Potential Pitfalls In Diagnosis Research Articles

Scarred for life: a review of cesarean section scar pregnancy and potential pitfalls in diagnosis.

Cesarean section scar pregnancy (CSSP) is defined as abnormal implantation of a gestational sac on or in a previous cesarean section scar. There is an increasing incidence of detection of CSSP, likely in part due to the growing rates of cesarean deliveries and the improved rates of detection with advancing ultrasound technology. Diagnosis of CSSP is critical due to the potentially life-threatening complications to the mother if left untreated. Pelvic ultrasound is the imaging modality of choice in the initial evaluation of suspected CSSP, with MRI potentially useful if ultrasound findings are equivocal, or if confirmation is requested prior to definitive intervention. Early and accurate diagnosis of CSSP allows for prompt management to avoid severe complications and the potential to preserve the uterus and future fertility. A combination of medical and surgical treatment strategies may be needed with specific therapy tailored to each patient. Follow-up after treatment should include serial beta-hCG levels and possible repeat imaging if there is clinical concern for complications or treatment failure. This article will provide a comprehensive review of this uncommon but important phenomenon, detailing the pathophysiology and types of CSSP, imaging presentations, potential pitfalls in diagnosis, and management options.

Potential pitfalls in diagnosis of immunotherapy-induced hypothalamic-pituitary-adrenal axis suppression.

We thank Bi and colleagues for their recent case report ‘Potential pitfalls in diagnosis of immunotherapy induced hypothalamic-pituitary-adrenal axis abnormalities: a clinical case’. It provides important lessons on the investigation and management of immunotherapy-related hypophysitis, which is an evolving area within endocrinology and oncology. As part of our work, in a hospital whose oncology service is the Irish national referral centre for several malignancies, we manage ever increasing numbers of immunotherapy-related hypophysitis and would like to share some further observations.

Pleural fluid metastasis of plasmacytoid urothelial carcinoma in comparison to micropapillary and conventional high-grade urothelial carcinoma: Cytologic and immuonohistochemical findings.

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

Sarcomatoid Mesothelioma with Bland Histologic Features: A Potential Pitfall in Diagnosis.

Sarcomatoid mesotheliomas can be challenging to diagnose on small biopsy specimens, where limited material may preclude definitive assessment of invasion and lesional cells can have relatively bland cytology with no mesothelial marker expression. We report a case of a patient who presented with a pleural effusion and had subsequent pleural biopsy that showed a bland, uniform spindle cell proliferation in a mildly myxoid background. There was little if any collagen; no chest wall, soft tissue, or fat; and mesothelial markers were negative. The cells were positive for pancytokeratin and GATA3 by immunohistochemistry, and in situ hybridization showed a "negative" result for homozygous loss of CDKN2A; however, there was partial (heterozygous) loss of one allele. A diagnosis of atypical spindle cell proliferation was made based on these findings. Several months later, the patient had a repeat pleural biopsy that showed spindled cells with more pleomorphism, areas of invasion into the chest wall, and the same partial loss of CDKN2A, consistent with a sarcomatoid mesothelioma. This case underscores the challenges present on small biopsy specimens, the fact that sarcomatoid mesotheliomas can be relatively bland appearing with focal pleomorphism, and that heterozygous loss of CDKN2A should be considered a positive result indicative of a neoplastic process.

Subungual melanoma with blue naevus-like morphological features: a clinicopathological retrospective analysis of nine cases

Melanocytic lesions in the nail apparatus are often challenging. Both subungual melanomas (SUM) and blue naevus of the nail are very rare. Occasionally, melanomas may mimic blue naevus histologically. Benign and malignant blue melanocytic lesions are commonly associated with G protein mutations, a distinct abnormality not associated with conventional subungual melanomas. We describe the clinical, histological and immunohistochemical features of nine cases of SUM with blue naevus-like morphological features. Mutations in exon 4 and 5 of GNAQ and GNA11 were investigated in two cases, which showed no mutations. RNA-seq of one case revealed unknown mutations along with mutations in ATM, METK and ARID1A. Our study delineates a variant of SUM that mimics blue naevus. Awareness of this pitfall is important when evaluating heavily pigmented lesions around the nail in order to avoid misdiagnosis. Appropriate sampling of subungual lesions and clinicopathological correlation are paramount to reach the correct diagnosis.

Calcifications in Chromophobe Renal Cell Carcinoma: A Potential Pitfall in Diagnosis

Abstract We report a case of chromophobe renal cell carcinoma (ChRCC) with extensive calcifications, which on biopsy was initially interpreted as a possible MiT translocation carcinoma, in part because of the young age of the patient. Upon resection, the tumor was typical for ChRCC. The tumor illustrates that calcifications may be prominent in ChRCC and that the most common tumors in young patients are sporadic and of the classic morphologic types.

Septic Arthritis Complicating a Gout Flare: Report of Two Cases and Review of the Literature.

Objective:To highlight potential pitfalls in diagnosis and management of patients with concomitant gout and septic arthritis.Methods:Presentation of two patients with concomitant gout and septic arthritis, the latter caused by Streptococcus agalactiae and Staphylococcus aureus, in one patient each. We also reviewed the English language literature on PubMed for similar cases.Results:Data on concurrent gout and septic arthritis is limited. Three case series of 14, 25, and 30 patients each where identified. The coexistence of septic arthritis and gout is an infrequent condition. Clinical appearance of the two diseases may be very similar and the presence of monosodium urate (MSU) crystals per se cannot exclude infection. On the other hand, patients with chronic tophaceous gout are prone to infection of MSU tophi and the development of biofilms on the latter may render the eradication of microbes particularly difficult. Vice versa, persistent activation of the immune system fuelled by the infection, together with prolonged hospitalisation and immobilisation, may increase the risk for a gout flare, thus initiating a vicious cycle.Conclusion:In patients with gout, a high index of suspicion for infection is needed by treating physicians, because septic arthritis is a medical emergency which can lead to rapid joint destruction.

Selective Pituitary Resistance to Thyroid Hormone: Clinical Hyperthyroidism with High TSH on Levothyroxine Administration in I-131 Ablated “Graves Disease”

Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.

Characterization of germinal matrix hemorrhage in extremely premature infants: recognition of posterior location and diagnostic pitfalls.

Traditionally, descriptions of germinal matrix hemorrhage (GMH), derived from observations in preterm and very preterm infants, indicate its location at the caudothalamic grooves. However, before the germinal matrix begins to recede at approximately 28weeks' gestational age (GA), it extends along the floor of the lateral ventricles far posterior to the caudothalamic grooves. Germinal matrix-intraventricular hemorrhage (GMH-IVH) can occur along any site from which the germinal matrix has not yet involuted. Therefore, as current advances in neonatology have allowed the routine survival of extremely preterm infants as young as 23weeks' GA, postnatal GMH-IVH can occur in previously undescribed locations. Hemorrhage in the more posterior GMH on head ultrasound, if unrecognized, may lead to errors in diagnosis and mislocalization of this injury to the periventricular white matter or lateral walls of the lateral ventricles instead of to the subependyma, where it is in fact located. Our aim is to describe posterior GMH in extremely premature infants, including its characteristic imaging appearance and potential pitfalls in diagnosis. Over a 5-year period, all consecutive extremely preterm infants of 27weeks' GA or less who developed GMH-IVH of any grade were included. A consecutive group of 100 very preterm infants of 31weeks' GA with a GMH-IVH of any grade served as controls. In 106 extremely preterm neonates (mean GA: 25weeks, range: 23.1-26.6weeks) with 212 potential lateral ventricular germinal matrix bleeding sites, 159 sites had bleeds. In 70/159 (44%), the GMH-IVH was located posterior to the caudothalamic grooves and the foramina of Monro, 52 (32.7%) were both anterior and posterior and 21 (13.2%) were exclusively anterior. In 16 ventricles with intraventricular hemorrhage, an origin site in the germinal matrix could not be determined. In the control population of very preterm infants, all hemorrhages were at the anterior caudothalamic grooves and 95% were grade I. Unlike the older very preterm and moderately preterm infants that form the basis of our GMH-IVH description and classification, the extremely preterm infants now routinely surviving have a more fetal pattern of germinal matrix distribution, which is reflected in a different distribution and size of germinal matrix injury. We report the postnatal occurrence of subependymal GMH-IVH in extremely preterm infants in these more primitive, posterior locations, its potential imaging pitfalls and sonographic findings.

Melanocytic hyperplasia associated with surgical scars in basal cell carcinoma re‐excision specimens: A single‐center retrospective study

Melanocytic hyperplasia (MH) overlying surgical scars has been reported but MH adjacent to the scar has not been previously addressed. We evaluated scar-associated MH in 489 re-excision specimens of basal cell carcinoma. Melanocytic density, confluence, atypia, suprabasal scatter, follicular extension, distance from the scar, correlation with clinicopathologic parameters, and PRAME expression were recorded. One hundred seventy-seven of 489 (36%) cases exhibited MH beyond the scar extending to 6.65 mm median distance, with a median density of 13 melanocytes/0.5 mm (6-24 mm), confluence in 74 (42%) cases, atypia in 14 (8%), suprabasal melanocytes in 25 (14%), and follicular extension in 21 (12%). Mean age of MH group was significantly lower than non-MH group (P< 0.0001). MH overlying the scar was significantly higher in specimens with elastosis than those without elastosis (P< 0.0001). PRAME expression was absent in 14 of 20 cases and present in rare melanocytes in 6 cases. Increased melanocytic density with confluence, mild atypia, suprabasal scatter, and superficial follicular extension may be observed in re-excision specimens adjacent to surgical scars in the absence of a melanocytic neoplasm. These observations are helpful for appropriate interpretation of melanoma re-excision specimens, to avoid potential pitfalls in diagnosis and unnecessary therapeutic measures.

Early detection of myeloma

Myeloma is a rare, life-limiting blood cancer arising from plasma cells. Early diagnosis is imperative to improve clinical outcomes for patients, by both improving overall survival and reducing the morbidity associated with myeloma-related end-organ damage. This can be challenging in primary care, as myeloma can be difficult to diagnose. It may present in a number of non-specific ways that overlap with a multitude of other conditions. Tests that indicate myeloma are readily available in primary care. This article will describe the pathology of myeloma, the range and timing of diagnostic tests, guide interpretation of results, and outline the diagnostic subcategories of plasma cell disorders. Two cases looking at different aspects and complications of myeloma diagnosis are discussed with the aim of raising awareness and potential pitfalls in diagnosis. Useful resources to aid clinicians are signposted.

Manifestations of Tuberculosis in Ear, Nose, Throat, Head and Neck Region – A Retrospective Study

Introduction &#x0D; Tuberculosis can involve any organ or site. Otorhinolaryngologist may encounter tuberculosis affecting lymph nodes, ear, larynx, deep neck spaces, salivary glands etc. which can mimic other chronic granulomatous conditions or malignancy. To ensure early diagnosis, it is important to recognize its cardinal signs and symptoms and to be aware of potential pitfalls in diagnosis. This study was done to learn the clinical presentation of tuberculosis in ear, nose, throat and head and neck region, and to assess the effectiveness of various investigations and treatment done for the same.&#x0D; Materials and Methods &#x0D; A retrospective study done in our institution involving 120 patients suffering from tuberculosis in ear, nose, throat and head and neck region who attended pulmonary medicine or ENT OPD or ward between January 2008 to December 2017 that is, 10 years. Study period for data collection and analysis was 1 month.&#x0D; Results&#x0D; Total 120 patients-69 males and 51 females. Most common site was cervical lymph nodes(77.5% patients), followed by larynx(8.3%),middle ear(7.5%),deep neck spaces(2.5%) and salivary glands and nose(1.7% each). Histopathology was highly sensitive(99. 1%).All except one patient responded to first-line antitubercular drugs, the other patient was given treatment for MDR-TB to which he responded.&#x0D; Conclusion&#x0D; Tuberculosis can involve any site in the head and neck region, most common being cervical lymph nodes mainly presenting as neck swelling. Variable nature of manifestations of tuberculosis makes it essential to have high degree of suspicion for early diagnosis.

Xp11 translocation renal cell carcinoma and clear cell renal cell carcinoma with TFE3 strong positive immunostaining: morphology, immunohistochemistry, and FISH analysis

TFE3 is accepted as a good marker for the diagnosis of Xp11 translocation renal cell carcinoma. However, the significance of TFE3 in other types of renal cell carcinomas remains unclear. We examined the expression of TFE3 using immunohistochemistry by automated Ventana BenchMark XT system in 1818 consecutive renal cell carcinomas and verified the strong positive cases with TFE3 break-apart fluorescence in situ hybridization and RNA sequencing. Among the 27 renal cell carcinomas with TFE3 strong positive immunostaining, 20 cases were diagnosed as Xp11 translocation renal cell carcinoma, and seven cases were diagnosed as clear cell renal cell carcinoma. We further analyzed the morphology, clinicopathological features, and immunohistochemistry markers (CK7, CD117, CD10, P504s, vimentin, CA-IX, AE1/AE3, EMA, HMB45, Melan-A, and cathepsin K) of them. Pale to eosinophilic flocculent cytoplasm and psammomatous calcification were seen only in Xp11 translocation renal cell carcinomas (P < 0.05). Tumor necrosis occurred in all four cases of Xp11 translocation renal cell carcinomas with pT3a stage, which had local recurrence and distant metastasis (two of them died) within 3 years. The expressions of Vimentin, CA-IX, AE1/AE3, and EMA were significantly different between them (P < 0.05). CA-IX was diffusely strong positive in clear cell renal cell carcinomas but negative or focally mild positive in Xp11 translocation renal cell carcinomas. Our study first demonstrates that a very small minority (0.4%) of clear cell renal cell carcinomas with TFE3 strong positive immunostaining, which points out a potential pitfall in diagnosis of Xp11 translocation renal cell carcinomas by TFE3 immunohistochemistry. CA-IX is a good marker to distinguish clear cell renal cell carcinoma with TFE3 strong positive immunostaining from Xp11 translocation renal cell carcinoma. Tumor necrosis could be a potential factor relevant to pT3a stage, which may be a high-risk factor for the patients with Xp11 translocation renal cell carcinomas.

Cutaneous Metastases: A Review and Diagnostic Approach to Tumors of Unknown Origin.

Cutaneous metastases from a distant malignancy are a diagnostic challenge for pathologists. Secondary involvement of the skin by a metastatic process portends a much worse clinical prognosis than any primary cutaneous malignant mimickers. Immunohistochemical staining methods continue to evolve and are of paramount importance in diagnosis. To review the clinical, histopathologic, and immunohistochemical staining patterns for commonly encountered entities and discuss potential pitfalls in diagnosis. A practical guide useful in approaching cutaneous metastases of unknown primary is outlined. An extensive search and review of literature in PubMed was performed, processed, and condensed. Cutaneous metastases have broad histopathologic patterns. They are nearly always dermal based, with an overall foreign appearance. They can be single papules/nodules or multiple in number, mimicking an inflammatory or infectious process. Ultimately, immunohistochemistry remains an essential diagnostic tool, and clinical correlation is paramount in the workup of these entities.

Delineating Extramammary Findings at Breast MR Imaging.

Breast magnetic resonance (MR) imaging is the only breast imaging modality that consistently encompasses extramammary structures in the thorax and upper abdomen. Incidental extramammary findings on breast MR images of patients with a history of breast cancer or other malignancies are significantly more likely to be malignant and may affect staging and treatment. An understanding of the frequency, distribution, and context of extramammary findings on breast MR images and a familiarity with common and uncommon sites of breast cancer metastasis inform the differential diagnosis and prompt the appropriate diagnostic next step, to differentiate benign from malignant findings. High-yield organ systems on breast MR images, as reflected by a high positive predictive value for malignancy, are correlated with known distant sites of breast cancer metastasis in the bone, lung, liver, and lymph nodes. Staging is considered when disease involves the skin and chest wall. Unusual sites of breast cancer metastasis from invasive lobular carcinoma are discussed, including the gastrointestinal tract, peritoneum, and adrenal glands. Nonmalignant clinically important findings involving the cardiovascular and gastrointestinal systems are reviewed, and potential pitfalls in diagnosis and interpretation are highlighted. A consistently systematic diagnostic approach is emphasized for identifying extramammary abnormalities on breast MR images. All things considered, the radiologist should be able to improve diagnostic sensitivity and specificity while interpreting extramammary findings on breast MR images. ©RSNA, 2017.

Intraventricular cerebrospinal fluid pulsation artifacts on low-field magnetic resonance imaging: Potential pitfall in diagnosis?

Background:Intraventricular cerebrospinal fluid (CSF) pulsation artifact can pose a diagnostic problem in fluid-attenuated inversion recovery (FLAIR) brain magnetic resonance images (MRI) appearing as intraventricular hyperintensity. The extent of this challenge among radiologists in Africa using low-field MRI systems is relatively sparsely documented in the literature. The purpose of this study was to identify the presence and frequency of ventricular CSF pulsation artifact (VCSFA) on FLAIR axial brain images with a low-field MR system.Materials and Methods:FLAIR axial images were obtained on a low-field 0.3T unit (6000 ms/108 ms/2 [repetition time/echo time/excitations], inversion time = 1700 ms, field of view = 28 cm, matrix = 195 × 256, and 6 mm contiguous sections). Two experienced radiologists independently rated VCSFA in the lateral, third, and fourth ventricles in 202 consecutive patients (age range 1–100 years) referred for brain MR for various indications. We reviewed the pattern of artifacts, to determine its relationship to age, gender, and third ventricular size.Results:The low-field FLAIR MR brain images of 33 patients (16.3%) showed VCSFA in at least one ventricular cavity. The fourth ventricle was the most common site of VCSFA (n = 10), followed by the third ventricle (n = 8) and the lateral ventricles (n = 7). Eight patients had VCSFA in multiple locations, one of them in all ventricles. A smaller third ventricular size and, to a lesser extent, younger age was significantly associated with VCSFA. CSF Pulsation of VCSFA did not occur across the brain parenchyma in the phase encoding direction.Conclusion:VCSFA may mimic pathology on low-field axial FLAIR brain images and are more common in young patients with smaller ventricular size. Although these artifacts are less frequently observed at lower magnetic field strengths, their recognition on low-field MRI systems is important in avoiding a misdiagnosis.

Intravasation of water-soluble contrast agent during hysterosalpingography: A potential pitfall in diagnosis

Hysterosalpingography (HSG) is an integral component of infertility investigation. Certain technical artifacts can lead to misdiagnosis. Intravasation of contrast is seen in 0.4-6.9% cases. Radiologists as well as gynecologists should be aware of this phenomenon as it can potentially be misinterpreted as free intraperitoneal spillage. Venous intravasation was seen during HSG in a 33-year-old woman with primary infertility and initially misdiagnosed. No serious systemic complications were noted. The tubal block was later confirmed on laparoscopy and chromopertubation. A review of literature was performed to identify potential risk factors, for example, tuberculosis, recent endometrial curettage, uterine anomalies, etc. Certain measures such as slow instillation of contrast have also been proposed for prevention of this phenomenon.

Can diffusion weighted image and apparent diffusion coefficient (ADC) differentiate benign from malignant cervical adenopathy?

BackgroundCervical adenopathy is a common problem and the differentiation of benign and malignant node is of crucial importance for therapy management. ObjectiveThis prospective study aimed to know if Diffusion weighted images (DWI) and apparent diffusion coefficient (ADC) can differentiate benign from malignant cervical lymphadenopathy. Patients and methodsThirty patients with cervical adenopathy were included in this study. Doppler ultrasound, DWI and ADC maps were automatically reconstructed and used for the measurement of ADC values. ResultsThe sensitivity and specificity of the RI cut-off value <0.69 in differentiation between benign and malignant cervical L.Ns was 88.8% and 71.4%, respectively. The optimal ADC cut off value for differentiation between benign and malignant lymph nodes was ⩽1.0×10−3mm2/s with an accuracy 96.7%, a sensitivity 100%, a specificity 88.9%, PPV 95.4% and NPV 100% and statistically significant P-value=0.000. ConclusionDWI and ADC were useful for differentiation between benign and malignant cervical lymphadenopathy and recommended to decrease the need of invasive biopsies. However, CDUS techniques can be used as preliminary technique but, they had potential pitfalls in diagnosis of malignant cervical lymphadenopathy cases.

The Trauma Symptom Checklist for Children and Misdiagnosis of PTSD in A Youth with Acute Lymphocytic Leukemia: A Brief Report

Many factors in a child’s experience with cancer can contribute to posttraumatic stress. However, posttraumatic stress disorder (PTSD), first identified in child cancer survivors in 1985, was not broadly recognized in the literature for more than a decade. While under-diagnosis is no longer the concern it once was, care must also be taken to avoid over-diagnosis. This case report documents a case in which a young man erroneously carried a PTSD diagnosis several years after completing treatment for acute lymphocytic leukemia (ALL). Potential pitfalls in diagnosis and the importance of confirmatory clinical interviewing are reviewed.

Drug development status for Alzheimer’s disease: present scenario

Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might ameliorate the disease process. Research in the field of Alzheimer's disease therapy has been partly successful in terms of developing symptomatic treatments, but also had several failures in terms of developing disease-modifying therapies. These successes and failures have led to a debate about the potential deficiencies in our understanding of the pathogenesis of Alzheimer's disease and potential pitfalls in diagnosis, choice of therapeutic targets, development of drug candidates, and design of clinical trials. Many clinical and experimental studies are ongoing, but we need to acknowledge that a single cure for Alzheimer's disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information on pieces of the complex Alzheimer's disease puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Several promising randomized controlled trials are ongoing, and the increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach for the treatment of Alzheimer's disease.