Diagnostic Challenge Research Articles

Case report: Hypertrophic lichen planus initially misdiagnosed as squamous cell carcinoma

Fewer than 26 case reports describe hypertrophic lichen planus (HLP) misdiagnosed as cutaneous squamous cell carcinoma (cSCC). It can be difficult to distinguish between HLP and cSCC, as these two conditions share many clinical and histopathological characteristics. Patients who are misdiagnosed with cSCC often undergo unnecessary medical and/or surgical interventions before receiving a diagnosis of HLP and improving on HLP-directed therapy. This case series highlights the course of three female patients, referred to a single tertiary institution between 2018 and 2022, who were initially misdiagnosed with cSCC before receiving a diagnosis of HLP. We have emphasized the clinical and histopathological distinguishing features between HLP and cSCC, the pathogenesis of HLP, and current and new HLP-directed therapy. We hope that this case series serves as a reminder to dermatologists, dermatologic surgeons, and dermatopathologists to be aware of this diagnostic challenge.

Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients

BackgroundMuscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity.MethodsThis study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification–negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%).ResultsWES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes.ConclusionWES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

Acute pancreatitis as a manifestation of multisystem inflammatory syndrome among children (MIS-C): A rare case

A multisystem inflammatory syndrome among children (MIS-C) has been linked to COVID-19, and it affects multiple organ systems in the body, including the gastrointestinal system. In present case report, a 14-year-old girl presented with clinico-laboratory and imaging evidence of acute pancreatitis but did not respond to the standard line of management for pancreatitis. Later, the laboratory investigations pointed to the diagnosis of MIS-C. She responded well to a pulse doses of methylprednisolone therapy. Acute pancreatitis as a lone manifestation of MIS-C poses a diagnostic challenge for paediatricians, and one should suspect MIS-C in acute non-responding pancreatitis.

Motor polyradiculoneuropathy as an unusual presentation of neurobrucellosis: a case report and literature review

Brucellosis, a zoonotic disease caused by Brucella species, poses a significant global health concern. Among its diverse clinical manifestations, neurobrucellosis remains an infrequent yet debilitating complication. Here, we present a rare case of neurobrucellosis with unusual presentations in a 45-year-old woman. The patient’s clinical course included progressive lower extremity weakness, muscle wasting, and double vision, prompting a comprehensive diagnostic evaluation. Notable findings included polyneuropathy, elevated brucella agglutination titers in both cerebrospinal fluid and blood, abnormal EMG-NCV tests, and resolving symptoms with antibiotic therapy. The clinical presentation, diagnostic challenges, and differentiation from other neurological conditions are discussed. This case underscores the importance of considering neurobrucellosis in regions where brucellosis is prevalent and highlights this rare neurological complication’s distinctive clinical and radiological features. Early recognition and appropriate treatment are crucial to mitigate the significant morbidity associated with neurobrucellosis.

Approach to the Atypical Wound.

The heterogeneity of atypical wounds can present diagnostic and therapeutic challenges; however, as the prevalence of atypical wounds grows worldwide, prompt and accurate management is increasingly an essential skill for dermatologists. Addressing the underlying cause of an atypical wound is critical for successful outcomes. An integrated approach with a focus on pain management and patient engagement is recommended to facilitate enduring wound closure. Advances in treatment, in addition to further research and clinical training, are necessary to address the expanding burden of atypical wounds.

Investigation of subtle Lisfranc injuries using weight-bearing computed tomography

Introduction: Lisfranc ligamentous injuries are common yet remain a diagnostic challenge. Automated analysis of weight-bearingcomputed tomography (WBCT) images has been investigated to diagnose various pathologies. However, it has not been studied forLisfranc ligament injuries. The objective of the study was to examine whether automated WBCT analysis could demonstrate diagnosticutility for these injuries. Methods: Serial sectioning of Lisfranc complex ligaments was conducted on 24 cadaveric limbs to simulate Lisfranc injuries. WBCT images were collected at each dissection condition under three loading conditions. Images were automatically segmented, and automated measures of specific angles and distances in the midfoot were calculated using digitally reconstructed radiographs. These were analyzed using repeated measures ANOVA and paired T-tests to identify significant differences between dissections at each loading condition. Results: Overall, minimal differences between dissection conditions were observed in automatically generated measures. Differences in axial angles of the metatarsals in severe dissections were observed, and there were fewer differences in angular measures across dissection conditions in fully loaded than unloaded conditions. Conclusions: Automated analysis of WBCT images may indicate severe Lisfranc ligamentous injury but is insufficient to diagnose ligament injuries without full capsule disruption. This lack of injury markers may be due to the imaging conditions, automated analysis, or biomechanics of Lisfranc injuries. More alignment differences were seen under unloaded conditions, suggesting that weight-bearing imaging may not be appropriate for this injury. Overall, automated analysis shows only minimal changes in alignment measures, and additional study is necessary to improve diagnostic tools for Lisfranc injuries. Evidence Level V; Mechanism-based reasoning.

Diagnostic challenges in bilateral thalamic infarction: national series of cases

Diagnostic challenges in bilateral thalamic infarction: national series of cases

Diagnostic Challenges in Pancreatic Tumors

Background: Pancreatic tumors have a large diversity, with an increasing incidence and mortality. Although the diagnosis methods have improved in recent years, establishing a diagnosis and a histopathological type of pancreatic tumor can still pose a challenge. Aim: We propose to present a concise list of difficulties regarding the clinical, biological, and imagistic diagnosis of pancreatic tumors. Key information: The clinical manifestations of pancreatic tumors depend on their location and size, on the presence of metastatic lesions, but the difficulty of orientation towards this diagnosis is determined by the fact that most lesions are asymptomatic or present in the early stages of non-specific symptoms. The usual biological parameters are non-specific in pancreatic tumors in the early stages, but studies are underway regarding a series of biomarkers, genetic micro-sequences, or inorganic nanomaterials that could be used in the early diagnosis of pancreatic cancers. An essential stage in the diagnosis of pancreatic tumors is represented by imaging investigations, which are associated with endoscopic and tumor biopsy procedures and can outline a picture regarding the presence of the tumor at the level of the pancreas, the relationship with the neighboring organs, the nature of the tumor and the histopathological type. There are a series of indications and limitations regarding each of these investigations, trying to develop various algorithms for the diagnosis of pancreatic tumors. Conclusion: The medical research conducted to develop new diagnostic procedures has the objective of ensuring an early diagnosis of pancreatic tumors, in a stage that offers the best chances of recovery for the patient.

Integrated single-cell and bulk RNA-Seq analysis enhances prognostic accuracy of PD-1/PD-L1 immunotherapy response in lung adenocarcinoma through necroptotic anoikis gene signatures

In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model’s utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model.

Unraveling TAFRO Syndrome: An In-Depth Look at the Pathophysiology, Management, and Future Perspectives.

TAFRO syndrome is a rare and aggressive inflammatory entity characterized by thrombocytopenia, anasarca, fever, renal failure, reticulin fibrosis, and organomegaly. This entity supposes a diagnostic and therapeutic challenge due to its significant overlap with Castleman's disease. However, distinct clinical and histological features warrant its classification as a separate subtype of idiopathic multicentric Castleman's disease (iMCD). While recent modifications have been made to the diagnostic criteria for iMCD, these criteria lack specificity for this particular condition, further complicating diagnosis. Due to its inflammatory nature, several complex molecular signaling pathways are involved, including the JAK-STAT pathway, NF-kB, and signal amplifiers such as IL-6 and VEGF. Understanding the involvement of immune dysfunction, some infectious agents, genetic mutations, and specific molecular and signaling pathways could improve the knowledge and management of the condition, leading to effective treatment strategies. The current therapeutic approaches include corticosteroids, anti-IL6 drugs, rituximab, and chemotherapy, among others, but response rates vary, highlighting the need for personalized strategies. The prognosis is uncertain due to diagnostic difficulties, emphasizing the importance of early intervention and appropriate targeted treatment. This comprehensive review examines the evolving landscape of TAFRO syndrome, including the pathophysiology, diagnostic criteria, treatment strategies, prognosis, and future perspectives.

Diagnostic Challenges of Lyme Co-infections: Lessons From a Lyme and Herpes Simplex Virus-1 (HSV-1) Cocktail

Diagnostic Challenges of Lyme Co-infections: Lessons From a Lyme and Herpes Simplex Virus-1 (HSV-1) Cocktail

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

Overcoming Diagnostic Challenges: A Rare Presentation of Primary Hemophagocytic Lymphohistiocytosis (HLH) in a Young Female and the Importance of Timely Recognition

Overcoming Diagnostic Challenges: A Rare Presentation of Primary Hemophagocytic Lymphohistiocytosis (HLH) in a Young Female and the Importance of Timely Recognition

Hamate Bone Fracture following a Sports-Related Accident: A Case Report

Fractures of the hamate bone are uncommon but can occur as a result of sports-related accidents and can present diagnostic challenges. This article presents a case report of a hamate bone fracture following a sports-related incident, with a focus on the use of CT scans for accurate diagnosis and treatment planning. The purpose is to highlight the significance of imaging techniques in evaluating hamate bone fractures and guiding appropriate treatment strategies.

Genomic insights into inherited bone marrow failure syndromes in a Korean population.

Inherited bone marrow failure syndromes (IBMFS) pose significant diagnostic challenges due to overlapping symptoms and variable expressivity, despite evolving genomic insights. The study aimed to elucidate the genomic landscape among 130 Korean patients with IBMFS. We conducted targeted next-generation sequencing (NGS) and clinical exome sequencing (CES) across the cohort, complemented by whole genome sequencing (WGS) and chromosomal microarray (CMA) in 12 and 47 cases, respectively, with negative initial results. Notably, 50% (n = 65) of our cohort achieved a genomic diagnosis. Among these, 35 patients exhibited mutations associated with classic IBMFSs (n = 33) and the recently defined IBMFS, aplastic anaemia, mental retardation and dwarfism syndrome (AmeDS, n = 2). Classic IBMFSs were predominantly detected via targeted NGS (85%, n = 28) and CES (88%, n = 29), whereas AMeDS was exclusively identified through CES. Both CMA and WGS aided in identifying copy number variations (n = 2) and mutations in previously unexplored regions (n = 2). Additionally, 30 patients were diagnosed with other congenital diseases, encompassing 13 distinct entities including inherited thrombocytopenia (n = 12), myeloid neoplasms with germline predisposition (n = 8), congenital immune disorders (n = 7) and miscellaneous genomic conditions (n = 3). CES was particularly effective in revealing these diverse diagnoses. Our findings underscore the significance of comprehensive genomic analysis in IBMFS, highlighting the need for ongoing exploration in this complex field.

Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment

AbstractCentral nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.

Sleep Apnea and Heart Failure-Current State-of-The-Art.

Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.

Concurrent Craniosynostosis and Positional Plagiocephaly: A Scoping Review

Background: Craniosynostosis and positional plagiocephaly (PP) both lead to deformities of the infant skull. In some cases, patients may present with concurrent craniosynostosis and PP. The forces exerted on the skull by both conditions can complicate and delay correct diagnosis and require adjustments to surgical planning. Objective: The purpose of this scoping review was to identify and analyze the existing peer-reviewed literature covering the diagnosis and treatment of concurrent craniosynostosis and PP. Design: In accordance with PRISMA guidelines, PubMed, MEDLINE, and EMBASE were searched for articles discussing concurrent diagnoses of craniosynostosis and PP. Results: Out of 633 articles discovered, 7 met inclusion criteria and discussed a cumulative total of 10 patients. The average age of referral to a craniofacial team was 17 ± 22.2 months. The most common reason for referral was craniofacial asymmetry (90%, n = 9). 40% presented with unilateral coronal synostosis (n = 4), 40% with lambdoid synostosis (n = 4), 10% with sagittal synostosis (n = 1), and 10% with metopic synostosis (n = 1). The most commonly reported clinical features were occipital flattening (90%, n = 9), ear displacement (80%, n = 8), and frontal bossing (30%, n = 3). Delayed or incorrect initial diagnosis was noted in 70% (n = 7) of patients. CT scan was the most commonly employed diagnostic tool, utilized in 100% of patients. 70% of patients (n = 7) underwent surgery at an average age of 6.75 ± 3 months. Two studies, accounting for 2 patients reported, noted altering their surgical technique to account for PP in addition to the synostotic suture. Conclusions: Coincident craniosynostosis and PP can pose a complicated diagnostic and therapeutic challenge. An in-depth understanding of the most reliable physical exam findings associated with each type of craniosynostosis combined with PP will facilitate accurate diagnosis. Consideration of the concurrent forces on the skull created by craniosynostosis and PP aid in the design of a tailored surgical plan.

Persistent Abdominal Pain with an Uncommon Presentation of Multiple Myeloma: A Case Study

Multiple myeloma (MM) is a widespread malignant condition characterized by the proliferation of transformed plasma cells in the bone marrow, disrupting its normal functions and infiltrating adjacent bone tissues. While typically confined to the bone marrow, in rare instances, patients may develop extramedullary disease. In these uncommon scenarios, the involvement of lymph nodes poses a diagnostic challenge for practitioners in their daily routines. This report details the case of a 49-year-old male experiencing chronic abdominal pain. A computed tomography (CT) scan revealed enlargement of retroperitoneal and mesenteric lymph nodes. Biopsies confirmed a plasma cell infiltrate positive for CD138 and kappa light chain, leading to the diagnosis of multiple myeloma with extramedullary localization in lymph nodes. Our case underscores the rare presentation of extramedullary involvement in multiple myeloma, characterized by an atypical clinical manifestation.

Glomangiopericytoma of the Nasal Sinus Mimicking Dacryocoele: A Case Report and Literature Review

Introduction: Glomangiopericytoma (GPC) of the nasal sinus is a rare mesenchymal tumor that can mimic various benign pathologies in this anatomical region. We report an unusual clinical case and describe the diagnostic and therapeutic challenges encountered. Case Presentation: A 62-year-old woman presented with swelling of the left inner eye angle, tearing, and ipsilateral nasal obstruction. Clinical examination and imaging initially suggested chronic dacryocystitis. A polypoid nasal sinus mass was detected on endoscopy and computed tomography. Complete excision was performed via endoscopic nasal sinus surgery. The histopathological analysis confirmed the definitive diagnosis of glomangiopericytoma. Discussion: Nasal sinus GPC is a rare tumor, typically benign, derived from perivascular cells. Its clinical presentation is nonspecific and can mimic more common pathologies. Diagnosis is based on imaging and histopathological analysis with immunohistochemistry. The treatment of choice is complete surgical excision, preferably via minimally invasive endoscopic approach. Long-term close monitoring is recommended due to the risk of local recurrence. Conclusion: This clinical case highlights the importance of considering glomangiopericytoma in the differential diagnosis of nasal sinus masses, even in cases of initial benign presentation. A multidisciplinary approach, involving imaging, surgery, and histopathological analysis, is essential for optimal management.