Narrow Differential Diagnosis Research Articles

Is there Progress? An Overview of Selecting Biomarker Candidates for Major Depressive Disorder.

Major depressive disorder (MDD) contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings.

Molecular diagnosis with the 92-Gene Assay (92-GA) and decision-impact on treatment: Final results from a prospective, multi-disciplinary study.

205 Background: Metastatic lesions with unknown or differential diagnoses pose significant challenges leading to suboptimal treatment and outcomes. Molecular diagnosis with the 92-GA has shown improved accuracy compared to IHC and improved survival in pts treated based on assay results. The following prospective, multi-institutional study assessed the utility and impact of the 92-GA in diagnosis and treatment decision-making in community clinical practice. Methods: Over 18 months, physicians (68 medical oncologists, 25 pathologists) completed standardized, discipline-specific questionnaires via a web-based data portal for 444 cases in which the 92-GA was ordered as part of routine clinical care for pts with unknown or differential diagnoses. Physician-reported utility and impact were characterized for oncologists and pathologists. Results: 92-GA molecular diagnoses included 22 different tumor types: pancreaticobiliary (21%), lung squamous (9%), lung adenocarcinoma (9%), and intestinal (9%) were most common. Factors contributing to ordering the 92-GA were interdisciplinary: for oncologists, no primary following clinical review and imaging (42%), pathology report of a differential diagnosis (21%) or unknown primary (20%), and differentiation between a new cancer or recurrence (16%) were most common; for pathologists, IHC inconclusive (50%; median 9 IHC stains) and oncology ordered due to unknown primary (30%) were most common. Oncologists reported that the diagnosis provided by the 92-GA resulted in changing the treatment option in 46% of cases. 75% of pts received therapy with a median time from biopsy to treatment of 25d. Following the 92-GA, predictive biomarkers (eg, EGFR, ALK) were ordered in 81% of cases diagnosed as lung and 67% diagnosed as colorectal cancer. Conclusions: This study demonstrated significant clinical utility of the 92-GA: changing treatment options in approximately half of pts. Clinical utility spanned a spectrum of diagnostic uncertainty for oncologists and pathologists, and helped narrow differential diagnosis. Additional biomarker testing was common after a diagnosis of lung or colorectal cancer was rendered by the 92-GA.

Imaging of the Lacrimal Gland and the Lacrimal Drainage System

A large number of different neoplastic, infective and autoimmunologic diseases can affect the lacrimal gland. Thorough imaging examinations can help to characterize lesions to narrow down possible differential diagnoses. Diseases of the lacrimal drainage system, especially obstructions with constant epiphora are often very irritating for the patients. Imaging examinations can assist in selecting the adequate therapy in interdisciplinary consensus. Moreover, interventional-radiological therapy (e. g. balloon-dacryocystoplasty) is an attractive minimally-invasive treatment alternative.

Acquired nystagmus as the initial presenting sign of chiasmal glioma in young children.

The aim of the study was to investigate the incidence of nystagmus at diagnosis in children with optic pathway glioma involving the chiasm and hypothalamus. Twenty-two patients with a measurable optic pathway/hypothalamic glioma (without neurofibromatosis-1) were followed in our center from 2001 to 2013. The medical files were retrospectively reviewed for demographic and clinical findings, and the imaging scans, for tumor characteristics. There were 9 boys and 13 girls of mean age 3.5±4.4years at diagnosis; 15 were aged <2 years. Tumor size ranged from 10×6mm to 62×29mm. Mean duration of follow-up was 8.3±5.4 years. Nystagmus was detected at diagnosis in 10 children (45%), all <2 years old (66.6% of the younger group); no child older than 2 years presented with nystagmus. Nystagmus, once present, did not resolve and continued throughout follow-up. There were no cases of new onset of nystagmus during follow-up in the children in whom it was not detected at diagnosis. Treatment consisted of partial resection/biopsy with/without shunting (n=13) and chemotherapy (n=19) with (n=2) or without adjuvant radiation. Of the 22 children, 6 had a radiographic response to treatment, 8 remained stable, and 8 (all of whom received chemotherapy) showed disease progression despite treatment. In conclusion, monocular nystagmus is a more common presenting sign of optic pathway/hypothalamic glioma in children <2 years old than previously estimated. Although subtle, nystagmus has a very narrow differential diagnosis, and its presence should raise suspicions of a chiasmal tumor with prompt referral for imaging. The visual prognosis is moderate to poor.

OT-03 * WHEN TO BIOPSY A PINEAL REGION MASS IN CHILDREN

Pineal region tumors account for 2.8-9% of all CNS malignancies in children. The differential diagnosis of a pediatric pineal region tumor is broad and diagnostic strategies can vary. Literature combining medical and radiographic data prior to considering surgical biopsy is sparse. At times a biopsy and/or resection may not be necessary and carries associated morbidity. By using specific criteria to direct diagnosis these risks can be minimized. The criteria utilized show how tumor markers and presence of bifocal disease are utilized to diagnose different germ cell tumors without a biopsy. A pineal region tumor with elevation of AFP or B-hCG greater than 100mIU/ml is consistent with a nongerminomatous germ cell tumor. A pineal region tumor with normal AFP and B-hCG elevated but less than <50mUI/ml is consistent with a germinoma. The presence of fat on MRI makes mature teratoma likely and upfront resection should be pursued. Other important imaging features that help narrow differential diagnosis include presence of central calcification engulfed by tumor can be seen in germinoma, presence of peripheral calification in pinealoblastoma. Low ADC values are typical of cellular tumors like papillary tumors of the pineal region, germ cell tumor, and pinealoblastoma. High ADC values are noted in tectal gliomas or mature teratomas. By combining clinical, laboratory and radiographic modalities to derive the most accurate pre-surgical diagnosis a high pretest probability is achieved. Our proposed model facilitates consistent decision making as to whether or not to biopsy pediatric pineal region tumors.

Successful strategies for integrating bedside ultrasound into undergraduate medical education.

Nearly all physician specialties currently utilize bedside ultrasound, and its applications continue to expand. Bedside ultrasound is becoming a core skill for physicians; as such, it should be taught during undergraduate medical education. When ultrasound is integrated in a longitudinal manner beginning in the preclerkship phase of medical school, it not only enhances teaching the basic science topics of anatomy, physiology, and pathology but also ties those skills and knowledge to the clerkship phase and medical decision-making. Bedside ultrasound is a natural bridge from basic science to clinical science. The Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine is currently in its fourth year of implementing an integrated ultrasound curriculum in the school of medicine. In our experience, successful integration of a bedside ultrasound curriculum should: align with unique focuses of a medical schools' mission, simplify complex anatomy through multimodal teaching, correlate to teaching of the physical examination, solidify understanding of physiology and pathology, directly link to other concurrent content, narrow differential diagnoses, enhance medical decision-making, improve procedural skills, match to year-group skillsets, develop teaching and leadership abilities, and have elective experiences for advanced topics.

Omental infarction and its mimics: imaging features of acute abdominal conditions presenting with fat stranding greater than the degree of bowel wall thickening.

The segmental omental infarction is a rare self-limited disorder presenting with aspecific clinical symptoms that may mimic several acute abdominal conditions. Therefore, a correct noninvasive diagnosis is important because treatment approaches range from monitoring to surgery. As omental infarction results in an important fat stranding that is much greater than the degree of bowel wall thickening, it suggests a narrower differential diagnosis: appendicitis, diverticulitis, epiploic appendagitis, and mesenteric panniculitis. In this pictorial essay, we point out the importance of imaging in identifying this typical sign allowing alternate diagnoses such as segmental omental infarction that can be conservatively managed.

Case of arthritis secondary to leprosy.

IntroductionLeprosy is a chronic granulomatous infectious disease, which is caused by Mycobacterium leprae. High numbers of people are still affected by this disease in some of the developing countries however, it is rarely seen in non-endemic regions.Cutaneous and neurological manifestations are the common and classical presentations of leprosy. Musculoskeletal involvement is the third most common manifestation but is less frequently reported.Joint involvement can present as acute symmetrical polyarthritis or chronic polyarthritis resembling rheumatoid arthritis. Leprosy can also present with tenosynovitis, either isolated or associated with arthritis.Case presentationWe report a case of 29-year-old man who developed tenosynovitis and acute symmetrical polyarthritis including small joints of hands and feet three weeks after appearance of typical cutaneous lesion of leprosy. Patient improved with steroid and anti leprosy treatment. Patient had another acute episode with symmetrical polyarthritis four months later while on treatment.Discussion and EvaluationIn the modern era, there is increase movement of population from developing countries to developed countries, it is likely that patient suffering from leprosy with arthritis may present to rheumatology clinic in those countries where leprosy is not endemic. Exact pathogenesis for musculoskeletal manifestations is still not fully known. Our patient presented with symmetrical polyarthritis, enthesitis and systemic involvement, which was secondary to lepra reaction.Having good knowledge of musculoskeletal manifestation of leprosy, will help narrow differential diagnosis and will prevent unnecessary diagnostic workup.ConclusionLeprosy can present with different rheumatologic manifestation including tenosynovitis and acute symmetrical polyarthritis. Type 2 lepra reaction (Erythema nodosum leprosum ENL) can present with systemic manifestation and can involve skin, nerves, joints, kidneys and liver.

The acutely swollen knee. Part two – Management of traumatic pathology

The acutely swollen knee is a common presentation of knee pathology in the emergency department and the primary care setting, whether on board ship, in a Regimental Aid Post, or in a Medical Centre. The swollen knee has both traumatic and atraumatic (systemic) causes, all of which can be accurately diagnosed with an understanding of the underlying injury patterns and patho-anatomy. In Part 2 of this paper we consider the traumatic causes and also suggest a combined approach to managing an acutely swollen knee. The taking of a detailed history combined with thorough clinical examination will establish the diagnosis or at least the narrow differential diagnosis in the majority of cases. The use of specialist examination techniques, diagnostic imaging and arthrocentesis can further assist the clinician in confirming the correct diagnosis and thus prescribing the appropriate treatment. This review will endeavour to give a consensus of opinion and structured guidelines in the diagnosis and initial management of patients presenting with acute or recent onset swelling of the knee.

Focal hand lesions: review and radiological approach.

Focal hand lesions are commonly encountered in clinical practice and are often benign. Magnetic resonance (MR) imaging is the imaging modality of choice in evaluating these lesions as it can accurately determine the nature of the lesion, enhancement pattern and exact location in relation to surrounding tissues. However, while MR features of various soft tissue lesions in the hand have been well described, it is often still difficult to differentiate between benign and malignant lesions. We review the MR imaging features of a variety of focal hand lesions presenting at our institution and propose a classification into “benign”, “intermediate grade” (histologically benign but locally aggressive with potential for recurrence) and frankly “malignant” lesions based on MR findings. This aims to narrow down differential diagnoses and helps in further management of the lesion, preoperative planning and, in cases of primary malignancy, local staging. Teaching Points • Hand lesions are often benign and MR is essential as part of the workup.• MR features of various hand lesions are well described but are often non-specific.• Certain MR features may help for the diagnosis but histological examination is usually required.• We aim to classify hand lesions based on MR features such as margin, enhancement and bony involvement.• Classifying these lesions can help narrow down differential diagnoses and aid management.

The acutely swollen knee Part 1: Management of atraumatic pathology

The acutely swollen knee is a common presentation of knee pathology in the Emergency Department and the primary care setting whether on board ship, a Regimental Aid Post or Medical Centre. The swollen knee has both traumatic and atraumatic (systemic) causes, all of which can be accurately diagnosed with an understanding of the underlying injury patterns and patho-anatomy. In Part One, we will be examining the management of non-traumatic causes, followed by Part Two, looking at traumatic causes, in the next issue of the Journal. A detailed clinical history combined with thorough clinical examination will establish the diagnosis, or at least the narrow differential diagnosis in the majority of cases. The uses of specialist examination techniques, diagnostic imaging and arthrocentesis can further assist the clinician in confirming the correct diagnosis and thus prescribing the appropriate treatment. This review will endeavour to give a consensus of opinion and structured guidelines in the diagnosis and initial management of patients presenting with acute or recent-onset swelling of the knee related to atraumatic pathology.

Short answer question case series: unique chest x-ray following blunt trauma

A 31-year-old African–American male with no significant past medical history presents to the emergency department via emergency medical services with chest pain and shortness of breath following a direct, broadside...

Symptoms and Signs of Neuro-otologic Disorders

Symptoms and signs of neuro-otologic disorders are critical components in the diagnostic assessment of patients with vestibular symptoms such as vertigo, dizziness, unsteadiness, and oscillopsia. Most diagnoses can be accomplished at the bedside. An understanding of key diagnostic principles is essential for all practicing neurologists, who are often faced with determining whether such patients warrant urgent diagnostic testing or hospital admission. This article introduces readers to core concepts and recent advances in the understanding of directed history taking and physical examination in patients with vestibular symptoms or suspected neuro-otologic disorders. International consensus definitions for vestibular symptoms have recently been published. During the past 5 years, a growing body of scientific evidence has demonstrated that the traditional approach to bedside diagnosis of patients with vertigo and dizziness is inadequate. Former teaching that history taking should first rely on categorizing symptoms by type (eg, vertigo, presyncope, disequilibrium, nonspecific dizziness) has been replaced by an emphasis on categorizing timing and triggers for vestibular symptoms, which focuses the clinician's attention on four key syndromic patterns: (1) acute, spontaneous, prolonged vestibular symptoms; (2) episodic, positional vestibular symptoms; (3) episodic, spontaneous vestibular symptoms; and (4) chronic unsteadiness (with or without oscillopsia). Each of these categories delineates a relatively narrow differential diagnosis within which a focused examination distinguishes between benign common causes and dangerous uncommon ones. A focused approach to bedside assessment of patients with vestibular symptoms is essential for accurate and efficient diagnosis. All neurologists should be aware of major recent advances.

Bilateral adrenal lesions

Bilateral adrenal lesions include a spectrum of disorders: neoplastic disorders (metastases, lymphoma, bilateral phaeochromocytoma, adrenocortical carcinoma and myelolipoma); longstanding congenital adrenal hyperplasia and macronodular adrenal hyperplasia; infections such as tuberculosis, histoplasmosis and blastomycosis; adrenal haemorrhage; adrenals in hypoperfusion complex and paediatric masses. Bilateral distribution in addition to other imaging characteristics can help narrow differential diagnoses in case of adrenal masses. We present a pictorial review highlighting the adrenal lesions that can present bilaterally.

Diagnostic Patient Care, Not Just Diagnosis

Diagnostic Patient Care, Not Just Diagnosis

Abnormal Urine Color

A change in urine color can be distressing for patients and physicians alike. Many of the causes of abnormal urine color are benign effects of medications and foods; however, a change in urine color may be a sign of an underlying pathological condition. The good news is that in many cases the diagnosis can be determined from a thorough history and urinalysis. This article presents many of the conditions physicians may encounter and will help them form a narrow differential diagnosis and treatment plan.

Bildgebende Diagnostik von Pneumonien

ZusammenfassungPneumonien stellen ein Krankheitsbild mit hoher epidemiologischer, klinischer und auch ökonomischer Relevanz dar. Die bildgebende Diagnostik spielt eine wichtige Rolle bei der Detektion, Differenzierung und Verlaufskontrolle pneumonischer Infiltrate. Selbst in der Computertomographie (CT) ist jedoch die Morphologie einer infiltrativen Erkrankung sehr unspezifisch. Rückschlüsse auf zugrunde liegende Erreger sind daher grundsätzlich schwierig, und nichtinfektiöse Differenzialdiagnosen müssen berücksichtigt werden. Die Kenntnis spezieller Erscheinungsformen, Verteilungsmuster und Differenzialdiagnosen pneumonischer Infiltrate sowie die Mitbeurteilung des klinischen Gesamtkontextes helfen jedoch bei der Eingrenzung auf die relevanten Differenzialdiagnosen und des Erregerspektrums. Der CT des Thorax kommt dabei speziell bei opportunistischen Infektionen und bei Patienten unter intensivmedizinischer Behandlung eine besondere Bedeutung zu.

One Hundred Consecutive Granulomas in a Pulmonary Pathology Consultation Practice

Lung biopsies showing granulomatous disease are commonly sent for expert pathology consultation. On the basis of features we and others have identified, an algorithmic approach to diagnosis of these cases was developed. We hypothesized that applying this approach would increase the likelihood of rendering a more specific diagnosis, or by rendering either a narrower or broader differential diagnosis, offer a more clinically useful diagnosis. One hundred consecutive lung biopsies from patients with granulomatous and giant cell reactions were retrieved from our consultation files. Cases were categorized into those in which a confident diagnosis was made at sign out, ones in which a specific diagnosis was strongly favored, and those in which a differential diagnosis was suggested. One year later follow-up information was obtained and consultation diagnoses were compared with clinical diagnoses to determine the reliability of the approach. A confident diagnosis was rendered in 27 cases, a specific diagnosis was strongly favored in 34, and in 39 a differential diagnosis was provided. Consultant diagnoses were more specific in 47 of 75 (63 %) cases. In 15 cases, the differential diagnosis was expanded. The most common unrecognized diagnosis was aspiration pneumonia and the most common diagnosis omitted from the differential diagnosis by the primary pathologist was hypersensitivity pneumonia. Follow-up in 49% of cases in which it was sought, confirmed the consultant's diagnosis or was inconclusive in 97% of cases. The use of a standardized algorithmic approach to the interpretation of granulomatous disease in lung biopsies yields more specific and clinically useful diagnoses for consideration.

45-Year-Old Woman With Recurrent Headache and Photophobia

45-Year-Old Woman With Recurrent Headache and Photophobia

Differenzialdiagnose der Bronchiektasen: High-resolution CT als wertvolle Hilfe: Imaging of bronchiectasis: The great value of high-resolution CT in differential diagnosis

Bronchiectasis is defined as localized irreversible dilatation of the bronchial tree. Brochiectasis has been associated with a wide variety of causes, but it is mostly caused by acute, chronic or recurrent infections. This paper should give a review about the manifestation of bronchiectasis and bronchioloectasis in HR-CT and discuss the causing entities. However, integration of bronchiectasis and other HR-CT findings may enable a narrower differential diagnosis, in some cases it is possible to give the correct diagnose directly.