Key Differential Diagnoses Research Articles

Common Diagnostic Challenges in Genitourinary Mesenchymal Tumors: A Practical Approach.

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls.

Cognitive–behavioural therapy for complex post-traumatic stress disorder

SUMMARY Complex post-traumatic stress disorder (CPTSD) was adopted as a new diagnosis in ICD-11. Trauma-focused cognitive–behavioural therapy (CBT) is effective in treating PTSD but with CPTSD being a recently defined diagnosis, the evidence for its effectiveness in that disorder is not as clear, but it is still promising. This article reviews the diagnosis, psychopathology and some key differential diagnoses, and looks at the two CBT approaches that are currently used in clinical practice: the phase-oriented approach and the unimodal approach. The key aims of this article are to clarify the concept of CPTSD, its differentiation from borderline personality disorder and prominent comorbidities, how it develops and how CBT is used to treat it.

Clinicopathologic correlation of dermatologic diseases in patients with darker pigmentation.

Cutaneous diseases that disproportionately affect patients with darker pigmentation and their histologic features are historically understudied and undertreated. This review article aims to highlight the key clinical features, histopathology, and diagnostic pearls of several cutaneous diseases that commonly present in patients with darker pigmentation. A literature search was conducted, and a list of cutaneous diseases that frequently affect patients with darker pigmentation was compiled. A group of experts expounded upon those that were most common or misdiagnosed according to scientific evidence and clinical practice. The diseases were divided into hypopigmented disorders, hyperpigmented disorders, scarring disorders, and alopecic disorders. Within each category, the etiology, clinical features, histopathology, and key histologic differential diagnoses are described and discussed. As many clinicians are taught that there are no effective treatment options or that these diseases are considered "cosmetic" in nature, patients often do not get a thorough medical workup or skin biopsy. This article aims to decrease the knowledge gap and serve as a resource for anyone involved in the care of patients with these cutaneous conditions.

Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis

Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy. To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD). This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023. MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features. Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala. In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.

Pediatric orbital lesions: non-neoplastic extraocular soft-tissue lesions.

Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.

Pediatric orbital lesions: bony and traumatic lesions.

Orbital pathologies can be broadly classified as ocular lesions, extraocular soft-tissue pathologies (non-neoplastic and neoplastic), and bony and traumatic lesions. In this paper, we discuss the key imaging features and differential diagnoses of bony and traumatic lesions of the pediatric orbit and globe, emphasizing the role of CT and MRI as the primary imaging modalities. In addition, we highlight the adjunctive role of ocular sonography in the diagnosis of intraocular foreign bodies and discuss the primary role of sonography in the diagnosis of traumatic retinal detachment.

Frontiers in diagnostic and therapeutic approaches in diabetic sensorimotor neuropathy (DSPN).

Diabetes sensory polyneuropathy (DSPN) is a significant complication of diabetes affecting up to 50% of patients in their lifetime and approximately 20% of patients suffer from painful diabetes neuropathic pain. DSPN - both painless and painful - leads to considerable morbidity including reduction of quality of life, increased lower limb amputations and is associated with worsening mortality. Significant progress has been made in the understanding of pathogenesis of DSPN and the last decade has seen newer techniques aimed at its earlier diagnosis. The management of painful DSPN remains a challenge despite advances made in the unravelling the pathogenesis of pain and its transmission. This article discusses the heterogenous clinical presentation of DSPN and the need to exclude key differential diagnoses. Furthermore, it reviews in detail the current diagnostic techniques involving both large and small neural fibres, their limitations and advantages and current place in the diagnosis of DSPN. Finally, the management of DSPN including newer pharmacotherapies are also discussed.

Frequency and prognosis of CVD and myocardial injury in patients presenting with suspected COVID-19 – The CoV-COR registry

The COVID-19 pandemic led to an alteration of algorithms in emergency medicine, which may influence the management of patients with similar symptoms but underlying cardiovascular diseases. We evaluated key differential diagnoses to acute COVID-19 infection and the prevalence and the prognosis of myocardial injury in patients presenting for suspected COIVD-19 infection. This prospective observational study includes patients presenting with symptoms suggestive of COVID-19 infection during the pandemic. In patients without COVID-19, leading diagnoses was classified according to ICD-10. Myocardial injury was defined as elevated high-sensitivity Troponin I with at least one value above the 99th percentile upper reference limit and its prevalence together with 90-days mortality rate was compared in patients with vs without COVID-infection. From 497 included patients (age 62.9±17.2years, 56% male), 314 (63%) were tested positive on COVID-19 based on PCR-testing, while another cause of symptom was detected in 183 patients (37%). Cardiovascular diseases were the most frequent differential diagnoses (40% of patients without COVID-19), followed by bacterial infection (24%) and malignancies (16%). Myocardial injury was present in 91 patients (COVID-19 positive: n=34, COVID-19 negative: n=57). 90-day mortality rate was higher in patients with myocardial injury (13.4 vs 4.6%, p=0.009). Cardiovascular diseases represent the most frequent differential diagnoses in patients presenting to a tertiary care emergency department with symptoms suggestive of an acute infection. Screening for cardiovascular disease is crucial in the initial evaluation of symptomatic patients during the COVID pandemic to identify patients at increased risk.Trial Registration:Clinicaltrials.gov Identifier: NCT04327479.

A Fibroblastic Reticular Cell Tumour Arising in the Oral Cavity: A Case Report and Review of the Literature

BackgroundTumours of dendritic or histiocytic lineage are amongst the rarest tumours and probably account for < 1% of tumours affecting the lymph nodes or soft tissue. Because several of these entities were poorly recognised until recently, the true incidence is not determined.MethodsWe present what we believe is the first reported case report of a fibroblastic reticular cell tumour arising in the oral cavity as well as reviewing the current literature regarding this rare subset of tumours.ResultsWe discuss the clinical and histopathological findings of our reported case and examine the literature regarding this entity. We discuss the key differential diagnoses to consider when making this diagnosis.ConclusionHistiocytic and dendritic cell derived tumours are exceptionally rare within the head and neck region although a number of these tumours have been reported within the oral cavity. We present what we believe is the first reported case of a fibroblastic reticular cell tumour arising within the oral cavity.

Solitary Fibrous Tumor of the Adrenal Gland.

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that can arise at various anatomic locations. It is characterized by inv12(q13q13)-derived NAB2::STAT6 fusion, resulting in the nuclear expression of STAT6. Primary SFT of the adrenal gland is rare. We launched a multi-institutional collaboration to comprehend the overarching demographics, clinical and follow-up, macroscopic, microscopic, IHC, and FISH features of 9 patients with SFT of the adrenal gland. We added a series of 9 patients to the collection of adrenal SFTs where the clinicopathologic parameters, including clinical presentation, imaging, histopathology, IHC, molecular profiles, and management and follow-up data, were analyzed comprehensively. A modified 4-variable risk stratification model, including age, tumor size, and necrosis, was applied. Our series consisted of 6 male and 3 female patients, ranging in age from 19 to 64 years (mean, 49.3 years). Abdominal pain (4) and fever with abdominal pain (1) were the presenting symptoms in 5 patients. In the remaining 4 patients, the tumors were detected by abdominal imaging for hypertension and diabetes. The size of the tumor ranged from 2 cm to 10.5 cm in maximum dimension. All tumors exhibited the morphology of a spindle cell SFT with a patternless architecture; 3 had a focal storiform arrangement. STAT6 positivity was observed in all tumors, and 7 were positive for CD34. Surgical resection was the primary modality of treatment. No adjuvant therapy was administered. Follow-up ranging from 7 months to 23 months was available for 7 patients. All were alive without disease recurrence or metastasis. Risk stratification placed 8 (88.9%) patients into a low-risk category and 1 into an intermediate-risk category. This series is the largest of adrenal SFTs to date. These tumors of the adrenal gland are predominantly spindle cell neoplasms with indolent behavior, with a wide age distribution and a slight male preponderance. Combining our cohort with the previously published cases, the majority of tumors fall into the low-risk category for the propensity to develop metastases. Owing to the rarity and age distribution associated with these tumors, the differential diagnosis is wide and requires a systematic approach for ruling out key differential diagnoses aided by STAT6 IHC.

Endometrial stromal tumors: Diagnostic updates and challenges.

Endometrial stromal tumors are rare uterine mesenchymal tumors of endometrial stromal origin. They are classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma by the current (2020) WHO classification. Correct diagnosis of endometrial stromal tumors is critical for proper patient management. However, due to infrequent encounters, overlapping morphological features and immunohistochemical profiles, the differential diagnoses among endometrial stromal lesions and their morphologic mimics are often challenging. Partially with our own experience, here we review and summarize the tumor morphology, immunohistochemical phenotype, as well as molecular feature of endometrial stromal tumors and key differential diagnoses, emphasizing the newest developments and their utilization in daily practice.

Differential diagnoses of severe COVID-19 in tropical areas: the experience of Reunion Island.

To identify the differential diagnoses of severe COVID-19 and the distinguishing characteristics of critically ill COVID-19 patients in Reunion Island to help improve the triage and management of patients in this tropical setting. This retrospective observational study was conducted from 11 March to 4 May 2020 in the only intensive care unit (ICU) authorised to manage COVID-19 patients in Reunion Island, a French overseas department located in the Indian Ocean region. All patients with unknown COVID-19 status were tested by polymerase chain reaction (PCR) on ICU admission; those who tested negative were transferred to the COVID-19-free area of the ICU. Over the study period, 99 patients were admitted to our ICU. A total of 33 patients were hospitalised in the COVID-19 isolation ward, of whom 11 were positive for COVID-19. The main differential diagnoses of severe COVID-19 were as follows: community-acquired pneumonia, dengue, leptospirosis causing intra-alveolar haemorrhage and cardiogenic pulmonary oedema. The median age of COVID-19-positive patients was higher than that of COVID-19-negative patients (71 [58-74] vs. 54 [46-63.5] years, P=0.045). No distinguishing clinical, biological or radiological characteristics were found between the two groups of patients. All COVID-19-positive patients had recently travelled or been in contact with a recent traveller. In Reunion Island, dengue and leptospirosis are key differential diagnoses of severe COVID-19, and travel is the only distinguishing characteristic of COVID-19-positive patients. Our findings apply only to the particular context of Reunion Island at this time of the epidemic.

Diagnostic algorithm for children presenting with epilepsia partialis continua.

To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. Fifty-four children fulfilled EPC criteria. Median age at onset was 7years (range 0.6-15), with median follow-up of 4.3years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion-positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P=.02). Preceding developmental concerns (odds ratio [OR] 22, P<.001), no seizures prior to EPC (OR 22, P<.001), bilateral slowing on electroencephalogram (EEG) (OR 26, P<.001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6months (range 3-15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole-exome sequencing on blood-derived DNA should be performed. Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis.

Retroperitoneal Sarcomas: An Update on the Diagnostic Pathology Approach.

Retroperitoneal sarcomas are a heterogenous group of rare tumors arising in the retroperitoneum. Retroperitoneal sarcomas comprise approximately 10% of all soft tissue sarcomas. Though any soft tissue sarcoma histologic types may arise in the retroperitoneal space, liposarcoma (especially well-differentiated and dedifferentiated types) and leiomyosarcoma do so most commonly. Retroperitoneal sarcomas are diagnostically challenging, owing to their diversity and morphological overlap with other tumors arising in the retroperitoneum. An accurate diagnosis is necessary for correct management and prognostication. Herein, we provide an update on the diagnostic approach to retroperitoneal sarcomas and review their key histologic findings and differential diagnoses.

Pediatric Obesity and Sports Medicine: A Narrative Review and Clinical Recommendations.

To review what is known about sports medicine and pediatric obesity, with a focus on injuries and MSK concerns. Systematically searched MEDLINE (PubMed) for all years, using search combinations to best identify potential publications. Manuscripts were reviewed, summarized, and discussed in detail. Experienced clinicians in sports medicine and pediatric obesity reviewed the final searches for substantive content. Inclusion criteria include English language publications, children ≤18 years old, related to the practice of sports medicine and pediatric obesity. Publications excluded that dealt with non-sports medicine aspects of pediatric obesity, such as increasing physical activity or exercise, or the prevention or treatment of obesity. Twenty-eight publications were included for review. Papers fell into 5 groupings: (1) MSK-increased incidence of MSK injury in children with obesity, hypothesized to be a result of changes in biomechanics; (2) weight management-gradual loss while maintaining proper hydration and nutrition for sports performance; (3) fitness/conditioning-children with overweight/obese showed decreased fitness measures and cardiopulmonary conditioning; (4) exertional heat illness-a concern for adolescent athletes with obesity, specifically in football; and (5) differential diagnoses-3 key differential diagnoses were identified for increased awareness: slipped capital femoral epiphysis, Blount's disease, and pes planus. Clinical topics pertinent to sports medicine and pediatric obesity were discussed. Sports medicine clinicians should be aware of the common MSK and sports-related conditions in children with obesity. Few studies have focused investigations on issues related to children with obesity participating in sports and other physical activities.

Primary round cell sarcomas of the urinary bladder with EWSR1 rearrangement: a multi-institutional study of thirteen cases with a review of the literature

Primary Ewingsarcoma (ES) of the urinary bladder is a rare and aggressive small blue round cell malignant neoplasm associated primarily with translocation involving EWSR1 and FLI1 genes located in the 22nd and 11th chromosomes, respectively. To date, 18 cases have been published in the literature as single-case reports, based chiefly on CD99 positivity (17 patients). Molecular confirmation by fluorescence in situ hybridization was performed in 9 patients, and FLI1 immunohistochemical (IHC) analysis was not performed in any of these published cases. Herein, we present thirteen patients of more comprehensive primary round cell sarcomas of the urinary bladder with EWSR1 rearrangement. Clinicopathologic parameters including demographics; clinical presentation; histopathologic, IHC, and molecular profiles; and management and follow-up data of 13 patients with primary round cell sarcomas with EWSR1 rearrangement (Ewingfamily of tumor) of the urinary bladder were analyzed. The studied patients (n = 13) included 6 females and 7 males; their age ranged from 4 years to 81 years (median=30 years). The most common clinical presentation was hematuria (n=7), followed by hydronephrosis (n=2, one with renal failure). The tumor size ranged from 2.9cm to 15cm in maximum dimension. Conventional ES architecture and histology was observed in 6 cases, and diverse histology was observed in 7 cases (adamantinomatous pattern [n=1], alveolar pattern [n=1], ganglioneuroblastoma-like pattern [n=2], and small cell carcinoma-likepattern [n=3]). All the tumors were muscle invasive (invasion into the muscularis propria). IHC analysis showed that all tumors expressed FLI1, CD99, and at least one neuroendocrine marker. Focal cytokeratin staining was positive in 2 patients, and RB1 was retained in all patients. EWSR1 rearrangement was seen in 12 of 12 tumors (in 12 patients) tested. A combined multimodal approach that included surgery with chemotherapy was instituted in all patients. Follow-up was available for 11 patients (ranging from 5 to 24 months). Six patients either died of disease (n=3) or other causes (n=3). Five patients were alive with metastases to the liver (n=1), liver and lung (n=2), liver and abdominal wall (n=1), and kidney (n=1). Based on our experience with the largest series to date and aggregate of the published data, ES/round cell sarcomas with EWSR1 rearrangement occurring in the bladder have bimodal age distribution with poor prognosis despite aggressive therapy. Owing to its rarity and age distribution, the differential diagnosis is wide and requires a systematic approach for ruling out key age-dependent differential diagnoses aided with molecular confirmation.

Hip disorders in childhood

Abstract Childhood disorders of the hip are encountered frequently in paediatric orthopaedic practice. They present initially to paediatricians, general practitioners and accident departments, and it is therefore important for both surgeons and generalists to have a good working knowledge of the common presentations. The challenge is to distinguish between disease processes that are benign and self-limiting (e.g. transient synovitis), acute and joint threatening (e.g. septic arthritis) or chronic and disabling (e.g. Perthes' disease). This review primarily considers the epidemiology and aetiology of childhood hip diseases and provides a diagnostic framework, based upon age and risk factors. The important investigations and treatment options for each of the key differential diagnoses are also considered.

Non-Neoplastic Masses of the Pancreas.

Benign non-neoplastic solid lesions of the pancreas are comprised of several separate entities, with their diagnostic identification best performed in correlation with the radiographic and clinical features. These include all of the pancreatitides, intrapancreatic spleen, and a few other rare entities. Preoperative imaging may suggest the correct diagnosis, but occasionally the preoperative imaging findings may be misleading because they overlap with those of pancreatic neoplasms. Masses associated with typical pancreatitides are rarely sampled due to their distinct clinical picture and relative frequency; however, the uncommon variants of pancreatitis may also present as mass lesions mimicking malignancy. Herein, we will discuss the cytopathologic findings of several solid pancreatic lesions, including acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, paraduodenal or groove pancreatitis, and other mass lesions, such as intrapancreatic accessory spleen and abscess. The key cytological features, ancillary studies, and differential diagnoses will also be discussed.

The evolving landscape of HPV-related neoplasia in the head and neck

Human papilloma virus (HPV) has emerged as the key etiologic driver in the majority of cancers at head and neck mucosal sites. First described in the uterine cervix and subsequently in oropharyngeal squamous cell carcinomas, the morphologic and clinical spectrum of HPV-related neoplasia has continued to expand and now includes a newly described entity in the sinonasal tract. A recent study has also suggested a role of HPV in some ocular adnexal sebaceous carcinomas. Herein, we review and concisely summarize the spectrum of HPV-driven neoplasia in the head and neck, with a focus on variant morphologies and newly-described entities including key differential diagnoses and clinical implications.

Pseudotumoral demyelinating lesions: diagnostic approach and long-term outcome.

To review the clinical findings, differential diagnosis, treatment and outcome of pseudotumoral demyelinating lesions including tumefactive demyelination and Baló's concentric sclerosis. MRI findings, such as dynamic restricted diffusion changes at the edge of pseudotumoral lesions help to discriminate atypical demyelination from key differential diagnoses, and together with histopathological data, indicate that tissue hypoxia may be important aetiologically. CT-PET imaging can help to distinguish pseudotumoral lesions from high-grade tumours. Although most patients with pseudotumoral lesions have or later develop multiple sclerosis, a proportion will experience a monophasic course or be diagnosed with neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination or acute disseminated encephalomyelitis (ADEM). Many patients with pseudotumoral demyelinating lesions have a favourable prognosis. Not all patients with pseudotumoral lesions require a brain biopsy but close follow-up of biopsied and nonbiopsied lesions is indicated once a diagnosis is established. Testing for AQP4-IgG and MOG-IgG is recommended when a pseudotumoral demyelinating lesion is identified. In the absence of large, prospective studies, it seems reasonable that patients with pseudotumoral lesions who fulfil multiple sclerosis diagnostic criteria are treated with multiple sclerosis therapies.