Differential Diagnostic Considerations Research Articles

Intraosseous hibernoma mimicking sclerotic bone metastasis-a case report.

Intraosseous hibernoma is an uncommon presentation of brown adipose tissue benign tumors. Imaging differential diagnoses include bone island, sclerotic metastasis, lymphoma, hemangioma, and sclerotic myeloma. In this report, a 72-year-old patient presented with right hip pain following a fall injury, leading to an extensive diagnostic workup. Initial CT of the pelvis without contrast suggested potential sclerotic metastatic disease. MRI findings could not be definitive. Further assessment with CT-guided biopsy and S-100 immunohistochemical staining confirmed a rare diagnosis of intraosseous hibernoma. This case describes multimodality imaging characteristics of a rare intraosseous hibernoma with discussion of imaging features of differential diagnostic considerations of related benign and malignant bone lesions.

Cytological features of ependymal and choroid plexus tumours.

Ependymal and choroid plexus tumours arise in anatomically related regions. Their intraoperative differential diagnosis is large and depends on factors such as age, tumour site and clinical presentation. Squash cytology can provide valuable information in this context. Cytological features of conventional ependymomas, subependymomas and myxopapillary ependymomas as well as choroid plexus tumours are reviewed and illustrated. Differential diagnostic considerations integrating morphological and clinical information are discussed.

Myositis and Its Mimics: Guideline Updates, MRI Characteristics, and New Horizons.

Myositis is defined as inflammation within skeletal muscle and is a subcategory of myopathy, which is more broadly defined as any disorder affecting skeletal muscle. Myositis may be encountered as a component of autoimmune and connective tissue disease, where it is described as idiopathic inflammatory myopathy. Myositis can also be caused by infections, as well as toxins and drugs, including newer classes of medications. MRI plays an important role in the diagnosis and evaluation of patients with suspected myositis, but many entities may have imaging features similar to myositis and can be considered myositis mimics. These include muscular dystrophies, denervation, deep venous thrombosis, diabetic myonecrosis, muscle injury, heterotopic ossification, and even neoplasms. In patients with suspected myositis, definitive diagnosis may require integrated analysis of imaging findings with clinical, laboratory, and pathology data. The objectives of this article are to review the fundamental features of myositis, including recent updates in terminology and consensus guidelines for idiopathic inflammatory myopathies, the most important MRI differential diagnostic considerations for myositis (i.e., myositis mimics), and new horizons, including the potential importance of artificial intelligence and multimodal integrated diagnostics in the evaluation of patients with muscle disorders.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240ng/ml; 28 out of 31 cases had AFP levels below 25µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

A case of fine-needle aspiration of a neck mass with atypical squamous cells and macrophages.

Head and neck lesions often undergo fine-needle aspiration to determine the appropriate management and therapeutic decisions. However, there are numerous diagnostic challenges encountered with these specimens, particularly, if atypical squamous cells are identified. Here, we present a case of an enlarging right neck mass in a 38-year-old female and discuss the diagnostic difficulties and potential pitfalls. Additionally, we review the approach to diagnosis, including differential diagnostic considerations as well as available ancillary testing.

Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases.

Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid morphology, together with sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma as top diagnostic considerations, it is vital to additionally consider the possibility of well-differentiated and de-differentiated liposarcoma. This study reports a series of 30 biopsy samples from sites in or around the kidney collected from four institutions in which the correct diagnosis was either well-differentiated or de-differentiated liposarcoma. The majority (26 of 30, 87%) of lesions were accurately diagnosed on biopsy sampling, all of which incorporated testing for MDM2 by immunohistochemistry (IHC), fluorescence in-situ hybridisation (FISH) or a combination of the two as part of the diagnostic work-up. Tumour expression of MDM2 by IHC without confirmatory FISH analysis was sometimes (30%) sufficient to reach a diagnosis, but demonstration of MDM2 amplification by FISH was ascertained in the majority (57%) of biopsy samples. A diagnosis of de-differentiated liposarcoma was not definitively established until resection in four (13%) patients, as no MDM2 testing was performed on the corresponding pre-operative biopsies. When a retroperitoneal tumour is not clinically suspected, histological consideration of a liposarcoma diagnosis may be overlooked. Implementation of ancillary immunohistochemical and cytogenetic testing can ultimately lead to a definitive diagnosis in this potentially misleading anatomical location.

Uncommon Causes of Interlobular Septal Thickening on CT Images and Their Distinguishing Features.

Interlobular septa thickening (ILST) is a common and easily recognized feature on computed tomography (CT) images in many lung disorders. ILST thickening can be smooth (most common), nodular, or irregular. Smooth ILST can be seen in pulmonary edema, pulmonary alveolar proteinosis, and lymphangitic spread of tumors. Nodular ILST can be seen in the lymphangitic spread of tumors, sarcoidosis, and silicosis. Irregular ILST is a finding suggestive of interstitial fibrosis, which is a common finding in fibrotic lung diseases, including sarcoidosis and usual interstitial pneumonia. Pulmonary edema and lymphangitic spread of tumors are the commonly encountered causes of ILST. It is important to narrow down the differential diagnosis as much as possible by assessing the appearance and distribution of ILST, as well as other pulmonary and extrapulmonary findings. This review will focus on the CT characterization of the secondary pulmonary lobule and ILST. Various uncommon causes of ILST will be discussed, including infections, interstitial pneumonia, depositional/infiltrative conditions, inhalational disorders, malignancies, congenital/inherited conditions, and iatrogenic causes. Awareness of the imaging appearance and various causes of ILST allows for a systematic approach, which is important for a timely diagnosis. This study highlights the importance of a structured approach to CT scan analysis that considers ILST characteristics, associated findings, and differential diagnostic considerations to facilitate accurate diagnoses.

Diagnosis of acute coronary syndrome

Acute coronary syndrome is one of the most important differential diagnostic considerations in emergency medicine. It describes the constellation of newly occurring clinical symptoms, often accompanied by typical 12-lead ECG changes and the release of cardiac troponins. The spectrum includes unstable angina pectoris, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). It is important to consistently carry out the diagnostic steps that are crucial for further therapeutic procedures to avoid delaying life-saving invasive coronary diagnostics, without losing sight of the diverse, sometimes time-critical differential diagnoses. Anamnesis and clinical examination form the basis of the further procedure. Further developments of biomarker assays with personalized limit values, new imaging modalities with ever higher resolution and faster imaging methods as well as advances in automated ECG analysis with integration of all findings through artificial intelligence will continue to offer many optimization options in the future diagnosis of acute coronary syndrome.

Glandular Lesions of the Urinary Bladder: Diagnostic and Molecular Updates.

Glandular lesions in the urinary tract or their associated pathologies can pose a diagnostic challenge. There is a variety of benign alterations and tumor types that need to be taken into account in differential diagnostic considerations. In recent times, efforts for better defining these alterations or lesions both on the histopathological and molecular levels have been undertaken. This article will provide an update on current diagnostic and molecular considerations of these lesions.

Upper Urothelial Tract Extraosseous Bone Formation: An Unexpected Finding and Differential Diagnostic Considerations.

Extraosseous bone formation of the upper urothelial tract is an unusual phenomenon with limited documentation in the uropathology literature, reported in only 2 clinical series of patients undergoing percutaneous nephrolithotomy for the management of renal stones. While speculations regarding the pathogenesis of this occurrence have been published, heterotopic ossification is still poorly understood. We report the finding of extraosseous bone formation in the renal pelvis of a 30-year-old male patient with a history of kidney stones. Histologic sections of the ureter and renal pelvis showed submucosal nodules of woven bone. Ancillary fluorescence in-situ hybridization studies were negative for MDM2 amplification and USP6 rearrangement.

PRIMARY OVARIAN LEIOMYOMA ASSOCIATED WITH MULTIPLE UTERINE LEIOMYOMAS: A CASE REPORT

Leiomyoma is a benign mesenchymal tumour, occurring frequently in uterus. But ovarian leiomyoma is rare, accounting less than 1% of all ovarian tumours. Ovarian leiomyoma is associated with uterine leiomyoma in about 78% of the cases. Being asymptomatic they are often incidentally detected in most of the patients. This is a case of ovarian leiomyoma associated with uterine leiomyomas in a 53 year old woman who had abdominal mass on examination during her regular check-up. Ultrasonography revealed multiple uterine fibroids and a unilocular cyst in right ovary. Total abdominal hysterectomy with bilateral salpingoophorectomy was performed. Gross examination showed left ovary totally replaced by grey-white firm mass. Microscopic features were typical of leiomyoma and was confirmed immunohistochemically. Major differential diagnostic considerations for this tumor in ovary were fibroma, thecoma and leiomyosarcoma. Though rare, ovarian leiomyoma should be considered in differential diagnosis of ovarian solid mass. The immunohistochemical staining with desmin, inhibin, and α-smooth muscle actin are useful to rule out the differential diagnosis.

Vasculitides

In everyday clinical practice, immunologically mediated systemic vasculitides are among the rare diseases, meaning that basic knowledge of major symptoms and indicative laboratory findings is crucial for the inclusion of these complex clinical entities in differential diagnostic considerations. For many years, systemic vasculitides have been classified according to the primarily affected vessel size, distinguishing large, medium-sized, and small vessels. Pain is very often one of the main complaints of these diseases, be it, for example, the temporally accentuated headache in giant cell arteritis, the early morning myalgias in the shoulder and hip girdle in polymyalgia rheumatica, or the mononeuritis multiplex in eosinophilic granulomatosis with polyangiitis. General symptoms such as fever, weight loss, and night sweats are often accompanied by greatly increased parameters of inflammation. In addition, organ-specific symptoms and/or laboratory abnormalities may provide crucial information. These include ENT symptoms, pulmonary or skin manifestations, as well as signs of renal involvement, such as peripheral edema, rise in blood pressure, hematuria, proteinuria, or arapid loss of kidney function. If there is reasonable suspicion of disease, patients should be transferred to specialized centers with an interdisciplinary team. In most cases, an immunosuppressive therapy regimen is required, although in recent years the path towards avoiding high glucocorticoid doses with many side effects has been paved by the use of novel therapies.

Modern corneal diagnostics as the key for the correct classification of the disease and optimal treatment decisions

Corneal diseases include awide spectrum of different manifestations (inflammatory/noninflammatory) that need to be accurately classified for precise diagnosis and targeted treatment. In addition to the anamnesis and slit lamp biomicroscopy, further device-based examinations can be performed to narrow down the diagnosis. Nowadays, modern corneal imaging provides avariety of technologies, such as topography, tomography, in vivo confocal microscopy and analysis of biomechanics, which are able to reliably classify different pathologies. Knowledge of the available examination modalities helps to guide differential diagnostic considerations, facilitating the indication for stage-appropriate microsurgical intervention.

Recent developments in the pathology of primary pulmonary salivary gland-type tumours.

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.

Approaching Headaches—A Guide to Differential-Diagnostic Considerations and Causal Claims

Headaches can be nociplastic, neuropathic, and nociceptive. Pain related to the latter two categories occurs in the presence of nerve lesions and nociceptive stimuli; attributing pain to the last category requires a list of potential causes and arguments supporting the causal claim. Taking a history and examining patients serves to assess diagnostic criteria and screen for disorders whose diagnosis requires additional examinations. Screening information occurs in two types: one indicates that patients have a headache due to another condition; the other suggests they are at risk. Aspiring to make causal claims for a headache is reasonable because if underlying disorders appear independently and randomly, it is probable that there is only one cause. Thus, having found a cause often implies having found the cause. The prerequisites for causal claims are temporal sequencing, correlation, and elimination of alternate causes. Mechanistic, manipulative, and probabilistic evidence supports the second criterion. The importance of headaches lies in their frequent appearance as an early symptom of an incipient disorder (“sentinel symptom”). Hence, they provide the opportunity to diagnose early diseases with potentially deleterious consequences. Thus, it is sensible to assess each attack carefully and systematically.

Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma.

To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis. Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease. Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities.

Inflammatory Lesions of the Breast.

Inflammatory lesions of the breast are rare but not infrequently pose problems both clinically and morphologically, particularly on needle core biopsies. These lesions range from acute inflammatory conditions to chronic lymphoplasmacytic and lymphohistiocytic to granulomatous inflammatory diseases. To provide a comprehensive overview of inflammatory lesions of the breast, with etiopathogenesis and clinical, radiologic, and pathologic features as well as differential diagnostic considerations, clinical management, and prognosis. The existing literature in the English language, including original research articles and review articles describing inflammatory lesions of the breast. Inflammatory lesions of the breast are characterized by a wide variety of clinical, radiologic, and morphologic features. The histopathologic differential diagnosis often includes a neoplastic process requiring ancillary studies and correlation with clinical and radiologic findings. Although most specimens display nonspecific findings precluding a definitive pathologic diagnosis, pathologists have a unique opportunity to play a crucial role in identifying key histologic features suggestive of certain entities, such as cystic neutrophilic granulomatous mastitis, immunoglobulin (Ig) G4 mastitis, or squamous metaplasia of lactiferous ducts, in the right clinical and radiologic context, and thereby guiding optimal and timely clinical management. The information presented herein will be helpful to practicing anatomic pathologists and pathology trainees in becoming more familiar with specific morphologic features and overcoming differential diagnostic challenges related to pathology reporting of inflammatory lesions of the breast.

Epidemiological and clinical characteristics of imported falciparum malaria in the Republic of North Macedonia : A13-year experience.

Plasmodium falciparum is the leading cause of imported malaria and the most common cause of death in returning travellers. To identify the main epidemiological and clinical characteristics of patients with imported falciparum malaria in the Republic of North Macedonia. Retrospectively analyzed were the epidemiological and clinical features of 34patients with imported falciparum malaria who were diagnosed and treated at the university clinic for infectious diseases and febrile conditions in Skopje from 2010 to 2022. Malaria diagnosis was based on the microscopic detection of parasites in thick and thin blood smears. All patients were male, with amedian age of 36years and arange of 22-60years. Of the patients 33 (97.1%) acquired the disease in Sub-Saharan Africa. All patients except one stayed in endemic regions for work/business purposes. Chemoprophylaxis was completely applied in 4(11.8%) patients. The median time of onset between the symptoms and diagnosis was 4 days, with arange of 1-12days. Prevailing clinical manifestations were fever, chills, and splenomegaly in 100%, 94%, and 68% of patients, respectively. Severe malaria was noticed in 8 (23.5%) patients. In 5 (14.7%) patients the initial parasitemia was higher than 5%. On admission, thrombocytopenia, hyperbilirubinemia, and elevated alanine aminotransferase were registered in 94%, 58%, and 62% of patients, respectively. Out of the 33patients with adequate follow-up, the outcome was favorable in 31(93.9%). In every febrile traveller returned from Africa, imported falciparum malaria should be an essential part of differential diagnostic considerations.

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.