Screening For Malignancy Research Articles

Optimising liver screening in patients with a Fontan circulation: a cost-effective approach to detection of Fontan associated liver disease which enhances patient care

Abstract Introduction Patients with Fontan circulation, require screening for liver cirrhosis and malignancy, to which they are susceptible with time. Surveillance biopsies reveal nearly all adult Fontan patients develop asymptomatic fibrosis, and a majority have abnormal liver function tests (LFTs). This presents significant financial healthcare burden and psychological stress with testing for patients. Objective We aim to present "real-world" liver screening data, from a leading Adult Congenital Heart Disease (ACHD) centre, to propose a cost-reducing testing regimen, which delivers effective screening, while taking account of the challenges of current guidance, patient compliance, and clinical practice. Methods We analysed liver screening data for Fontan patients at a leading ACHD centre, focusing on biochemical tests (bilirubin, ALT, GGT) and imaging. We evaluated the 10-year financial impact of current practices, versus a hypothetical model based on age and risk factors, alongside biannual and annual screening strategies. Tariffs for biochemical test were provided by the local pathology service and we used NHS HRG tariffs for imaging and phlebotomy. Results We included data from 114 patients with a Fontan circulation (median age 32 range 19-56, 42% females). Eighteen patients developed liver cirrhosis diagnosed on imaging (median age 32, range 22-48). None developed hepatocellular carcinoma. A lack of clear and agreed local screening guidelines (over years) resulted in vastly different investigations for FALD, with inconsistent time intervals for testing. Bilirubin was elevated in 59% (55% in age 18-29), ALT was elevated in 41% (31% in age 18-29), GGT was elevated in 83% (80% in age 18-29). We found 3 cases of cirrhosis in the age group 18-29, all with hypoplastic left heart; 4 cases of cirrhosis in age group 30-34 - all had significant comorbidities; 33% had normal bilirubin, LFT and GGT, potentially not requiring further screening until the age of 35. Eleven patients (22%) age 35+ had confirmed cirrhosis (Figure 1). Performing full FALD screening with biochemistry and liver ultrasound every 12-24 months would increase the cost of screening three- to six-fold. We propose rationalising liver screening by age and underlying risk (Figure 2) to minimise the economic burden and equally the psychological impact of frequent testing on patients. Conclusions Our analysis underscores the necessity for an optimised liver screening protocol in Fontan patients, balancing diagnostic accuracy with cost-efficiency. By integrating this data, we have identified a pathway to streamline screening, tailoring it to individual risk profiles and age groups, thereby reducing unnecessary tests, lowering costs and reducing the impact of testing on patients. This approach not only fosters better patient care, but also provides a framework for developing clearer, cost-effective screening guidelines, to monitor liver health, in these complex CHD patients.

Clinical utility of EBV DNA testing of blood in immunocompetent and immunocompromised patients: A single-center experience.

Epstein-Barr virus (EBV) causes different clinical presentations in immunocompetent and immunocompromised persons, and thus indications for testing vary between these populations. We reviewed our institution's EBV DNA testing across these populations to understand its clinical utility and appropriateness. We conducted a retrospective chart review of adult patients with positive EBV nucleic acid amplification (NAAT) testing from November 2022 to 2023. We recorded demographics, indications for testing, EBV-related diagnosis, laboratory results, and whether testing influenced patient treatment. Of 3560 EBV NAAT tests, 187 (5.3%) were positive, representing 124 unique adult patients (51 immunocompetent and 73 immunocompromised). Reactivation of EBV was the most common diagnosis in both populations, followed by acute EBV infection in the immunocompetent and non-posttransplant lymphoproliferative disorder malignancies in the immunocompromised. In immunocompromised patients, positive tests led to treatment changes more frequently than in immunocompetent patients (27.4% vs 11.7%, P=.06). Testing affected clinical management in 0% to 2% of cases when sent for sepsis/shock and nonspecific viral syndromes compared to 37% to 49% of cases when sent for posttransplant and malignancy screening/monitoring. EBV NAAT testinginfrequently influenced clinical management in immunocompetent individuals but had a notable impact in immunocompromised patients, particularly those undergoing posttransplant or malignancy screening. This underscores the need for targeted testing to optimize resource utilization and cost-effectiveness.

The Current State-or Lack Thereof-of Screening and Prevention for Gynecologic Malignancies for Patients With Lynch Syndrome.

Lynch syndrome (LS) is an autosomal dominant genetic disorder that results in an increased risk of ovarian and endometrial cancers. The aim of this paper was to explore the management of this risk through screening and prevention. Published materials and evidence were explored and summarized. This paper demonstrated that while there has been increased awareness and advances in the identification and diagnosis of patients with LS, recommendations for screening and prevention remain less evidence-based. In decisions of management of patients with LS, a shared decision-making model should be used considering individual patient goals.

A Case of Idiopathic Multicentric Castleman Disease Developing in a Patient with a History of Biopsy Proven Membranous Nephropathy

Abstract Introduction/Objective Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disorder involving two or more lymph node sites. It is usually associated with systemic inflammatory symptoms and organ dysfunction related to hypercytokinemia. Renal involvement in iMCD has only been described in a limited number of studies and case reports. Of note, only one previous case report has described results from renal biopsies taken prior to the development of iMCD. Methods/Case Report Our patient is a 43 year old female who was first diagnosed with membranous nephropathy in early 2020. She had PLA2 R negative and Exostosin-2 positive disease. Age appropriate screening for malignancy was unremarkable. She had positive ANA titres and normal complement levels but did not meet criteria for SLE per rheumatology. Her proteinuria was improved and maintained on Lisinopril for 3 years. In October 2023, her proteinuria suddenly increased. Repeat renal biopsy was unchanged from the initial biopsy. This time, she also noticed acute swelling over her subpectoral region. PET-CT scan revealed multiple areas of avid lymphadenopathy on either sides of the diaphragm but the highest yield PET- avidity was in the subpectoral region. Biopsy of the right subpectoral lymph node was performed. According to the WHO Classification, 5th edition, diagnostic criteria for iMCD-NOS was met with the histological features displaying grade 3 plasmacytosis, grade 2 regressed germinal centers, follicular dendritic cell prominence, increased hyperplastic follicles and increased vascularity. Immunohistochemical staining for CD138 highlighted abundant plasma cells, CD21 highlighted follicular dendritic cell prominence. Vascular proliferation was seen by CD34 staining. Kappa and Lambda- ISH demonstrated polytypic staining pattern and HHV-8 was negative. Results (if a Case Study enter NA) NA Conclusion There is a significant clinical, histologic and immunologic overlap between iMCD, autoimmune or infectious disorders and malignancy. HHV-8 negative/iMCD is less well understood and has no specific biomarkers. It is important to follow the available clinicopathologic diagnostic criteria for early diagnosis, follow up and treatment. Timely recognition can help prevent multiple organ system dysfunction, systemic inflammatory symptoms, cytopenias and polyclonal lymphoproliferation. Although the pathophysiology maybe unclear, this case may also suggest that in patients with a previously diagnosed membranous nephropathy, iMCD may play a role in recurrence and worsening of the disease.

B-076 Detection of KLHL11 Autoantibodies Using a New Cell-based Indirect Immunofluorescence Assay

Abstract Background Autoantibodies against kelch-like protein 11 (KLHL11) were first described in 2019 as markers of paraneoplastic encephalitis. Early diagnosis and treatment are imperative to improve prognosis and outcome of affected patients. Rat brain immunohistochemistry was reported to be not useful in routine screening for KLHL11 antibodies. This study evaluates the performance of a new recombinant cell-based assay for the standardized detection of KLHL11-specific IgG and reports the characteristics of the examined patients. Methods Serum (n=9), CSF (n=5) and/or plasmapheresis (n=1) samples from 10 patients with clinical presentations compatible with anti-KLHL11 encephalitis as well as sera from 100 healthy blood donors were analyzed using a prototype indirect immunofluorescence assay (IFA; EUROIMMUN) based on recombinant HEK293 cells expressing human KLHL11. Results KLHL11 autoantibodies were detected at high titers in all samples (serum >1:1,000; CSF >1:320; plasma >1:100,000) from all (10/10) patients but in none (0/100) of the blood donors, indicating 100% sensitivity and specificity. Anti-KLHL11-positive patients had a median age of 52 years (range 27-71) and 80% were male. The most common reported clinical presentations were cerebellar syndrome (ataxia), brainstem diencephalic encephalitis, rhombencephalitis and limbic encephalitis. Testicular or ovarian tumors were found in 87.5% (7/8) of the cases with available results from malignancy screening. Conclusions The new cell-based IFA enables the sensitive and specific detection of KLHL11 autoantibodies, thus supporting the diagnosis of patients with predominantly paraneoplastic brainstem cerebellar syndrome. Future studies will evaluate assay performance in larger patient cohorts to address the reported association of KLHL11 autoimmunity with a wider spectrum of syndromes and tumors.

Detection of malignant breast tissue using SAR observation with microwave imaging and convolutional neural network

The research paper introduces a deep learning approach for distinguishing between benign and malignant breast tissues using Ultra Wide Band (UWB) microwave imaging. A multi-resonant monopole microstrip patch antenna was crafted and placed on a female breast phantom model containing a tumor. The phantom’s dielectric properties were adjusted to mimic those of benign and malignant tissues. The Specific Absorption Rate (SAR) was analyzed by rotating the antenna at various angles throughout the phantom’s trajectory. Images capturing the SAR distribution over the breast phantom at different antenna resonances were obtained. The popular Convolutional Neural Network (CNN) based AlexNet model was employed for autonomous feature learning from SAR images. To address the challenge of overfitting with a limited dataset, the study utilized image augmentation and transfer learning methods. The proposed model achieved an impressive 98.59% accuracy in classifying benign and malignant breast phantom images, surpassing the performance of three other CNN models—VggNet16, GoogleNet, and ResNet. Notably, this microwave imaging system based on SAR images detected tumors as small as 1 mm with an accuracy of 97.08% outperforming existing malignancy screening techniques.

High-Performance Metabolic Profiling of High-Risk Thyroid Nodules by ZrMOF Hybrids.

Thyroid nodules (TNs) have emerged as the most prevalent endocrine disorder in China. Fine-needle aspiration (FNA) remains the standard diagnostic method for assessing TN malignancy, although a majority of FNA results indicate benign conditions. Balancing diagnostic accuracy while mitigating overdiagnosis in patients with benign nodules poses a significant clinical challenge. Precise, noninvasive, and high-throughput screening methods for high-risk TN diagnosis are highly desired but remain less explored. Developing such approaches can improve the accuracy of noninvasive methods like ultrasound imaging and reduce overdiagnosis of benign nodule patients caused by invasive procedures. Herein, we investigate the application of gold-doped zirconium-based metal-organic framework (ZrMOF/Au) nanostructures for metabolic profiling of thyroid diseases. This approach enables the efficient extraction of urine metabolite fingerprints with high throughput, low background noise, and reproducibility. Utilizing partial least-squares discriminant analysis and four machine learning models, including neural network (NN), random forest (RF), logistic regression (LR), and support vector machine (SVM), we achieved an enhanced diagnostic accuracy (98.6%) for discriminating thyroid cancer (TC) from low-risk TNs by using a diagnostic panel. Through the analysis of metabolic differences, potential pathway changes between benign nodule and malignancy are identified. This work explores the potential of rapid thyroid disease screening using the ZrMOF/Au-assisted LDI-MS platform, providing a potential method for noninvasive screening of thyroid malignant tumors. Integrating this approach with imaging technologies such as ultrasound can enhance the reliability of noninvasive diagnostic methods for malignant tumor screening, helping to prevent unnecessary invasive procedures and reducing the risk of overdiagnosis and overtreatment in patients with benign nodules.

Breast Malignancy: Evaluating Perception and Adoption of Methods of Screening among Women in Urban Areas of Ondo State Nigeria

Background: Mortality from breast malignancy (cancer) is assuming a worldwide epidemic among women in recent times. The increasing mortality rate is partly due to poor level of adoption of early detection methods. The purpose of this study was to evaluate the perception and adoption of methods of screening for breast malignancy among women in Ondo State, Nigeria.  Methods: A cross sectional design was employed to carry out this research while 427 respondents were randomly selected through multistage sampling technique. The data instrument was piloted for accuracy and reliability. Statistical analysis was done using SPSS Version 25. Findings: This study indicated that most respondents (63.9%) were young adults >35years while the mean age was 38.0 years. There was a positive perception (90.2%) about breast malignancy screening among respondents. Notably, majority (82.2%) of respondents utilized Breast Self-Examination (BSE) screening method while only (14.1%) utilized mammography. Findings also revealed obesity and age as predictors of breast malignancy while family/friends remain the potent source of awareness of breast malignancy screening. Chi- square test revealed an association between occupation and practice of breast malignancy screening (P-value = 0.04*; X2 = 8.02) and educational qualification (P-value = 0.000*; X2 = 31.9). Findings also showed a correlation between perception and breast malignancy screening method (r = 0.218**; p-value = 0.00) and reasons for breast malignancy screening (r = 0.250**; p-value = 0.00).  Conclusion: Government should prioritize compulsory free screening initiatives for early detection of breast malignancy in women to avert the mental agony of loss of lives.

Clinician-Reported Management Recommendations in Response to Universal Germline Genetic Testing in Patients With Prostate Cancer.

Identification of pathogenic germline variants in patients with prostate cancer can help inform treatment selection, screening for secondary malignancies, and cascade testing. Limited real-world data are available on clinician recommendations following germline genetic testing in patients with prostate cancer. Patient data and clinician recommendations were collected from unselected patients with prostate cancer who underwent germline testing through the PROCLAIM trial. Differences among groups of patients were determined by 2-tailed Fisher's exact test with significance set at P < .05. Logistic regression was performed to assess the influence of test results in clinical decision-making while controlling for time of diagnosis (newly vs previously diagnosed). Among 982 patients, 100 (10%) were positive (>1 pathogenic germline variant), 482 (49%) had uncertain results (>1 variant of uncertain significance), and 400 (41%) were negative. Patients with positive results were significantly more likely than those with negative or uncertain results to receive recommendations for treatment changes (18% vs 1.4%, P < .001), follow-up changes (64% vs 11%, P < .001), and cascade testing (71% vs 5.4%, P < .001). Logistic regression demonstrated that positive and uncertain results were significantly associated with both changes to treatment and follow-up (P < .001) when controlling for new or previous diagnosis. Germline genetic testing results informed clinical recommendations for patients with prostate cancer, especially in patients with positive results. Higher than anticipated rates of clinical management changes in patients with uncertain results highlight the need for increased genetic education of clinicians treating patients with prostate cancer.

Secondary Solid Cancers Among Patients with Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Multicenter Study.

We investigated the occurrence and characteristics of secondary solid cancers (SSC) in Philadelphia chromosome-negative myeloproliferative neoplasm (Ph- MPN) patients from Türkiye. We identified the potential risk factors for SSC development including the impact of cytoreductive therapies and assess the influence of SSC on patient survival. 1013 Ph- MPN patients diagnosed between 1995 and 2022 was retrospectively analyzed. Data related to demographics, clinical and laboratory parameters, SSC development, cytoreductive therapy exposure and survival outcomes were collected. Statistical analyses were performed using SPSS 26.0 software. Of the Ph- MPN patients, 6.6% developed SSC, with carcinoma being the most common type. Older age at Ph- MPN diagnosis and male gender were associated with SSC occurrence. Ph- MPN patients diagnosed with SSC and patients with no diagnosis of SSC showed no significant difference for complete blood count, spleen size, Ph- MPN diagnostic groups and driver mutation frequencies. However, SSC patients showed a higher frequency of arterial thrombosis and tendency towards increased rate for total thrombosis (p=0.030, p=0.069; respectively). In multivariate analysis, arterial thrombosis was the sole independent risk factor and interferon (IFN)-based therapy the sole protective factor for SSC development. Median overall survival (OS) did not differ between patients with and without SSC except for polycythemia vera (PV) patients with SSC, who had shorter OS (175±15 and 321±26 months, respectively; p = 0.005). Our study highlights the prevalence and characteristics of SSC in Turkish patients diagnosed with Ph- MPN. Arterial thrombosis was associated with increased SSC risk while IFN-based therapy offered potential protection from SSC. Screening for SSC in Ph- MPN patients with arterial thrombosis may be relevant. These findings emphasize the importance of malignancy screening in Ph- MPN patients, especially in high-risk subgroups and call for further research to elucidate the underlying mechanisms and optimize treatment strategies.

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing's Syndrome.

Food-dependent Cushing's syndrome (FDCS) is a rare presentation of hypercortisolism from adrenal origin, mostly observed in primary bilateral macronodular adrenal hyperplasia (PBMAH) but also in some cases of unilateral adrenocortical adenoma. FDCS is mediated by the aberrant expression of glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) in adrenocortical cells. GIP, secreted by duodenal K cells after food intake, binds to its ectopic adrenal receptor, and stimulates cortisol synthesis following meals. FDCS was first described more than 35 years ago, and its genetic cause in PBMAH has been recently elucidated: KDM1A inactivation by germline heterozygous pathogenic variants is constantly associated with a loss-of-heterozygosity of the short arm of chromosome 1, containing the KDM1A locus. This causes biallelic inactivation of KDM1A, resulting in the GIPR overexpression in the adrenal cortex. These new insights allow us to propose the KDM1A genetic screening to all PBMAH patients with signs of FDCS (low fasting cortisol that increases after a mixed meal or oral glucose load) and to all first-degree relatives of KDM1A variant carriers. Given that KDM1A is a tumor suppressor gene that has also been associated with monoclonal gammopathy of uncertain significance and multiple myeloma, the investigation of FDCS in the diagnostic management of patients with PBMAH and further genetic testing and screening for malignancies should be encouraged.

Polymyalgia Rheumatica Presenting as Nocturnal Pyrexia of Unknown Origin: A Case Report

Background. Polymyalgia rheumatica (PMR) is a rheumatic disorder characterized by musculoskeletal stiffness and pain, primarily affecting the shoulder, neck, and hip areas. It is more common in females, with the peak incidence usually after the age of 70. Case Report. A 74-year-old man presented with a two-month history of low-grade nocturnal fever up to 100oF (37.7oC) which did not respond to multiple courses of antibiotics. There was unintentional weight loss of 5 kg and mild shoulder stiffness. The patient had a history of Type 2 diabetes mellitus treated with 34 units of insulin (Humulin 70/30) daily and active smoking of 40 pack-years. On examination, mild tenderness of both shoulder girdle muscles and discomfort on external rotation were noted. The initial blood work-up revealed raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Serologies for syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were negative. Given the negative results of infective and malignancy screening, along with raised inflammatory markers and mild shoulder stiffness, a diagnosis of PMR was made and a trial of prednisolone was initiated, resulting in the resolution of symptoms. Conclusions. The present case report highlights the importance of thoroughly investigating all differential diagnoses of pyrexia of unknown origin, regardless of the patient’s ethnic origin, to facilitate timely diagnosis.

The Role of Routine Pathologic Assessment After Pediatric Osteochondroma Excision.

Osteochondromas are benign osseous lesions often excised for pain, growth abnormalities, and aesthetic concerns. While characteristic clinical and radiographic features leave little diagnostic ambiguity in most cases of osteochondroma, pathologic analysis to confirm the diagnosis and screen for malignancy is routinely performed following surgical excision. The purpose of this study was to determine the clinical and economic value of routine pathologic analysis after osteochondroma excision in a pediatric population. A retrospective review of clinical records from 2 pediatric orthopaedic hospitals (St. Louis Children's Hospital and Shriner's Hospital for Children, St. Louis) identified 426 osteochondroma lesions surgically resected from 201 patients. Patients with solitary and multiple lesions were included. Clinical, radiographic, and surgical data were recorded for each resection surgery. Pathologic reports were evaluated. Costs incurred for routine pathologic assessment was also noted. Totally, 132 patients were treated with surgical resection of a solitary osteochondroma lesion, while an additional 291 lesions were resected from 69 patients with multiple lesions. Average age at the time of surgical resection was 13.0 years (2.1 to 17.9). The most common anatomic locations of excised lesions included the distal femur (110, 25.8%), proximal tibia/fibula (95, 22.3%), and distal radius/ulna (58, 13.6%). All resected specimens were sent for pathologic analysis. The average size of the resected lesions was 19.9 mm 3 (0.02 to 385.0mm 3 ). In all cases, the histologic diagnosis confirmed benign osteochondroma. The total charges of pathologic analysis including processing and interpretation fees was ∼$755.00 for each lesion assessed, for a total cohort charge of $321,630. We propose that in most cases of pediatric osteochondroma excision procedures, postoperative histologic analysis is not strictly indicated as it rarely, if ever, alters diagnosis or management. We suggest using a "gross only" analysis in these cases. However, we do believe that with preoperative diagnostic ambiguity, or if patients present with concerning features such as rapidly expansile lesions or cortical destruction, have axial skeleton or pelvic involvement, or enlarged cartilaginous caps, full histologic evaluation of the excised lesions will continue to be prudent. Level IV-case series.

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (&gt;10,000 IU/L for ELISA and &gt;20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease.

#1494 Immunotactoid glomerulopathy: a comprehensive analysis of three cases

Abstract Background Immunotactoid glomerulopathy (ITG) is an uncommon cause of glomerular disease encountered in approximately 0.06% of native kidney biopsies. This fibrillary disease is strongly associated with haematologic disorders, including lymphoma (mainly chronic lymphocytic leukaemia/small lymphocytic lymphoma), monoclonal gammopathy, and multiple myeloma. It is usually managed with oral steroids and/or treatment of an underlying lymphoproliferative disorder. Here, we report three cases of ITG, all female patients with varying severity of the disease, timing of malignancy and required treatment. Case Scenarios: Case 1: A 76-year-old lady with no significant medical background presented in May 2020 with confusion and progressive peripheral oedema. She had AKI (serum creatinine 210 µmol/L from baseline 68 µmol/L) and a sodium of 104 mmol/l. Urine PCR was 1182 mg/mmol. She was admitted to the ITU, where hyponatraemia was managed with a good clinical response. Blood screening showed negative immune, myeloma and virology screens. Complement was low. A renal biopsy showed a diagnosis of ITG. She had an extensive malignancy screen, but no malignancy was detected. She was started on prednisolone 60 mg once daily and eventually weaned off the drug by March 2021, as she maintained remission of her disease. Two years after her initial presentation, she was seen by the ophthalmologist for a right lacrimal gland mass. This was excised, and a biopsy revealed a MALT Lymphoma. Case 2: A 50-year-old lady with splenomegaly being investigated under the haematology service was referred to our renal clinic for proteinuria in June 2019. Her serum creatinine was within normal limits, and her UPCR was 302 mg/mmol. She had no paraprotein in her blood, low serum immunoglobulins, low C3 and a negative viral screen. Perindopril, initiated by her GP, was up-titrated. Renal biopsy revealed features in keeping with Immunotactoid Glomerulopathy, and completed haematological investigations revealed Chronic Lymphocytic Leukaemia. Her UPCR peaked at 842 mg/mmol before reducing to 190 mg/mmol within a year after treatment with Veneclotax and Rituximab after not tolerating FCR (Fludarabine, Cyclophosphamide, Rituximab) Chemotherapy. Case 3: A 69-year-old lady presented to the renal clinic with proteinuria in September 2018. She had a background of breast cancer diagnosed in 2007 (She had surgical resection followed by radiotherapy). Her 24-hour urine protein was 2g, and UPCR was 155 mg/mmol. Serum creatinine was 81 µmol/l and eGFR 66 ml/min. P- ANCA was positive, while PR3 and ANA were negative. She had bilateral leg oedema due to long-standing lymphedema. The biopsy report showed immunotactoid glomerulopathy. Regular surveillance of previous breast cancer with mammography and CT-CAP has shown no evidence of malignancy recurrence, hepatitis virology and paraprotein were negative, and C3/C4 were within normal limits. She had improved UPCR and maintained normal kidney function on full-dose Losartan. Conclusion Immunotactoid Glomerulopathy is a rare form of glomerular disease with a strong association with lymphoproliferative malignancies, which may precede, occur concomitantly or present years after the initial diagnosis. This common association highlights the need for diligence in screening for malignancy in each case, and it is a reason for careful follow-up of these patients. Treatment of underlying disorders is associated with positive renal outcomes, and in some cases, there is a good response to steroids.

#1305 Analysis of clinicopathological characteristics of membranous nephropathy with concomitant malignancy and literature review

Abstract Background and Aims In recent years, the incidence of membranous nephropathy (MN) with malignancy has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Method Patients diagnosed with renal biopsy-proven MN and comorbid malignancy detected within 5 years before and after MN diagnosis were included. The control group were diagnosed with renal biopsy-proven IMN with no malignancy and no other clear secondary cause for MN. We present a comprehensive analysis of MN with concomitant malignancy in our cohort and literature review. Results A total of 19 MN patients with concomitant malignancy were evaluated at our center; among them, 13 (68.4%) were male, and the median age was 57.0 (45.0, 69.0) years. Malignancy occurred after the onset of renal disease in 61.1% of patients, with digestive system malignancy (36.8%) ranking as the predominant type. 8 (8/11) patients achieved either PR or CR during the follow-up period. Most patients had pathology typical of IMN. IF showed strong positivity for IgG (100%), whereas only 13 (68.4%) patients were positive for C3. IEM showed electron-dense deposits predominantly located in subepithelial. Specific MN antigen staining of renal tissues from 19 patients showed that the highest percentage was 68.4% (13/19) for PLA2R-only positivity followed by 15.8% (3/19) for THSD7A-only positivity. Specific MN antigen staining of malignant tissue was performed in 5 patients whose tumor samples were available. Only 2 patients expressed the same antigen on kidney and tumor. Screening 17 articles encompassing a total of 21 patients in whom MN-specific antigen staining was performed on both renal and tumor tissues simultaneously. Among these patients, 71.4% (15/21) were male, with a median age of 61.0 years (56.3, 72.8). In this cohort, malignancy was diagnosed before or simultaneously with MN in 15 patients (75.0%), with digestive system malignancy constituting the most prevalent comorbid malignancy, at 33.3%. Notably, THSD7A accounted for the highest proportion of MN antigens, at 66.7% (14/21); among these patients, 78.6% (11/14) also exhibited positive tumor THSD7A staining. Of the 21 patients, 72.2% (13/18) achieved CR or PR. No significant difference between the baseline characteristics was observed between the 19 patients from our center and 21 patients documented in the literature. Therefore, the clinicopathological data of these 40 patients were pooled and compared with 101 IMN patients without malignancy at our center. Compared to patients without malignancy, MN patients with malignancy were older at the time of renal biopsy (P = 0.017), had a lower eGFR (P = 0.035) and demonstrated a lower rate of CR or PR after treatment (P &amp;lt; 0.001). The rate of PLA2R positivity in the glomeruli of MN patients with concomitant malignancy was significantly lower (40.0% vs. 92.1%, P &amp;lt; 0.001), while the rate of THSD7A positivity was significantly higher (42.5% vs. 2.0%, P &amp;lt; 0.001). Renal tissue IgG subclass staining showed that the rate of IgG4 positivity was significantly decreased compared with that in IMN patients (59.3% vs. 90.1%, P &amp;lt; 0.001), and the rate of IgG2 positivity was significantly increased (36.0% vs. 16.5%, P = 0.033). Conclusion To conclude, malignancy screening should be more actively performed for MN patients presenting with the above characteristics.

The exploration of cell population data in clinical use: Beyond infectious diseases

AbstractCell population data (CPD) is regarded as the fingerprint of a blood cell at a given moment. CPD parameters harbor information associated with cell morphology and can be automatically generated using modern hematological analyzers. Various studies have revealed many unique clinical applications for CPD, especially for infectious diseases, such as sepsis. For example, one monocyte‐related CPD parameter is the monocyte distribution width (MDW), which can be generated using a Beckman Coulter hematological analyzer. MDW has received FDA and CE approval for aiding in sepsis diagnosis in adult patients in the emergency department. Additionally, MDW can serve as a diagnostic biomarker in patients infected with SARS‐CoV‐2. CPD has also been widely explored for possible clinical applications beyond infectious diseases, such as for predicting myelodysplastic syndromes, screening for hematological malignancies, and detecting sterile inflammation. CPD parameter measurements are easily obtained and quite cost‐effective, making them practical for clinical use. However, there are some potential drawbacks of CPD parameters. Some pre‐analytical conditions can affect CPD values. Furthermore, CPD are specific to certain hematological analyzers and the result cannot be transferred between different analyzers. The practical usefulness of CPD reference intervals is also still questionable. In this review, wesummarize the current studies related to CPD and its clinical applications. Additional well‐designed clinical studies related to CPD are still expected.

Abstract PO4-12-02: Screening adherence for second primary malignancies in breast cancer survivors: a cross-sectional study assessing behaviors, facilitators, and barriers to enhance quality care

Abstract Background: Continuous advancements in medical care have significantly increased the life expectancy of breast cancer (BC) patients. Due to this increased lifespan, combined with genetic, hormonal and environmental factors, BC patients have an increased risk of developing a 2nd primary malignancy. Therefore, regular screening for other types of cancer is of utmost importance for comprehensive care of BC survivors (BCS). The aim of this study was to evaluate the level of compliance with screening for cervical, lung, and colorectal cancer among BCS. Additionally, the study aimed to identify the facilitators and barriers influencing cancer screening (CS) adherence. Methods: An online survey for BCS was developed to assess sociodemographic data, risk perception of developing a 2nd primary malignancy, attitudes towards CS, and compliance with CS. It was distributed through the social media of Mexican oncology-related NGOs. Results: In total, 52 BCS (median age: 44 years, range: 28-67 years) answered the survey. Most were diagnosed with stage III (38%) or II (29%) BC. The majority had completed at least high-school education (90%), had public health insurance (60%) or no insurance (25%), and reported a monthly income &amp;lt; 500 USD (52%). A total of 3 (6%) cases of 2nd primary malignancies were reported, including 2 cases of contralateral BC and 1 cervical carcinoma. Among 50 participants with an indication for cervical CS, 37 (74%) had a pap smear within the past 3 years. Only 7/24 (29%) eligible participants underwent colorectal CS within the last 10 years. Screening modalities included 6 colonoscopies and 1 occult blood test. The primary reason for non-compliance in both cervical and colorectal CS was the absence of a physician's recommendation, accounting for 79% and 88% of the cases, respectively. None of the participants had an indication for lung CS, thus no low-dose computed tomographies were performed for this purpose. Participants demonstrated a mean knowledge score of 72/100 (SD=19) regarding CS. Most respondents mentioned that, compared to the general population, they considered themselves to be at no/very low/low risk of developing cervical (75%), colon (73%), or lung cancer (75%). In terms of attitudes towards CS, an overwhelming majority of participants (98%) affirmed that BCS should undergo screening for other types of cancer. Most stated that, if recommended by a physician, they would agree/strongly agree (96%) to undergo screening for other neoplasms. Nearly all agreed/strongly agreed (98%) that being screened for other types of cancer would be beneficial for their own health; and agreed/strongly agreed (98%) that CS is the most effective way to approach other types of cancer. Additionally, most agreed/strongly agreed (96%) their CS would benefit their family members. On univariate analysis, no sociodemographic or clinical factors were associated with CS adherence. However, it is important to note that the study may have been underpowered to detect significant associations due to the limited sample size. Conclusion: In conclusion, even though most BCS acknowledge its importance, screening for 2nd primary malignancies in this group exhibits suboptimal rates. This study highlights the potential role that BC oncologists could play on increasing CS uptake by reminding patients of their corresponding recommendations to detect other types of cancer. Further research is crucial to enhance our understanding of the key factors influencing these outcomes and to contribute to the development of targeted strategies aimed at enhancing CS adherence. Citation Format: Fernanda Mesa-Chavez, Misael Salazar-Alejo, Cynthia Villarreal-Garza. Screening adherence for second primary malignancies in breast cancer survivors: a cross-sectional study assessing behaviors, facilitators, and barriers to enhance quality care [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-02.

Real-world implications of IMACS malignancy screening guidelines for idiopathic inflammatory myopathies: An evaluation of compliance and economic impact at a tertiary referral center.

An inaugural set of consensus guidelines for malignancy screening in idiopathic inflammatory myopathy (IIM) were recently published by an international working group. These guidelines propose different investigation strategies based on "high", "intermediate" or "standard" malignancy risk groups. This study compares current malignancy screening practices at an Australian tertiary referral center with the recommendations outlined in these guidelines. We conducted a retrospective analysis of newly diagnosed IIM patients. Relevant demographic and clinical data regarding malignancy screening were recorded. Existing practice was compared with the guidelines using descriptive statistics; costs were calculated using the Australian Medicare Benefit Schedule. Of the 47 patients identified (66% female, median age: 63 years [IQR: 55.5-70], median disease duration: 4 years [IQR: 3-6]), only one had a screening-detected malignancy. Twenty patients (43%) were at high risk, while 20 (43%) were at intermediate risk; the remaining seven (15%) had IBM, for which the proposed guidelines do not recommend screening. Only three (6%) patients underwent screening fully compatible with International Myositis Assessment and Clinical Studies recommendations. The majority (N = 39, 83%) were under-screened; the remaining five (11%) overscreened patients had IBM. The main reason for guideline non-compliance was the lack of repeated annual screening in the 3 years post-diagnosis for high-risk individuals (0% compliance). The mean cost of screening was substantially lower than those projected by following the guidelines ($481.52 [SD 423.53] vs $1341 [SD 935.67] per patient), with the highest disparity observed in high-risk female patients ($2314.29/patient). Implementation of the proposed guidelines will significantly impact clinical practice and result in a potentially substantial additional economic burden.

Evaluation of Prevalence and Patterns of Oncogenic Driver Mutations in Nonsmall Cell Lung Cancer in a Tertiary Care Center - A Cross-sectional Study

Abstract Background: Better understanding of the molecular pathways that drive malignancy led to the development of agents that target specific molecular pathways that target the malignant cells. Identification of specific driver mutation is the key to targeted therapy in advanced nonsmall-cell carcinomas. This study was done to assess the prevalence and patterns of driver oncogenic mutations in nonsmall cell lung cancer (NSCLC) among the patients subjected to molecular study in a tertiary care center. Materials and Methods: This is a cross-sectional study done in 1.5 years in a tertiary care center in 103 patients diagnosed with NSCLC. Patients with NSCLC were subjected to molecular study in the department of oncology as a part of management. The demographics, clinical details, laboratory parameters, and pathology were noted from the medical records. The molecular study was done from the biopsied specimen in an outside laboratory. The frequency of driver oncogenic mutation, along with other clinical parameters was studied. Results: Out of 103 patients subjected to the study, 46 (44.6%) subjects had driver oncogenic mutations. Among them, 38 (36.9%) subjects had epidermal growth factor receptor mutations, 7 (6.8%) had anaplastic lymphoma kinase mutations, and 1 (1%) had ROS mutation. Conclusion: The frequency of driver oncogenic mutations is higher in our population, compared to the Western population. From a clinical point of view, there is a dire need for advocacy and increased awareness for screening and early detection of thoracic malignancies, and advanced treatment options, including targeted therapy, so that disease-related morbidity and mortality can be reduced to an extent.