Diagnostic Adjunct Research Articles

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Claudin-4 Expression in the Distinction of Mammary and Extramammary Paget Disease From Morphologic Mimics: Diagnostic Utility and Pitfalls.

Claudin-4 Expression in the Distinction of Mammary and Extramammary Paget Disease From Morphologic Mimics: Diagnostic Utility and Pitfalls.

The EMS stress view: occult pelvic instability revealed by pre-hospital pelvic binder placement.

To describe and evaluate the serendipitous pelvic binder stress radiographs of lateral compression type (LC) pelvic ring injuries. This was a retrospective case series performed at a single, level I academic trauma center from 2016 to 2018. All patients presenting with a minimally displaced LC pelvic ring injury were reviewed (< 10cm displacement on static pelvic radiographs). Patients with X-rays (XR) in a pelvic binder (EMS stress) and with the pelvic binder removed were included. Pelvic ring stability was determined by attending surgeon evaluation of EMS stress radiographs versus static XR of the pelvis. Patients were treated non-operatively and allowed to weight bear or taken to the operating room for exam under anesthesia (EUA) and potential operative fixation. Clinical success of treatment was determined by evaluation of further displacement at the completion of their most recent follow-up. Thirty-seven patients of the initial 398 reviewed met inclusion criteria. Fourteen of 37 patients (38%) were categorized as stable with no significant pelvis displacement seen on EMS stress and were treated non-operatively without further sequelae (4.6 months mean follow-up). The remaining 23/37 (62%) were treated operatively. Occult instability was identified on EMS stress in 14 (61%) of those 23 patients and the remainder were determined to be unstable based upon fracture pattern or EUA. All patients went on to successful treatment without significant pelvic deformity (7.8 months mean follow-up). The EMS stress XR is a valuable, opportunistic evaluation in LC pelvic ring injuries. This evaluation is a useful diagnostic adjunct to alert the provider that additional stress imaging may be indicated to evaluate for occult pelvic ring instability.

Distinguishing Glaucoma, Cataract, and Glaucoma Suspect Based on Visual Symptoms.

Cataract, glaucoma, and glaucoma suspect patients report differing visual symptoms. Asking patients about their visual symptoms may provide useful diagnostic information and inform decision-making in patients with comorbid conditions. To compare visual symptoms in glaucoma, glaucoma suspect (controls), and cataract patients. Glaucoma, cataract, and glaucoma suspect patients at Wilmer Eye Institute responded to a questionnaire rating the frequency and severity of 28 symptoms. Univariate and multivariable logistic regression determined the symptoms that best differentiate each disease pair. In all, 257 patients (mean age: 67.4 ± 13.4y; 57.2% female; 41.2% employed), including 79 glaucoma, 84 cataract, and 94 glaucoma suspect patients, participated. Compared with glaucoma suspects, glaucoma patients were more likely to report poor peripheral vision (OR 11.29, 95% CI: 3.73-34.16), better vision in 1 eye (OR 5.48, 95% CI: 1.33-22.64), and light sensitivity (OR 4.85, 95% CI: 1.78-13.24), explaining 40% of the variance in diagnosis (ie, glaucoma vs. glaucoma suspect). Compared with controls, cataract patients were more likely to report light sensitivity (OR 3.33, 95% CI: 1.56-7.10) and worsening vision (OR 12.20, 95% CI: 5.33-27.89), explaining 26% of the variance in diagnosis (ie, cataract vs. glaucoma suspect). Compared with cataract patients, glaucoma patients were more likely to report poor peripheral vision (OR 7.24, 95% CI: 2.53-20.72) and missing patches (OR 4.91, 95% CI: 1.52-15.84), but less likely to report worsening vision (OR 0.08, 95% CI 0.03-0.22), explaining 33% of the variance in diagnosis (ie, glaucoma vs. cataract). Visual symptoms distinguish disease state to a moderate degree in glaucoma, cataract, and glaucoma suspect patients. Asking about visual symptoms may serve as a useful diagnostic adjunct and inform decision-making, for example, in glaucoma patients considering cataract surgery.

Assessment of artificial intelligence-aided reading in the detection of nasal bone fractures.

Artificial intelligence (AI) technology is a promising diagnostic adjunct in fracture detection. However, few studies describe the improvement of clinicians' diagnostic accuracy for nasal bone fractures with the aid of AI technology. This study aims to determine the value of the AI model in improving the diagnostic accuracy for nasal bone fractures compared with manual reading. A total of 252 consecutive patients who had undergone facial computed tomography (CT) between January 2020 and January 2021 were enrolled in this study. The presence or absence of a nasal bone fracture was determined by two experienced radiologists. An AI algorithm based on the deep-learning algorithm was engineered, trained and validated to detect fractures on CT images. Twenty readers with various experience were invited to read CT images with or without AI. The accuracy, sensitivity and specificity with the aid of the AI model were calculated by the readers. The deep-learning AI model had 84.78% sensitivity, 86.67% specificity, 0.857 area under the curve (AUC) and a 0.714 Youden index in identifying nasal bone fractures. For all readers, regardless of experience, AI-aided reading had higher sensitivity ([94.00 ± 3.17]% vs [83.52 ± 10.16]%, P< 0.001), specificity ([89.75 ± 6.15]% vs [77.55 ± 11.38]%, P< 0.001) and AUC (0.92 ± 0.04 vs 0.81 ± 0.10, P< 0.001) compared with reading without AI. With the aid of AI, the sensitivity, specificity and AUC were significantly improved in readers with 1-5 years or 6-10 years of experience (all P< 0.05, Table4). For readers with 11-15 years of experience, no evidence suggested that AI could improve sensitivity and AUC (P= 0.124 and 0.152, respectively). The AI model might aid less experienced physicians and radiologists in improving their diagnostic performance for the localisation of nasal bone fractures on CT images.

The Influence of Computerized Tomography Imaging on Treatment of Periprosthetic Proximal Femur Fractures.

Introduction Periprosthetic femur fractures (PPFF) are increasing in incidence and management of such injuries requires a specialized skill set combined with detailed knowledge of component design. To assist with planning, computed tomography (CT) can beusedpre-operatively to give a surgeon more information. No study to date has shown the utility of obtaining preoperative CT. The goal of this study is to show that CT is a useful diagnostic adjunct and report any differences in how subspecialties such as orthopedic traumatologists and arthroplasty surgeonsuse it. Methods Seventeen PPFF cases met our inclusion criteria.They were shown to six faculty, three trauma and three arthroplasty surgeons. They viewed the plain radiographs and then CTs. After each they filled out the same questionnaire that included their assessment of diagnosis and proposed treatment plan both before and after access to CT imaging. Fleiss and Cohen kappa were used to compare inter- and intra-observer reliability. Results The interobserver kappa values (k) in diagnosis were 0.348 pre- and 0.371 post-CT, while trauma and arthroplasty were 0.328 to 0.260 and 0.821 to 0.881 respectively. The interobserver reliability in treatment was 0.336 pre- and 0.254 post-CT, while trauma and arthroplasty were 0.323 to 0.288 and 0.688 to 0.519. For intraobserver the average k for diagnosis and treatment were 0.818 and 0.671. Broken down by subspecialty they were 0.874 and 0.831 and 0.762 and 0.510 for trauma and arthroplasty. There were 11 diagnostic and 24 treatment changes. Conclusion CT provides diagnostic changes 10% and treatment changes 24% of the time. However, it does not lead to greater agreement among the surgeons on either. Arthroplasty uses CT more to guide both their treatment and the diagnosis, and they agree more than trauma surgeons. Most of the treatment changes come from adding or removing a plate, and the most common diagnostic change was shared by A to B1 and B2 to B3. This suggests fracture extension and bone stock are better evaluated by CT.

E003 Why do rheumatologists request PET-CT scans and what do they show: an audit from a tertiary London Hospital

Abstract Background/Aims (18F)FDG PET-CT is an imaging tool with utility in the diagnosis of inflammation, infection and malignancy. In rheumatology settings, it is most commonly used for the diagnosis and monitoring of large vessel vasculitis (LVV), sarcoidosis, polymyalgia rheumatica (PMR), IgG-4 disease and myositis. Whilst PET-CT is highly sensitive for the detection of inflammation, concurrent corticosteroid use impairs this. Furthermore, uptake can be non-specific and incidental abnormalities are often reported. Few cohorts have investigated the real-life use of PET-CT including clinical indication, rheumatological and non-rheumatological findings and patient outcomes. Methods 98 PET-CT scans were requested by the rheumatology department at St Georges NHS Foundation Trust from January 2017 to December 2021. Data including patient demographics, pre-existing rheumatological disease, corticosteroid use and inflammatory marker levels were collected. Indication for PET-CT and PET-CT findings were reviewed. Results As summarised in Table 1, PET-CT scans were most commonly requested for the investigation of raised inflammatory markers, poor response to therapy, concerning clinical features, for the characterisation of abnormal imaging findings and for routine monitoring of disease. LVV and malignancy were the most commonly considered differential diagnoses. At the time of PET-CT scan, 59 (60%) patients were taking corticosteroids. 58 of these patients were prescribed prednisolone (dose ranging between 2mg to 80mg, mean dose 19.6mg OD, median dose 15mg OD) In our audit, 39.8% of PET-CT showed active rheumatological disease. 32.6% showed non-rheumatological abnormalities with 2% demonstrating new cancer diagnoses. The detection of incidental non-specific imaging findings commonly led to the request of further diagnostic tests including ultrasound imaging (11 patients) and endoscopy (7 patients). Conclusion In conclusion, PET-CT is a useful imaging tool in the diagnosis and monitoring of rheumatological inflammatory conditions. Despite a majority of patients taking corticosteroids at the time of scan, PET-CT remained an effective diagnostic adjunct. A large number of non-rheumatological imaging abnormalities were seen in our cohort; in most cases, the clinical significance was not immediately clear and further investigations were needed. Further guidance is needed to determine the characterisation and management of these incidental findings to avoid unnecessary, costly and sometimes invasive tests. Disclosure K. Biddle: None. K. Chaabo: None.

Diagnostic accuracy of clinical examination to identify life- and limb-threatening injuries in trauma patients

BackgroundTimely and accurate identification of life- and limb-threatening injuries (LLTIs) is a fundamental objective of trauma care that directly informs triage and treatment decisions. However, the diagnostic accuracy of clinical examination to detect LLTIs is largely unknown, due to the risk of contamination from in-hospital diagnostics in existing studies. Our aim was to assess the diagnostic accuracy of initial clinical examination for detecting life- and limb-threatening injuries (LLTIs). Secondary aims were to identify factors associated with missed injury and overdiagnosis, and determine the impact of clinician uncertainty on diagnostic accuracy.MethodsRetrospective diagnostic accuracy study of consecutive adult (≥ 16 years) patients examined at the scene of injury by experienced trauma clinicians, and admitted to a Major Trauma Center between 01/01/2019 and 31/12/2020. Diagnoses of LLTIs made on contemporaneous clinical records were compared to hospital coded diagnoses. Diagnostic performance measures were calculated overall, and based on clinician uncertainty. Multivariate logistic regression analyses identified factors affecting missed injury and overdiagnosis.ResultsAmong 947 trauma patients, 821 were male (86.7%), median age was 31 years (range 16–89), 569 suffered blunt mechanisms (60.1%), and 522 (55.1%) sustained LLTIs. Overall, clinical examination had a moderate ability to detect LLTIs, which varied by body region: head (sensitivity 69.7%, positive predictive value (PPV) 59.1%), chest (sensitivity 58.7%, PPV 53.3%), abdomen (sensitivity 51.9%, PPV 30.7%), pelvis (sensitivity 23.5%, PPV 50.0%), and long bone fracture (sensitivity 69.9%, PPV 74.3%). Clinical examination poorly detected life-threatening thoracic (sensitivity 48.1%, PPV 13.0%) and abdominal (sensitivity 43.6%, PPV 20.0%) bleeding. Missed injury was more common in patients with polytrauma (OR 1.83, 95% CI 1.62–2.07) or shock (systolic blood pressure OR 0.993, 95% CI 0.988–0.998). Overdiagnosis was more common in shock (OR 0.991, 95% CI 0.986–0.995) or when clinicians were uncertain (OR 6.42, 95% CI 4.63–8.99). Uncertainty improved sensitivity but reduced PPV, impeding diagnostic precision.ConclusionsClinical examination performed by experienced trauma clinicians has only a moderate ability to detect LLTIs. Clinicians must appreciate the limitations of clinical examination, and the impact of uncertainty, when making clinical decisions in trauma. This study provides impetus for diagnostic adjuncts and decision support systems in trauma.

Utilizing ultrasound in suspected necrotizing enterocolitis with equivocal radiographic findings

BackgroundTo examine the use of abdominal ultrasound (AUS) as a diagnostic adjunct in the diagnosis of necrotizing enterocolitis (NEC) in cases where abdominal radiography (AXR) is equivocal in order to reduce unnecessary antibiotic use in neonates.MethodsRetrospective study (2017–2019) of infants undergoing NEC evaluation with equivocal AXR findings (n = 54). Paired AXR and AUS were reviewed with respect to presence or absence of pneumatosis. Concordance of AUS findings with decision to treat for NEC was evaluated.ResultsAmong 54 infants where AXR was equivocal, AUS demonstrated presence of pneumatosis in 22 patients (41%), absence of pneumatosis in 31 patients (57%), and was equivocal in 1 patient. All patients with pneumatosis on AUS were treated for NEC. Of 31 patients without pneumatosis on AUS, 25 patients (78%) were not treated for NEC. Patients without pneumatosis on AUS received a significantly shorter mean duration of antibiotics compared to those with pneumatosis (3.3 days (+/− 4.8 days) vs 12.4 days (+/− 4.7 days)); p < 0.001). Of those patients not treated, none required treatment within 1 week following negative AUS.ConclusionAUS is a valuable tool for evaluating the presence or absence of pneumatosis in the setting of equivocal AXR. Absence of pneumatosis on AUS informs clinical decision making and reduces unnecessary treatment and antibiotic usage.

β-catenin, Pax2, and Pten Panel Identifies Precancers Among Histologically Subdiagnostic Endometrial Lesions.

Despite refinements in histologic criteria for the diagnosis of endometrioid precancers, many challenging cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, Pax2, and Pten was identified as a useful diagnostic adjunct. However, previous studies focused either on cancers or diagnostically unambiguous precancers, leaving questions about the applicability and utility of the panel in endometria with architectural features near or below the threshold of accepted histologic criteria for endometrioid precancers. Here, in a retrospective study of 90 patients, we evaluated the performance of the 3-marker panel. Notably, the panel detected a subset of disordered proliferative endometria (8/44, 18%), nonatypical hyperplasias (19/40, 48%), and cases with ambiguous features (3/6, 50%) with aberrancy for ≥1 markers. Marker-aberrant cases were more likely to progress to endometrioid precancer or cancer (P=0.0002). Patterns of marker aberrancy in the index and progressor cases from individual patients provided evidence for origin in a common precursor, and next-generation sequencing of the progressor cases rationalized marker aberrancy for β-catenin and Pten. The results unequivocally demonstrate that some lesions that do not approach current histologic thresholds are bona fide neoplastic precursors with clinically-relevant driver events that can be detected by the 3-marker panel. The findings provide further validation for the diagnostic utility of the panel in clinical practice and its application in difficult or ambiguous cases.

Appendiceal Inversion Presenting as a Cecal Polypoid Mass on Screening Colonoscopy: A Case Report and Review of Available Diagnostic Adjuncts to Differentiate Benign From Malignant Colorectal Pathology

Appendiceal inversion is uncommon. It may be a benign finding or seen in association with malignant pathology. When detected, it masquerades as a cecal polyp which poses a diagnostic dilemma with malignancy in the differential. In this report, we highlight a case of a 51-year-old patient with an extensive surgical history as a newborn in the setting of omphalocele and intestinal malrotation, who was found to have a 4 cm cecal polypoid growth on screening colonoscopy. He underwent a cecectomy for tissue diagnosis. Ultimately, the polyp was found to be an inverted appendix without evidence of malignancy. Currently, suspicious colorectal lesions which cannot be removed by polypectomy are primarily addressed with surgical excision. We reviewed the literature for available diagnostic adjuncts to better differentiate benign from malignant colorectal pathology. The application of advanced imaging and molecular technology will allow for improved diagnostic accuracy and subsequent operative planning.

ISUOG Practice Guidelines (updated): performance of fetal magnetic resonance imaging.

ISUOG Practice Guidelines (updated): performance of fetal magnetic resonance imaging.

Evaluation of myocardial performance by serial speckle tracking echocardiography in diagnosis and follow-up of a patient with eosinophilic myocarditis

BackgroundSpeckle tracking echocardiography (STE) has been used as an adjunct diagnostic modality in patients with eosinophilic myocarditis. Its serial dynamic nature, however, has never been reported before.Case presentationA 17-year-old boy presented in cardiogenic shock state. His full blood count revealed an absolute eosinophilic count of 11.18 × 103/μL. An emergency 2D echocardiogram (2DE) showed global left ventricular hypokinesia with LVEF = 9.0% by Simpson’s method and a large amount of pericardial effusion. STE showed a global longitudinal strain (GLS) of − 4.1%. Because of his poor clinical status and presence of marked hypereosinophilia and the possibility of eosinophilic myocarditis (EM), parenteral pulse therapy with methylprednisolone and inotropes was started with subsequent improvement within the next 48 h. Over the next few days, he had his first cardiovascular magnetic resonance imaging (CMR), which showed late gadolinium enhancement (LGE) in different cardiac regions. After two weeks of therapy, he left the hospital in a stable condition, with LVEF = 38.0%, and GLS = − 13.9%. He did well during his two months of outpatient follow-ups and was found to have an absolute eosinophil count of 0.0% on several occasions. Unfortunately, he was re-admitted because of treatment non-compliance with almost the same, albeit milder, symptoms. The WBC count was 18.1 × 103 per microliter, and the eosinophilic count was 5.04 × 103/μL (28%). Heart failure treatment and high-dose prednisolone were started. After 15 days of admission, he got better and was discharged. During both hospital admissions and several months of follow-up, he had multiple 2DEs, STE, and two CMR studies. None of his STEs were identical to the prior studies and were dynamic with frequent wax and wanes throughout the admissions and follow-ups. Thus a single admission-time STE study was not sufficient enough to properly predict the patient’s outcome. Follow-up STEs showed new sites of myocardial involvement despite the absence of eosinophilia.ConclusionThe use of STE in this patient, proved to have an added value in the evaluation and stratification of the left ventricular function in patients with EM and can be used as a diagnostic adjunct to CMR for diagnosis of EM.

Comparing Emergency Department Stress of Lateral Compression Type 1 Pelvis Fractures With a Validated Instability Scoring System.

Lateral compression type 1 (LC1) pelvic ring injuries represent a heterogeneous group of fractures with controversial surgical indications. Recently, multiple institutions have suggested the safety and reliability of an emergency department (ED) stress to evaluate for occult instability. The purpose of this study was to correlate ED stress examination of LC1 pelvis fractures against a validated fracture instability scoring system. This was a retrospective review of a consecutive series of 70 patients presenting with minimally displaced LC1 fractures at a level 1 academic trauma center. All patients were stressed in the ED radiology suite, and displacement was measured by comparing calibrated stress radiographs with static radiographs (>10 mm displacement defined positivity). ED stress results were compared with radiographic scores assigned according to the validated Beckmann scoring system (score <7: stable-nonsurgical recommendation; score 7 to 9: indeterminant recommendation; and score >9: unstable-surgical recommendation). Thirteen patients had a positive ED stress examination, and 57 patients stressed negative. The mean displacement was significantly different between the three groups (Beckmann 5 to 6: 3.31 mm, SD = 2.4; Beckmann 7 to 9: 4.23 mm, SD = 3.2; Beckmann 10+: 12.1 mm, SD = 8.6; P < 0.001). Zero of 18 patients in the stable group stressed positive, and only 3 of 38 patients in the indeterminant group stressed positive (7.9%). Finally, 10 of 14 patients in the unstable group stressed positive (71.4%; P < 0.001) . Sacral displacement ( P = 0.001), superior ramus location ( P < 0.02), and sacral columns ( P < 0.001) significantly predicted ED stress positivity in multivariate analysis. Comparison of a validated instability scoring system with ED stress examination of minimally displaced LC1 fractures in awake and hemodynamically stable patients showed excellent correlation. This suggests that the ED stress examination is a useful diagnostic adjunct. LC1 fracture characteristics should be analyzed to determine which pelvic fracture characteristics determine occult instability before stress examination. Level III diagnostic.

GLI1 Immunohistochemistry Distinguishes Mesenchymal Neoplasms With GLI1 Alterations From Morphologic Mimics.

Glioma-associated oncogene 1 ( GLI1 ) alterations have been described in pericytoma with t(7;12), gastroblastoma, plexiform fibromyxoma, and an emerging class of GLI1 -rearranged or amplified mesenchymal neoplasms including "nested glomoid neoplasm". The immunophenotype of these tumor types is nonspecific, making some cases difficult to diagnose without sequencing. The utility of GLI1 immunohistochemistry (IHC) in distinguishing nested glomoid neoplasms and pericytomas with t(7;12) from morphologic mimics is unknown. To investigate the diagnostic value of GLI1 IHC, we determined its sensitivity and specificity in a "test cohort" of 23 mesenchymal neoplasms characterized by GLI1 alterations, including 12 nested glomoid neoplasms (7 GLI1 -rearranged, 4 GLI1 amplified, and 1 unknown GLI1 status), 9 pericytomas with t(7;12), 1 gastroblastoma, and 1 malignant epithelioid neoplasm with PTCH1 :: GLI1 fusion. GLI1 IHC was 91.3% sensitive in this cohort; all tumors except 2 pericytomas with t(7;12) expressed GLI1. GLI1 was also expressed in 1 of 8 (12%) plexiform fibromyxomas. Nineteen of 22 GLI1-positive tumors showed nuclear and cytoplasmic staining, while 3 showed nuclear staining only. GLI1 IHC was 98.0% specific; among morphologic mimics [40 well-differentiated neuroendocrine tumors, 10 atypical lung carcinoids, 20 paragangliomas, 20 glomus tumors, 20 solitary fibrous tumors, 10 Ewing sarcomas, 10 alveolar rhabdomyosarcomas (ARMS), 10 BCOR -altered sarcomas, 10 myoepitheliomas, 9 myopericytomas, 9 epithelioid schwannomas, 9 ossifying fibromyxoid tumors, 10 biphasic synovial sarcomas, 10 PEComas, 31 gastrointestinal stromal tumors, 10 inflammatory fibroid polyps, 11 pseudoendocrine sarcomas], 5 of 249 tumors expressed GLI1 (2 well-differentiated neuroendocrine tumors, 1 ARMS, 1 Ewing sarcoma, 1 BCOR -altered sarcoma). GLI1 IHC was also performed on a separate cohort of 13 molecularly characterized mesenchymal neoplasms in which GLI1 copy number gain was identified as a putatively secondary event by DNA sequencing (5 dedifferentiated liposarcoma [DDLPS], 2 adenosarcomas, 2 unclassified uterine sarcomas, 1 leiomyosarcoma, 1 ARMS, 1 intimal sarcoma, 1 osteosarcoma); 2 DDLPS, 1 ARMS, and 1 unclassified uterine sarcoma expressed GLI1. Lastly, because pleomorphic sarcomas sometimes show GLI1 amplification or copy number gain, GLI1 IHC was performed on a separate "pleomorphic sarcoma" cohort: GLI1 was expressed in 1 of 27 DDLPS, 1 of 9 leiomyosarcomas, and 2 of 10 pleomorphic liposarcomas, and it was negative in 23 well-differentiated liposarcomas and 9 unclassified pleomorphic sarcomas. Overall, GLI1 IHC was 91.3% sensitive and 98.0% specific for mesenchymal tumor types with driver GLI1 alterations among morphologic mimics. GLI1 expression was less frequent in other tumor types with GLI1 copy number gain. Given its specificity, in the appropriate morphologic context, GLI1 IHC may be a useful diagnostic adjunct for mesenchymal neoplasms with GLI1 alterations.

Recurrent FOSL1 rearrangements in desmoplastic fibroblastoma.

The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic fibroblastoma is characterised by overexpression of FOSL1. However, previous studies using cytogenetic and molecular techniques did not identify an underlying somatic change involving the FOSL1 gene to explain this finding. Prompted by an unusual index case, we report the discovery of a novel FOSL1 rearrangement in desmoplastic fibroblastoma using whole-genome and targeted RNA sequencing. We investigated 15 desmoplastic fibroblastomas and 15 fibromas of tendon sheath using immunohistochemistry, in situ hybridisation and targeted RNA sequencing. Rearrangements in FOSL1 and FOS were identified in 10/15 and 2/15 desmoplastic fibroblastomas respectively, which mirrors the pattern of FOS rearrangements observed in benign bone and vascular tumours. Fibroma of tendon sheath, which shares histological features with desmoplastic fibroblastoma, harboured USP6 rearrangements in 9/15 cases and did not demonstrate rearrangements in any of the four FOS genes. The overall concordance between FOSL1 immunohistochemistry and RNA sequencing results was 90%. These findings illustrate that FOSL1 and FOS rearrangements are a recurrent event in desmoplastic fibroblastoma, establishing this finding as a useful diagnostic adjunct and expanding the spectrum of tumours driven by FOS gene family alterations. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Modified Myocardial Performance Index in Fetal Growth Disturbances as Diagnostic and Prognostic Adjunct.

Fetal growth disturbance can be associated with cardiac dysfunction. This study aimed to assess the modified myocardial performance index in growth-restricted and appropriate for gestational age fetuses and evaluate both its prognostic value in perinatal period and also its association with adverse perinatal outcomes. Totally 131 pregnant women were included in this prospective study. Of these, 56 cases were in study group with a diagnosis of small fetus and 75 cases were in control group with a diagnosis appropriately grown fetus. Fetal echocardiography was performed in all pregnant women to measure modified myocardial performance index. Umbilical, middle cerebral and uterine artery Doppler ultrasound parameters were measured in the study group. Small fetuses were categorized into 2 subgroups of late-onset fetal growth restriction and small for gestational age. Modified myocardial performance index was significantly higher in small fetuses compared to controls (0.45 vs. 0.37, P <.001). Newborn intensive care unit admission rates were significantly higher in small fetuses than in controls (chi-square test, P <.001). The highest mean modified myocardial performance index was recorded in the late-onset fetal growth restriction subgroup (0.45 vs. 0.41 vs. 0.37). The sensitivity and specificity of modified myocardial performance index in predicting adverse outcomes at a cut-off value of 0.41 were 63% and 75%, respectively. There was a significant negative correlation between modified myocardial performance index values and birth weights. We found higher left fetal heart modified myocardial performance index values in small fetuses indicating the presence of prenatal cardiac dysfunction. Fetal myocardial performance deteriorates in concordance with severity of growth restriction. Modified myocardial performance index can also be used to predict adverse perinatal outcomes among growth-restricted fetuses.

Management of stenosing flexor tenosynovitis in primary care.

Management of stenosing flexor tenosynovitis in primary care.

Evaluating the expression of immunohistochemical panel of p53, CDX2, IMP3 and AMCAR in grading dysplasia of Barrett’s esophagus and predicting the progression to esophageal adenocarcinoma

Abstract Objective Barrett’s esophagus (BE) is an established precursor to esophageal adenocarcinoma, which has a poor prognosis unless detected at an early stage. The progression of BE to adenocarcinoma is slow and unpredictable. Currently, the best predictor of adenocarcinoma is histological detection of dysplasia. Accurate grading of dysplasia and especially discriminating low-grade dysplasia LGD from high-grade dysplasia HGD is important for management. Marked variability exists when diagnosing dysplasia in BE. This highlights the need for a diagnostic adjunct, especially in histologically challenging cases. This study aims at evaluating the role of immunohistochemical expression of (p53, IMP3, AMCAR and CDx2) in Barrett’s oesophagus spectrum, to increase the diagnostic accuracy of grading dysplasia and predicting progression risk. Methods This is a retrospective immunohistochemical study, performed on selected 52 cases of esophageal biopsies. Results The p53 was negative in nondysplastic Barrett’s esophagus (ND-BE) and LGD and strong positivity towards HGD/esophageal adenocarcinoma (EAC). CDX2 showed highest expression among ND-BE and decreased towards EAD. IMP3 and AMCAR were negative in all cases of ND-BE with gradual increase among HGD/esophageal adenocarcinoma cases. IMP3, AMCAR, and CDX2 were found to be more sensitive in detecting HGD (80%, 70% &amp; 70%). Meanwhile, p53 is more specific (100%), IMP3 and AMCAR are more sensitive discriminating LGD from HGD (80%) than p53 and CDX2 (60%, 70%). Conclusion This combined panel of p53, CDX2, IMP3, and AMACR could be used in conjunction with histology as a promising tool to accurately predict progression form BE to HGD/adenocarcinoma with a great value for early detecting high grade dysplasia, discriminating it from LGD, improving risk stratification in BE, and optimizing patient care.

Role of neutrophil-to-lymphocyte, neutrophil-to-eosinophil and platelet-to-lymphocyte ratios in the diagnosis of bullous pemphigoid and Pemphigus disease.

Bullous pemphigoid (BP) and "Pemphigus diseases" (PD) can have overlapping clinical manifestations and accurate distinction is crucial for appropriate management. The study aimed at analyzing the utility of simple hematological markers of systemic inflammation like neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER), and platelet-to-lymphocyte ratio (PLR) in clinical decision making in the setting of clinical differentials of BP and PD in a particular case. This single-centre based retrospective observational analytical study included adult subjects newly diagnosed to have BP (n=66) or PD (n=53), confirmed with direct immune-fluorescence testing, over a period of six years. Blood counts performed using Coulter™ hematology analyser, at the time of their initial presentation, were retrieved from the hospital medical records, and the leucocyte ratios were calculated. The data were compared between the two groups, using Mann-Whitney U test and chi-square test /Fisher's exact test. ROC curve analysis was performed to estimate cut-off values. The BP group had a significantly higher NLR, total leukocyte counts (TLC), absolute eosinophil counts (AEC), and absolute lymphocyte counts (ALC), and lower NER values compared to the PD group (P < 0.05). Areas under ROC for NLR, NER, TLC, AEC, and ALC were between 0.5 and 0.7. NLR ≥ 7, AEC ≥ 2055/cumm, and TLC ≥ 15,000/cumm had a specificity of 90.6, 100, and 100% respectively for identifying BP patients out of the two groups, but with a low sensitivity of 22.7, 21, and 22.7%, respectively. NLR can be a valuable diagnostic adjunct in subtyping autoimmune bullous disorders, albeit in a small proportion of cases.