Atypical Diagnosis Research Articles

Comparative Analysis of AI Models for Atypical Pigmented Facial Lesion Diagnosis.

Diagnosing atypical pigmented facial lesions (aPFLs) is a challenging topic for dermatologists. Accurate diagnosis of these lesions is crucial for effective patient management, especially in dermatology, where visual assessment plays a central role. Incorrect diagnoses can result in mismanagement, delays in appropriate interventions, and potential harm. AI, however, holds the potential to enhance diagnostic accuracy and provide reliable support to clinicians. This work aimed to evaluate and compare the effectiveness of machine learning (logistic regression of lesion features and patient metadata) and deep learning (CNN analysis of images) models in dermoscopy diagnosis and the management of aPFLs. This study involved the analysis of 1197 dermoscopic images of facial lesions excised due to suspicious and histologically confirmed malignancy, classified into seven classes (lentigo maligna-LM; lentigo maligna melanoma-LMM; atypical nevi-AN; pigmented actinic keratosis-PAK; solar lentigo-SL; seborrheic keratosis-SK; and seborrheic lichenoid keratosis-SLK). Image samples were collected through the Integrated Dermoscopy Score (iDScore) project. The statistical analysis of the dataset shows that the patients mean age was 65.5 ± 14.2, and the gender was equally distributed (580 males-48.5%; 617 females-51.5%). A total of 41.7% of the sample constituted malignant lesions (LM and LMM). Meanwhile, the benign lesions were mainly PAK (19.3%), followed by SL (22.2%), AN (10.4%), SK (4.0%), and SLK (2.3%). The lesions were mainly localised in the cheek and nose areas. A stratified analysis of the assessment provided by the enrolled dermatologists was also performed, resulting in 2445 evaluations of the 1197 images (2.1 evaluations per image on average). The physicians demonstrated higher accuracy in differentiating between malignant and benign lesions (71.2%) than in distinguishing between the seven specific diagnoses across all the images (42.9%). The logistic regression model obtained a precision of 39.1%, a sensitivity of 100%, a specificity of 33.9%, and an accuracy of 53.6% on the test set, while the CNN model showed lower sensitivity (58.2%) and higher precision (47.0%), specificity (90.8%), and accuracy (59.5%) for melanoma diagnosis. This research demonstrates how AI can enhance the diagnostic accuracy in complex dermatological cases like aPFLs by integrating AI models with clinical data and evaluating different diagnostic approaches, paving the way for more precise and scalable AI applications in dermatology, showing their critical role in improving patient management and the outcomes in dermatology.

Trajectory of Subsequent Breast Cancer Diagnoses in a Diverse Patient Cohort with Breast Atypia.

Proliferative breast atypical lesions, including atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasms (LIN), represent benign entities that confer an elevated risk of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). However, the timing of disease progression is variable and risk factors associated with the trajectory of disease are unknown. Patients diagnosed with ADH or LIN from 1992 to 2017 at an academic center were identified. Early progression was defined as DCIS or IBC diagnosed within 5years following the initial atypia diagnosis. Unadjusted cancer-free survival was estimated using the Kaplan-Meier method. Demographics, clinicopathologic features, and use of chemoprevention were compared between the early and late development groups. Overall, 418 patients were included-73.7% with ADH and 26.3% with LIN. Over a median follow up of 92.1 months, 71/418 (17.0%) patients developed IBC (57.7%) or DCIS (42.3%). Almost half (47.9%, 34/71) were diagnosed within 5 years of their initial atypia diagnosis, and 52.1% (37/71) were diagnosed after 5 years. Patient and atypia characteristics were not associated with rate of events or time to events. There was a trend of early events being more often ipsilateral (76.5% early vs. 54.1% late; p=0.13) versus contralateral. In a large cohort of patients with breast atypia and long-term follow up, 17% experienced subsequent breast events, with approximately half of the events occurring within the first 5years following the initial atypia diagnosis. Clinical features were not associated with the trajectory to subsequent events, supporting that atypia signals both local and overall malignancy risk.

Subsequent percutaneous breast biopsies after initial atypia diagnosis: The patient burden of long-term follow up

BackgroundBreast atypia increases overall breast cancer risk, potentially necessitating future interventions. This study examines the frequency and outcomes of additional percutaneous biopsies after an atypia diagnosis. MethodsAdult patients with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ) at a single institution were reviewed for subsequent core needle biopsies (CNBs) and corresponding malignant outcomes. ResultsAmong 432 patients, median age at diagnosis was 54.8 ​y. Seventy-one (71/432, 16.4 ​%) patients developed a breast malignancy. During a median follow-up of 7.4 ​y, 113 patients underwent 149 additional CNBs. Twenty-six patients (26/113, 23.0 ​%) had >2 additional CNBs. Approximately half (79/149, 53.0 ​%) of all additional CNBs occurred within 5 years after breast atypia diagnosis. ConclusionA considerable number of patients with breast atypia undergo additional percutaneous biopsies, especially within 5 years post-atypia diagnosis. Our study highlights the significant burden of surveillance and the need for tailored follow-up strategies.

Validation of anorexia nervosa and Bulimia nervosa diagnosis coding in Danish hospitals assisted by a natural language processing model

IntroductionThe Danish Health Care Registers rely on the International Statistical Classification of Diseases and Related Health Problems (ICD)-classification and stand as a widely utilized resource for health epidemiological research. Eating disorders are multifaceted syndromes where two distinctive diagnoses are defined, anorexia nervosa (AN) and bulimia nervosa (BN). However, the validity of the registered diagnoses remains to be verified. Manuel chart review is often the method for validation of diagnosis codes, but there is limited research on how natural language processing (NLP) models could enhance this process. ObjectiveTo investigate the accuracy of the clinical use of ICD-10 diagnosis codes F50.0, F50.1, F50.2, and F50.3 in the Danish Health Care Registers, using a manual chart review assisted by NLP. MethodFrom a cohort of all individuals attending hospitals in Region of Southern Denmark with registered electronic health information, we extracted medical information from the electronic health journal on 100 individuals with each of the four diagnosis codes. After extraction, an NLP model with regular expression search patterns identified relevant text passages for manual chart review. ResultsOverall, 372 of the 400 diagnosis codes (93%) were correct. A diagnosis code for AN was correct in 90% of instances, 96% for atypical AN, 96% for BN and 90% for an atypical BN diagnosis code. ConclusionWe found that the accuracy of a diagnosis code F50.0, F50.1, F50.2, and F50.3 to be high. This confirms that the generally well-documented validity of the Danish health care registers also applies to the eating disorder diagnoses.

Atypical Presentation of a Cardiac Lipoma

Cardiac masses can have atypical presentations and diagnosis can be difficult because of limitations in imaging modalities. We report the case of a 69-year-old man with a history of hypertension and hyperlipidemia who presented with several months of dyspnea with exertion. There was a soft systolic murmur on exam. Transthoracic echocardiogram showed a large right atrial mass that appeared to be adherent to the interatrial septum. Considering the size and apparent attachment to the interatrial septum the suspicion was a myxoma. After further imaging however, including transesophageal echocardiogram, cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI) the diagnosis changed to a lipoma. The patient had surgical resection of the mass which confirmed the diagnosis. A multi-imaging approach may be helpful and required to accurately diagnose cardiac masses.

ASO Author Reflections: Trajectory of Subsequent Breast Cancer After Breast Atypia Diagnosis Suggests Need for Vigilant Follow-up.

ASO Author Reflections: Trajectory of Subsequent Breast Cancer After Breast Atypia Diagnosis Suggests Need for Vigilant Follow-up.

THADA-IGF2BP3 gene fusions in thyroid fine needle aspiration is involved in the pathway to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features".

The increased usage and adaptation of molecular testing of thyroid fine needle aspirations (FNA) has expanded the variety and number of gene fusions identified. While the identified number of molecular alterations is increasing, the definitive association between preoperative molecular analysis and phenotype has yet to be established. The aim of this study was to examine Thyroid adenoma-associated (THADA)-IGF2BP3 molecular fusions with FNA categorization, surgical pathology diagnosis, and other molecular alterations detected by ThyroSeq Genomic Classifier testing. FNA cytology samples of thyroid nodules from 04/2017 to 01/2023 with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) or follicular neoplasm suspicious for follicular neoplasm (FN/SFN; Bethesda IV) with associated ThyroSeqV3 testing were reviewed. Parameters including patient demographics, FNA diagnosis, ThyroSeq V3 results, and surgical pathology follow up were examined. 87 out of 249 (35%) FNA specimens of thyroid nodules displayed molecular alterations. 64 cases (74%) had a cytology diagnosis of AUS and 23 (26%) had FN. RAS mutation was observed in 48 cases. On surgical follow-up, 17 (35%) cases showed non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), while 14 (29%) patients had a malignant diagnosis. THADA-IGF2BP3 fusions were seen in 8 cases, all with NIFTP on surgical pathology follow-up (100%). Analysis of THADA-IGF2BP3 fusion, in our institutional series, shows close association with NIFTP cases. THADA-IGF2BP3 fusion, which seems to be a favorable prognostic indicator in general, may serve as a molecular marker for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

Incidentally detected abdominal mass - atypical origin, atypical diagnosis

Incidentally detected abdominal mass - atypical origin, atypical diagnosis

#1231 Atypical uremic hemolytic syndrome diagnosis, therapeutic management, control and follow-up in pregnancy: about a case

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a clinical entity characterized by non immune hemolytic anemia, thrombopenia, and renal failure in which the lesions are mediated by a process of thrombotic microangiopathy, mutations in its genes that lead to uncontrolled activation. of C5 and formation of the membrane attack complex. Its correct diagnosis allows prescribing treatment based on eculizumab, a C5 inhibitor. The clinical case of a patient with aHUS is presented, who three months after diagnosis, becomes pregnant. The objective is to highlight the importance of early differential diagnosis for the early establishment of effective treatment of this pathology, as well as management during pregnancy, childbirth and the postpartum period. The pathophysiology, diagnosis and genetic study are updated, as well as the therapeutic management of aHUS. Case Reports 27 year old women with no personal or family history of interest. She went to the emergency room in the full pandemic by SARSCov2 due to choluric urine along with fever of 38, myalgias and generalized arthralgias. At that time, PCR positive SARSCov2, deterioration of renal function was noted with Creatinine of 1.8 mg/dl (previous normal), LDH 1954 u/l, Platelets 21000, Hemoglobin 14.4 g/dl without schistocytes in smear, albumin/creatinine ratios 8700 and intense hematuria. It was interpreted as thrombotic thrombocytopenic purpura receiving corticosteroids, rituximab and plasmapheresis. After 48 hours, thrombopenia persists, schistocytes appear in smears and renal function deteriorates creatinine to 2.8 mg/dl. ADAMS 13 is received at normal values, considering at this time a diagnosis of aHUS, the previous treatment is interrupted and a dose of eculizumab 900 mg is received, doses of 900 per week are scheduled for 4 weeks in the fifth week 1200 mg and from Then on biweekly dose 1200 mg of eculizumab. At the third week of treatment, renal function has already normalized, hemolysis data have disappeared, Htcro and platelets have returned to normal. Proteinuria and hematuria disappears which has been maintained up to now. Good tolerance to treatment without any incidence, presenting a positive pregnancy test at three months. During pregnancy treatment with eculizumab is maintained. We continued with the biweekly regimen with 1200 mg of eculizumab until delivery. Labor is induced at week 37 receiving a extra dose of 1200 mg in the first 24 hours of delivery and continuing with 4 doses of 1200 mg once a week. Afterwards the dose is changed to a biweekly dose without modifying it throughout lactation until it ends. The reason is to avoid complement deregulation in the context of pregnancy and therefore ensure blockade. Subsequently it is done Switch to ravulizumab when breastfeeding begins as follows: A loading dose of 2700 mg (according to the interval of patient's weight) 15 days after the last dose of eculizumab. The maintenance dose is 3300 mg every 8 weeks starting 2 weeks after the loading dose. Normal kidney function has been maintained. She presented on debut positive serology for parvovirus B19, receiving treatment with Immunoglobulins and PCR SARSCov2 was positive prescribing treatment with remdesivir. Vitus (CMV, HBV, HCV and HIV) serology was negative and autoimmune study as well as study of complement and proteinogram were negative or within normal limits. No data suggestive of a neoplastic process. Genetic study has been detected a pathogenic variant associated with aHUS. Conclusion We found a heterozygous carrier patient in genetic study, who developed aHUS during a Sars-cov2 infection, which could have been a trigger for its clinical expression. The clinical course of this case highlights how crucial it is to identify atypical hemolytic uremic syndrome. The early initiation of eculizumab improves the prognosis and quality of life, with pregnancy becoming increasingly more likely and therapy with eculizumab does not have safety problems in this regard, although pregnant patients with aHUS should be closely monitored close during pregnancy and postpartum.

Abstract PO2-17-11: Management guidelines for epithelial atypia diagnosed in breast screening, based on an analysis of a large prospective cohort study (Sloane Project)

Abstract Background: Epithelial atypia in the breast is most frequently detected through breast screening. Internationally, guidelines differ between advising diagnostic surgical excision of screen-detected atypia versus vacuum-assisted excision (VAE), often with annual follow up surveillance mammography. Prospective data with detailed follow-up and outcomes for subsequent cancer events is lacking. We evaluated a large prospective cohort of screen-detected atypia (Sloane Project) and an expert consensus meeting to develop management recommendations. Methods: We undertook an observational analysis of women with screen-detected epithelial atypia (Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Lobular In Situ Neoplasia (LISN), or mixed atypia) reported to the National Health Service (NHS) Breast Screening Programme (BSP) between 01/04/03 and 20/06/18. We estimated cumulative incidence of invasive cancers per 1000 women within 1 and 2 subsequent screening rounds using cumulative incidence functions and repeated these by women’s age, type of atypia and year of diagnosis. Flexible parametric modelling produced hazard ratios (HR). The results were presented at a consensus meeting with clinical experts, patient representation, national decision-makers and commissioners from the NHS in England. A consensus on management recommendations was reached. Results: Among 3238 women (19088 person-years of follow up) with screen-detected atypia, diagnoses increased from 2010 (n=119) to 2015 (n=502). This coincided with the introduction of digital mammography into English screening centres from 2010 and changes in biopsy technique. A total of 141 invasive breast cancers were detected up to December 2018. Cumulative incidence of invasive breast cancer per 1000 women with atypia (ADH, FEA, LISN or mixed) was 14.2 (95% CI 10.3, 19.1) and 45.0 (36.3, 55.1) at 3- and 6-years post atypia based on 40 and 94 cancers, respectively. Women diagnosed with atypia during 2013-2018 had an invasive cancer detected less frequently within 3 years than women with an atypia diagnosis between 2003-2007 or 2008-2012 (6.0 invasive cancers (3.1, 10.9) per 1000 women in 2013-2018 Vs 24.3 (13.7, 40.1) and 24.6 (14.9, 38.3) in 2003-2007 and 2008-2012), suggesting that atypia diagnosis may increasingly contribute to ‘overdiagnosis’. Cancers detected were similar to the general screening population regarding grade, size and nodal involvement. Ipsilateral and contralateral cancers were detected in equal numbers, supporting the concept that atypia represents a risk factor rather than precursor of invasive cancer in the short term. Results by age and type of atypia did not suggest a need for risk-stratified management. Considering subsequent invasive cancer, VAE appeared to be as safe as diagnostic surgical excision of atypia (HR 0.75 (0.45, 1.25)). The expert consensus considered that increased screening of women with screen-detected atypia over and above routine 3-yearly screening was not beneficial, given the overall low numbers of cancers at three years. This applied to all types of atypia and all women who received digital mammography and diagnosis of atypia on core or vacuum-assisted biopsy followed by VAE within a quality assured NHS BSP. Conclusions: Breast atypia represents a risk factor for invasive cancer and does not necessitate surgical excision. Changes to mammography (digital vs plain film) and biopsy techniques (gauge of needle and use of vacuum-assistance) may lead to detection of atypia which is then ‘over-managed’. Current recommendations for annual mammography for 5 years after a diagnosis of epithelial atypia may be overly cautious. We suggest that women with screen detected atypia should be followed up with routine screening appointments. Citation Format: Karoline Freeman, David Jenkinson, Karen Clements, Matthew Wallis, Sarah E Pinder, Elena Provenzano, Hilary Stobart, Nigel Stallard, Olive Kearins, Nisha Sharma, Abeer Shaaban, Cliona Kirwan, Bridget Hilton, Alastair Thompson, Sian Taylor-Phillips. Management guidelines for epithelial atypia diagnosed in breast screening, based on an analysis of a large prospective cohort study (Sloane Project) [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 PO2-17-11.

Patient Characteristics Impact Performance of AI Algorithm in Interpreting Negative Screening Digital Breast Tomosynthesis Studies.

Background Artificial intelligence (AI) is increasingly used to manage radiologists' workloads. The impact of patient characteristics on AI performance has not been well studied. Purpose To understand the impact of patient characteristics (race and ethnicity, age, and breast density) on the performance of an AI algorithm interpreting negative screening digital breast tomosynthesis (DBT) examinations. Materials and Methods This retrospective cohort study identified negative screening DBT examinations from an academic institution from January 1, 2016, to December 31, 2019. All examinations had 2 years of follow-up without a diagnosis of atypia or breast malignancy and were therefore considered true negatives. A subset of unique patients was randomly selected to provide a broad distribution of race and ethnicity. DBT studies in this final cohort were interpreted by a U.S. Food and Drug Administration-approved AI algorithm, which generated case scores (malignancy certainty) and risk scores (1-year subsequent malignancy risk) for each mammogram. Positive examinations were classified based on vendor-provided thresholds for both scores. Multivariable logistic regression was used to understand relationships between the scores and patient characteristics. Results A total of 4855 patients (median age, 54 years [IQR, 46-63 years]) were included: 27% (1316 of 4855) White, 26% (1261 of 4855) Black, 28% (1351 of 4855) Asian, and 19% (927 of 4855) Hispanic patients. False-positive case scores were significantly more likely in Black patients (odds ratio [OR] = 1.5 [95% CI: 1.2, 1.8]) and less likely in Asian patients (OR = 0.7 [95% CI: 0.5, 0.9]) compared with White patients, and more likely in older patients (71-80 years; OR = 1.9 [95% CI: 1.5, 2.5]) and less likely in younger patients (41-50 years; OR = 0.6 [95% CI: 0.5, 0.7]) compared with patients aged 51-60 years. False-positive risk scores were more likely in Black patients (OR = 1.5 [95% CI: 1.0, 2.0]), patients aged 61-70 years (OR = 3.5 [95% CI: 2.4, 5.1]), and patients with extremely dense breasts (OR = 2.8 [95% CI: 1.3, 5.8]) compared with White patients, patients aged 51-60 years, and patients with fatty density breasts, respectively. Conclusion Patient characteristics influenced the case and risk scores of a Food and Drug Administration-approved AI algorithm analyzing negative screening DBT examinations. © RSNA, 2024.

Evaluation of Immunophenotypic Markers in Diagnosis and Prognosis of Atypical Chronic Lymphocytic Leukemia

Abstract: BACKGROUND: Atypical chronic lymphocytic leukemia diagnosis (aCLL) constitutes of monoclonal B lymphocytes of more than 5000 with unique morphological and immunophenotypic features different from classical or typical CLL. By immunophenotyping, aCLL is differentiated from typical CLL in the negative expression of either one or two immunophenotypic markers, mostly CD23 and/or CD5, provided that the patient does not have the diagnostic criteria of any other lymphoid neoplasm. aCLL patients are usually presented clinically in an aggressive manner and have worse outcomes compared to classic CLL. MATERIALS AND METHODS: This cross-sectional study includes 36 patients diagnosed as aCLL compared to 36 patients diagnosed as typical CLL. Diagnosis depends on blood film morphology and immunophenotyping by 8-color flow cytometry, the markers that are used for diagnosis depend on Matutes scoring system of CLL with the addition of CD200 and CD43, in addition to prognostic markers CD38 and CD305. The clinical staging system was applied, and the patients were divided into low-, intermediate-, and high-risk groups. Follow-up program for 6–12 months with evaluation of their hematological and clinical response and assessment of their remission state as was instituted in the hematological center. RESULTS: CD5 and CD23 are negative in 16.6% and 33.3% of aCLL patients, respectively, whereas CD200 and CD43 are positively expressed in 100% and 83.33% of aCLL patients, respectively, co-expression percentage of both markers in 83.33%. aCLL cases were commonly presented with high-risk group and usually have markers that are linked to poor prognosis, including negative expression of CD305 in 83.3% and positive CD38 expression in 75% of cases and only 5.56% of patients achieved remission state. CONCLUSIONS: aCLL is characterized by immunophenotypic differences in comparison to typical CLL. A definitive diagnosis needs additional markers, mainly CD200 and CD43; the prognosis of aCLL is worse than classical CLL.

Application of the newly published International System for Reporting Serous Fluid Cytopathology in atypical and suspicious diagnosis: a four-year retrospective analysis

Serous fluids offer crucial diagnostic insights, but inconsistent analysis hampers reporting quality, especially in indeterminate (ID) categories like atypia of undetermined significance (AUS) and suspicious for malignancy (SFM). The 2020 International System for reporting Serous Fluid Cytopathology (TIS) aims to standardize communication and reduce reporting disparities. This study evaluates TIS's role in AUS and SFM categories within our institution. A 4-year retrospective search of cytopathology reports from December 2015 to December 2019 for AUS and SFM diagnoses in pleural, ascitic, pericardial fluids, and peritoneal washings was performed and results reclassified using TIS definitions. The risk of malignancy (ROM) was calculated for existing and reclassified diagnoses. Over 4 years, we received 2998 serous fluid specimens. AUS constituted 2.3% (70 cases), while SFM constituted 0.5% (16 cases). Excluding repeats, 80 cases were TIS-reviewed. Sixteen cases of ID diagnoses were reclassified. Two cases of AUS were changed to negative for malignancy (NFM) and 12 to SFM. Two SFM cases were upgraded to malignancy. ROM shifted from 63% to 60% for AUS and 100% to 85% for SF (TIS's ROM range: AUS: 66% ± 10%; SFM: 82% ± 4.8%). This institution's ID diagnosis rate is low. AUS ROM is challenging but aligns with TIS, primarily favoring benign. All SFM diagnoses are highly suspicious but quantitatively inadequate for definitive malignancy, explaining the elevated ROM. AUS rate should gauge quality, not serve as a catch-all category. Algorithmic cytology with cell blocks and ancillary studies aids reclassification. TIS is user-friendly and is a consistent methodology for standardized reporting. Further studies are needed to evaluate ROM and define reproducible diagnostic criteria for each category for better system utilization.

Role of Uterine Artery Ligation and Chemotherapy in Atypical Cases of Gestational Trophoblastic Disease: A Case Report of Atypical GTD Diagnosis & Management

Introduction Gestational trophoblastic disease[1 i ] is a rare developmental form of proliferative trophoblastic tissue in women of reproductive age that involves both benign and malignant entities that include hydatidiform mole (complete or partial), choriocarcinoma, invasive mole, epithelioid trophoblastic tumor (ETT), and placental site trophoblastic tumor (PSTT). Four of these known as gestational trophoblastic neoplasia [2 ii], and hydatidiform is most common type of GTD. Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease that is almost always malignant, and can metastasize and be fatal if not treated. The ultimate treatment for GTD includes surgery (evacuation of the proliferative trophoblastic tissue, hysterectomy), chemotherapy regimens, radiotherapy and emerging targeted therapies. It is one of the most chemotherapy responsive and highly curable cancer. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a case of atypical GTD {uncommon, that is not fitting a single diagnosis} treated by chemotherapy and bilateral uterine artery ligation.

Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort.

Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored. Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ). Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ=0.73-0.91) and follow-up histopathology (κ=0.66-0.85). The agreement was lowest in the inadequate (κ=0.05) and atypical (κ=0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16). Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS.

Morgellons disease: a narrative review.

Morgellons disease is characterized by the persistent delusion of skin infestation, ultimately inflicting wounds and impairing quality of life. There is insufficient and conflicting research pertaining to this condition, imposing challenges on clinicians in understanding, diagnosing, and treating it. In this review, we summarize the available literature on Morgellons disease including its historical evolution, epidemiology, proposed pathophysiology, underlying structural and functional brain pathologies, typical and atypical clinical presentations, diagnosis, and treatment. A comprehensive review of the literature was conducted on PubMed, Embase, and Scopus using specified keywords. Selected articles were screened by two independent reviewers based on set inclusion and exclusion criteria. Conflicts were resolved by a third reviewer as needed. No limit to the date of selected articles was set due to the scarce literature available on the subject. Morgellons disease is an underdiagnosed entity, owing mostly to the lack of an established pathophysiology and treatment guidelines. While many authors classify it as a type of delusional infestation (DI), others correlate MD with an underlying spirochetal infection, namely Lyme disease. Neuroimaging studies have revealed abnormalities in the "fronto-striato-thalamo-parietal network", a finding common to patients with DI, in addition to alterations in structures related to the "Itch Processing Pathway". Patients tend to extract fibers from their skin lesions and place them in a match box hence the term "match box sign". The diagnosis is that of exclusion, requiring extensive work up to rule out secondary causes and differential diagnoses. Treatment is largely based on the use of antipsychotics, with or without cognitive behavioral therapy. Despite being a diagnosis of exclusion, clinicians must be aware of this entity and have a profound understanding of the pathogenesis underlying it. Upon clinical suspicion, secondary Morgellons should always be ruled out through a thorough history taking, physical examination, and laboratory exams. Despite the challenges brought by the heterogeneous presentation of the condition and the paucity of research revolving around it, the great impact that Morgellons disease has on patients' quality of life forms a pressing need for its adequate detection, diagnosis, and treatment.

Impact of Implementing Paris System on Diagnostic Precision and Management of Urinary Bladder Neoplasms.

The diagnosis of atypia has always been under question both by the pathologist and the clinician. It was one of the main aims of the Paris system (TPS) to reduce the number of cases under the AUC (Atypical urothelial cells) category. With the strict criteria laid down by the Paris system, the rate of diagnosis of this category has reduced markedly. This study was done to test the impact of implementing TPS categories and criteria in comparison to our previously used system. TPS is one of the important deciding factors for the management of the patient. The management of patients with AUC diagnosis often varies depending on the treating physician (urologist/nonurologist). For further categorization of the diagnosis of AUC, markers like p53 and Ki67 can be used. One hundred urinary cytology specimens received for the period of 6months were included in the study. The presentation of the categorical variables was done in the form of numbers and percentages (%). Interrater kappa agreement was used to find out the strength of the agreement between the Paris system and the traditional system. Using histopathological diagnosis as the gold standard, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic accuracy were calculated. Immunohistochemistry was performed on the cell block for Ki67 and p53, and their values were correlated with histopathological examination, using Spearman's rank correlation. The interrater kappa agreement analyzed between the traditional reporting system and the Paris system was 0.522. Around 32% (6/19) of cases that were reported as AUC by the traditional system were recategorized under negative for high-grade urothelial carcinoma (NHGUC) by the Paris system. Thus, obliviating the need for further management and decreasing the unnecessary cost of the health care system with a decrease in patient anxiety. Histopathology was available in 28 cases and diagnostic accuracy of urine cytology classified by TPS was 89.2% with a sensitivity of 94.4%, specificity of 80%, positive likelihood ratio of 89.4, and negative likelihood ratio of 88.6. The correlation coefficient of p53 with grading of carcinoma was found to be strong at 0.864. The correlation coefficient of Ki67 with grading of carcinoma was also as strong as 0.885. TPS along with immunohistochemistry improves the performance of urine cytology by reclassifying the AUC category into other groups and increases the sensitivity for detecting HGUC.

Examining the placement of atypical anorexia nervosa in the eating disorder diagnostic hierarchy relative to bulimia nervosa and binge-eating disorder.

Some individuals meet the criteria for atypical anorexia nervosa and another eating disorder simultaneously. The current study evaluated whether allowing a diagnosis of atypical anorexia nervosa to supersede a diagnosis of bulimia nervosa (BN) or binge-eating disorder (BED) provided additional information on psychological functioning. Archival data from 650 university students (87.7% female, 69.4% white) who met Eating Disorder Diagnostic Survey for DSM-5 eating disorder criteria and completed questionnaires assessing quality of life, eating disorder-related impairment, and/or eating pathology at a single time point. Separate regression models used diagnostic category to predict quality of life and impairment. Two diagnostic schemes were used: the DSM-5 diagnostic scheme and an alternative scheme where atypical anorexia nervosa superseded all diagnoses except anorexia nervosa. Model fit was compared using the Davidson-Mackinnon J test. Analyses were pre-registered (https://osf.io/2ejcd). Allowing an atypical anorexia nervosa diagnosis to supersede a BN or BED diagnosis provided better fit to the data for eating disorder-related impairment (p = .02; n = 271), but not physical, psychological, or social quality of life (p's ≥ .33; n = 306). Allowing an atypical anorexia nervosa diagnosis to supersede a BN or BED diagnosis provided a better fit in cross-sectional models predicting purging (p = .02; n = 638), but not body dissatisfaction, binge eating, restricting, or excessive exercise (p's ≥ .08; n's = 633-647). The current data support retaining the DSM-5 diagnostic scheme. More longitudinal work is needed to understand the predictive validity of the atypical anorexia nervosa diagnosis. The current study examined how changes to the diagnostic categories for eating disorders may change how diagnoses are associated with quality of life and impairment. Overall, findings suggest that the diagnostic hierarchy should be maintained.

SAT244 Hypercalcemia Induced By Inconspicuous Histoplasmosis Infection

Abstract Disclosure: M. Alkhathlan: None. Y. Li: None. A. Siddiqui: None. S. Goud: None. Background: Hypercalcemia is a common condition with a variety of etiologies. In general, it can be categorized as either parathyroid hormone (PTH) dependent or independent. In those with non-PTH mediated hypercalcemia, elevated 1, 25 vitamin D is one of the causes and among pathologies behind it are sarcoidosis, malignancy, and to less extent infectious process. An important determinant in the management of elevated 1,25vitD is to identify the source of 1,25vitD overproduction as the choice of treatment can affect the outcomes and increase the risk of mortality. Clinical Case: Our patient is an 81-year-old man who had been admitted to the hospital for nonspecific fatigue and weakness for two months. He was discharged from another hospital with similar complaints without resolution. At the time of admission, he was noted to have elevated total calcium 12.5 mg/dL (8.4-10.2) with albumin 3.0 g/dL (3.5-5.2), subacute kidney injury with creatinine 3.46 mg/dL (0.7-1.3), suppressed parathyroid hormone (PTH) and markedly elevated 1,25-dihydroxy vitamin D (1,25OH2D) 128 pg/mL (19.9-79.3). His calcium and kidney function were normal 4 months ago. The hypercalcemia was refractory to intravenous fluid, loop diuretic or calcitonin administration. Extensive workup eventually revealed disseminated histoplasmosis infection with blood and urine positive for histoplasmosis antigens. Bone marrow aspiration showed scattered non-necrotizing granulomas. With antifungal treatment, his calcium level returned to the normal range in two weeks (8.9 mg/dL) and was maintained in the normal range. Conclusion: Hypercalcemia is a rare presentation of histoplasmosis. Pubmed keyword search of hypercalcemia and histoplasmosis returned 18 clinical case reports from 1977 to 2021. The case review showed a striking similarity in atypical clinical presentation and diagnosis challenges. Hypercalcemia is most developed in histoplasmosis disseminated cases with elevated 1,25vitD levels and pathology identification of granulomas in some of the cases. With successful antifungal treatment, patients will have prompt recovery of hypercalcemia. Steroid treatment is a well know and effective treatment by suppressing 1-alpha hydroxylation of 25-vitD. However, treatment with steroids before establishing diagnosis due to Inconspicuous presentations or delay in diagnosis may lead to mortality quickly. Presentation: Saturday, June 17, 2023

Co-producing principles to guide health research: an illustrative case study from an eating disorder research clinic

BackgroundThere is significant value in co-produced health research, however power-imbalances within research teams can pose a barrier to people with lived experience of an illness determining the direction of research in that area. This is especially true in eating disorder research, where the inclusion of co-production approaches lags other research areas. Appealing to principles or values can serve to ground collaborative working. Despite this, there has not been any prior attempt to co-produce principles to guide the work of a research group and serve as a basis for developing future projects.MethodsThe aim of this piece of work was to co-produce a set of principles to guide the conduct of research within our lived experience led research clinic, and to offer an illustrative case for the value of this as a novel co-production methodology. A lived experience panel were recruited to our eating disorder research group. Through an iterative series of workshops with the members of our research clinic (composed of a lived experience panel, clinicians, and researchers) we developed a set of principles which we agreed were important in ensuring both the direction of our research, and the way in which we wanted to work together.ResultsSix key principles were developed using this process. They were that research should aim to be: 1) real world—offering a clear and concrete benefit to people with eating disorders, 2) tailored—suitable for marginalised groups and people with atypical diagnoses, 3) hopeful—ensuring that hope for recovery was centred in treatment, 4) experiential—privileging the ‘voice’ of people with eating disorders, 5) broad—encompassing non-standard therapeutic treatments and 6) democratic—co-produced by people with lived experience of eating disorders.ConclusionsWe reflect on some of the positives as well as limitations of the process, highlighting the importance of adequate funding for longer-term co-production approaches to be taken, and issues around ensuring representation of minority groups. We hope that other health research groups will see the value in co-producing principles to guide research in their own fields, and will adapt, develop, and refine this novel methodology.