Diagnostic Challenge Research Articles

Ring-shaped meniscus with absent anterior cruciate ligament: A rare association with review of the literature

A spectrum of congenital and anatomical variants of a lateral meniscus can be encountered, including discoid meniscus, ring meniscus, double-layered meniscus, hypoplastic meniscus, and accessory meniscus in the knee joint. These can be associated with a plethora of abnormalities predominantly involving the anterior cruciate ligament (ACL) of the knee. Morphological abnormalities of the menisci can present in unusual ways, leading to clinical dilemmas and providing a diagnostic challenge. We report a case of a 26-year-old male presenting with a rare combination of ring meniscus, a hypoplastic ACL, and an oblique inter-meniscal ligament to raise awareness of the condition. Pertinent literature is also reviewed.

Neuropsychological Profiles of Deployment-Related Mild Traumatic Brain Injury: A LIMBIC-CENC Study.

Traumatic brain injury (TBI) is a concern for US service members and veterans (SMV), leading to heterogeneous psychological and cognitive outcomes. We sought to identify neuropsychological profiles of mild TBI (mTBI) and posttraumatic stress disorder (PTSD) among the largest SMV sample to date. We analyzed cross-sectional baseline data from SMV with prior combat deployments enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Latent profile analysis identified symptom profiles using 35 indicators, including physical symptoms, depression, quality of life, sleep quality, postconcussive symptoms, and cognitive performance. It is important to note that the profiles were determined independently of mTBI and probable PTSD status. After profile identification, we examined associations between demographic variables, mTBI characteristics, and PTSD symptoms with symptom profile membership. The analytic sample included 1,659 SMV (mean age 41.1 ± 10.0 years; 87% male); among them 29% (n = 480) had a history of non-deployment-related mTBI only, 14% (n = 239) had deployment-related mTBI only, 36% (n = 602) had both non-deployment and deployment-related mTBI, and 30% (n = 497) met criteria for probable PTSD. A 6-profile model had the best fit, with separation on all indicators (p < 0.001). The model revealed distinct neuropsychological profiles, representing a combination of 3 self-reported functioning patterns: high (HS), moderate (MS), and low (LS), and 2 cognitive performance patterns: high (HC) and low (LC). The profiles were (1) HS/HC: n=301, 18.1%; (2) HS/LC: n=294, 17.7%; (3) MS/HC: n=359, 21.6%; (4) MS/LC: n=316, 19.0%; (5) LS/HC: n=228, 13.7%; and (6) LS/LC: n=161, 9.7%. SMV with deployment-related mTBI tended to be grouped into lower functioning profiles and were more likely to meet criteria for probable PTSD. Conversely, SMV with no mTBI exposure or non-deployment-related mTBI were clustered in higher functioning profiles and had a lower likelihood of meeting criteria for probable PTSD. Findings suggest varied symptom and functional profiles in SMV, influenced by injury context and probable PTSD comorbidity. Despite diagnostic challenges, comprehensive assessment of functioning and cognition can detect subtle differences related to mTBI and PTSD, revealing distinct neuropsychological profiles. Prioritizing early treatment based on these profiles may improve prognostication and support efficient recovery.

Status epilepticus and psychosis: Lessons from SEEG

Psychotic manifestations are a classic feature of non-convulsive status epilepticus (NCSE) of temporal origin. For several decades now, the various psychiatric manifestations of NCSE have been described, and in particular, the diagnostic challenges they pose. However, studies using stereotactic-EEG (SEEG) recordings are very rare. Only a few cases have been reported, but they demonstrated the anatomical substrate of certain manifestations, including hallucinations, delusions, and emotional changes. The post-ictal origin of some of the manifestations should be emphasized. More generally, SEEG has shown that seizures affecting the temporal and frontal limbic systems can lead to intense emotional experiences and behavioural disturbances.

Advancements and Challenges in Aptamer-Based Therapeutics and Diagnostics Across Diverse Medical Domains: A Comprehensive Review

Advancements and Challenges in Aptamer-Based Therapeutics and Diagnostics Across Diverse Medical Domains: A Comprehensive Review

Role of Minimally Invasive Techniques in the Management of Early-Stage Carcinoma of the Uterine Cervix.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury.

Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary tract. It is regarded as one of the most prevalent causes of acute kidney injury (AKI), accounting for 5%-10% of cases. Acute severe obstruction of the urinary tract is a potentially threatening situation for the kidneys and therefore requires prompt identification and management to relieve obstruction. The aim of the present article is to review and synthesize available evidence on obstructive uropathy, providing a clinical guideline for clinicians. A literature review on obstructive uropathy in the context of AKI was performed, focusing on the least clarified aspects regarding diagnosis and management. Recent literature searching was conducted in English and top-level evidence articles including systematic reviews, metanalyses and large series were prioritized. Acute obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the kidney. Early recognition of the leading cause and its exact location is essential to ensure prompt urinary drainage together with the most suitable drainage technique selection. A multidisciplinary approach, including urologists, nephrologists, and other medical specialties, is best suited to correctly manage concomitant hemodynamic changes, fluid and electrolyte imbalances, and other related issues. Obstructive uropathy is one of the leading causes of AKI. Recognition of patients suitable for early diversion and feasibility or adequate selection of the indicated technique is sometimes challenging. A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management.

Duress and Distress Versus a Neurocognitive Mess: The Challenges of Procedural Sedation in Pediatric B-ALL.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

A Detailed Examination of Retroperitoneal Undifferentiated Pleomorphic Sarcoma: A Case Report and Review of the Existing Literature.

This detailed review focuses on retroperitoneal undifferentiated pleomorphic sarcoma (UPS), a particularly aggressive soft-tissue sarcoma that poses unique diagnostic and therapeutic challenges due to its rarity and complex presentation. By documenting a new case of retroperitoneal UPS and conducting a comprehensive review of all known cases, this article aims to expand the existing body of knowledge on the epidemiology, molecular pathogenesis, and treatment strategies associated with this rare disease. The complexity of diagnosing UPS is emphasized given that it rarely occurs in the retroperitoneal space and its histological and molecular complexity often complicates its recognition. This review highlights the need for specialized diagnostic approaches, including advanced imaging techniques and histopathological studies, to accurately diagnose and stage the disease. In terms of treatment, this paper advocates a multidisciplinary approach that combines surgery, radiotherapy and chemotherapy and tailors it to individual patients to optimize treatment outcomes. This review highlights case studies that illustrate the effectiveness of surgical intervention in the treatment of these tumors and emphasize the importance of achieving clear surgical margins to prevent recurrence. Furthermore, this review discusses the potential of new molecular targets and the need for innovative therapies that could bring new hope to patients affected by this challenging sarcoma.

Unveiling cystinosis in India

BackgroundCystinosis, a rare autosomal recessive disease, stems from genetic alterations in the CTNS gene, leading to a malfunction of lysosomal ‘cystinosin’ protein. This dysfunction causes intracellular cystine accumulation, resulting in nephropathic and ocular abnormalities. Cystinosis is relatively rare in Asian countries, partly due to underreporting and lack of awareness, and cases often lack sufficient genetic evidence to support their diagnosis. This study presents a descriptive case series involving four Indian patients with cystinosis, elucidating clinical and genetic aspects.MethodsAll four patients underwent comprehensive ophthalmic evaluations. The corneal cystine crystal (CCC) score was determined using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). Genetic testing was performed using whole exome sequencing (WES).ResultsCorneal crystal deposition, a hallmark of cystinosis, was evident in all cases. Systemic analysis revealed manifestations such as polyuria, bony abnormalities, growth retardation, hypothyroidism, and developmental delay. Genetic testing in two patients identified a homozygous pathogenic variant c.18_21delGACT (p.Thr7PhefsX7) in the CTNS gene, previously reported to cause cystinosis in different ethnic populations.ConclusionsOur case series sheds light on underrepresented cases of cystinosis in the Indian population. The rarity of this condition poses diagnostic challenges, leading to delayed or inaccurate diagnoses. AS-OCT can serve as a viable alternative to IVCM for assessing corneal crystal density status in cystinosis. Timely recognition and management are crucial in preventing complications, and the inclusion of genetic testing can expedite cystinosis diagnosis.

Eustachian Tube Dysfunction Diagnostic Pathway-What Is the Current State of the Art and How Relevant Is Chronic Nasal Disease?

Background: Eustachian tube dysfunction (ETD) presents a complex diagnostic challenge in otolaryngology, compounded by its multifaceted nature and overlapping symptoms with chronic nasal disease. This article examines the intricacies of ETD diagnosis, emphasising the necessity for a consensus on diagnostic procedures. Methods: A review of the literature was performed through the OVID research tool in the Pubmed/Medline databases to identify relevant articles that discuss eustachian tube dysfunction diagnostics as well as its correlation with chronic nasal disease. Results: The literature review harvested 201 articles, and only 51 of them were included in the full text review. A consensus statement was identified on eustachian tube dysfunction, function and diagnostics. It appears that there is significant variability in the diagnostic tools used to identify eustachian tube dysfunction. The main diagnostic approaches used are tympanometry, tubomanometry and sonotubometry, combined with the Patient-Reported Outcome Measure ETDQ-7 questionnaire to support the diagnosis of the condition. Nasal pathology is mostly absent from the retrieved studies, while ear pathology is more commonly mentioned in the current literature. Conclusions: There is no gold standard diagnostic tool to determine the presence of eustachian tube dysfunction. Further discussion, large multicentre studies and focused research are required to achieve a consensus on a diagnostic approach. The authors suggest a diagnostic pathway that combines subjective and objective diagnostic tools to determine the presence of eustachian tube dysfunction. This pathway is simple and can be used in district ENT departments, highlighting the nasal pathology relevance to ETD.

Unlocking Precise Lung Cancer Detection Through Minimal Panel Immunostaining in Small Biopsy Samples.

Introduction Lung cancer diagnosis faces challenges due to morphological heterogeneity and limited biopsy tissue. This study evaluates the efficacy of a minimal panel immunostaining technique using immunohistochemical markers like napsin A, thyroid transcription factor 1 (TTF-1), p63, and synaptophysin to improve the precision of lung carcinoma subclassification. Methods A retrospective analytical study was conducted at the Histopathology Laboratory of Saveetha Medical College and Hospital, Chennai, from January 2018 to February 2024. A total of 64 lung carcinoma cases were analyzed. Inclusion criteria included biopsy samples from lung lesions with a confirmed diagnosis of lung carcinoma based on histomorphological examination, covering all age groups and both genders. Non-carcinomatous lung lesions were excluded. Clinical data were obtained from the Medical Information Archiving Software (MIAS) database and histopathological examination request forms. Under a light microscope, tissue samples were examined after beingfixed in formalin, processed, and stained with hematoxylin and eosin (H&E). Additionally, a minimal panel of immunohistochemical markers, including napsin A, TTF-1, p63, and synaptophysin, was used to subclassify lung carcinomas. Results The age group older than 50 years was the most affected, with a higher incidence in males. Histologically, 49% of cases were adenocarcinoma, 42% were squamous cell carcinoma, and 9% were small cell carcinoma. Immunohistochemistry (IHC) results adjusted these proportions to 54.6% adenocarcinoma, 31.2% squamous cell carcinoma, and 14% small cell carcinoma, showing a 5.6% increase in adenocarcinoma cases. The most common adenocarcinoma pattern was mixed, followed by acinar. TTF-1 and napsin A were crucial for identifying adenocarcinoma, while p63 was key for squamous cell carcinoma. Synaptophysin confirmed neuroendocrine differentiation in small cell carcinoma. Conclusion Incorporating a minimal panel of IHC markers significantly enhances the accuracy of lung carcinoma subclassification, addressing diagnostic challenges posed by morphological heterogeneity and limited sample size. This approach supports more precise and efficient clinical care for patients with lung cancer. Further validation in diverse clinical settings is recommended.

Pathogenesis and Diagnostic Challenges of Mucormycosis

Pathogenesis and Diagnostic Challenges of Mucormycosis

A self-reported symptom-based decision-making model helps to rule out outpatient cases at low risk for CRC before colonoscopy

ObjectivesEffective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios. MethodsIn total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers. A decision-making model was constructed using 60 self-reported symptom parameters collected from the questionnaire. Further internal and external validation cohorts were built to evaluate the discriminatory power of the CRC model. The discriminatory power of the CRC model was assessed by the C-index and calibration plot. After that, the clinical utility and user experience of the CRC model were evaluated. ResultsNine symptom parameters were identified as valuable predictors used for modeling. Internal and external validation cohorts verified the adequate discriminatory power of the CRC model. In the clinical application step, all 17 physicians found the model easy to grasp, 99.9 % of the patients were satisfied with the survey form. Application of this model detected all CRC cases. The total consistency ratio of outpatient cases undergoing colonoscopy was 81.4 %. None of the low-risk patients defined by the CRC model had been diagnosed with CRC. ConclusionThis multicenter study developed and validated a simple and user-friendly decision-making model covering self-reported information. The CRC model has been demonstrated to perform well in terms of rapid outpatient decision-making scenarios and clinical utility, particularly because it can better rule out low-risk outpatient cases.

Terbinafine-resistant T. indotineae due to F397L/L393S or F397L/L393F mutation among corticoid-related tinea incognita patients.

Tinea incognita (TI) can mimic other dermatoses, presenting a diagnostic challenge for dermatologists. In some uncertain cases, it is crucial to accurately identify the causative agent using internal transcribed spacer (ITS) sequencing. The global issue of drug-resistant dermatophytosis is increasing, with Trichophyton (T.) indotineae being the main cause. This study presents four cases of TI (diagnosed as eczema) by terbinafine-resistant T.indotineae strains and reviews the current global TI epidemiology based on geographical continent and related conditions. Furthermore, squalene epoxidase (SQLE)-associated resistance mechanisms are evaluated. Lesions caused by terbinafine-resistant T.indotineae strains do not respond to allylamine antifungals, thus allowing the infection to spread. Among T.indotineae isolates, the SQLE F397L substitution is the most prevalent mutation contributing to azole resistance. F397L and L393F replacements in SQLE were detected in all isolates that exhibited high-level resistance. L393S was seen in isolates with low-resistant strains. Interestingly, and for the first time, an L393F amino acid substitution in the SQLE gene product was detected in the Iranian clinical T.indotineae strain. Also, a genomics-based update on terbinafine resistance that focuses on T.indotineae is discussed in this study.

Ethambutol induced subacute cutaneous lupus erythematosus in an elderly female with co-morbidities

Papulosquamous lesions in an elderly female with multiple co-morbidities often pose diagnostic challenge. We present an interesting case of anti-tubercular treatment (ATT) induced sub-acute cutaneous lupus erythematosus. The patient presented with papulosquamous lesions in generalised distribution, which showed interface dermatitis on histopathology. The serology for anti-nuclear antibodies, anti-Ro and anti-La was positive. The rash resolved spontaneously after stopping all the suspected drugs. Oral provocation was performed with first line anti-tubercular drugs and ethambutol was found to be the culprit drug, which was later confirmed by reappearance of skin rash by inadvertent ingestion of one dose of ethambutol by the patient.

Diagnostic approach to hepatic vascular lesions: a paediatric perspective.

The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered.

Diagnostic and therapeutic challenges of tuberculosis in kidney transplant recipients; a case series study

Diagnostic and therapeutic challenges of tuberculosis in kidney transplant recipients; a case series study

Fine-needle aspiration cytology of retroperitoneal myoepithelial carcinoma: A rare encounter with diagnostic dilemmas.

Myoepithelial carcinoma (MC) arises from the myoepithelial cells. It is a rare tumor with a predilection for salivary glands. MC in soft tissue is uncommon. Soft tissue MC exhibits dual epithelial and smooth muscle phenotype. The extremities and limb girdles are commonly affected. We present cytological findings of retroperitoneal MC with an accurate diagnosis being rendered with the aid of immunocytochemistry on the cell block and demonstration of EWSR1 rearrangements by fluorescence in situ hybridization on cytology smear. The smears were cellular, showing loose clusters and sheets of tumor cells embedded in dense eosinophilic to myxoid matrix material. The cells were oval to polygonal, with focal areas showing moderate nuclear pleomorphism, vesicular to coarse chromatin, and vacuolated cytoplasm with clearing. On immunocytochemistry, tumor cells were positive for epithelial membrane antigen, pan-cytokeratin, calponin, smooth muscle actin, and S-100. A literature review shows only a handful of cases of soft tissue MC. The current report emphasizes the need for cytomorphological awareness with the employment of ancillary testing for accurately diagnosing this rare tumor at an uncommon location. We also discuss the diagnostic challenges and troubleshooting.

Nonneoplastic and neoplastic sclerosing lesions of the breast.

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplasticentities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.

Predominantly multiple focal non-cystic renal lesions: an imaging approach.

Multiple non-cystic renal lesions are occasionally discovered during imaging for various reasons and poses a diagnostic challenge to the practicing radiologist. These lesions may appear as a primary or dominant imaging finding or may be an additional abnormality in the setting of multiorgan involvement. Awareness of the imaging appearance of the various entities presenting as renal lesions integrated with associated extrarenal imaging findings along with clinical information is crucial for a proper diagnostic approach and patient work-up. This review summarizes the most relevant causes of infectious, inflammatory, vascular, and neoplastic disorders presenting as predominantly multiple focal non-cystic lesions.