Tissue Diagnosis Research Articles

Varied Lineage Thyroid Malignancies in Longstanding Thyroid Swellings: A Series of Three Cases

Long-standing thyroid swellings can present therapeutic and diagnostic challenges. Although benign, these nodules can harbour malignancies of diverse lineages ranging from those of follicular cell origin to rare malignancies such as lymphomas and paragangliomas. Here, the authors are sharing their three clinical experiences with thyroid neoplasms of long duration. The first case is a 42-year-old male patient who presented with an anterior neck swelling of 12 years’ duration. Postoperatively, a diagnosis of Mucosa-associated Lymphoid Tissue (MALT) lymphoma was made based on histopathology and immunohistochemistry. In the second case, a 43-yearold male presented with a neck swelling with eight years of history. Intraoperatively, the lesion was found to be locally aggressive with infiltration into the strap muscles and trachea. A tissue diagnosis of paraganglioma of the thyroid gland was made postoperatively. The third case involves a 72-year-old female who had undergone a left thyroidectomy 10 years back and presented to the Outpatient Department (OPD) with a history of right-sided neck swelling associated with dysphagia and a change in voice. The patient was diagnosed with anaplastic carcinoma, specifically squamous cell carcinoma. Thyroid lesions of abnormally large size create intraoperative problems concerning securing an adequate airway, locating anatomical structures, especially the Recurrent Laryngeal Nerve (RLN), parathyroids, and great vessels of the neck. Postoperatively, the tissue features may be very uncharacteristic, making reaching a proper diagnosis difficult. The use of immunohistochemistry helps in determining the cell lineage and type of malignancy

Cardiac Amyloidosis: Approach to Diagnosis

Amyloid is an amorphous, fibrillar material formed from various abnormally folded proteins that deposits locally or systemically. Over 95% of cases have been attributed to light chain deposition (AL) or transthyretin deposition (ATTR) amyloidosis. The basic investigations in the evaluation of cardiac amyloidosis include the electrocardiogram, echocardiography and cardiac biomarkers. Echocardiography in a patient with cardiac amyloidosis shows biatrial enlargement, biventricular hypertrophy, diastolic dysfunction, interatrial septal thickening, valvular thickening, a glistening appearance of the interventricular septum, and pericardial effusion. Magnetic resonance imaging can help distinguish amyloidosis from other causes of infiltrative/restrictive cardiomyopathy, from example, sarcoidosis, hemochromatosis, and Fabry disease based on characteristic enhancement patterns in these diseases. The latest Expert Consensus recommends that serum/urine immunofixation electrophoresis along with a serum free light chain assay must be done in all the cases of suspected cardiac amyloidosis. If the light chain assays are positive, we proceed with tissue diagnosis for confirmation of AL amyloidosis. If the screening assays are negative for monoclonal gammopathy, the next step is to obtain cardiac scintigraphy. If the nuclear scan is negative, but the index of suspicion remains high, an endomyocardial biopsy can be done. Once amyloid is demonstrated in histopathologic specimens, it must be typed to distinguish between AL and ATTR. The ideal method for this is tandem mass spectrometry, although this may not be widely available. It has a sensitivity of 88% and specificity of 96% higher than other techniques 23. In resource-poor settings, immunohistochemistry or immunoelectron microscopy can allow this distinction, although with lesser sensitivity.

Touch Imprint Cytology in Oral Cancer Diagnosis: A Narrative Review

Touch Imprint Cytology (TIC) is a simple, economical, and cost-effective method that can be used as a rapid tool for tissue diagnosis. It has been used for the intraoperative diagnosis of cancer, evaluation of surgical cut margins, evaluation of sentinel lymph nodes, diagnosis of head and neck lesions, and postmortem diagnosis. Intraoperative diagnosis includes both frozen section and TIC, which provide rapid pathological consultation. Brush biopsy can also be used for cytological diagnosis and acts as an adjunct to histopathological and TIC diagnosis. It has been found that TIC yields satisfactory and adequate material for diagnosis, allowing early counselling and preparation of the patient for further processes without having to wait for the results of histopathology. As technology continues to evolve, ongoing research aims to enhance the utility and accuracy of TIC in oral cancer diagnosis. Advancements in imaging techniques, such as confocal microscopy and molecular analysis of TIC samples, hold promise for improving diagnostic sensitivity and specificity

A Silver-Induced Absorption Red-Shifted Dual-Targeted Nanodiagnosis-Treatment Agent for NIR-II Photoacoustic Imaging-Guided Photothermal and ROS Simultaneously Enhanced Immune Checkpoint Blockade Antitumor Therapy.

Tumor metastasis remains a leading factor in the failure of cancer treatments and patient mortality. To address this, a silver-induced absorption red-shifted core-shell nano-particle is developed, and surface-modified with triphenylphosphonium bromide (TPP) and hyaluronic acid (HA) to obtain a novel nanodiagnosis-treatment agent (Ag@CuS-TPP@HA). This diagnosis-treatment agent can dual-targets cancer cells and mitochondria, and exhibits maximal light absorption at 1064nm, thereby enhancing nesr-infrared II (NIR-II) photoacoustic (PA) signal and photothermal effects under 1064nm laser irradiation. Additionally, the silver in Ag@CuS-TPP@HA can catalyze the Fenton-like reactions with H2 O2 in the tumor tissue, yielding reactive oxygen species (ROS). The ROS production, coupled with enhanced photothermal effects, instigates immunogenic cell death (ICD), leading to a substantial release of tumor-associated antigens (TAAs) and damage-associated molecular patterns, which have improved the tumor immune suppression microenvironment and boosting immune checkpoint blockade therapy, thus stimulating a systemic antitumor immune response. Hence, Ag@CuS-TPP@HA, as a cancer diagnostic-treatment agent, not only accomplishes targeted the NIR-II PA imaging of tumor tissue and addresses the challenge of accurate diagnosis of deep cancer tissue in vivo, but it also leverages ROS/photothermal therapy to enhance immune checkpoint blockade, thereby eliminating primary tumors and effectively inhibiting distant tumor growth.

Nephrotic Syndrome Secondary to Primary Membranoproliferative Glomerulonephritis in a 27 Years Old Nigerian Male

Abstract: Membranoproliferative glomerulonephritis (MPGN) is not a common cause of nephrotic syndrome (NS) in adults unlike in children. It is commonly steroid-resistant in adults unlike in children. Tissue diagnosis needed for effective management could be unavailable due to cost, particularly in resource poor settings. Patient was examined, had urine analysis, serum biochemistry assay, kidney scan and a kidney biopsy for histological diagnosis. The patient had generalized oedema, with ascites, elevated blood pressure (156/90 mmHg) and massive proteinuria (4.6 g/day). The haemogram showed haematocrit of 32%, with absolute lymphocytosis (72%). Fasting lipids showed hypercholesterolemia (533 mg/dl), elevated LDL (274 mg/dl), low HDL (27 mg/dl) and hypertriglyceridemia (302 mg/dl). Ultrasound showed enlarged kidneys. Histological findings were mesangial hypercellularity, double-contour formation along the glomerular capillary wall (tram track appearance) and endocapillary proliferation. He was managed with intravenous methylprednisolone, (followed by gradually reducing oral doses), frusemide, atorvastatin, antibiotics and had daily weighing. He responded well to treatment. He was counselled on good compliance and has been on follow-up visits. His clinical and laboratory parameters have been normal. Nephrotic syndrome from MPGN should be looked out for in adults presenting with NS and their treatment with steroids could be very beneficial.

Endoscopic evaluation of indeterminate biliary strictures: Cholangioscopy, endoscopic ultrasound, or both?

Accurate and timely diagnosis of biliary strictures can be challenging. Because the diagnostic sensitivity and accuracy of standard endoscopic retrograde cholangiopancreatography-based tissue sampling for malignancy are suboptimal, additional endoscopic evaluation by cholangioscopy and/or endoscopic ultrasound (EUS) is often necessary to differentiate between malignant and benign biliary strictures to guide clinical management. While direct visualization by cholangioscopy and/or high-resolution imaging by EUS are often the first step in the evaluation of an indeterminate biliary stricture (IDBS), tissue diagnosis by cholangioscopy-guided biopsy and/or EUS-guided fine-needle tissue acquisition is the preferred modality to establish a diagnosis of malignancy. Because each modality has its own strengths and limitations, selection of cholangioscopy and EUS is best guided by thebiliary stricture location and local expertise. Artificial intelligence-assisted diagnosis, biopsy forceps with improved design, contrast-enhanced EUS, and dedicated fine-needle biopsy devices are recent technological advances that may further improve the diagnostic performance of cholangioscopy and EUS in patients with IDBS.

Surface-enhanced Raman spectroscopy in women with benign and malignant endometrial diseases

Background. This study aimed to enhance early detection of endometrial cancer in women and distinguish benign conditions from endometrial cancer using surface-enhanced Raman scattering (SERS) analysis of blood plasma, thus increasing diagnostic efficacy.
 Materials and methods. The study of blood plasma from 95 female patients aged 22–79 years was performed. The patients were divided into four groups: group 1 included 29 women with endometrial adenocarcinoma, group 2 included 31 patients with endometrial polyp, group 3 included 10 women with endometrial hyperplasia, and the comparison group consisted of 25 healthy women. Blood plasma was analyzed via SERS, with three Raman spectra recorded per sample. Spectral measurements of the SERS substrate were assessed using dried samples on an experimental bench equipped with the spectrometric system RL785 (LLC “Foton-Bio”, Russia), incorporating a CCD detector, laser radiation source with a wavelength of 785 nm, and ADF U300 microscope (ADF, China). A silver substrate composed of dried silver colloid was used to demonstrate the enhancement effect on the Raman signal from the surface of the blood plasma.
 Results. Spectral and specific features that distinguish adenocarcinoma, polyps, and endometrial hyperplasia were identified and evaluated. Spectral and quantitative differences specific to each condition, which are crucial for the differential diagnosis of pathologic tissues, were also identified. The accuracy rates of the optical diagnostics in distinguishing endometrial adenocarcinoma from the control group and endometrial hyperplasia were 87% and 85%, respectively, for the calibration and verification spectral sets (where the sensitivity and specificity were 66% and 92% for the spectral verification set, respectively). The accuracy rates of distinguishing control from endometrial hyperplasia and endometrial adenocarcinoma were 86% and 85%, respectively, and the accuracy of distinguishing endometrial hyperplasia from control and endometrial adenocarcinoma was 81% for the calibration and verification sets of spectra. In addition, the study demonstrated improved accuracy in differentiating adenocarcinoma from hyperplasia, including polyps. The accuracy rate was 93% in the calibration set of spectra, with sensitivity and specificity of 96% and 90%, whereas in the validation set, it was 91%, with sensitivity and specificity of 93% and 88%, respectively.
 Conclusions. The study demonstrated the potential use of SERS for differentiating expression patterns in endometrial cancer from those in benign conditions.

Dual Tumor-Selective β-Carboline-Based Fluorescent Probe for High-Contrast/Rapid Diagnosis of Clinical Tumor Tissues.

Given that precise/rapid intraoperative tumor margin identification is still challenging, novel fluorescent probes HY and HYM, based on acidic tumor microenvironment (TME) activation and organic anion transporting polypeptide (OATPs)-mediated selective uptake, were constructed and synthesized. Both of them possessed acidic pH-activatable and reversible fluorescence as well as large Stokes shift. Compared with HY, HYM had a higher (over 9-fold) enhancement in fluorescence with pH ranging from 7.6 to 4.0, and the fluorescence quantum yield of HYM (ΦF = 0.49) at pH = 4.0 was 8-fold stronger than that (ΦF = 0.06) at pH = 7.4. Mechanism research demonstrated that acidic TME-induced protonation of the pyridine N atom on β-carbolines accounted for the pH-sensitive fluorescence by influencing the intramolecular charge transfer (ICT) effect. Furthermore, HYM selectively lit up cancer cells and tumor tissues not only by "off-on" fluorescence but also by OATPs (overexpressed on cancer cells)-mediated cancer cellular internalization, offering dual tumor selectivity for precise visualization of tumor mass and intraoperative guidance upon in situ spraying. Most importantly, HYM enabled rapid and high-contrast (tumor-to-normal tissue ratios > 6) human tumor margin identification in clinical tumor tissues by simple spraying within 6 min, being promising for aiding in clinical surgical resection.

Risk of malignancy in incidental oropharyngeal lesions exhibiting fluorodeoxyglucose uptake which proceed to tissue biopsy.

Utilization of positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose is increasing in use for a variety of indications, including surveillance of cancer patients. There is a paucity of evidence pertaining to the significance of incidental PET-avid oropharyngeal lesions. This study aims to examine the clinical and radiological features of these incidental oropharyngeal lesions in patients undergoing PET for indications other than head and neck cancer. Retrospective cohort study of three Australian tertiary hospitals, from 2015 to 2021, on adult patients undergoing biopsy of incidental PET-avid oropharyngeal lesions. Primary outcome of interest was the incidence of malignancy. Patients with a previous history of, or undergoing investigations for, head and neck cancer were excluded. Thirty-one patients were included, wherein 21 patients had tonsillar uptake, and 13 patients had base of tongue uptake. Tonsillar disease was mostly asymmetrical (n = 15/21), bilateral (n = 11/21), and had median SUVmax 9.35 (n = 12, IQR 7.4-11.15). Base of tongue was mostly asymmetrical (n = 7/13, 54%), bilateral (n = 8/13, 62%), and had median SUVmax 8.2 (n = 10, IQR 6.9-12.65). Seven patients had malignancy confirmed on tissue biopsy: five biopsies confirmed the tissue diagnosis of suspected lymphoma, and two incidental findings of unexpected malignancies: one p16 positive tonsillar squamous cell carcinoma, and one metastatic breast cancer. In 31 patients undergoing tissue biopsy for incidental PET-avid oropharyngeal lesions, there were two unexpected malignancies. Our study results indicate that although unexpected malignancies are uncommon, a malignant diagnosis cannot be excluded from clinical features alone.

Clinicopathological Profile of Sinonasal Masses in a Tertiary Care Center in Central India: A Retrospective Study.

Diseases of the nose and paranasal sinuses have a significant impact on the patient's functional and structural aspects. They affect all age groups and both sexes. Due to its proximity to vital structures, diseases of the nose and paranasal sinuses sometimes lead to very grave prognoses. This was a retrospective study done in one of central India's largest tertiary care centers. We studied 227 cases of sinonasal masses in both the non-neoplastic and neoplastic categories. Clinicopathological characteristics of masses were analyzed with the help of clinical and imaging findings and subsequently confirmed by tissue diagnosis. The mean age of presentation was 45.5 years, with a male-to-female ratio of 1.25:1. Most of our patients were from lower-middle socioeconomic groups with educational qualifications below the 10th standard. Nasal obstruction was the most common symptom. A computed tomography scan was the preferred radiological investigation. Sinonasal undifferentiated carcinoma was the most common variant of malignancy, with a total number of six out of 22 (27%). The evaluation of sinonasal masses should be carried out systematically and meticulously. Since the initial presentation of most of the diseases of the nose and paranasal sinuses is the same, a proper clinical, radiological, and tissue diagnosis should be carried out to avoid causing malignant lesions.

Significance of Histopathology of Appendectomy Specimens: Analysis From a Teaching Hospital of Pakistan.

Background Histopathology of a tissue specimen plays a crucial role in formulating the final diagnosis of any disease. It confirms whether the histopathological findings are in correspondence with the clinical diagnosis and thus suggests an optimal management plan. Standard surgical practices guide that every human tissue specimen must undergo postoperative tissue analysis unless indicated otherwise. Objective To determine the significance of histopathology in determining the final diagnosis of appendectomy specimens. Materials and methods This retrospectiveclinical studyconducted in May 2022 included 100 patients operated for appendectomy from January 1, 2021, to December 31, 2021, in the emergency room of the Department of General Surgery, Unit-III, Lahore General Hospital, Lahore. Data were retrieved from patients' records and the picture archiving and communication system (PACS). A Google Forms-based pro forma(Google, Mountain View, CA) was generated to include the demographic details, clinical manifestations, and histopathology reports of the patients. Descriptive analysis was completed using a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA). Results Fifty-two patients were females out of the total 100. The mean age at presentation was 23.02 ± 12.02 years. Of the samples, 54% were not sent for histopathology. Among the remaining ones, 27% of cases were proven to be acute appendicitis. Alvarado score was 7-10 in 50% of patients. Other lesions proven by histopathology were appendiceal phlegmon (4%), perforated appendix (4%), mucocele (1%), carcinoid tumor (1%), tuberculosis (1%), and adenocarcinoma (1%). Conclusions Histopathological analysis is the gold standard for the tissue diagnosis of a disease. The high percentage of the samples not sent for histopathology is alarmingsince the appendix is not only a site for inflammatory pathologies but for neoplastic lesions as well. This practice depicts that the incidence of non-inflammatory pathologies is being ignored by healthcare professionals and there is a dire need to emphasize the significance of acquiring histopathology reports for the specimens of appendectomy in all circumstances.

Detection of Circulating Tumor DNA After Stereotactic Ablative Radiotherapy in Patients With Unbiopsied Lung Tumors (SABR-DETECT)

For patients with stage I/IIA non–small-cell lung cancer (NSCLC), surgical resection is the standard treatment. However, some of these patients are not candidates for surgery or refuse a surgical option. Definitive stereotactic ablative radiotherapy (SABR) is a standard approach in these patients. Approximately 15% of patients undergoing SABR for localized NSCLC will experience a recurrence within 2 years. Furthermore, many of these patients are deemed appropriate for SABR without a tissue diagnosis, based on the likelihood of malignancy which can be calculated by validated models. A liquid biopsy, detecting ctDNA, would be useful in early detection of recurrences, and documenting a cancer diagnosis in patients without a biopsy. This is a multi-institutional study enrolling patients with suspected stage I/IIA NSCLC and a pretreatment likelihood of malignancy of ≥60% using the validated models for patients without a tissue diagnosis, in cohort 1 (n = 45). The second cohort will consist of biopsied patients (n = 30-60). SABR will be delivered as per risk-adapted protocol. Plasma will be collected for ctDNA analysis prior to the first fraction of SABR, 24 to 72 hours after first fraction, and at 3, 6, 9, 12, 18, and 24-months. The patients will be followed up with imaging at 3, 6, 9, 12, 18, and 24-months. The primary objective is to assess whether a cancer detection liquid biopsy platform can predict recurrence of NSCLC. The secondary objectives are to assess the impact of SABR on detection rates of ctDNA in patients undergoing SABR and to correlate ctDNA positivity and pretreatment probability of malignancy (NCT05921474).

Spectroscopy of Testicular Tissues as a Tool for Azoospermia Visualization During Micro-TESE and IVF: a Feasibility Study

Non-obstructive azoospermia observed in 10% of infertile men and 0,6% of all men is the most severe form of male infertility. The histological structure of testicular tissue in patients with non-obstructive azoospermia is heterogeneous and is represented by various disorders of spermatogenesis. The only way to achieve pregnancy in the families of patients with non-obstructive azoospermia is the method of in vitro fertilization with intracellular sperm injection. The most effective method of detecting spermatozoa suitable for in vitro fertilization in testicles is the micro-TESE method. It is based on a subjective visual assessment of tissues and allows detecting spermatozoa in non-obstructive azoospermia only in 38-60% of cases. To increase the effectiveness of micro-TESE, the method used must be objective, high-specific, safe for reproductive cells, and also implemented during the operation in real time. The existing approaches to solving the problem of identifying seminal tubules with preserved spermatogenesis, such as multiphoton microscope, Raman spectroscopy, optical coherence tomography and etc., are either associated with the use of laser radiation with unproven safety or cannot be implemented intraoperatively and operationally. The paper considers the possibility of creating a specialized microsurgical system for intraoperative evaluation of testicular tissues histological structure using the spatial distribution of its spectral characteristics. We proposed to implement such a system based on multispectral imaging of the studied tissues with real-time data processing and displaying the results using augmented reality methods. The reflectance spectrum of testicular tissue with varying degrees of preservation of spermatogenesis in the visible and near infrared spectral ranges was studied. Spectral regions were identified that potentially provide the best differentiation of healthy tissues and tissues with impaired spermatogenesis. The described approach can be implemented intraoperatively and safely and may serve to automate and objectify the diagnosis of testicular tissues in micro-TESE.

Label- and slide-free tissue histology using 3D epi-mode quantitative phase imaging and virtual hematoxylin and eosin staining.

Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical assessment of tissue. However, the typical formalin-fixation, paraffin-embedding (FFPE) process is laborious and time consuming, often limiting its usage in time-sensitive applications such as surgical margin assessment. To address these challenges, we combine an emerging 3D quantitative phase imaging technology, termed quantitative oblique back illumination microscopy (qOBM), with an unsupervised generative adversarial network pipeline to map qOBM phase images of unaltered thick tissues (i.e., label- and slide-free) to virtually stained H&E-like (vH&E) images. We demonstrate that the approach achieves high-fidelity conversions to H&E with subcellular detail using fresh tissue specimens from mouse liver, rat gliosarcoma, and human gliomas. We also show that the framework directly enables additional capabilities such as H&E-like contrast for volumetric imaging. The quality and fidelity of the vH&E images are validated using both a neural network classifier trained on real H&E images and tested on virtual H&E images, and a user study with neuropathologists. Given its simple and low-cost embodiment and ability to provide real-time feedback in vivo, this deep-learning-enabled qOBM approach could enable new workflows for histopathology with the potential to significantly save time, labor, and costs in cancer screening, detection, treatment guidance, and more.

JAMES LIND ALLIANCE FIRST TIME SOFT TISSUE KNEE INJURIES PRIORITY SETTING PARTNERSHIP: TOP TEN RESEARCH PRIORITIES

IntroductionThe knee is the most commonly injured joint in sporting accidents, leading to substantial disability, time off work and morbidity (1). Treatment and assessment vary around the UK (2), whilst there remains a limited number of high-quality randomised controlled trials assessing first time, acute soft tissue knee injuries (3,4). As the clinical and financial burden rises (5), vital answers are required to improve prevention, diagnosis, treatment, rehabilitation, and delivery of care. In association with the James Lind Alliance, this BASK, BOSTAA and BOA supported prioritising exercise was undertaken over a year.MethodsThe James Lind Alliance methodology was followed; a modified nominal group technique was used in the final workshop. An initial survey invited patients and healthcare professionals to submit their uncertainties regarding soft tissue knee injury prevention, diagnosis, treatment, rehabilitation, and delivery of care. Seventy-four questions were formulated to encompass common concerns. These were checked against best available evidence. Following the interim survey, 27 questions were taken forward to the final workshop in January 2023, where they were discussed, ranked, and scored in multiple rounds of prioritisation by groups of healthcare professionals, patients, and carers.ResultsOver 1000 questions were submitted initially. Twenty-seven were taken forward to the final workshop following the surveys. Nearly half of the responses were from patients/carers. The Top 10 (Figure 1) includes prevention, diagnosis, treatment, and rehabilitation questions, reflecting the concerns of patients, carers, and a wider multidisciplinary team.ConclusionThis validated process has generated an important, wide- ranging Top 10 priorities for future soft tissue knee injury research. These have been submitted to the National Institute for Health and Care Research and are now available for researchers to investigate. The final 27 questions which were taken to the final workshop have also been published on the James Lind Alliance website. Research into these questions will lead to future high-quality research, thus improving patient care & outcomes.For any figures or tables, please contact authors directly.

Abstract A113: National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary

Abstract Introduction: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and genomic characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created in July 2020 in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate the diagnostic, prognostic and therapeutic impact of this NatCUPMTB after 30 months of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between July 2020 and January 2023 were included. Pts and tumors characteristics, pathological and genomic analyses including WGS, WES and transcriptome analysis performed on the two PFMG2025 (French Genomic Medecine Plan 2025) national sequencing laboratories, multidisciplinary tumor board (MTB) conclusions, and follow-up after MTB were collected. Results: 151 pts were included. The median age at diagnosis was 58 yo, 55% were female, and the majority of patients had an OMS status <2. The median number of metastatic sites at diagnosis was 2, with a majority located in the lymph nodes (63%). The median time between diagnosis and first MTB presentation was 4 months (1-20). At the time of analysis, NatCUPMTB conclusions and long-term follow up (30 months) were available for 93 pts alive at the second MTB presentation. MTB investigations enabled to identify a likely primary origin in 62/93 (67%) pts, the most frequent being renal carcinoma (N=10), lung carcinoma (N=9) and breast carcinoma (N=8). The most frequently molecular alterations found were in TP53 (37%), KRAS (19%), CDKN2A (18%), NF2 (12%), KMT2C (10%), CDKN2B (9%), PBRM1 (9%) genes. MTB diagnoses were based on the combination of clinical, pathological and genomic investigations in 34/93 (37%) of pts. The others were based on pathological and genomic investigations in 15/93 pts (16%), genomic in 4/93 pts (4%), clinical and genomic in 3/93 pts (3%), clinical and pathological in 3/93 pts (3%) and pathological in 3/93 pts (3%). After a median follow-up of 11.2 months, the median overall survival (OS) was 11.9 months from the 2nd MTB presentation. Importantly, a personalized therapeutic strategy was recommended by NatCUPMTB in 79/93 (85%) of pts. Among these recommendations, 38/79 (49%) were based on the diagnosis of tissue of origin (TOO), 12/79 (15%) on an actionable molecular alteration, 24/79 (30%) on both the TOO and an actionable molecular alteration, and 5/79 (6%) were based on an unguided clinical trial. Conclusion: NatCUPMTB provides significant diagnostic and therapeutic benefit in 85% of pts with CUP. Early presentation of pts at NatCUPMTB as soon as CUP diagnosis is suspected should be recommended. Citation Format: Ivan Bieche, Maud Kamal, Nicolas Jacquin, Célia Dupain, Isabelle Guillou, Etienne Rouleau, Julien Masliah Planchon, Isabelle Soubeyran, Christelle De La Fouchardière, Camille Tlemsani, Hélène Blons, Laëtitia Marisa, Anna Patrikidou, Fabienne Escande, Pierre Blanc, Jennifer Wong, Pierre Saintigny, Sandrine Boyault, Adrien Buisson, Yves Allory, Anne Vincent-Salomon, Vincent Cockenpot, Janick Selves, Christophe Le Tourneau, Sarah Watson. National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A113.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Revealing the inhibitory effect of VASH1 on ovarian cancer from multiple perspectives

ABSTRACT The function of Vasohibin-1 (VASH1) in human cancer has not been thoroughly or comprehensively examined. Here, we identified the tumor suppressor part of VASH1 across cancers, including epithelial ovarian tumors. Our study carefully contrasted the expression of VASH1 in pancancer and nontumorous tissues in a public database to explore its regulatory role in clinical prognosis, diagnosis, tumor purity, and immune cell infiltration. Next, we explored the antitumor mechanism of VASH1 through drug sensitivity, functional enrichment, and phenotypic experiments in ovarian cancer. Research suggests that the expression of VASH1 in neoplastic tissues is lower than that in normal tissues. VASH1 affects the OS and RFS of several tumor types. In addition, VASH1 expression resulted in a high OS and RFS in the diagnosis of tumor and nontumor tissues and negatively regulated tumor purity. Moreover, VASH1 controls the tumor microenvironment by regulating immunocyte infiltration. In ovarian cancer, VASH1 can serve as a biomarker to estimate the efficacy of chemotherapy. Functional enrichment analysis suggests that VASH1 plays a tumor suppressor role by regulating the extracellular matrix receptor pathway. VASH1 inhibition of the malignant phenotype of ovarian cancer cells was further confirmed by in vivo experiments. These results indicate that VASH1 acts as a cancer-inhibiting factor and potential therapeutic target in ovarian cancer.

Image-guided core-needle or surgical biopsy for neuroblastoma diagnosis in children: A systematic review and meta-analysis from the International Society of Pediatric Surgical Oncology (IPSO).

Image-guided core-needle biopsy (IGCNB) is a widely used and valuable clinical tool for tissue diagnosis of pediatric neuroblastoma. However, open surgical biopsy remains common practice even if children undergo more invasive and painful procedures. This review aims to determine the diagnostic accuracy and safety of IGCNBs in pediatric patients with neuroblastoma. We conducted a systematic review of peer-reviewed original articles published between 1980 and 2023, by searching "pediatric oncology," "biopsy," "interventional radiology," and "neuroblastoma." Exclusion criteria were patients older than 18years, studies concerning non-neurogenic tumors, case reports, and language other than English. Both the systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 533 abstracts articles were analyzed. Of these, eight retrospective studies met inclusion criteria (490 infants, 270 surgical biopsies [SB], 220 image-guided biopsies). Tissue adequacy for primary diagnosis (SB: n=265, 98%; IGCNB: n=199, 90%; p=.1) and biological characterization (SB: n=186, 95%; IGCNB: n=109, 89%; p=.15) was similar with both biopsy techniques, while intraoperative transfusion rate (SB: n=51, 22%; IGCNB: n=12, 6%; p=.0002) and complications (%) (SB: n=58, 21%; IGCNB: n=14, 6%; p=.005) were higher with surgical biopsy. Length of stay was similar in both groups; however, no additional data about concurrent diagnostic or treatment procedures were available in the analyzed studies. IGCNB is a safe and effective strategic approach for diagnostic workup of NB and should be considered in preferance to SB wherever possible.

Expression of Ki-67 and E-cadherin in patients with non-small cell lung cancer attending a tertiary care hospital

Background: E-cadherin and Ki-67 expressions may provide real-time insights into the tumor's status and can be utilized as targeted therapeutics for lung cancer. We aimed to explore the expression of Ki-67 and E-cadherin in non-small cell lung cancer (NSCLC) patients and to identify their association with clinicopathological features. Methods: In this cross-sectional study, forty formalin-fixed paraffin-embedded (FFPE) NSCLC tissue blocks were identified from January to October 2022, based on hospital records from the Department of Pathology of National Institute of Diseases of the Chest and Hospital, Dhaka Medical College and Hospital. Samples were reevaluated for tissue quality, diagnosis, and exclusion-inclusion criteria. Finally, twenty-five samples were analyzed, and relevant clinicopathological data were collected from patients or authorized representatives. Ki-67 and E-cadherin expression were analyzed by immunohistochemistry and their relationships with each other. Results: Ki-67 expression was positive in 40% of the NSCLC tissue, and E-cadherin was negative in 40% of the NSCLC tissue. No statistically significant relation was found between the expressions of Ki-67 and E-cadherin. No statistically significant association was found in Ki-67 and E-cadherin expressions with clinicopathological characteristics except E-cadherin with comorbidity. Conclusion: Positive expression of Ki-67 and negative expression of E-cadherin was found in two-fifths of NSCLC tissues but not significant. Simultaneous estimated of Ki-67 and E-cadherin may contribute to the treatment planning and predict prognosis of the NSCLC patients.