Differential Diagnostic Challenges Research Articles

Viral pneumonia in a patient treated with pembrolizumab - similarity with immune-related pneumonitis.

Immunotherapy is one of the fundamental treatment modalities, especially in the treatment of metastatic non-small cell lung carcinoma, but it is also applied in neoadjuvant, or adjuvant therapy. A certain limitation continues to be immune-mediated toxicity and the broad clinical spectrum of its manifestations, which can present considerable differential diagnostic challenges. We present a case of a female patient who has been treated at our institute since February 2023 for metastatic squamous cell carcinoma of the right lung with first-line systemic therapy of pembrolizumab in initial combination with carboplatin and paclitaxel. Reassessment after four cycles of treatment showed a significant regression of the oncological finding, but also partial fibrotic changes in both lungs. The patient was completely asymptomatic and after consultation with her, it was decided to continue the treatment, now with pembrolizumab monotherapy. Several days after administration, the patient developed resting dyspnea, cough, and fevers. She consulted this deterioration of her condition only at the next scheduled appointment. Persistent dyspnea raised suspicion of immune-mediated pneumonitis. CT of the chest showed significant involvement of all lung lobes and treatment with corticosteroids and antibiotics was initiated. Through bronchoalveolar lavage, positivity for rhinovirus and enterovirus was detected. Viral pneumonia was assessed as the most likely cause of the clinical finding. The established corticosteroid treatment was gradually reduced and after discussion with the patient, we continued the administration of pembrolizumab. A follow-up CT of the lungs showed both further significant regression of the tumor and significant regression of inflammatory changes. Currently, the patient is after a total of 14 cycles of chemo/immunotherapy (of which 9 cycles of pembrolizumab after re-initiation), clinically in excellent condition, while a significant therapeutic response continues. Our case report emphasizes the need for a broader differential diagnosis in the event of pulmonary complications during the administration of immunotherapy. Correct diagnosis of these complications can, among other things, fundamentally affect oncological treatment.

Differential diagnostic challenges for ophthalmic diseases: a case report

Differential diagnostic challenges for ophthalmic diseases: a case report

Severe spontaneous long-lasting hypoglycaemia. Differential diagnostic challenges thorough a case report

Severe spontaneous long-lasting hypoglycaemia. Differential diagnostic challenges thorough a case report

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.

Application of Contrast-Enhanced Ultrasound in the Diagnosis of Gastrointestinal Acute Gvhd - Single Centre Experience

Introduction: Acute graft versus host disease (aGVHD) is one of the most common complications after allogeneic stem cell transplant, with gastro-intestinal (gut) involvement being associated with increased morbidity and mortality. The gastrointestinal symptoms are common and therefore pose differential diagnostic challenges. Biopsy with histopathological exam by endoscopy represent the gold standard for the diagnosis of gut aGVHD. In clinical practice, the endoscopy exam, a minimal invasive investigation, is difficult to tolerate by the patient and sometimes risky to perform due to the severe thrombocytopenia. For this reason, there is an urgent need to find some non-invasive diagnostic methods, such as standard ultrasound and contrast-enhanced ultrasound (CEUS), hoping that these investigations will help in the early diagnosis as well as in the follow-up response treatment. Aim: The aim of this study was to present our experience with CEUS in diagnosis of gut aGVHD after allogeneic stem cell transplantation Results: Between January 2019 and March 2022, in Fundeni Clinical Institute, 168 allogeneic stem cell transplants were performed. 20/168 were readmitted into the hospital with non-infectious diarrhea and with suspicion of gut aGVHD. All patients were investigated by classical GI tract ultrasound and CEUS. For 12 patients out of 20 we had histopathological confirmation of gut GVHD and could thus corelate with the CEUS findings. For all patients the bowel wall thickness was increased, and the most affected areas were ileal loops, followed by ileocecal region and ascending colon. The most common feature, contrast agent migration in the intestinal lumen (the penetration of microbubbles in the bowel lumen) was observed in 3/12 patients, but, 9/12 remaining patients performed CEUS after the first dose of treatment with corticotherapy. In conclusion, CEUS represent a noninvasive, simple and viable investigation for gut aGVHD, most valuable probably for ileal localization, where the endoscopic approach is difficult. Therefore, it is important to establish which is the exact period after the onset of symptoms when the microbubbles migrate in the bowel lumen and if this parameter can be used to monitor the response to treatment. Based on these results, we aim to introduce CEUS evaluation as standard investigation for aGVHD and monitor all the patients.

Atypical segmental multicystic dysplastic kidney with severe reflux in a newborn

Segmental cases of multicystic dysplastic kidney (SMCDK) are rare and hard to diagnose, imaging characteristics are not evident. SMCDK can be presented with duplex collecting system, vesicoureteral reflux (VUR), pyeloureteric junction obstruction and orthotopic ureterocele. Typical cases are localized to the upper pole of a duplex collecting system. Atypical cases are rarely reported. We present an unique atypical SMCDK case, with unconventional disease manifestation to bring attention to the variable presentation of this rare disorder and to draw attention to differential diagnostic challenges of cystic kidney malformations. In our patient newborn screening abdominal ultrasound detected severe hydronephrosis and hydroureter of the lower pole of the right kidney. Dynamic renal scintigraphy and sonocystography confirmed duplication of both collecting systems and severe VUR in the right lower pole. Heminephrectomy was performed. The suspected diagnosis of atypical SMCDK was confirmed by histopathology. The patient recovered uneventfully. This unusual case of atypical SMCDK highlights the importance of considering the possibility of SMCDK in patients with partial kidney malformation or unusual appearance of congenital kidney disease.

A Review on the Clinical Diagnosis of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare, adult-onset, progressive neurodegenerative disorder with major diagnostic challenges. Aiming for a better diagnostic accuracy particularly at early disease stages, novel Movement Disorder Society criteria for the diagnosis of MSA (MDS MSA criteria) have been recently developed. They introduce a neuropathologically established MSA category and three levels of clinical diagnostic certainty including clinically established MSA, clinically probable MSA, and the research category of possible prodromal MSA. The diagnosis of clinically established and clinically probable MSA is based on the presence of cardiovascular or urological autonomic failure, parkinsonism (poorly L-Dopa-responsive for the diagnosis of clinically established MSA), and cerebellar syndrome. These core clinical features need to be associated with supportive motor and non-motor features (MSA red flags) and absence of any exclusion criteria. Characteristic brain MRI markers are required for a diagnosis of clinically established MSA. A research category of possible prodromal MSA is devised to capture patients manifesting with autonomic failure or REM sleep behavior disorder and only mild motor signs at the earliest disease stage. There is a number of promising laboratory markers for MSA that may help increase the overall clinical diagnostic accuracy. In this review, we will discuss the core and supportive clinical features for a diagnosis of MSA in light of the new MDS MSA criteria, which laboratory tools may assist in the clinical diagnosis and which major differential diagnostic challenges should be borne in mind.

Dissosiativ identitetsforstyrrelse i utredning av barn og ungdom: Teori og kliniske utfordringer

Background: Clinical practice and recent research indicate that dissociative symptoms and disorders are left unidentified and undiagnosed by health professionals. Based on a clinical case from our work setting, this article describes relevant literature regarding dissociation and dissociative disorders to add to the knowledge of the theoretical and phenomenological features of complex dissociative disorders. Further, we describe differential diagnostic challenges that may arise in clinical practice. Methods: The authors work in specialized health care and have extensive clinical expertise in complex dissociative symptomatology in children. Both systematic and non-systematic literature searches were performed. Findings: Recent research shows the Trauma model to be central to understanding dissociative disorders. Symptoms can be mistaken for cognitive difficulties, oppositional issues or other somatic symptoms. Quantitative measures, systematic observations and clinical evaluations are fundamental for identifying dissociative symptoms and disorders. Implications: There is potential for identifying and evaluating dissociative symptoms at an earlier stage. Interdisciplinary and differential diagnostic evaluations are crucial to provide adequate understanding, assessment, and treatment of these patients. Keywords: Dissociative identity disorder, dissociation, somnambulism, biopsychosocial framework, clinical practice

Differential Diagnostic Challenges During the Covid-19 Pandemic for Pediatricians in an Eastern European Country

Differential Diagnostic Challenges During the Covid-19 Pandemic for Pediatricians in an Eastern European Country

Patients with both Langerhans cell histiocytosis and Crohn's disease highlight a common role of interleukin-23.

AimTo present the first case series of patients with Langerhans cell histiocytosis (LCH) also affected by Crohn's disease (CD), both of which are granulomatous diseases, and in LCH investigate the role of interleukin (IL)‐23, which is a well‐described disease mediator in CD.MethodsA case series of three patients with LCH and CD were described; a cohort of LCH patients (n = 55) as well as controls (n = 55) were analysed for circulating IL‐23 levels; and the relation between the percentage of LCH cells in lesions and circulating IL‐23 levels was analysed in seven LCH patients.ResultsDifferential diagnostic challenges for these two granulomatous diseases were highlighted in the case series, and it took up to 3 years to diagnose CD. Elevated IL‐23 levels were found in LCH patients. The amount of lesional LCH cells correlated with the levels of circulating IL‐23.ConclusionBoth CD and LCH should be considered in patients with inflammatory gastrointestinal involvement. The IL‐23 pathway is a common immunological trait between these two granulomatous diseases.

Current approaches to treatment of uveitis in immune-mediated inflammatory rheumatic disease

Non-infectious uveitis is the leading and insufficiently studied cause of irreversible decline in visual functions in patients with immune-mediated inflammatory rheumatic disease (IMIRDs). A multidisciplinary approach to the diagnosis and treatment of uveitis in patients with IMIRDs, involving close collaboration of rheumatologists and ophthalmologists, is the key factor for achieving favorable clinical outcomes. This article sheds light on current clinical, differential diagnostic and therapeutic challenges related to non-infectious uveitis in IMIDs-patients, with specific emphasis on state-of-the art approaches to therapy.

Klinische Wertigkeit der Bestimmung von DFS70-Antikörpern für den Ausschluss von Kollagenosen

Connective tissue diseases (CTD) are autoimmune diseases highly associated with the presence of antinuclear antibodies (ANA). Since ANA and musculoskeletal symptoms are not uncommon in the general population, differential diagnostic challenges frequently occur for the treating physician. Dense fine speckled antibodies (DFS70) were recently discovered but their presence appeared to be rare in CTD. In this cross-sectional study atotal of 270 patients treated in the Rheumatism Center of the Ruhr Area (Rheumazentrum Ruhrgebiet) were preferentially included, when they were ANA+ (≥1:80). Other autoantibodies and DFS70 antibodies were also investigated. The diagnosis of CTD was confirmed by rheumatologists. The sensitivity, specificity and the positive predictive value of DFS70 antibodies were differentially evaluated for various ANA titers. In 91 (33.7%) of the ANA+ patients (33.7%) the diagnosis of CTD was confirmed and in 84 (92.3%) the ANA titer was ≥1:160. The DFS70 antibodies were detected in 17 out of 130 ANA+ patients without CTD (13.1%) versus 2ANA+ patients (2.2%) with CTD (p = 0.027). None of the patients with ANA 1:80 had DFS70 antibodies. The specificity of DFS70 antibodies to detect the absence of CTD was 97.6%, the sensitivity was 13.1% and the positive predictive value was 89.5%. There was almost no effect of the strength of the different ANA titers. It was found that DFS70 antibodies are rarely present in ANA+ patients with CTD but the diagnosis of CTD cannot be reliably ruled out solely by the presence of DFS70 antibodies; however, the high specificity of DFS70 antibodies can be of clinical importance in unclear situations and in cases of anxious patients.

Differential diagnostic challenges of abdominal wall endometriosis from the radiologist's point of view

The incidence of endometriosis, including atypical forms of the disease, has been continuously growing, thus increasingly challenging for the imaging specialists as well. We conducted a retrospective study to analyze the results of ultrasound-guided interventions between 2016 and 2018. All interventions were performed in female patients due to uncertain abdominal wall lesions at the University of Szeged, Hungary. The abdominal wall lesions were incidentally detected, one by CT, the others by ultrasound examinations. We identified 12 cases during the study period. The average age of the patients was 59 years (29-79), 8 of them had abdominal surgery in their medical history. The mean diameter of the masses was 34.4 mm (20-49 mm). Since the indication of imaging examinations was the evaluation of a known or suspected malignancy, four patients had undergone an MRI prior to the biopsy. In addition, ultrasound-guided biopsy was not performed in another two patients, and the diagnosis was established by histological examination of the surgically removed specimens. The histological examination revealed malignant primary serous epithelial tumor in one case, metastases in six cases, endometriosis in six patients and abdominal wall abscess was found in one patient. Endometriosis was more frequent in the younger patients. The likelihood of endometriosis as a cause of abdominal wall lesions of younger, premenopausal female patients is rather high, especially with obstetrical or gynaecological operations in the medical history. Ultrasound plays a primary role in the detection and therapy planning of these lesions. Orv Hetil. 2019; 160(35): 1395-1403.

Effect of Copper Staining in Wilson Disease: A Liver Explant Study.

Wilson disease is a rare genetic disease with clinical and histopathologic differential diagnostic challenges. In this study, we evaluated the histopathologic findings of explanted livers in Wilson disease, with special emphasis on copper histochemistry. Our study group was recruited by reviewing archived histopathology reports and the liver transplant clinic patient records retrospectively for patients who had liver transplant for Wilson disease between January 2010 and June 2015, at Turgut Ozal Medical Center. Archival slides were reevaluated. When needed, relevant clinical and laboratory data were obtained from patient medical records. During the selected period, there were 33 patients fitting the study criteria (22 male, 11 female, mean age of 22 ± 11 y). All patients had mild to moderate septal inflammation. We found that 29 patients (88%) showed glycogenated hepatocyte nuclei and 27 patients (79%) showed nuclear pleomorphism. Other histopathologic findings were cholestasis (48%) and macrovesicular steatosis (39%). There was no special finding in hilar regions except for 2 patients who had recanalized portal vein thrombosis. In terms of copper histochemistry, 2 copper stains, Timm silver sulfide and rhodanine, were performed in all cases, with orcein staining only done for 25 of the cases. Positivity rates for these copper stains were 85%, 82%, and 36%. Periodic acid-Schiff-diastase- and periodic acid-Schiff-positive granules were detected in 7 of 33 patients (21%). Iron deposition was seen in 12 patients (focal and/or minimal in 11, more than focal in 1). There was no dysplasia or malignancy in any of the patients. On routine hematoxylin and eosin-stained slides, detection of glycogenated hepatocyte nuclei and the finding of the nuclear pleomorphism should alert the pathologist for the possibility of Wilson disease, especially with cryptogenic liver disease. Timm stain is a more convenient histochemical stain in revealing copper deposition in liver.

Thymomas

Thymomas are rare tumors but are one of the most common mediastinal neoplasms in adults and exhibit an enormous variability in histological, biological and genetic features. The morphological spectrum within agiven entity is enormous and some tumors with histological patterns of more than one entity are more common than pure histological subtypes. Due to a lack of subtype-specific markers classification of thymomas often requires complex diagnostic algorithms. The refined presentation including the definition of obligatory and optional features and of diagnostic immunohistochemical profiles, is the focus of the new World Health Organization (WHO) classification of thymomas, aiming at improving diagnostic reproducibility. This review highlights novel aspects of the WHO classification of thymomas and addresses typical differential diagnostic challenges with afocus on diagnostic pitfalls.

Practical Approaches for Post-Operative and Post-Traumatic Lymphoedemas

Swelling of the extremities is frequently observed after traumatic lesions and poses differential diagnostic challenges. Causes include seromas, haematomas and thromboses, as well as lymphostatic oedemas, which may become chronic if left untreated. These are characterized by a high percentage of protein and, over the long term, they can lead to considerable impairment and complications such as recurrent erysipelas as a result of fibrotic tissue rearrangement. Usually a clinical diagnosis is made, which presupposes that the symptoms are known. The most important treatment option is complete decongestive therapy, with manual lymphatic drainage and lymphological multicomponent bandaging being applied at least on a daily basis. Surgical intervention is only possible in individual cases. Because their chronic progression can lead to disablement, post-traumatic lymphoedemas are often the subject of assessments in private and statutory accident insurance proceedings. This paper explains the formation mechanism of post-traumatic lymphoedemas and provides an overview of differential diagnostic methods and current treatment recommendations. The authors also touch on insurance-related aspects.

Utility of testing for apraxia and associated features in dementia

IntroductionExisting literature suggests that the presence or absence of apraxia and associated parietal deficits may be clinically relevant in differential diagnosis of dementia syndromes.AimThis study investigated the profile of these...

Metastatic Papillary Thyroid Carcinoma with Multifocal Synchronous Transformation to Anaplastic Thyroid Carcinoma.

Papillary thyroid carcinoma is a common malignancy to affect the thyroid and is typified by a nonaggressive nature and low rates of mortality. In contrast, anaplastic thyroid carcinoma is the most aggressive thyroid malignancy with a mortality rate of nearly 90% and survival typically of only six months after the diagnosis is made. The transformation of papillary thyroid carcinoma to anaplastic thyroid carcinoma is well documented in the literature but is uncommon and in most instances is reported as a case report or small series only. Transformation of papillary thyroid carcinoma to anaplastic thyroid carcinoma usually takes place in the thyroid itself or in the adjacent lymph nodes. Only on rare occasions does a transformation occur in a papillary thyroid carcinoma metastasis outside of these locations. In the present case report and subsequent discussion we highlight an unusual case of PTC with transformation to anaplastic thyroid carcinoma, which is shown to involve numerous locations to include near total lung parenchyma obliteration. We also discuss the differential diagnostic challenges when faced with a thyroid malignancy that is negative for thyroglobulin.

Cardiac sarcoidosis: the challenge of radiologic-pathologic correlation: from the radiologic pathology archives.

Cardiac sarcoidosis is a rare but potentially fatal disorder with a nonspecific spectrum of clinical manifestations, including conduction disorders, congestive heart failure, ventricular arrhythmias, and sudden cardiac death. Although early treatment to improve morbidity and mortality is desirable, sensitive and accurate detection of cardiac sarcoidosis remains a challenge. Except for the histopathologic finding of noncaseating granulomas in an endomyocardial biopsy specimen, most diagnostic tests are limited and nonspecific at best. Therefore, the decision to initiate treatment is based largely on the patient's clinical symptoms and the course of the disease, rather than histologic confirmation. Successful recognition of cardiac sarcoidosis ultimately requires rigorous collaboration among a clinician, radiologist, and pathologist. Advanced imaging modalities, such as cardiac magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose, have become increasingly useful in facilitating diagnosis and therapeutic monitoring, although limited prospective studies exist. This article describes the clinical parameters and pathologic findings of cardiac sarcoidosis and the advanced imaging features and differential diagnostic challenges that must be considered for a successful diagnostic approach. In addition, to improve the understanding of abnormalities detected with different imaging modalities, we suggest a unified terminology in describing radiologic findings related to cardiac sarcoidosis.

Pulmonary manifestations of connective tissue diseases

Systemic autoimmune diseases are responsible for about 25% of all deaths due to interstitial lung disease; therefore, an early identification of patients with pulmonary manifestation changes the management. Detection, differential diagnostic classification and staging of the pneumological pattern of findings are largely based on high-resolution computed tomography (HR-CT). The main differential diagnostic challenges are interstitial manifestations which present with radiological-histopathological phenotypes of interstitial pneumonia. The most common form of interstitial pulmonary reaction form of connective tissue diseases is the nonspecific interstitial pneumonia (NSIP) pattern. In rheumatoid arthritis, a usual interstitial pneumonia (UIP) pattern is dominant. Uncharacteristic reactions of airways and pleura can be the leading symptom or present as accompanying findings. A serious complication is pulmonary hypertension. Drug-induced lung lesions can present with similar HR-CT morphology as connective tissue diseases and can only be differentiated in the temporal and clinical context.