Diagnostic Challenge Research Articles

Uncovering the Diagnostic Challenge of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Study of Acute Bilateral Vision Loss

Uncovering the Diagnostic Challenge of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Study of Acute Bilateral Vision Loss

Endometriosis MRI: Atypical cases, pitfalls and mimics.

Endometriosis is a common but often underdiagnosed chronic gynaecological disease. Endometriosis mimics other diagnoses both clinically and radiographically, presenting a diagnostic challenge. Endometriosis can be categorised as superficial pelvic endometriosis, deep invasive endometriosis (DIE) or endometrioma. Endometrioma and DIE, including polypoid endometriosis, can masquerade as invasive neoplasms. Endometriosis can be misdiagnosed in less common locations or during pregnancy. Ultrasound is the initial investigation for endometriosis; however, MRI is advantageous in providing a larger field of view for increased detection of nodules as well as distinguishing malignancy with greater certainty. This review highlights endometriosis mimics, pitfalls and atypical cases on MRI.

Epiploic Appendagitis: Systematic Review of a Distinctive Pathology.

Introduction: Epiploic appendagitis (EA) is an essential cause of abdominal pain that can be confused with more typical causes such as acute diverticulitis and appendicitis. Epiploic appendagitis accounts for 1% of all cases of abdominal pain in adults. The scarcity of information has limited its recognition as an essential nonsurgical cause of acute abdominal pain.Methods: We performed a systematic review of all EA cases published. We searched Scopus, Medline, Web of Science, and Google Scholar to retrieve all available studies from January 2000 to November 2023.Results: 196 case reports and case series were analyzed, with 371 patients with EA included. The mean age at the time of diagnosis was 39 years. Most patients were male (59%). The primary presenting symptoms were pain (100%), tenderness (59.5%), and rebound tenderness (27.4%). The left abdomen was the most common localization of pain (53%). The most frequently identified differential diagnoses were acute appendicitis (26.4%) and acute diverticulitis (16.1%). Most patients (53%) were treated conservatively, and 98 (26.4%) underwent surgical treatment. A significant difference in the choice of treatment was found for signs and symptoms such as rebound tenderness, nausea, anorexia, and diarrhea.Conclusions: Acute EA is an essential clinical condition of rare occurrence that might present a diagnostic challenge, as it can masquerade as another acute abdominal pain etiology. The optimal management of EA is conservative, so a higher recognition by surgeons and emergency physicians is essential to avoid unnecessary surgical interventions and their associated consequences.

Peritoneal Dialysis-Induced Encapsulating Peritonitis: Diagnostic and Therapeutic Challenges in Women with Benign Gynecological Pathology

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy) or secondary to medications (beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates. This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein, we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. Over 12 years, we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In five cases (7.9%), we diagnosed EPS. Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes in the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, an increased duration of the surgical intervention and a high rate of incidents and accidents. Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention.

A disease warranting attention from neurosurgeons: primary central nervous system post-transplant lymphoproliferative disorder

BackgroundPrimary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents.MethodsFrom 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT).ResultsFour patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness (n = 4), headache (n = 2), confusion (n = 2), and nausea (n = 2), with ring-enhancing (n = 5), typically solitary (n = 3) and supratentorial (n = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy (n = 4) or craniotomy (n = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases (n = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab (n = 3), surgical resection (n = 2), zanubrutinib (n = 1), whole-brain radiation (n = 1), and methotrexate (n = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive.ConclusionIn patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.

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

Diagnostic Challenges in Pancreatic Tumors

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called “other oncocytic tumors”, namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

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.

Perspectives on Resolving Diagnostic Challenges between Myocardial Infarction and Takotsubo Cardiomyopathy Leveraging Artificial Intelligence

Perspectives on Resolving Diagnostic Challenges between Myocardial Infarction and Takotsubo Cardiomyopathy Leveraging Artificial Intelligence

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