Differential Diagnostic Considerations Research Articles

Increased risk of brucellosis misdiagnosis in regions that lose their endemicity.

Over the last decades, the epidemiology of human brucellosis globally has been subjected to significant changes, with the eradication of many existing endemic hot spots. This paper describes three cases with initial misdiagnosis of brucellosis that were managed during 2011-2017 in Republic of North Macedonia, country that until recently has been declared as endemic region. In spite of the fever, constitutional symptoms, focal disease (spondylitis, pneumonia and orchitis) and previous contact with domestic animals, brucellosis was not initially recognized, and patients were inadequately managed. Brucellosis should be part of differential diagnostic considerations in patients exposed to contacts with animals, with osteoarticular symptoms and signs, constitutional manifestations and different organ involvements in endemic regions where its incidence is diminishing.

Protocol for the development and testing of the schiZotypy Autism Questionnaire (ZAQ) in adults: a new screening tool to discriminate autism spectrum disorder from schizotypal disorder

BackgroundAutism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each.MethodsWe aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2).ConclusionsThe aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ).FundingFunding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma.Trial registrationClinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1.

Top 10 Significant Spindled Head and Neck Lesions to Scrutinze.

Spindled lesions are a challenging area in head and neck pathology. This is particularly true in the sinonasal tract, where several uncommon entities with both unique and overlapping morphologic, immunophenotypic, and/or molecular features can occur. Review. The clinicopathologic characteristics of biphenotypic sinonasal sarcoma and nine important differential diagnostic considerations with one or more overlapping feature are summarized to establish a practical framework for approaching spindled lesions of the sinonasal tract. Morphologic evaluation is central to the work up of sinonasal spindle cell lesions-in particular, cellular morphology, tumor architecture and growth pattern, and the presence of admixed epithelial elements - however, focused immunohistochemical analysis of neural, myogenic, rhabdomyoblastic, epithelial, and/or melanocytic marker expression and/or ancillary tests for tumor-specific molecular alterations may be necessary for definitive diagnosis.

Acute dyspnea

The leading symptom "acute dyspnea" and the causal underlying diseases have a high risk potential for an unfavorable course of treatment with a high letality. This overview of possible causes, diagnostic procedures and guideline-based therapy is intended to help implement a targeted and structured emergency medical care in the emergency department. The leading symptom "acute dyspnea" is present in 10% of prehospital and 4-7% of patients in the emergency department. The most common conditions in the emergency department with the leading symptom "acute dyspnea" are heart failure in 25%, COPD in 15%, pneumonia in 13%, respiratory disorders in 8%, and pulmonary embolism in 4%. In 18% of cases, the leading symptom "acute dyspnea" is sepsis. The in-hospital letality is high and amounts to 9%. In critically ill patients in the non-traumatologic resuscitation room, respiratory disorders (B-problems) are present in 26-29%. In addition to cardiovascular disease, noncardiovascular disease may underlie "acute dyspnea" and requires differential diagnostic consideration. A structured approach can contribute to a high degree of certainty in the clarification of the leading symptom "acute dyspnea".

Imaging of Central Nervous System Demyelinating Disorders

This article summarizes neuroimaging findings in demyelinating disease, the most common being multiple sclerosis. Revisions to criteria and treatment options have been ongoing, and MRI plays a pivotal role in diagnosis and disease monitoring. The common antibody-mediated demyelinating disorders with their respective classic imaging features are reviewed, as well as the differential diagnostic considerations on imaging. The clinical criteria of demyelinating disease rely heavily on imaging with MRI. With novel antibody detection, the range of clinical demyelinating syndromes has expanded, most recently with myelin oligodendrocyte glycoprotein-IgG antibodies. Imaging has improved our understanding of the pathophysiology of multiple sclerosis and disease progression, and further research is underway. The importance of increased detection of pathology outside of the classic lesions will have an important role as therapeutic options are expanding. MRI has a crucial role in the diagnostic criteria and differentiation among common demyelinating disorders and syndromes. This article reviews the typical imaging features and clinical scenarios that assist in accurate diagnosis, differentiation between demyelinating diseases and other white matter diseases, the importance of standardized MRI protocols in clinical practice, and novel imaging techniques.

A data driven machine learning approach to differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder based on the best-practice diagnostic instruments for autism

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two frequently co-occurring neurodevelopmental conditions that share certain symptomatology, including social difficulties. This presents practitioners with challenging (differential) diagnostic considerations, particularly in clinically more complex cases with co-occurring ASD and ADHD. Therefore, the primary aim of the current study was to apply a data-driven machine learning approach (support vector machine) to determine whether and which items from the best-practice clinical instruments for diagnosing ASD (ADOS, ADI-R) would best differentiate between four groups of individuals referred to specialized ASD clinics (i.e., ASD, ADHD, ASD + ADHD, ND = no diagnosis). We found that a subset of five features from both ADOS (clinical observation) and ADI-R (parental interview) reliably differentiated between ASD groups (ASD & ASD + ADHD) and non-ASD groups (ADHD & ND), and these features corresponded to the social-communication but also restrictive and repetitive behavior domains. In conclusion, the results of the current study support the idea that detecting ASD in individuals with suspected signs of the diagnosis, including those with co-occurring ADHD, is possible with considerably fewer items relative to the original ADOS/2 and ADI-R algorithms (i.e., 92% item reduction) while preserving relatively high diagnostic accuracy. Clinical implications and study limitations are discussed.

Diagnostically Challenging Subtypes of Invasive Lobular Carcinomas: How to Avoid Potential Diagnostic Pitfalls.

Invasive lobular carcinoma is the most common special breast carcinoma subtype, with unique morphological (discohesive cells, single-cell files, targetoid pattern) and immunohistochemical (loss of E-cadherin and β-catenin staining) features. Moreover, ILC displays a poor response to neoadjuvant therapy, a different metastatic pattern compared to invasive breast carcinoma of no special type, as well as unique molecular characteristics. In addition to the classic variant of invasive lobular carcinoma, several other well-recognized variants exist, including classic, alveolar, tubulolobular, solid, pleomorphic, signet-ring, and mixed. Furthermore, three novel variants of invasive lobular carcinoma, i.e., with extracellular mucin production, papillary features, and tubular elements, have been described during the last decade. We herewith focus on the unique morphological and immunohistochemical characteristics of these novel varieties of invasive lobular carcinoma, as well as differential diagnostic considerations and potential diagnostic pitfalls, especially when dealing with biopsy specimens.

Post-COVID-19 condition: current evidence and unanswered questions

Post-COVID-19 condition: current evidence and unanswered questions

Embryonal Rhabdomyosarcoma of the Uterine Cervix: A Clinicopathologic Study of 94 Cases Emphasizing Issues in Differential Diagnosis Staging, and Prognostic Factors.

Embryonal rhabdomyosarcoma of the uterine cervix (cERMS) is rare and frequently associated with DICER1 mutations. We report 94 tumors that arose in patients aged 7 to 59 (median=23) years and presented with vaginal bleeding (52), protruding vaginal mass (17), cervical polyp (8), or expelled tumor fragments per vagina (5). Nine had DICER1 syndrome, 8 of whom had other syndromic manifestations including ovarian Sertoli-Leydig cell tumor (7), multinodular goiter (3), pleuropulmonary blastoma (2), pineoblastoma (1), and osteosarcoma (1). Syndromic patients were younger than nonsyndromic patients (16 vs. 24y). Tumor size ranged from 2 to 24 (median=4.5)cm. Ninety-two tumors were polypoid, most being grape-like (77 of 92). They were characterized by aggregates of primitive cells, almost always exhibiting a cambium layer, within a variably myxoedematous stroma and were hypocellular (63), moderately cellular (22), or hypercellular (9). Entrapped glands, typically scant, were present in 84 tumors. Primitive hyperchromatic ovoid to spindled cells with minimal cytoplasm predominated but differentiated rhabdomyoblasts with abundant eosinophilic cytoplasm (having cross-striations in 30) were seen in 83 tumors; they were often sparse but predominated in three. Nine tumors showed areas of intersecting fascicles and 4 zones with densely cellular (solid) growth. Cartilage was present in 38. Anaplasia was seen in 15 tumors, as was necrosis. Mitotic activity ranged from 1 to 58/10 high-power fields (median=8). The varied microscopic features resulted in a spectrum of differential diagnostic considerations, mainly typical and cellular forms of fibroepithelial polyps, Mullerian adenosarcoma, and other sarcomas. Follow-up was available for 79 patients ranging from 6 to 492 (median=90) months. Treatment information was available in 62 and included polypectomy in 6 patients (2 also received chemotherapy), limited resection in 26 (14 also received chemotherapy), hysterectomy in 29 (15 with adjuvant chemotherapy), and biopsies only in 1 (with chemotherapy). Staging was possible in 56 tumors; according to the "uterine sarcoma" system (tumor size and extent) they were: stage I (10/56; could not be further subclassified as size not available), IA (22/56), IB (18/56), IIA (2/56), IIB 3/56), IIIC (1/56). According to the "adenosarcoma" system (depth of invasion and extent) they were: stage IA (26/56), IB (14/56), IC (10/56), IIA (2/56), IIB (3/56), IIIC (1/56). Eight patients had local recurrence following incomplete excision (10%). Eleven of 79 patients had extrauterine recurrences (14%) and 9 died of disease (11%). Older age was associated with extrauterine recurrence (median 44 vs. 22; P =0.002) and decreased disease-specific survival (median 44 vs. 22; P =0.02). For patients with tumors initially confined to the cervix, the adenosarcoma staging system was superior to the uterine sarcoma staging system for predicting survival ( P =0.02). Three patients with DICER1 syndrome who underwent fertility-preserving surgery developed a second primary cERMS 7, 7, and 12 years after their primary tumor. All 9 patients with DICER1 syndrome had tumors confined to the cervix and none died of disease. This study highlights the intriguing clinical aspects of cERMS including its long-known tendency to occur in the young but also more recently appreciated association with DICER1 syndrome. Establishing the diagnosis may still be difficult because of the hazard of sampling a neoplasm which in areas may appear remarkably bland and also because of its potential confusion with other neoplasms. This study indicates that this tumor has a good prognosis at this site and in selected cases a conservative surgical approach is a realistic consideration.

Adverse effects of opioids, antidepressants and anticonvulsants on sex hormones : Often unnoticed but clinically relevant

Androgen insufficiency under treatment with opioids, antidepressants and anticonvulsants in chronic pain diseases is aside effect with ahigh prevalence. It can lead to clinical metabolic alterations, adynamia, stress intolerance, anemia or osteoporosis and has asignificant impact on the quality of life. Opioids, antidepressants and anticonvulsants affect the hypothalamic-pituitary-gonadal axis of sex hormones. A urologist, andrologist or endocrinologist should be involved in the treatment at an early stage. The recommendation of adifferential therapeutic selection of certain substances is only indicative and does not meet evidential criteria. The indications for androgen substitution must be individualized and in consideration of the risk-benefit profile. Awareness of this side effect of an otherwise lege artis medicinal pain therapy must be sharpened and compulsory included in the differential diagnostic considerations.

Consensus statement of the Austrian Sleep Medicine Society on the management of residual excessive daytime sleepiness in obstructive sleep apnea

Six to ten percent of patients with obstructive sleep apnea suffer from residual excessive daytime sleepiness (rEDS) despite adequate nocturnal positive airway pressure therapy or effective alternative treatment. The differential diagnosis of rEDS is an interdisciplinary challenge in clinical practice. Development of aclear guideline for the detection, differential diagnostic considerations, and options for the continuing treatment of rEDS in clinical practice. MeSH analysis-based research and interdisciplinary consensus among specialists in internal medicine and pneumology, neurology, as well as psychiatry and psychotherapy. The SPAIN checklist for systematic differential diagnostic exploration of rEDS with the parameters: Sleep behavior, Psychological causes, Anamesis of medication, Internal causes and Neurological causes. rEDS should be recognized as asymptom worthy of treatment. It requires an interdisciplinary assessment and the individual adaptation of the treatment to the needs of the affected person.

Capillary telangiectasia

Brain capillary telangiectasia is usually a small collection of dilated capillary-like vessels. In most cases it is aharmless incidental finding with no clinical significance. They are most commonly located in the pons. In terms of image morphology, they show brush-like signal extinction in T2*/SWI (susceptibility-weighted imaging) sequences and contrast enhancement in T1-weighted images. Other sequences are usually unremarkable unless they involve unusually large capillary telangiectasias. Angiographically they usually remain silent. Sometimes they are associated with venous abnormalities and/or cavernomas. Their distinctive radiographic features usually allow for areliable diagnosis. Differential diagnostic considerations, such as differentiation from atumorous or inflammatory process, are sometimes necessary.

An Approach to Nonurothelial Malignancies of the Urinary Bladder in Urine Cytology.

Urine cytology is an economical and convenient method of triaging patients who present with urinary symptoms as well as surveying those who have previously been diagnosed with urothelial carcinoma for recurrent or persistent disease. While the vast majority of malignancies diagnosed in urine cytology are urothelial carcinomas, it is important to recognize nonurothelial elements to inform patient prognosis and raise the possibility of involvement by a urothelial carcinoma variant, nonurothelial malignancy of the bladder, or a nonbladder primary, which may alter patient management pathways. As such, becoming familiar with morphologic features of nonurothelial malignancies in urine cytology as well as their related clinical risk factors, radiologic and cystoscopic features, differential diagnostic considerations, and the utility and pitfalls of ancillary tests can facilitate optimal patient care.

Best Practices in CD30 Immunohistochemistry Testing, Interpretation, and Reporting: An Expert Panel Consensus.

Although CD30 testing is an established tool in the diagnostic workup of lymphomas, it is also emerging as a predictive biomarker that informs treatment. The current definition of CD30 positivity by immunohistochemistry is descriptive and based on reactivity in lymphomas that are defined by their universal strong expression of CD30, rather than any established threshold. Challenges include inconsistencies with preanalytic variables, tissue processing, pathologist readout, and with the pathologist and oncologist interpretation of reported results. To develop and propose general best practice recommendations for reporting CD30 expression by immunohistochemistry in lymphoma biopsies to harmonize practices across institutions and facilitate assessment of its significance in clinical decision-making. Following literature review and group discussion, the panel of 14 academic hematopathologists and 2 clinical/academic hematologists/oncologists divided into 3 working groups. Each working group was tasked with assessing CD30 testing by immunohistochemistry, CD30 expression readout, or CD30 expression interpretation. Panel recommendations were reviewed and discussed. An online survey was conducted to confirm the consensus recommendations. CD30 immunohistochemistry is required for all patients in whom classic Hodgkin lymphoma and any lymphoma within the spectrum of peripheral T-cell lymphoma are differential diagnostic considerations. The panel reinforced and summarized that immunohistochemistry is the preferred methodology and any degree of CD30 expression should be reported. For diagnostic purposes, the interpretation of CD30 expression should follow published guidelines. To inform therapeutic decisions, report estimated percent positive expression in tumor cells (or total cells where applicable) and record descriptively if nontumor cells are positive.

Suspected factitious disorder: identifying self-inflicted wounds in plastic surgery

Patients with factitious disorders artificially generate, aggravate or feign injuries or illnesses, which can result in severe physical impairment and misuse of the healthcare system. The symptomatology is characterized by a protracted course of disease with frequent changes of practitioners and multiple invasive procedures due to anomalous, mostly chronic findings. Elaborate clinical presentations, lack of knowledge of disease characteristics and the fast-paced everyday clinical practice can lead to maintaining the disease through non-recognition or mistreatment. Based on selective literature research and clinical case reports from a university clinic for plastic surgery, this article provides a review about common features of factitious disorders as well as treatment strategies. If a factitious disorder is suspected, invasive treatments should be restricted and psychosomatic or psychiatric expertise obtained. Within an empathic physician-patient relation and with psychotherapeutic support, patients can be gradually introduced to the diagnosis and therapy options and treatment terminations could be avoided. Knowledge of indicators for factitious disorders, which may become evident in medical history, findings and illness-affirming behaviour, is key to identify affected patients and initiate appropriate treatment. For this purpose, factitious disorders should be included in differential diagnostic considerations even in primarily somatic medical specialties. Since the diagnosis is often based on evidence and complicated by withheld information or medical confidentiality, the establishment of a central reporting register could facilitate the diagnostic process and improve therapy in the future.

Disc-like lesions in the intestinal tract after renal transplantation.

We report a case of intestinal lesions in a patient with a history of lupus nephritis and renal transplantation. Biopsy revealed an EBV‐driven post‐transplant lymphoproliferative disease (PTLD). An EBV‐driven PTLD is a major complication after renal transplantation and is an important differential diagnostic consideration in the follow‐up of renal transplant recipients.

A Newborn with an Incidental Finding on Cranial Ultrasonography.

A Newborn with an Incidental Finding on Cranial Ultrasonography.

Treatment decision for femoroacetabular impingement syndrome : Differential diagnostic considerations and the introduction of astage concept for treatment

Anamnestic findings, clinical examination and radiological findings are presented, as well as thoughts for differential diagnosis and the introduction of astage concept for treatment. The treatment of FAI is based on a patient's individual symptoms, the clinical examination and radiological findings. The procedure depends on anumber of facts. Individual conditions have to be considered, and the procedure needs to follow principal rules. Therefore, we propose astandard for treatment, which ranges from purely conservative measurements to extensive surgery.

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients

BackgroundComprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far.ObjectiveTo analyze systematically the CSF profile in COVID-19.MethodsRetrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centersResultsThe most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3–240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF l-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2–4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease.ConclusionsThe CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and ‘long COVID’. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.

MRI of Muscular Neoplasms and Tumor-like Lesions: A 2020 World Health Organization Classification-based Systematic Review

Imaging findings of pneumonia are diverse, with frequent overlap between the various infectious etiologies of pneumonia, as well as various other disease conditions, including inflammatory conditions, vasculitis, and malignancy. In the appropriate clinical context, a number of imaging findings and the patterns that they form on imaging may provide clues that enable radiologists and clinicians to narrow the differential diagnostic considerations. Although a definite diagnosis can rarely be provided based on imaging findings alone, the combination of clinical, imaging, and laboratory findings are usually sufficient for accurate diagnosis and management decisions. It is important for radiologists to recognize the wide variety of imaging patterns that occur with different causes of pneumonia, and recognize specific imaging signs of certain infections when present, thereby facilitating diagnosis and optimizing patient care.