-benzyl-2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetamide (NS4-BA), while N2S4-Pa had the lowest. The complex integrity of [197m/gHg][Hg(N2S4-Py)]2+ and [197m/gHg][Hg(N2S4-Thio)]2+ in both human serum and glutathione was notably lower compared to the [197m/gHg][Hg(NS4-BA)]2+ complex. However, the [197m/gHg][Hg(N2S4-Py)]2+ and [197m/gHg][Hg(N2S4-Thio)]2+ complexes remained above 70% intact over 82 h when competed against biologically relevant metals (ZnCl2, FeCl3, CuCl2, MgCl2 and CoCl2), suggesting the selectivity of the ligands for Hg2+. This study illustrates the importance of the macrocyclic backbone size and electron-donor groups of the donor pendant arms in the design of chelators for 197m/gHg-radiopharmaceuticals, as both affect the radiolabeling properties and complex inertness.

Multifocality and Detectability of Prostate Cancer with 3‐Tesla Multiparametric Magnetic Resonance Imaging: Correlation with Radical Prostatectomy Mapping Histopathology

Background. We aimed to determine the multifocality and detectability of prostate cancer (Pca) with 3‐Tesla (3T) multiparametric magnetic resonance imaging (mpMRI). Methods. The data of the patients who underwent radical prostatectomy in our institution between April 2020 and April 2021 were analyzed. Patients were included in the study at the stage of radical prostatectomy. Demographic and histopathological data were retrospectively collected, and then MRIs of eligible patients were re‐evaluated for the study. Suspicious regions of interest (ROIs) were evaluated by a radiologist with 4 years of experience in uroradiology and scored based on Prostate Imaging Reporting and Data System (PIRADS) v2.1. The reader was blinded to the pathological outcomes of any biopsy specimen. Lesions with a PIRADS score ≥3 were considered positive and included in the study. All cases were evaluated histopathologically by a pathologist with ten years of experience in uropathology. We utilized the mapping method which provided exactly the same information as the whole‐mount histopathology along with processing the entire prostatectomy specimen. Results. A total of 142 histopathologic tumoral lesions were detected among 70 patients. In relation to postoperative histopathology, tumor multifocality was established in 78.6% (n = 55), and 52.1% (n = 74) of 142 foci recognized were clinically significant. By detecting a total of 67 lesions, mpMRI showed an overall sensitivity of 47%. Whilst the sensitivity was 73% (54/74) in clinically significant lesions, the sensitivity was only 17.6% (12/68) in clinically insignificant lesions. For the group with detected tumors, the mean prostate‐specific antigen (PSA) and PSA density were higher, there were more high‐grade lesions, and the rate of the extraprostatic extension was significantly greater (p < 0.05, respectively). According to the multivariate analysis, only tumor size and Gleason Score (GS) were independent predictors regarding the ability of mpMRI to detect tumor foci within the prostate (p < 0.0001). Conclusion. mpMRI exhibited an acceptable sensitivity in detecting high‐risk and large Pca foci. The diagnostic accuracy is observed to be markedly diminished in small, low GS, and nonindex tumors. A considerable percentage of missed lesions are clinically significant.

Porcine-human glioma xenograft model. Immunosuppression and model reproducibility

BackgroundGlioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. MethodsImmunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. ResultsTumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. ConclusionThis report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.

Robot-assisted Partial Nephrectomy With Selective Artery Clamping for Renal Cell Carcinoma in Horseshoe Kidney.

Robot-assisted partial nephrectomy (RAPN) has become the standard treatment for small renal tumors, including highly complex cases. However, applying RAPN to renal tumors in the horseshoe kidney (HSK) is clinically challenging due to malformations and complex blood supply. Herein, we present two cases of RAPN in patients with HSK treated using selective artery clamping methods. A 61-year-old male with a 15 mm renal tumor located on the upper pole of the right HSK was referred to our Department. The patient underwent RAPN via the transperitoneal approach, following a three-dimensional computed tomography (3D-CT) assessment. Additionally, before surgery, we confirmed which renal arteries would be clamped in surgery by examining the kidney regions supplied by each renal artery. The second patient referred to our Department, a 45-year-old male, had a 46 mm renal tumor located on the isthmus of the HSK. His tumor received blood supply from two renal arteries, with the bilateral collecting systems converging and forming a ureter on 3D-CT. The patient underwent RAPN through an intraperitoneal approach in the semi-lateral position, with port placement lower than in standard RAPN. Pathological examinations revealed clear-cell renal cell carcinoma with negative surgical margins in both cases. Both patients had no recurrences or metastases at 53 and 13 months post-surgery, respectively. We present cases successfully treated with RAPN with selective artery clamping methods for HSK using 3D-CT without encountering complications, even in isthmus tumors.

Bronchospasm Complicating A Small Intestine Neuroendocrine Tumor Resection: A Case Report

Small intestinal neuroendocrine tumors (SI-NETs) are rare neoplasms with increasing incidence, known for their diverse clinical presentations and potential hormonal complications. We present the case of a 65-year-old male with a history of chronic smoking and alcoholism, who presented with right iliac fossa pain, liquid diarrhea, and weight loss. Imaging revealed a neuroendocrine tumor of the small intestine, and the patient underwent surgical resection. However, postoperatively, he developed respiratory distress suggestive of bronchospasm, requiring intensive care management. Histopathological analysis confirmed a well-differentiated neuroendocrine tumor, Grade 2. This case underscores the importance of early recognition and management of hemodynamic complications following surgical resection of SI-NETs. Preoperative assessment for carcinoid syndrome and optimization of cardiac function are crucial to minimize perioperative risks. Surgical resection with meticulous attention to complete tumor removal and mesenteric dissection remains the mainstay of treatment for SI-NETs. Further research is needed to refine perioperative management strategies and improve long-term outcomes for patients with SI-NETs.

Small Insulinoma Followed-up as an Indolent Pancreatic Tumor: A Case Report.

A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.

Spontaneously Regressing Retropharyngeal Neuroblastoma – A Rare Cause of Upper Airway Obstruction in a Neonate: A Case Report with Review of Literature

Abstract Background: Retropharyngeal masses may rarely cause persistent respiratory distress, stridor, and feeding difficulties in a neonate. We report a rare case of a primary cervical neuroblastoma presenting as a retropharyngeal mass, which underwent spontaneous regression. Clinical Description: A 29-day-old male baby was referred for recurrent vomiting since day 10 of life followed by severe difficulty in breathing since day 14 of life. At admission, the baby had stridor, cyanosis with respiratory failure, without any facial dysmorphism or cardiovascular involvement. Management and Outcome: After initial stabilization, investigations showed pneumonia in chest X-ray, with no evidence of sepsis. On intubation, a retropharyngeal bulge was noticed which was later confirmed by direct laryngoscopy. Later, computed tomography delineated the soft-tissue mass extending from C2–C5. Endoscopy with marsupialization of the tumor was done, and on histopathological examination, it was diagnosed as a small round blue cell tumor, suggestive of neuroblastoma, along with positive immunohistochemistry. According to the International Neuroblastoma Staging System, the tumor belonged to Stage I. As the baby had started improving clinically, further management by a multidisciplinary team was collectively decided to continue conservative observation. On follow-up, there was spontaneous regression in size of tumor with no recurrence of symptoms till the last follow-up at 11 months. Conclusion: Neuroblastoma, the most common solid tumor malignancy in children, may rarely have a primary cervical presentation, causing breathing and feeding difficulties. Depending on the course of symptoms, a strategy of observation and close monitoring by a multidisciplinary team can be taken, as such tumors may regress spontaneously.

Ewing’s Sarcoma of the Mandible with Extensive Bony Metastasis in a Young Male: A Case Report

Ewing’s Sarcoma Family of Tumours (ESFTs) comprises locally aggressive, undifferentiated small round blue-cell tumours of neuroectodermal origin, predominantly seen in adolescents. These tumours arise from non random chromosomal translocations involving the Ewing’s Sarcoma (EWS) gene. ESFTs in the mandible are uncommon. A 14-year-old male patient presented with a painless swelling in the right jaw. Plain radiographs, ultrasonography, contrast-enhanced Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) revealed a large, partially well-defined, highly vascular soft tissue mass in the right mandibular region. It measured approximately 80×82×75 mm (anteroposterior x transverse x craniocaudal), with both solid and cystic components. The mass was destroying the underlying right temporomandibular joint, head, ramus and posterior body of the right hemimandible, including extensive sunray-type bony spiculations. There were multiple lytic lesions in the skull and facial bones, as well as, altered marrow signal intensity in the calvarium, bilateral humeri and clavicles, and cervical and thoracic vertebrae, indicating a locally aggressive tumour with extensive metastasis into the bones and marrow. The diagnosis was confirmed by histopathology, which showed fibrocollagenous tissue infiltrated by sheets of small round cells with scanty eosinophilic cytoplasm and prominent nuclei. Management typically involves a combination of chemotherapy, radiation and surgery. However, metastatic Ewing’s Sarcoma has a poor prognosis.

Toll-like receptors 1-9 in small bowel neuroendocrine tumors-Clinical significance and prognosis.

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the expression of TLRs 1-9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1-2 and 4-9 were expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1-9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.028). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07-14.3). The expression of TLRs 1-6 and 8-9 in lymph node metastases were not associated with survival. SB-NETs and their lymph node metastases express cytoplasmic TLR 1-2 and 4-9 and nucleic TLR5. High TLR7 expression in SB-NET lymph node metastases was associated with worse prognosis. The current research has future perspective, as it can help create base for clinical drug trials to target specific TLRs with agonists or antagonists to treat neuroendocrine tumors.

The Value of Computed Tomography in Differentiating Heterotopic Pancreas from Small Gastrointestinal Stromal Tumor.

It is critical for an accurate preoperative diagnosis of heterotopic pancreas (HP) and small gastrointestinal stromal tumor (GIST), given the unique treatment and prognosis of the two tumors. This study aims to investigate HP's computed tomography (CT) features and identify the distinguishing characteristics between HP and small GIST. From January 2016 to August 2020, our hospital database was searched for confirmed histopathological results and CT scans for HP and GIST for further analysis. The statistically significant variables were determined by using Fisher's exact test, the Mann-Whitney U test, the receiver operating characteristic (ROC) curve and the inverse probability weighting method. CT images and clinical data were reviewed for 24 participants with HP and 34 patients with small GIST. Contour, border, relative enhancement grade, surface dimple, duct-like structure, short diameter (SD), attenuation of each lesion in the unenhanced phase (Lp), and the enhancement ratio of tumor in the venous phase (ER) were significant for differentiating HP from small GIST. Threshold values for SD and Lp were 1.40 cm and 42.33 Hounsfield units, respectively. Ill-defined border, surface dimple, ductlike structure, and Lp were independent factors that differentiated HP from small GIST. Additionally, SD and ER were also found to be independent factors. Contour, relative enhancement grade, SD, and Lp could effectively differentiate HP from small GIST, demonstrating improved diagnostic performance compared to other parameters. The presence of ductlike structures and surface dimples could further characterize HP. These findings may help distinguish HP from small GIST and avoid unnecessary invasive examination and therapy in individuals with asymptomatic HP.

Outlook for 615 Small Intestinal Neuroendocrine Tumor Patients: Recurrence Risk after Surgery and Disease-Specific Survival in Advanced Disease.

Small intestinal neuroendocrine tumors (siNET) are one of the most common neuroendocrine neoplasms. Radical surgery is the only curative treatment. We utilized a single-center study including consecutive patients diagnosed from 2000 to 2020 and followed them until death or the end of study. Disease-specific survival and recurrence-free survival (RFS) were investigated by Cox regression analyses with the inclusion of prognostic factors. Aims/primary outcomes: We identified three groups: (1) disease specific-survival in the total cohort (group1), (2) RFS and disease-specific survival after intended radical surgery (group2), (3) disease specific-survival in patients with unresectable disease or residual tumor after primary resection (group3). In total, 615 patients, with a mean age (SD) 65 ± 11 years were included. Median (IQR) Ki-67 index was 4 (2-7)%. Median disease-specific survival in group1 was 130 months. Median RFS in group2 was 138 months with 5- and 10-year RFS rates of 72% and 59% with age, plasma chromogranin A (p-CgA) and Ki-67 index as prognostic factors. The ten year disease-specific survival rate in group2 was 86%. The median disease-specific survival in group3 was 85 months with age, Ki-67 index, p-CgA and primary tumor resection as prognostic factors. When proliferation was expressed by WHO grade, no difference was observed between G1 vs. G2 for any of the primary outcomes. Recurrence rates remained high 5-10 years after surgery (group2) supporting long-term follow-up. Median disease-specific survival in patient with unresectable disease (group3) was 7 years, with a favorable impact of primary tumor resection. Our data does not support the current grading system since no significant prognostic information was detected in G1 vs. G2 tumors.

Mesenchymal Chondrosarcoma of the Mandible, a Big Dilemma: Report of a Rare Case in Mesenchymal Chondrosarcoma of the Mandible—Report of a Case With Discussion of Diagnostic and Therapeutic Dilemmas

Chondrosarcomas are a group of malignant neoplasms with cartilaginous matrix production mostly found in flat and peripheral long bones. Mesenchymal chondrosarcoma is one of the most unusual and rare histological variants of chondrosarcoma, with a distinct histopathological appearance and biologically aggressive behavior. The amount of cartilage in mesenchymal chondrosarcoma may be so abundant that it is easily found in random sections or so scarce that numerous sections are required to discover it. In such cases, it is tough to make an accurate diagnosis, which leads to a big dilemma for pathologists and surgeons regarding diagnosis and treatment. Here, we report a mandibular mesenchymal chondrosarcoma in a 38‐year‐old male with a diagnosis of malignant small round cell tumor in incisional biopsy without any bone or chondroid formation. After ruling out lymphoma, a complete lesion excision was done. Diagnosis of mesenchymal chondrosarcoma was confirmed with small foci of chondroid material and strong positivity of tumoral cells for CD99 and S100. We highlight the fact that incisional biopsy frequently fails to provide sufficient tissue to establish the diagnosis of mesenchymal chondrosarcoma. Adequate tissue with multiple sections, detailed histopathological examination, and adjunctive IHC study are the keys to a definitive diagnosis.

EFFICIENT SEGMENTATION MODEL USING MRI IMAGES AND DEEP LEARNING TECHNIQUES FOR MULTIPLE SCLEROSIS CLASSIFICATION

The segmentation models employing deep learning offer successful outcomes over multiple medical image complex data resources and public data resources important for huge pathologies. During the identification of multiple sclerosis, the observation of entire tumors from the magnetic resonance imaging (MRI) sequence is complex. Furthermore, it is necessary to identify the small tumors from the images in the prognosis phase to offer good treatment. The deep learning-assisted identification models solve the issue of the imbalance data, and the false positive results are more in the conventional models. Besides, these methodologies offer a good tradeoff between the precision measure and recall measure. Thus, the latest deep learning-assisted MRI image segmentation and categorization model is developed to detect multiple sclerosis at the initial stage. In this study, the MRI images are initially gathered. The gathered images are directly given to the image segmentation process, where the Multi-Scale Adaptive TransResunet++ (MSAT) is adopted to perform the lesion segmentation appropriately. The attributes present in the MSAT are optimized with the support of the developed random opposition of cicada swarm optimization (ROCSO). Then, the segmented pictures are subjected to the categorization process where the hybrid and dilated convolution-based adaptive residual attention network (HDCARAN) is utilized. The HDCARAN categorizes the lesions from the MRI images very effectively and detects the multiple sclerosis of patients. Here, the attributes present within the HDCARAN are tuned via the same ROCSO. The implementation results are analyzed through the previously developed multiple sclerosis detection schemes to evaluate the effectiveness of the designed model with respect to several functionality measures. The implementation of HDCARAN results in the detection of lesions in the initial stages, with a 94% specificity level, as well as efficiency performance based on existing models. The model also obtains a 94.5% accuracy, as opposed to the other conventional systems. The results show the proposed method performs better than other machine learning models.

Dynamic Analysis of a Mathematical Model of the Anti-Tumor Immune Response

This study discusses the dynamic analysis, the Hopf bifurcation, and numerical simulations. The mathematical model of the anti-tumor immune response consists of three compartments namely Immature T Lymphocytes (L1), Mature T Lymphocytes (L2) and Tumor Cells (T). This research was conducted to represent the behavior between immune cells and tumor cells in the body with five γ conditions. Where γ is the intrinsic growth rate of mature T lymphocytes. This study produces R0 > 1 in conditions 1 to 4 while in condition 5 produces R0 < 1. The disease-free equilibrium point is stable only in condition 5, while the endemic equilibrium point is stable only in conditions 2 and 4. Hopf bifurcation occurs at the endemic equilibrium point. Numerical simulation graph in condition 1 shows that tumor cells will increase uncontrollably. In condition 2 the graph show that the endemic equilibrium point for large tumors is stable. In condition 3 the graph show that there will be a bifurcation from the endemic equilibrium point by the disturbance of the parameter value γ. In condition 4 the graph show the small tumor endemic equilibrium point is stable. Finally, in condition 5, the graph show a stable disease-free equilibrium point.

Enhancing liquid biopsies are a promising approach for the early detection of cancer

Cancer is a formidable threat to human life, a cure for which in advanced stages remains challenging. Early detection and treatment of cancer are paramount, yet a substantial number of cancer patients receive diagnoses at an advanced stage, resulting in a lower 5-year survival rate. Early-stage cancers, however, frequently elude detection. Conventional tumor screening techniques, such as tumor biopsy, serve as essential means for an early cancer diagnosis. However, these procedures are invasive and may inadvertently facilitate cancer metastasis. A current research focal point involves liquid biopsy technologies, offering a potential solution to mitigate the above-mentioned issues, but often exhibiting low sensitivity. A research team from the Massachusetts Institute of Technology has recently pioneered an innovative approach to enhance the sensitivity of liquid biopsy for cancer diagnosis. By administering a pre-treatment agent 1–2 h prior to sampling, a greater than 10-fold increase in collected ctDNA was obtained. Subsequent tumor analysis using ctDNA not only demonstrated heightened sensitivity in detecting small tumors (>75%) but also presented a promising avenue for early clinical cancer detection and diagnosis. This discovery holds significant potential for advancing the prospects of early cancer detection, diagnosis, and treatment.

Diffuse low-grade glioma: What is the optimal linear measure to assess tumor growth?

Radiological follow-up of diffuse low-grade gliomas (LGGs) growth is challenging. Approximative visual assessment still predominates over objective quantification due to the complexity of the pathology. The infiltrating character, diffuse borders and presence of surgical cavities demand LGG-based linear measurement rules to efficiently and precisely assess LGG evolution over time. We compared optimized 1D, 2D, and 3D linear measurements with manual volume segmentation as a reference to assess LGG tumor growth in 36 patients with LGG (340 magnetic resonance imaging scans), using the clinically important mean tumor diameter (MTD) and the velocity diameter expansion (VDE). LGG-specific progression thresholds were established using the high-grade gliomas-based RECIST, Macdonald, and RANO criteria, comparing the sensitivity to identify progression/non-progression for each linear method compared to the ground truth established by the manual segmentation. 3D linear volume approximation correlated strongly with manually segmented volume. It also showed the highest sensitivity for progression detection. The MTD showed a comparable result, whereas the VDE highlighted that caution is warranted in the case of small tumors with multiple residues. Novel LGG-specific progression thresholds, or the critical change in estimated tumor volume, were increased for the 3D (from 40% to 52%) and 2D methods (from 25% to 33%) and decreased for the 1D method (from 20% to 16%). Using the 3D method allowed a ~5-minute time gain. While manual volumetric assessment remains the gold standard for calculating growth rate, the 3D linear method is the best time-efficient standardized alternative for radiological evaluation of LGGs in routine use.