Dilemma In Diagnosis Research Articles

Classification Criteria and Diagnostic Tests for Vasculitides

Most rheumatic diseases, in adults or children, do not have objective clinical or laboratory measures that allow physicians to diagnose a specific disease with certainty. In order to overcome the clinical dilemma of a proper diagnosis, classification criteria have been proposed for several rheumatic diseases. Classification criteria are therefore an essential tool for clinical research since they allow comparison of patients with similar clinical and laboratory characteristics across studies. In the vasculitis research field several classification criteria have been proposed for the adult population, and more recently for children. These criteria have been derived through 2 major methodological approaches: consensus and consensus/data-driven. In brief, the consensus-based criteria are specifically derived through the combination of judgments from a group of experts in a particular field after thorough literature review and sometimes developed using consensus techniques such as the Delphi technique and nominal group technique1,2. To the consensus-based criteria we can ascribe the Chapel Hill International Consensus Conference3 that essentially provided proper nomenclature for systemic vasculitides, and the Childhood Vasculitis Working Group of the Paediatric Rheumatology European Society (PRES) for preliminary classification criteria of childhood vasculitis4. These criteria have their main strength in the panel of contributors who are usually very well recognized experts/experienced clinicians in that particular research/clinical field. The second approach of consensus/data-driven usually starts from consensus-based criteria and adds a formal statistical validation based on collected data in order to provide accuracy measures (classic methods), or other alternative methods such as the classification tree5. Only the classical approach is discussed here. With the classic approach, the accuracy measures that are considered include sensitivity (ability of a classification criterion to identify a patient as having the disease based on a gold standard; also called true-positive rate); specificity (ability of classification criteria … Address correspondence to Dr. Ruperto; E-mail: nicolaruperto{at}ospedale-gaslini.ge.it

The Respiratory Course of Extremely Preterm Infants: A Dilemma for Diagnosis and Terminology

Antenatal corticosteroids, postnatal surfactant treatment, and new strategies for respiratory care have modified the clinical presentation, lung outcome, and survival of extremely low birth weight (ELBW) infants. These changes over the last 10-20 years have resulted in a large population of ELBW survivors that have clinical courses that are quite different from those observed before the general use of surfactant and antenatal corticosteroids. The classic definitions and diagnoses for respiratory problems developed for larger preterm infants may not be accurate for this ELBW population.

Left atrial myxoma with aortobifemoral thromboembolism, rhabdomyolysis, acute tubular necrosis and ischaemic paraparesis mimicking metastatic renal cell carcinoma

A 56-year-old man presented with aortobifemoral thromboembolism, ischaemic paraplegia, rhabdomyolysis and acute renal tubular necrosis while awaiting nephrectomy for a right renal tumour. An echocardiogram to investigate the source of embolism revealed a 7 x 3 cm mass attached to the left atrial septal wall which prolapsed through the mitral valve. The patient successfully underwent bilateral femoral embolectomy and staged operations for the excision of the left atrial mass, reported on histopathology as myxoma, and open partial nephrectomy of a high grade papillary type renal cell carcinoma. We discuss the dilemmas of diagnosis and the staging of various surgical interventions in a patient of known malignancy who presents with aortobifemoral thromboembolism with multiorgan complications and also harbours a cardiac mass which could be another thrombus, an unrelated primary benign or malignant tumour or a metastasis from the primary renal tumour.

Treatment of Neurocritical Care Emergencies in Pregnancy.

OPINION STATEMENT: Neurologic emergencies are a major cause of morbidity and mortality in pregnant women. In part because the patient population is young, the nihilistic approach that often accompanies neurologically devastating disorders in other contexts is largely absent. A number of studies have demonstrated improved patient outcomes in the setting of aggressive care delivered by neurointensivists in a specialty-specific environment. It stands to reason that young, pregnant women who suffer from neurologically devastating disorders and who have a wide range of prognosis may also benefit from such specialized care. Close collaboration between obstetricians and neurointensivists is critical in this context. A number of unique considerations in diagnosis and management present dilemmas in the context of pregnancy, such as radiation dose from diagnostic neuroimaging, choice of pharmacotherapy for seizures, anticoagulation, and the method of delivery in the context of cerebral mass lesions and elevated intracranial pressure. Patients and their physicians are often faced with the additional challenge of balancing the relative risks and benefits of the impact of a management approach on both mother and fetus. In general, this balance tends to favor the interests of the mother, but the impact on the fetus becomes more relevant over the course of the pregnancy, especially in the third trimester. A low threshold for admission to an intensive care unit (ideally one that specializes in neurointensive care) should be used for pregnant patients. Because of the limited information regarding long-term outcomes in this population, rigid prognosis formation and early care limitations should be deferred in the immediate period. After the patient is stabilized and a plan has been charted for the remainder of the pregnancy, every effort should be made to engage patients in aggressive, urgent neurologic rehabilitation.

'Omics' Approaches to Understanding Interstitial Cystitis/Painful Bladder Syndrome/Bladder Pain Syndrome

Recent efforts in the generation of large genomics, transcriptomics, proteomics, metabolomics and other types of 'omics' data sets have provided an unprecedentedly detailed view of certain diseases, however to date most of this literature has been focused on malignancy and other lethal pathological conditions. Very little intensive work on global profiles has been performed to understand the molecular mechanism of interstitial cystitis/painful bladder syndrome/bladder pain syndrome (IC/PBS/BPS), a chronic lower urinary tract disorder characterized by pelvic pain, urinary urgency and frequency, which can lead to long lasting adverse effects on quality of life. A lack of understanding of molecular mechanism has been a challenge and dilemma for diagnosis and treatment, and has also led to a delay in basic and translational research focused on biomarker and drug discovery, clinical therapy, and preventive strategies against IC/PBS/BPS. This review describes the current state of 'omics' studies and available data sets relevant to IC/PBS/BPS, and presents opportunities for new research directed at understanding the pathogenesis of this complex condition.

Multicentric synchronous recurrent aggressive fibromatosis

Extra-abdominal desmoid tumors are known as aggressive fibromatosis (AFM). Synchronous and metachronous multicentric aggressive fibromatosis are rare lesions and pose dilemma in diagnosis and management. A rare and interesting case of recurrent multicentric, synchronous AFM is presented which to the best of our knowledge has not been reported earlier. A young male presented with well defined, hard, fixed swelling on the thigh. Resected tumor mass on histopathology was diagnosed as an extra abdominal fibromatosis. He presented again after two months with swelling at the same site; and two more swellings on the foot. Fine needle aspiration cytology (FNAC) from all three sites was performed; and was suggestive of benign spindle cell lesion of fibrogenic origin with the possibility of multicentric synchronous recurrent aggressive fibromatosis.

Adenoameloblastoma: A Dilemma in Diagnosis

Adenoameloblastoma or adenomatoid odontogenic tumor (AOT) is an uncommon, benign, epithelial lesion of odontogenic origin. It is a rare benign odontogenic tumor of the jaw affecting mostly young individuals with predominance in female. It occurs mostly in maxillary anterior region. On the basis of clinical and radiographical picture, it is often misdiagnosed as an odontogenic cyst. We report on a rare case of a 13-year-old male patient with a follicular variety of AOT in mandibular left anterior region which is unusual for the same. Clinically and radiographically, the lesion was mimicking as a dentigerous cyst. Later surgical enucleation was done and specimen was sent for microscopic examination and was diagnosed as AOT along with a dentinoid-like deposits which is a rare finding.

The Onset of a Peripheral Ameloblastoma

Incipient odontogenic tumors often display intermediate features between two or more lesions leading to diagnosis dilemma. We report the onset of a peripheral ameloblastoma fortuitously found subjacent to a nondysplastic leukoplakia in the region of missing 38 teeth of a 52-year-old man. The aim of this paper is the discussion of the microscopical features observed in the case reported which allowed the establishment of the final diagnosis of an early peripheral ameloblastoma.

Detection of Acute HIV Infection: We Can’t Close the Window

Acute human immunodeficiency virus (HIV) infection poses a dilemma for diagnosis, clinical management, and public health. It has been variously defined as the transient symptomatic illness associated with high-titer viral replication [1], the period from initial infection to complete seroconversion [2], and the phase between the appearance of detectable HIV RNA and detectable antibodies to HIV [3]. In the context of therapeutic trials, primary HIV infection includes the acute infection interval and the first 6 months after seroconversion, during which viral set point is established [4, 5]. ‘‘Detecting acute infection’’ has also been used synonymously with ‘‘closing the window,’’ the period during which tests for HIV are negative in persons who are infected. In this issue of the journal, Rosenberg et al [6] evaluated how well the Determine HIV-1/2 Ag/Ab Combo rapid test (Combo RT) compared with an algorithm of parallel antibody tests followed by RNA polymerase chain reaction. The Combo RT, designed for use at the point of care with finger-stick whole blood to detect HIV antibody and HIV antigen (and distinguish the two) in 20 minutes, did not fare very well in this comparison. The Combo RT is a lateral flow test (ie, an immunoassay that incorporates all necessary reagents into a single test strip). The test result is read visually, without instrumentation, after the specimen flows across the strip. Lateral flow tests have revolutionized HIV testing because they are easy to perform, require minimal training, have long-term stability, require no dedicated instrumentation, and can use whole blood specimens. In the United States, lateral flow HIV tests are used extensively in nonclinical settings. However, high hopes for point-of-care rapid tests able to identify acute infection, predicated on detecting p24 antigen, may be unrealistic. Recently developed fourthgeneration HIV antigen-antibody (Ag/Ab) combination assays, designed for use in the laboratory, detect both p24 antigen and antibodies against HIV but do not distinguish between the two. They exhibit an analytic sensitivity for p24 antigen of 11–18 pg/mL [7], equivalent to approximately 30 000–50 000 copies/mL of HIV RNA [8]. In contrast, lateral flow assays using colloidal gold have a lower limit of detection in the range of 1 ng/mL [9], 100-fold higher than the p24 antigen concentration usually present in plasma [8]. With the ultrasensitive procedure that includes heat dissociation of p24 antigen–antibody immune complexes, signal amplification, and instrumentation, the limit of detection for p24 (without additional pretreatment of the specimen to disrupt viral particles) can be $250 000 RNA copies/mL [10]. The findings of Rosenberg et al substantiate this: ultrasensitive methods were used to test 7 of the 8 acute specimens and failed to detect p24 antigen in 2 that had RNA concentrations of 45 000 and $750 000 copies/mL. In contrast, the ability of the Combo RT to establish the presence of antibodies to HIV was excellent. The Combo RT was positive for antibody in 162 (99.4%) of the 163 persons with established infection and in 2 of the 8 patients with acute HIV infection who were negative on other antibody tests. This latter finding suggests that the Combo RT might be able to identify many of the earliest infections. As shown in Table 1, antibody tests differ in their sensitivity to detect HIV during seroconversion [11]. Most lateral flow rapid tests in current use (and also Western blot analysis) are based on second-generation immunoassay principles that detect only immunoglobulin (Ig) G–class antibodies and become positive, on average, 20–25 days after RNA appears [12]. The antibody component of the Combo RT detects both IgMand IgGclass antibodies. Several studies suggest Received and accepted 9 November 2011; electronically published 29 December 2011. Correspondence: Bernard M. Branson, MD, CDC, 1600 Clifton Rd, MS D-21, Atlanta, GA 30333 (bbranson@cdc.gov). The Journal of Infectious Diseases 2012;205:521–4 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011. DOI: 10.1093/infdis/jir793

Paranasal sinus and skull base fibro‐osseous lesions: when is biopsy indicated for diagnosis?

Paranasal sinus fibro-osseous (FO) lesions represent a heterogeneous group, often sharing overlapping radiographic and pathologic features posing a dilemma in accurate diagnosis. The objective of this study was to correlate preoperative radiologic and postoperative histologic diagnosis to help guide a diagnostic algorithm. Retrospective analysis of 60 FO lesions between 1994 and 2010. The mean age was 42.3 years with average follow-up of 12.5 months. The preliminary radiologic diagnosis was osteoma in 22 (36.7%), fibrous dysplasia (FD) in 9 (15%), ossifying fibroma (OF) vs FD in 5 (8.3%), and OF in 3 (5%) cases. The diagnosis was indeterminate in 21 (35%) cases. Management consisted of excision in 29 (48.3%), observation in 17 (28.3%), and biopsy in 14 (23.3%) patients. For patients undergoing resection or biopsy, positive predictive value of preoperative radiology was 100% (10/10) for osteoma, 85.7% (6/7) for FD, and 33.3% (1/3) for OF cases. For the indeterminate lesions, most common pathologic diagnoses for 21 patients included osteoma in 4 (17.4%), arrested pneumatization in 3 (14.3%), OF in 3 (14.3%), and FD in 2 (9.5%). For FD vs OF cases, 3 underwent surgery, revealing osteoma, FD, and OF in 1 patient each. In this series, radiologic-histopathologic correlation was high for osteoma and FD and low for OF and OF vs FD. This data suggests that patients with classic radiologic characteristics of osteoma and FD may be observed, unless resection is warranted based on clinical symptomatology. Preoperative diagnosis of OF, OF vs FD, or indeterminate lesions may warrant a biopsy to establish firm diagnosis to guide definitive management, especially if preoperative computed tomography (CT) imaging is concerning for an aggressive FO neoplasm.

A Case of Juvenile Polyposis Syndrome: Dilemmas in Differential Diagnosis and Management

A Case of Juvenile Polyposis Syndrome: Dilemmas in Differential Diagnosis and Management

Deep Vein Thrombosis in a Young Marathon Athlete

Resident's case problem. A 21-year-old athletic male college student presented to a direct-access physical therapy clinic with complaints of left calf pain 4 days in duration. After initial examination, a working diagnosis of calf strain was formulated. Three days following initial examination, the patient reported 80% improvement in symptoms and was performing activities of daily living pain free. Four weeks later, the patient returned with complaints of reoccurring calf pain. The patient's signs, symptoms, and history at subsequent follow-up no longer presented a consistent clinical picture of calf strain; therefore, a D-dimer assay was ordered to rule out a deep vein thrombosis (DVT). The D-dimer was elevated so the patient was admitted to the hospital and started on low-molecular-weight heparin. A compression ultrasound revealed an extensive left superficial femoral and popliteal DVT in this otherwise healthy athlete. Lower extremity DVT is a serious and potentially fatal disorder. Physical therapists need to be diagnostically vigilant for vascular pathology in all patients with extremity pain and swelling. Employing the best current evidenced-based screening tools to rule out vascular pathology, such as deep and superficial vein pathology, should be the goal of every clinician. The Wells score is one such screening tool that has proven to be beneficial in this area. This case report presents a dilemma in diagnosis and illustrates the importance of revisiting differential diagnoses with each patient encounter. Clinicians must consider the possibility of a DVT with every patient seen with posterior leg pain. Diagnosis, level 4. doi:10.2519/jospt.2011.3823.

Sickle Cell Anemia—Molecular Diagnosis and Prenatal Counseling: SGPGI Experience

To study the issues and dilemmas in prenatal diagnosis of Sickle cell anemia (SCA) and to evaluate the role of genetic modifiers in counseling the families. The authors studied the genotype in 47 individuals with increased HbS and three representative families were taken as an example for describing various issues which need to be sorted out for appropriate counseling. Of 47 individuals 24 were S beta thalassemia, 14 were homozygous sickle cell anemia (SS) and 9 were HbS trait. In the S beta thalassemia and homozygous SS cases, anemia was presenting manifestation in all. The transfusion requirement in these varied from 0-12 transfusions/ year. Hepatosplenomegaly was seen in 27 cases (71%) and only splenomegaly in 9 cases (23.7%). Jaundice was observed in 34 cases (84.2%). All the 47 subjects (including HbS trait) were studied by Hb Variant system and underwent DNA analysis for beta globin gene mutations, alpha globin gene number and XmnI polymorphism. One or two alpha gene deletion of 3.7kb (-α3.7/αα or -α3.7/-α3.7) was found in 11 out of 47 cases whereas alpha triplication was found in 2 cases. 28 cases were heterozygous (+/-) for XmnI polymorphism, 9 were homozygous negative (-/-) and 10 were homozygous positive (+/+). Patients with SCA co-inherited with α-thalassemia have less hemolysis as revealed by lower reticulocyte counts than with normal alpha genotype. The authors further discuss the issues and dilemmas faced during prenatal counseling of three families during this study. The knowledge of the relationship between genotype and phenotype, effect of the modifier genes has an important role in genetic counseling and for planning individualized treatment for sickle cell anemia.

Spontaneous Intracranial Hypotension: Dilemmas in Diagnosis

Intracranial hypotension is not an uncommon diagnosis after lumbar puncture or neurosurgery. However, spontaneous intracranial hypotension (SIH) is a poorly understood entity that can present with a wide variety of symptoms/signs ranging from headache to coma. SIH may result from an occult spinal cerebrospinal fluid (CSF) leak. Alternatively, because a CSF leak is not always found, some posit that SIH is caused by venous hypotension that results in increased CSF absorption. The true incidence of SIH is unknown and the diagnosis is frequently missed given the wide range of presenting symptoms and imaging findings that are mistaken for other diagnoses (ie, subdural hematomas, Chiari malformation). Here, based on a comprehensive literature review, we describe the epidemiology, presentation, diagnostic workup and treatment of SIH.

Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature

Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient's triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.

Congenital lobar emphysema in neonates: Anaesthetic challenges

Congenital lobar emphysema (CLE) is a potentially reversible, though possibly life-threatening, cause of respiratory distress in the neonate. It poses dilemma in diagnosis and management. We are presenting a 6-week-old baby who presented with a sudden onset of respiratory distress related to CLE affecting the left upper lobe. Lobectomy was performed under general anaesthesia with one lung ventilation. The details of anaesthetic challenges and management are described here.

Fibrous Dysplasia and Ossifying Fibroma-an advent in their diagnosis

Objectives: Fibro-osseous lesions of the craniofacial complex comprise of a diverse, interesting and challenging group of conditions that pose difficulties in classification and treatment. The two most confused benign fibro-osseous lesions are fibrous dysplasia and ossifying fibroma. Sometimes, the classic clinical, radiologic or pathologic features of fibrous dysplasia or ossifying fibroma may not be evident, but overlapping features of both may be seen. The dilemma in diagnosis of these lesions rests in the bony trabeculae as well as in the fibrous stroma. Cases of fibrous dysplasia showing lamellated bony trabeculae and osteoblastic rimming have been reported which may confound diagnosis because of resemblance with ossifying fibroma. In the present study, an attempt has been made to demonstrate the fibrous element of these two lesions using histochemical stains. Study design: The sections of fibrous dysplasia & ossifying fibroma were stained with Haematoxylin and Eosin, Trichrome stain and Peracetic acid-aldehyde fuschin-modified Halmi stain. Result: The study revealed that the oxytalan fibers were more numerous in ossifying fibroma (seen with both Trichrome and modified Halmi stains). Conclusion: Although the ultimate diagnosis of fibrous dysplasia and ossifying fibroma is arrived at by correlating clinical, radiographic and routine histopathologic examination, the differences in the configuration of the stroma using histochemical stains may help in the diagnosis of these two lesions.

Desmoplastic small round cell tumor of the pancreas: An unusual primary site for an uncommon tumor

Pancreas is a rare location for desmoplastic small round cell tumor. The present case highlights the dilemma in diagnosis and ascertaining the site of tumor origin. Morphologic and immunohistochemical features were complemented with the molecular markers and tumor origin which was initially nebulous was subsequently confirmed on exploratory laparotomy.

Musculoskeletal Sonography Facilitates the Diagnosis of Adolescent Anterior Superior Iliac Spine Avulsion Fracture

Anterior superior iliac spine (ASIS) avulsion fractures are not common. We describe a 15-year-old boy who suffered from sudden onset of pain on the left side of his groin when running a race, accompanied by weakness in raising his left leg. Physical examination revealed local tenderness over left ASIS area, initial pelvic radiograph showed no abnormalities, but kidney-ureter-bladder radiograph revealed a small indistinct radiopaque shadow lateral to iliac bone. Then, musculoskeletal sonography disclosed the displacement of the apophysis from the left ASIS, and avulsion fracture was impressed. Pelvic computed tomography confirmed the diagnosis. The patient gradually recovered after conservative treatment. Groin pain in athletes is a dilemma in diagnosis, and careful correlation of the clinical condition and radiological findings is essential to avoid misdiagnosis. Musculoskeletal ultrasound is a useful tool for quick screening and to facilitate diagnosis.

CD34-positive myxoid sarcoma of the retroperitoneum: a dilemma in differential diagnosis of multiple biopsy specimens.

The author reports a case of CD34-positive malignant myxoid sarcoma in the retroperitoneum with a dilemma of differential diagnosis in multiple biopsy specimens of different locations. A 79-year-old man was diagnosed with right renal pelvic carcinoma and nephrectomy was performed. The carcinoma was urothelial carcinoma (2 cm in diameter) without invasion. The patient was followed up, and a large retroperitoneal tumor was found two years after the operation. Multiple needle biopsies were performed. The patient then showed a hepatic metastasis, and died of cachexia one year after the detection of the retroperitoneal tumor. The needle biopsy specimens showed spindle cell sarcoma in the myxomatous stroma (80%) and in the non-myxomatous stroma (20%). Immunohistochemically, the tumor cells were positive for vimentin, CD34, CD99, bcl-2 and p53 protein. They were negative for cytokeratins, desmin, alpha-smooth muscle actin, S100 protein, melanosome, CEA, neuron specific enolase, CD68, factor VIII-related antigen, CD31, KIT, and PDGFRA. Ki67 labeling was 30%. A genetic analysis for KIT gene (exons 9, 11, 13 and 17) and PDGFRA gene (exons 12 and 18) showed no mutations. Although the differential diagnosis is problematic and difficult, the present case is probably dedifferentiated liposarcoma. The needle biopsy diagnosis of sarcomas is difficult and limited because sarcomas show heterogeneous histologies with regard to locations in the same tumor.