Neoplastic Lesions Research Articles

Screening for colorectal cancer by full colonoscopy in first-degree relatives of colorectal cancer patients: a multicentric study by the Italian League for the Fight against Cancer.

Colorectal cancer currently presents the third-highest incidence of cancers worldwide, making secondary prevention through screening programs for colorectal cancer, usually by Fecal Occult Blood Testing, an essential preventive medicine intervention. First-degree relatives of colorectal cancer patients are a particularly at-risk group, with indications to consider direct screening by full colonoscopy. Colonoscopy is considered the gold standard for diagnosing colorectal cancer, as it has high sensitivity and specificity, and is both a diagnostic and therapeutic tool. However, it requires significant organizational and financial resources, and has a small but relatively higher risk of complications as opposed to fecal occult blood testing. The present study aimed to assess the appropriateness of a screening program without age restrictions of CRC by full colonoscopy in asymptomatic, first-degree adult relatives of patients with colorectal cancer, aiming both to actively increase screening coverage and to determine the detection rate of precancerous lesions and colorectal cancer in this population. Uncontrolled interventional study - colorectal cancer screening by full colonoscopy for at-risk population. The Italian League for the Fight against Cancer started a colorectal cancer screening program by full colonoscopy for first-degree relatives of colorectal cancer patients in 1998 in the province of Latina, Lazio Region, Italy. The program was expanded to the provinces of Rieti, Lazio Region, and Sassari, Sardinia Region, in 2014 and 2016 respectively, and was concluded in 2018. Subjects were actively and voluntarily recruited by the study's working group. Subjects that had already been subjected to a full colonoscopy in the preceding 5 years were excluded from this study. Identified neoplastic lesions were treated either directly or referred to the Day Hospital setting, and histologically diagnosed following World Health Organization guidelines. In total, 2,288 subjects (age range 15-88, mean 52.3 yrs, M/F = 946/1,204) were screened by colonoscopy, of which 103 (4.5%) were incomplete and 2,173 (95.0%) complete, with data on colonoscopy performance missing for 12 participants. Out of 468 positive outcomes on colonoscopy, diagnosis for 422 (204M/173F), 19.4% of total subjects, was adenomatous polyps and 46 (20M/20F), 2.1% of total subjects, was colorectal cancer. Female sex was a protective factor against a positive test outcome, with a 35% reduction compared to male sex, with OR=0.64 95%CI (0.52-0.80). On the other hand, being over 50 years of age was found to be a risk factor, making a positive outcome more than twice as likely, with OR=2.3 95%CI (1.8-2.9). Subjects over 50 also had significantly more instances of multiple adenomas being found, however the size distribution of found adenomas was not significantly different between subjects under and over 50, despite size being a predictor of risk of neoplastic progression. Given the high detection rate of precancerous lesions and colorectal cancer in the studied population, it is our opinion that guidelines should continue to recommend earlier and more frequent screening in first-degree relatives of patients with colorectal cancer, and, barring the introduction of more cost-effective and/or lower risk procedures with a similar efficacy profile, maintain the use of colonoscopy as the main screening option.

Histopathological spectrum of endometrial biopsies in abnormal uterine bleeding at tertiary care centre, Jodhpur

Introduction: Abnormal uterine bleeding (AUB) shows spectrum of patterns on histopathology and pathologist plays a vital role in reporting of endometrial biopsies and helps in differentiating nonneoplastic lesion from neoplastic lesions, early detection of the precursor lesions and exclusion of malignancy. Aim - The aim of this study is to study the spectrum of endometrial patterns in women with AUB and to correlate it with the different age groups. Materials and Methods: 200 samples of endometrial biopsies with AUB were received from the gynecology department, processed and stained with hematoxylin & eosin and subjected to histopathological examination. Results: The peak incidence is observed in the age group of 41-50 years. The predominant histological pattern observed is secretory and proliferative pattern and disordered endometrium (68%) followed by endometrial hyperplasia (10%) and the least common pattern is atrophic endometrium (1%). 2% cases are of endometrial carcinoma found in our study. Conclusion: AUB significantly affects the quality life of women and leads to anemia. Hence histopathological examination should be considered which plays a critical role in early diagnosis of endometrial pathology and to provide appropriate gynecological management. Endometrial sampling is an effective diagnostic tool and it needs to be considered in all patients from peri- and post-menopausal age groups with AUB so to provide appropriate management.

Enhancing the referral process for surgical management of spinal metastases: insights from a 12-year, bi-institutional study of 533 patients.

Delayed surgical management of spinal metastases (SMs) can have detrimental effects on patient survival and quality of life, leading to pain and potential neurological impairment. This study aimed to assess the impact of delayed referral for SMs on clinical outcomes by analyzing patients managed in emergency situations. We retrospectively reviewed the data of all patients admitted on either emergency or elective basis who underwent surgery for the treatment of neoplastic spine lesions at our two institutions (tertiary referral neurosurgical units) between January 2008 and December 2019. We analyzed 210 elective (EGp) and 323 emergency patients (UGp); emergencies increased significantly over the 12-year period, with a Friday peak (39.3%) and frequent neurological impairment (61.6% vs. 20%). Among the UGp patients, 186 (7.5%) had a previously monitored primitive cancer, including 102 (31.6%) with known SMs. On admission, 71 of the 102 (69.9%) patients presented with neurological deficits. UGp patients were more likely to undergo a single decompression without fixation. Outcomes at the 3-month follow-up were significantly worse for UGp patients ([very] poor, 29.2 vs. 13.8%), and the median overall survival for UGp patients was statistically lower. Risk factors for patients with SM undergoing emergency management included short delay between onset of symptoms and first contact with a spine surgeon, and an initial motor deficit. Many patients with previously identified metastases, including those with neurological deficits, are urgently referred. Optimization is needed in the oncology pathway, and all stakeholders must be made aware of the factors contributing to the improvement in the clinical and radiological identification of potential complications affecting patient survival and quality of life.

Peptidic heterodimer-based radiotracer targeting fibroblast activation protein and integrin αvβ3.

Several studies have demonstrated the advantages of heterodimers over their corresponding monomers due to the multivalency effect. This effect leads to an increased number of effective targeted receptors and, consequently, improved tumor uptake. Fibroblast activation protein (FAP) and integrin αvβ3 are found to be overexpressed in different components of the tumor microenvironment. In our pursuit of enhancing tumor uptake and retention, we designed and developed a novel peptidic heterodimer that synergistically targets both FAP and integrin αvβ3. FAP-RGD was synthesized from FAP-2286 and c(RGDfK) through a multi-step organic synthesis. The dual receptor binding property of 68Ga-FAP-RGD was investigated by cell uptake and competitive binding assays. Preclinical pharmacokinetics were determined in HT1080-FAP and U87MG tumor models using micro-positron emission tomography/computed tomography (micro-PET/CT) and biodistribution studies. The antitumor efficacy of 177Lu-FAP-RGD was assessed in U87MG tumor models. The radiation exposure and clinical diagnostic performance of 68Ga-FAP-RGD were evaluated in healthy volunteers and cancer patients. Bi-specific radiotracer 68Ga-FAP-RGD exhibited high binding affinity for both FAP and integrin αvβ3. In comparison to 68Ga-FAP-2286 and 68Ga-RGDfK, 68Ga-FAP-RGD displayed enhanced tumor uptake and longer tumor retention time in preclinical models. 177Lu-FAP-RGD could efficiently suppress the growth of U87MG tumor in vivo when applied at an activity of 18.5 and 29.6MBq. The effective dose of 68Ga-FAP-RGD was 1.06 × 10-2mSv/MBq. 68Ga-FAP-RGD demonstrated low background activity and stable accumulation in most neoplastic lesions up to 3h. Taking the advantages of multivalency effect, the bi-specific radiotracer 68Ga-FAP-RGD showed superior tumor uptake and retention compared to its corresponding monomers. Preclinical studies with 68Ga- or 177Lu-labeled FAP-RGD showed favorable image contrast and effective antitumor responses. Despite the excellent performance of 68Ga-FAP-RGD in clinical diagnosis, experimental efforts are currently underway to optimize the structure of FAP-RGD to increase its potential for clinical application in endoradiotherapy.

Acute amnestic syndrome in fornix lesions: a systematic review of reported cases with a focus on differential diagnosis

IntroductionAcute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff and transient global amnesia (TGA). Structural lesions of the fornix account for a minority of cases of acute amnestic syndromes. Etiology varies from iatrogenic injury to ischemic, inflammatory, or neoplastic lesions. A prompt diagnosis of the underlying pathology is essential but challenging. The aim of this review is to systematically review the existing literature regarding cases of acute amnestic syndrome associated with non-iatrogenic lesions of the fornix.MethodsWe performed a systematic literature search on PubMed, Scopus, and Web of Science up to September 2023 to identify case reports and case series of patients with amnestic syndrome due to fornix lesions. The systematic review was conducted according to PRISMA guidelines. The research was limited to articles written in English. Cases of fornix damage directly ascribable to a surgical procedure were excluded.ResultsA total of 52 publications reporting 55 cases were included in the review. Focusing on acute/subacute onset, vascular etiology was highly prevalent, being responsible for 78% of cases, 40/55 (74%) of which were due to acute ischemic stroke. The amnestic syndrome was characterized by anterograde amnesia in all patients, associated with retrograde amnesia in 27% of cases. Amnesia was an isolated presentation in most cases. Up to two thirds of patients had persistent memory deficits of any severity at follow-up.DiscussionAcute amnestic syndrome can be rarely caused by fornix lesions. In most cases of acute/subacute presentation, the etiology is ischemic stroke, mainly caused by strokes involving the subcallosal artery territory. The differential diagnosis is challenging and a distinction from common mimics is often difficult on a clinical basis. A high index of suspicion should be maintained to avoid misdiagnosis and provide adequate acute treatment to patients with time-dependent disease, also employing advanced neuroimaging. More research is needed to better understand the outcome and identify prognostic factors in patients with amnestic syndrome due to fornix lesions.

Endoscopic Evaluation of the Ileal Pouch.

Structural and inflammatory adverse sequelae are common after restorative proctocolectomy and IPAA. On rare occasions, neoplasia can occur in patients with ileal pouches. Pouchoscopy plays a key role in the diagnosis, differential diagnosis, disease monitoring, assessment of treatment response, surveillance, and delivery of therapy. A systematic review of the literature was performed, and principles and techniques of pouchoscopy were described. PubMed, Google Scholar, and Cochrane databases. Relevant articles on endoscopy in ileal pouches published between January 2000 and May 2023 were included based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnostic, surveillance, and therapeutic endoscopy in ileal pouch disorders were included. Accurate characterization of the ileal pouch in healthy or diseased states. The main anatomic structures of a J- or S-pouch are the stoma closure site, prepouch ileum, inlet, tip of the "J," pouch body, anastomosis, cuff, and anal transition zone. Each anatomic location can be prone to the development of structural, inflammatory, or neoplastic disorders. For example, ulcers and strictures are common at the stoma closure site, inlet, and anastomosis. Leaks are commonly detected at the tip of the "J" and anastomosis. Characterization of the anastomotic distribution of inflammation is critical for the differential diagnosis of subtypes of pouchitis and other inflammatory disorders of the pouch. Neoplastic lesions, albeit rare, mainly occur at the cuff, anal transition zone, or anastomosis. This is a qualitative, not quantitative, review of mainly case series. Most structural, inflammatory, and neoplastic disorders can be reliably diagnosed with a careful pouchoscopy. The endoscopist and other clinicians taking care of pouch patients should be familiar with the anatomy of the ileal pouch and be able to recognize common abnormalities. See video from symposium.

P215 Mir-135b, an Early Biomarker of Sporadic and IBD-Related Colorectal Carcinogenetic Progression

Abstract Background Although the rates of IBD-related-CRC are decreasing over time, CRC is still a leading cause of mortality and reason for colectomy in patients with IBD. Among the different cancer biomarkers, microRNAs (miRs) have emerged as noninvasive tools for diagnosis, monitoring, and prognosis in tissues and biofluids of patients with IBD. Therefore, we aimed to investigate the role of miRs in the development and natural course of IBD-related CRC, in order to identify potential early biomarkers for IBD-related CRC screening and progression. Methods The cases were retrospectively collected from the archives of the Surgical Pathology and Cytopathology Unit at the University of Padua. We analysed 9 miRs in colonic tissue specimens of IBD patients with adenoma or dysplasia, with IBD related-CRC, other than 2 control groups of patients with sporadic CRC and of healthy subjects (HC). In addition, we included tissue samples from a colonoscopy that patients with IBD with adenoma or dysplasia underwent some years before the development of mucosal lesions (from 2 to 5 years before), therefore without evidence of adenoma or dysplasia. Results were analyzed with ThermoFisher Connected™ Software and a p-value < 0.05 was considered significant. Results Compared to HC, all nine analysed miRs were significantly up-regulated in patients with sCRC, with IBD-related CRC and in IBD patients with adenoma. While, only 3 miRs (miR-135b, mir-21, miR-224) were significantly upregulated in IBD patients with dysplasia (and in their own controls) compared to HC (p<0.0001). Notably, no differences in miRs expression levels were found in patients with IBD-related CRC compared to those found in patients with sCRC. Among all miRs analyzed, only miR-135b and miR-21 resulted significantly up-regulated in patients with IBD. Considering the levels of miR-135b in the tissue samples of IBD patients, we observed an evident increasing trend going from tissue specimens without lesions to those with adenoma or dysplasia and then to those with neoplastic lesions. miR-21 was significantly upregulated in patients with IBD-related CRC compared to both IBD patients with adenoma and their own control samples from a previous negative colonoscopy (p=0.003 and p=0.006, respectively). Likewise, a significant difference in miR-21 levels was observed between patients with IBD-related CRC and those with dysplasia (p=0.02). Conclusion miR-21 and miR-135b are involved in the carcinogenesis process of patients with IBD. They could be potential candidate biomarkers for diagnostic purpose, prognostic and predictive stratification of patients.

Origin and survival outcomes of Pseudomyxoma peritonei-A retrospective study.

Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin material-rich ascites. It was first described by Werth in 1884. Ever since, its clinical presentation, definition, site of origin, and prognosis have been a subject of debate. However, many histopathologic, immunohistochemical, and genetic studies have attempted to locate the primary lesion in the appendix in both genders. To analyze the histological origin and survival outcomes of pseudomyxoma peritonei in patients treated at a regional cancer center. Fifteen cases of PMP were diagnosed during the five-year study period. The demographic and clinicopathological details were retrieved; the slides were reviewed and histological parameters reassessed. Descriptive statistics were used to express proportions. Continuous variables were recorded as mean (SD) or median (IQR). Kaplan-Meier (KM) curve was used to estimate overall survival. Mean age for PMP was found to be 47.5 years for low grade Mucinous Carcinoma Peritonei (MCP), 54.2 years for high grade MCP, and 58 years for high grade MCP with signet ring cells. Most common overall presentation was abdominal distension in 53.3% (8/15) of cases, followed by acute appendicitis in 20% (3/15) cases. PMP was detected synchronous with the primary tumor in 9/15 cases (60%). Primary lesion in the appendix was grossly identified in 7/15 cases, while it was not explored in the remaining eight cases. Yet, by combined clinical, radiological, histopathological, and immunohistochemical analysis, we identified that most of the cases (14/15) had an appendiceal origin (93.3%). The overall survival for 12 months was 50% and for 18 months was 37%. The surgeon and radiologist may well bear in mind the most common possibility of an appendiceal origin for PMP and resect the appendix, irrespective of the presence of a grossly or radiologically detectable lesions. We emphasize that immunohistochemistry helped to detect the site of origin even when the primary was occult.

Hyperplastic, dysplastic and neoplastic lesions associated with a model of carcinogenesis induced by DMBA in the salivary glands of BALB-c mice

The aim of this work was to develop a mouse model of submandibular salivary gland carcinogenesis by chemical induction and to perform a revision of the literature on similar models using the carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA). The descriptive review was carried out on published works in English and Spanish languages, from the period 1977-2023, which included different animal models of chemical carcinogenesis induced by DMBA in salivary glands. Articles were reviewed in order to analyze the effectiveness of the carcinogenesis induction. For our model, BALB/c mice were used. Animals were anesthetized and after surgery to expose the submandibular gland, each mouse was injected with solution of DMBA 2% in corn oil. Mice were monitored weekly until sacrifice at week 12. The samples were processed with the routine histological methods. The results from the descriptive review showed that DMBA is mainly administered by Intraglandular injections into the submandibular glands after surgical exposure, being both pellets and solutions used for the induction, and rats more common than mice. This revision summarizes the research results of previous studies and demonstrates which model has greater reproducibility. Our results showed that one single injection of DMBA directly into the surgically exposed submandibular gland was an optimal technique to induce the tumor at the desired site. Edema was observed in the surgical area during the first 2 weeks. From week 5, the mice presented internal hardness and hair loss in the glandular area; 50% of the animals presented palpable and measurable tumor masses from week 10. Microscopic observations showed that 89% of the mice developed malignant neoplasms: Carcinomas in situ, micro-invasive and invasive (6/8); sarcomas (1/8), and carcinosarcoma (1/8). Associated lesions were atypical ductal hyperplasia; periductal fibrosis, and sarcomatous stroma. This model marks a difference with the subcutaneous injection technique, without surgery, which does not allow the carcinogen to be adequately directed to the gland.

Abstract B068: Retrospective pilot study of a natural language processing model approach for earlier identification of patients with pancreas cancer

Abstract The traditional cancer paradigm, in which radiographic scan precedes biopsy which precedes diagnosis, has several limitations, but lack of patient identification prior to biopsy lies at the crux. Here we describe the results of our retrospective pilot study, in which we characterize the output of a natural language processing (NLP) model we utilized to review and flag radiology reports suspicious for pancreas cancer and demonstrate its potential for identification of patients with pancreas cancer at earlier points in the diagnostic framework. A RadBERT based NLP model was utilized to identify radiology reports suspicious for pancreas cancer that were generated within the Northwell Health system in January 2023. These outputs were then manually reviewed retrospectively and labelled as non-suspicious non-cystic, non-suspicious cystic, or suspicious non-cystic. For patients with suspicious non-cystic lesions, chart review was performed to determine whether these findings were indicative of a new pancreatic malignancy, and if so, whether the patient had received further care. Our NLP reviewed 17,339 radiology reports in January 2023 and identified 917 of these reports as suspicious for pancreas cancer, representing imaging from 852 patients across our health system. 38% of patients had normal or atypical but non-suspicious non-cystic lesions (322). 46% of patients had non-suspicious cystic lesions (389) and 17% of patients had suspicious non-cystic lesions suspicious for a primary pancreatic neoplasm (149); 10 of these reports observed simultaneous cystic and neoplastic pancreas lesions. Of the patients with suspected neoplastic lesions, 55% had been previously diagnosed with pancreas cancer. 45% were new diagnoses and upon chart review, of these, only 36% underwent biopsy in our health system with an average of 22 days between radiology report and biopsy while 30% were seen by an outpatient oncologist within our health system with an average of 32 days between radiology report and visit. 64% did not proceed to further workup in our health system with 35% for whom further workup was not recommended, 19% who elected against further workup, 23% who were scheduled for internal follow-up that did not occur, and 23% who were scheduled for external follow-up. Notably, when compared to the January outputs of other cohort building tools, NLP identified 67 new patients with pancreas cancer, while pathology report identified 15, ICD10 problem list identified 17, and cancer registry identified 13. Our NLP approach identified the greatest proportion of patients with newly diagnosed pancreas cancer compared to traditional identification measures and of these patients identified by our model, in the context of the traditional cancer care paradigm, only 1/3 proceeded to further workup within our health system before facing a striking nearly month of lead-time between radiology report and biopsy/outpatient oncology visit. We are now working to leverage this model to prospectively identify and navigate patients identified by NLP to address this gap in real-time. Citation Format: Kristen M. John, Anthony Carvino, Shama Khan, Ellen Chen, Deepak Saluja, Matthew Barish, Daniel A. King. Retrospective pilot study of a natural language processing model approach for earlier identification of patients with pancreas cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B068.

Inter-Sphincteric Resection of Rectum for Ulcerated S-100 Negative Large Granular Cell Tumour

Non-neural granular cell tumor was first described in 1991 as an unusual primitive, polypoid variant of the conventional GCT (granular cell tumor). To date, this neoplasm remains as a rare entity and the cell of origin is uncertain. While the histological features are similar to the conventional (traditional) GCTs, it represents a distinct entity, as it is negative for S-100 and lacks true nerve sheath differentiation. We report here a case of a 49-year-old male patient with S-100 negative, vimentin positive large benign, ulcerated, bleeding non-neural GCT in the lower rectum. We confirmed the diagnosis histopathologically and immunohistochemically. We treated it by ISRR (Inter-Sphincteric Resection of Rectum) and primary colo-anal anastomosis. We find no other report of non-neural GCT located in the rectum in surgical literature. This is probably the first case of non-neural GCT identified in the rectum. This case report is presented here to document a non-neural GCT located in the rectum for the first time ever reported, and also to highlight the optimum best surgical approach, as we deemed here for this large ulcerated bleeding tumor in the rectum. This rectal non-neural GCT posed here as an unusual differential diagnosis from such more common neoplastic bleeding lesions in the rectum as carcinoma rectum, hemorrhoid, rectal polyp, etc. Here we like to discuss our experience, reviewing in brief the available literature implicating the biological behavior, histopathological and immunohistochemical features, differential diagnosis and therapeutic considerations of neural and non-neural GCTs. KYAMC Journal Volume: 14, No: 03, October 2023: 181-187.

Abstract A055: Context-dependent role of acid sphingomyelinase in pancreatic ductal adenocarcinoma

Abstract Sphingolipids, a class of lipids that includes the bioactive molecules ceramide and sphingosine-1-phosphate (S1P), play a contrasting role in the regulation of cancer cell death and survival. Acid sphingomyelinase (SMPD1) is the key enzyme that breaks down sphingomyelin into ceramide, accounting for more than 50% of the cellular ceramide supply and influencing the development of cancer. Here, we studied the role of SMPD1 in different cellular compartments during pancreatic ductal adenocarcinoma (PDAC) carcinogenesis. We performed a targeted quantitative plasma metabolite analysis of 637 patients (PDAC, 356; nonpancreatic disease, 281). We completed the IHC multiplex staining in the TMA of 124 patients with PDAC. Using CRISPR-Cas9 gene editing, SMPD1 was deleted in PDAC cell lines. The influence of SMPD1-KO on proliferation, colony formation, and migration was studied. Tumor progression and carcinogenesis was monitored in an orthotopic PDAC model and metastasis models using SMPD1 null cells, as well as in KC and KPC mice. Plasma metabolite analysis of 637 patients (PDAC, 356; nonpancreatic disease, 281) revealed the most pronounced changes in the group of complex lipids with the highest prevalence of sphingomyelins and ceramides. Overall survival was significantly correlated with high SMPD1 expression in tumor tissue in two independent cohorts. Interestingly, IHC multiplex analysis of SMPD1 'high expression' in cancer cells was associated with poorer survival, while SMPD1 'high expression' in immune cells was associated with longer overall survival. Expression level of Smpd1 differed from preneoplastic to neoplastic lesions in PDAC mouse tissue. Smpd1-KO in PDAC cell lines resulted in decreased proliferation, colony formation, and migration. In an orthotopic mouse model, Smpd1-KO clones resulted in significantly lower tumor weight and size compared to WT clones. Furthermore, the injection of WT clones into global Smpd1het-KO mice resulted in a significant increase in tumor weight compared to the injection of WT clones into WT mice. In two different metastasis models, injecting Smpd1-KO led to a significantly reduced formation of metastases in the lung and liver compared to WT clones. Interestingly, injecting WT clones into global Smpd1het-KO mice resulted in a significant decrease in metastasis formation in the lung compared to the injection of WT clones into WT mice. In general, we show a significant increase in survival in an orthotopic PDAC model using PDAC Smpd1-KO cells. In conclusion, SMPD1 has a context-dependent role in cancer cells and immune cells in PDAC. Inhibition of SMPD1 specifically in cancer cells is a viable therapeutic option, which should be explored in future studies. Citation Format: Ahmed Alnatsha, Qi Li, Klea Ricku, Prince Allawadhi, Jianying Xu, Didem Saka, Theresa Weltermann, Quan Zhaou, Nicole Schreiner, Kirsten Lauber, Ivonne Regel, Ujjwal Mukund Mahajan, Julia Mayerle. Context-dependent role of acid sphingomyelinase in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A055.

Abstract B113: Characterization of the epigenomic landscape of the human pancreas and early pancreatic neoplastic lesions

Abstract Study of early pancreas neoplasia in humans had previously been limited by lack of available tissue. Recent work by our group on deceased donor pancreata identified pancreatic intraepithelial neoplasia (PanIN) lesions in non-diseased organs and defined a transcriptomic signature for the microenvironment of these pre-cancerous lesions. Prevalence of PanINs in healthy human tissue was higher than expected and established a novel model to expand understanding of the complex biology of these precursor lesions. Epigenetic changes in chromatin structure and the subsequent effects on gene expression are essential processes in neoplasia that have yet to be described at the single cell level in the human pancreas. We hypothesized that characterization of the epigenomic landscape in donor pancreata would identify differences in chromatin structure and gene expression between healthy human tissue and PanINs, thereby expanding prior knowledge and identifying novel targets of study in the biology of early neoplasia in the pancreas. Single nuclei from five donor pancreata (six total samples including one replicate sample from a single donor pancreas) were isolated for transposase-accessible chromatin preparation followed by high-throughput sequencing (ATAC-seq) using the 10x Genomics platform. Data analysis was conducted using CellRanger, Seurat, Signac, and AUCell to identify and label chromatin peaks in individual nuclei corresponding to acinar, ductal, and PanIN origin according to gene signatures identified by scRNA on matched pancreata (Carpenter et al 2023, Cancer Discovery). Using this method, cells corresponding to these gene signatures, including PanIN-like cells, were indeed identified in preliminary analysis. Differentially accessible regions of the genome were then analyzed for motif enrichment between these cell types. Motifs enriched in cells identified as PanINs compared to either ductal or acinar cells included several transcription factors implicated in tumorigenesis, including members of the AP-1/Fos/Jun family and multiple zinc-finger protein family members, such as the KLF. These results are similar to previously demonstrated essential factors in pancreatic neoplasia. Differentially expressed motifs between ductal and acinar cells included factors associated with differentiation, including Myod1, Ptf1a, and the TCF family of transcription factors. Together, this study demonstrates that PanINs can be identified in human pancreas tissue by ATAC-seq and that differentially expressed motifs can be identified this model, providing opportunity for further integration with transcriptomic information to elucidate detailed understanding of early neoplasia in the pancreas. Citation Format: Jamie N. Mills, Joyce Thompson, Jacqueline Morales, Padma Kadiyala, Ahmed M. Elhossiny, Howard Crawford, Eileen Carpenter, Marina Pasca di Magliano, Filip Bednar, Simone Benitz. Characterization of the epigenomic landscape of the human pancreas and early pancreatic neoplastic lesions [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B113.

Spectrum of intestinal lesion: A clinicopathological study in a tertiary care centre

Intestine has wide spectrum of diseases comprising neoplastic and non-neoplastic lesions. Inflammatory bowel diseases are showing increasing trend and intestinal neoplasms are the most frequently observed and leading cause of death in India. This study aims to find the occurrence of various intestinal lesions, classify them as neoplastic and non-neoplastic and to correlate the histopathological findings with clinical profile of patient in tertiary care hospital of north India. 1129 biopsies and resection specimens of intestinal lesions were examined over a period of two years. Sections were fixed, paraffin embedded and stained by H&E. Immunohistochemistry was applied wherever required. Nearly two third patients were males in their second decade who presented with abdominal pain as the most common complaint and majority were diagnosed with non-neoplastic diseases. Among non-neoplastic lesions non-specific inflammation was predominant in small intestine (47.04% cases) and appendicitis (55.0%) in large intestine. Adenocarcinoma was predominant in both small and large intestine with 80.77% and79.45% of neoplastic cases respectively. This work gives a panoramic view of different intestinal pathologies and emphasises on the need of planning accurate diagnostic and screening strategies along with effective treatment plans both for neoplastic as well as non-neoplastic diseases.

Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity.

Lung carcinoma is one of the most common cancers and has one of the lowest survival rates in the world. Cytokines such as interleukin-12 (IL-12) have demonstrated considerable potential as robust tumour suppressors. However, their applications are limited due to off-target toxicity. Here we report on a strategy involving the inhalation of IL-12 messenger RNA, encapsulated within extracellular vesicles. Inhalation and preferential uptake by cancer cells results in targeted delivery and fewer systemic side effects. The IL-12 messenger RNA generates interferon-γ production in both innate and adaptive immune-cell populations. This activation consequently incites an intense activation state in the tumour microenvironment and augments its immunogenicity. The increased immune response results in the expansion of tumour cytotoxic immune effector cells, the formation of immune memory, improved antigen presentation and tumour-specific T cell priming. The strategy is demonstrated against primary neoplastic lesions and provides profound protection against subsequent tumour rechallenge. This shows the potential for locally delivered cytokine-based immunotherapies to address orthotopic and metastatic lung tumours.

Histopathological Study of Ovarian Cysts in Derna

Ovarian cysts, which are sacs filled with fluid located in the ovaries, represent the primary reason for enlarged ovaries, impacting approximately 20% of women who experience a pelvic mass at least once during their lifetime. The present work was carried out to focus on the frequency, gross appearance and histopathological features of each type of ovarian cysts in Derna-City East of Libya. This work included 54 cases of ovarian cysts, out of 338 samples submitted to Noor-AL-Huda Medical Center Pathology Laboratory in Derna City –East of Libya during the period between January 2022 and April 2023, samples were formalin fixed, processed, then H &E sections were obtained for histologic diagnosis and subtyping. The age of patients ranges from 5 – 68 years, the predominant age group was 30– 39 years, 26 (48.14%) were on the right side, 23(42.59%) were on the left side, 5(9.25%) were bilateral. The commonest presenting symptoms were both incidental in 21(38.8%) and pain in 18(33.33%); the cyst mainly obtained from Cystectomy operation 39 (72.22%). Gross appearance of each type was studied. Out of the included 54 ovarian cysts 29 (53.70%) were non –neoplastic and25 (46.29%) were neoplastic. Follicle cysts represented (37.93%) of the non-neoplastic lesions, while serous cyst adenoma represented (40%) of the neoplastic lesions. We concluded that non-neoplastic cysts are the most common types of ovarian cysts. Among non-neoplastic ovarian cysts, the functional cysts including follicular and corpus luteal cysts were the most common, while serous cysts and teratomas are the common neoplastic cysts. Most ovarian cysts are found on the right side. Histopathological examination is essential for accurate diagnosis and proper management of ovarian cysts.

The World Health Organization Reporting System for Pancreaticobiliary Cytopathology.

The World Health Organization (WHO) Reporting System for Pancreaticobiliary Cytopathology (WHO System) is the product of a joint venture between the World Health Organization, the International Academy of Cytology, and the International Agency for Research on Cancer. The WHO System revises the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System) and replaces the 6-tiered system with a 7-tiered system. To explain the WHO System and the differences with the PSC System. The WHO System and the PSC System of Reporting Pancreaticobiliary Cytopathology. The diagnostic categories of the WHO System are "Insufficient/Inadequate/Nondiagnostic"; "Benign (Negative for Malignancy"'; "Atypical"; "Pancreaticobiliary Neoplasm, Low Risk/Low Grade (PaN-Low)"; "Pancreatic Neoplasm, High Risk/High Grade (PaN-High)"; "Suspicious for Malignancy"; and "Malignant." In the WHO System, the "benign" category includes both nonneoplastic and neoplastic lesions, so the "Neoplastic: Benign" category of the PSC system has been eliminated. Low-grade malignancies, pancreatic neuroendocrine tumors (PanNETs), and solid-pseudopapillary neoplasm (SPN) classified as "Neoplastic: Other" in the PSC System are classified as "Malignant" in the WHO System, leaving in the "Neoplasm" category intraductal lesions, which are divided into 2 new diagnostic categories: "Pancreaticobiliary Neoplasm (PaN)-Low Risk/Grade" and "PaN-High Risk/Grade." As with the PSC System, the WHO System advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (carcinoembryonic antigen [CEA] and amylase) and molecular testing. The WHO System includes risk of malignancy per category, and reporting and diagnostic management options that recognize the variations in resources of low- and middle-income countries.

The diagnostic performance of ultrasound in the diagnosis of indeterminate adnexal masses based on the O-RADS US scoring system

BackgroundOne of the most frequent reasons for gynecologic imaging is adnexal masses. The aim of the study is to assess the diagnostic performance of ultrasonography in the identification of ambiguous adnexal masses using the O-RADS US scoring system.MethodsThis study included 108 cases and involved females with indeterminate adnexal masses, with any age group who were sent to the diagnostic ultrasonography department for evaluation of a worrisome adnexal mass lesion. We excluded patients who refused the examination despite informed discussion with the sonographer and patients with a previous history of operated adnexal lesion.ResultsBased on the O-RADS US score, more than half masses (52.8%) were diagnosed as O-RADS 3, which is low-risk malignant, and 47.2% were diagnosed as O-RADS 4, being intermediate-risk malignant. Regarding US O-RADS categorization in relation to the reference results by pathology, 57 lesions were categorized as O-RADS 3 by the US, and 18 of them was diagnosed as malignant according to pathology. Out of 51 lesions categorized as O-RADS 4 by the US, 30 were diagnosed as benign by pathology. At cutoff 4, the O-RADS US score for malignancy gave a sensitivity of 93.13% (95% CI 25.13–80.78), specificity of 66.72% (95% CI 34.49–76.81), PPV of 93.18% (95% CI 26.07–58.16), and NPV of 75.42% (95% CI 52.13–81.17) with an overall accuracy of 92.56% (95% CI 38.10–72.06).ConclusionsIn order to distinguish between benign and malignant neoplastic lesions, the US O-RADS classification system is a crucial non-invasive diagnostic tool for suspected ovarian tumors.

Cytological Analysis of Thyroid lesions According to the Bethesda System for Reporting Thyroid Cytology and their Correlation with Histopathology: A Prospective Study

Introduction: Fine-needle aspiration cytology (FNAC) has a crucial role in differentiating between nonneoplasticand neoplastic lesions of the thyroid. It is a quick outpatient department (OPD) procedure. It greatlyaffects the treatment decision. The current study was done to evaluate the role of FNAC as a diagnostic tool inthyroid lesions and establish a clinico-cytological and histological correlation.Aim: To study efficacy of Bethesda system for reporting (TBSRTC) FNAC of thyroid in view of offering guidancefor patient management, for review of distribution of diagnostic categories and correlation with histopathology.Materials and Methods: It is a prospective study of thyroid lesions carried out at the Department of Pathology, CAIMS,Karimnagar over a period of 3 years (January 2020 to January 2023) A total of 303 patients of neck swelling (thyroid),with satisfactory cases on 290 patients in cytology were undertaken for histopathology. Their clinico-cytological,biochemical, and histological correlation was done only in 133 patients only. Their statistical analysis was done.Results: Majority of cases were non neoplastic. The accuracy of cytodiagnosis was 89.3% and overall malignancyrate on histopathology was 16% (37 cases).Conclusion: FNAC of lesions in thyroid gland has a high accuracy in differentiating between malignant andbenign lesions. It is safe cost effective, minimally invasive, and OPD procedure. Using FNAC as the first line ofinvestigation which streamline the reporting terminologies and the number of surgeries on thyroid lesion hasreduced greatly.

Cytohistological Evaluation of Chest wall Nodules: A Series of Rare Entities from a Tertiary Care Centre

Chest wall is a complex system which provides rigid protection to the vital organs. Many pathologic processessuch as congenital and developmental anomalies, inflammatory and neoplastic lesions involve the chest wall. Dueto the wide spectrum of disease involvement it is quite challenging for the clinicians as well as pathologists for anaccurate diagnosis of these lesions. In many of these cases, FNAC (Fine needle aspiration cytology) is not sufficientfor exact categorization of these lesions for which histopathological evaluation along with special stains and IHC(Immunohistochemistry) plays important role. In the literatures, very few studies of cytohistological evaluation ofchest wall nodules are described. In this case series, we described cytohistological evaluation of four rare entitiesof chest wall. We reported epithelioidhemangioendothelioma, Askin’s tumor, Pilomatricoma and Inflammatorypseudotumor one case each.