Role Of Core Needle Biopsy Research Articles

Role of Core Needle Biopsy in Liver Metastases: A Histopathological and Immunohistochemical Approach

Abstract Background: The liver is the second most common organ involved by secondary neoplasms. Core needle biopsy of oncological patients requires an accurate histological diagnosis for the subsequent prescription of adequate management plans. Objectives: The aim of this study was to evaluate the diagnostic accuracy of core needle biopsy for suspected hepatic metastasis and to assess factors that influence the accuracy of the procedure. Materials and Methods: A cross-sectional study randomly enrolled 74 percutaneous ultrasound-guided core needle biopsies from patients with suspected hepatic neoplasm. A 16-gauge tru-cut biopsy needle was performed for all patients. Patient characteristics, procedure information, histopathology reports, and slides were collected from the Department of Histopathology at Al-Jamhorii Teaching Hospital, Mosul City, Iraq. All cases were analyzed using SPSS software, version 18.0. Results: Among 74 patients diagnosed with liver metastasis, the median age was 57 years (range 33–90 years) at the time of biopsy; of them, 61 patients (82.4%) reported a previous history of malignancy, P = 0.003. Histologically, metastatic adenocarcinoma was the most common neoplasm identified in 56 patients (75.7%), with the predominance of colorectal carcinoma. Forty-seven (63.5%) patients underwent two–five passes, which was statistically correlated with an increase in diagnostic accuracy (k = 0.21, 95% confidence interval [CI]= 0.038–1.189, P = 0.04). The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of tru-cut biopsies were 100%, 97.1%, 95.7%, 100%, and 98.2%, respectively. Conclusions: The core needle biopsy is a reliable and valid diagnostic option for the histological assessment of suspected liver metastasis, particularly when supplemented by ancillary immunohistochemistry.

Follicular lymphoma of the thyroid and the role of core needle biopsy.

Primary thyroid lymphoma (PTL) is a rare malignancy, accounting for less than 5% of all thyroid neoplasms. The follicular subtype is even more rare, accounting for approximately 10% of all PTL cases. We report a case of a 64-year-old woman, who presented with a rapidly growing goitre with mass effect and B symptoms. She had a history of Hashimoto's thyroiditis and her thyroid ultrasound revealed diffuse goitre with a dominant nodule (56 × 63 × 60 mm) within the right thyroid lobe. Ultrasound-guided percutaneous fine-needle aspiration of the right thyroid nodule was classified as benign, according to Bethesda System, with lymphocytic thyroiditis. A CT scan of the neck showed diffuse enlargement of the thyroid gland extending towards the anterior mediastinum with tracheal deviation and lymphadenopathy within levels VII and right II-IV. The core needle biopsy of the right thyroid nodule revealed a follicular non-Hodgkin's B cell lymphoma with a Ki67 of 60%. According to the Ann Arbor staging system, she was at stage IIIE. She underwent chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with remarkable clinical improvement and is currently in remission 2 years after the diagnosis. PTL is an extremely rare malignancy that usually arises in a lymphocytic thyroiditis background, presenting as a rapidly enlarging goitre, which can lead to compressive symptoms or airway comprise. Primary thyroid lymphoma (PTL) is a rare malignancy, accounting for less than 5% of thyroid neoplasms. PTL should be suspected when a patient presents with a rapidly enlarging goitre, especially in the setting of Hashimoto's thyroiditis. Fine-needle aspiration has a limited capacity for PTL diagnosis due to similar cytomorphological features of lymphoma with thyroiditis. Therefore, in case of clinical suspicion and if fine needle aspiration fails to diagnose PTL, a tissue biopsy should be performed. Treatment is dependent on both the stage and histology of PTL. Chemotherapy and local radiotherapy remain the mainstay treatment for PTL.

Investigating the role of core needle biopsy in evaluating tumor-stroma ratio (TSR) of invasive breast cancer: a retrospective study.

Tumor-stroma ratio (TSR) of invasive breast carcinoma has gained attention in recent years due to its prognostic significance. Previous studies showed TSR is a potential biomarker for indicating the tumor response to neoadjuvant chemotherapy. However, it is not clear how well TSR evaluation in biopsy specimens might reflect the TSR in resection specimens. We conducted a study to investigate whether biopsy evaluation of TSR can be an alternative method. We collected cases with invasive breast carcinoma of no special type (IBC-NST) from University of Yamanashi hospital between 2011 and 2017 whose biopsy and resection specimens both had a pathologically diagnosis of IBC-NST (n = 146). We conceptualized a method for evaluating TSR in biopsy specimens within a preliminary cohort (n = 50). Within the studied cohort (n = 96), biopsy-based TSR (b-TSR) and resection-based TSR (r-TSR) were scored by two pathologists. We then evaluated our method's validity and performance by measuring interobserver variability between the two pathologists, Spearman's correlation between b-TSR and r-TSR, and the receiver operating characteristics (ROC) analysis for defining stroma-rich and stroma-poor tumors. Intra-class coefficient between the two pathologists was 0.59. The correlation coefficients between b-TSR and r-TSR in the two pathologists were 0.45 and 0.37. The ROC areas under the curve were 0.7 and 0.67. By considering an r-TSR of < 50% as stroma-rich, the sensitivity and specificity of detecting stroma-rich tumors were 64.1% and 66.7%, respectively, when b-TSR was < 40%. Our current b-TSR evaluation method can provide information about r-TSR and facilitate pre-treatment therapy follow-up.

The role of core needle biopsy in the diagnosis of primary thyroid lymphoma and anaplastic thyroid carcinoma: a systematic review and meta-analysis

The role of core needle biopsy in the diagnosis of primary thyroid lymphoma and anaplastic thyroid carcinoma: a systematic review and meta-analysis

The role of core needle biopsy in diagnostic breast pathology

During the last several years core needle biopsies, with or without vacuum assistance, have become the gold standard sampling procedure for diagnosis of palpable and non-palpable mammary lesions. The advantages of core needle biopsy over fine needle aspiration and open surgical biopsies are well-established. In the era of de-escalation of therapy and with the greater use of neoadjuvant treatment, the pathologists are ever more critical in guiding management decisions in breast pathology so there is an imperative for precision of core needle biopsy diagnosis. However, the fragmented nature or the small size of the sample, may cause diagnostic pitfalls and precise radiologic-histopathologic correlation is needed for optimal patient management. This article provides a review on several issues regarding the evaluation of core needle biopsies.

The role of core needle biopsy in parotid glands lesions with inconclusive fine needle aspiration.

Usefulness of preoperative tissue sampling and pathology diagnoses in parotid gland tumors were accepted worldwide. We investigate the role of CNB in the parotid gland lesions when FNA results are inconclusive. We conducted a cross sectional study to evaluate CNB results from fifty-two patients with history of parotid gland lesion and inconclusive previous fine needle aspiration. In this study, 45 out of 52 CNB results determined definite histological subtype diagnosis. Four CNB reports were inconclusive and three CNB results were compatible with malignancies, but did not define definite diagnosis. Calculated sensitivity for diagnosis of malignancy was 96% and specificity was 85%. Negative predictive value, positive predictive value, and accuracy for CNB in detecting malignancy, were calculated 94%, 90%, and 92%, respectively. When FNA is not conclusive, CNB may be used as a precise method to evaluate the parotid gland lesions.

Core Needle Biopsy in Suspicious Malignant Thyroid Nodules with Repeated Nondiagnostic Fine Needle Aspiration.

The clinician could have CNB in mind for thyroid nodules when FNA results were nondiagnostic. Our study would suggest CNB a safe and efficient method for investigating thyroid nodules. Usefulness of preoperative tissue sampling and pathology diagnoses in thyroid tumors were accepted worldwide. We investigate the role of Core needle biopsy (CNB) in the thyroid nodules lesions when FNA results are nondiagnostic. We conducted a cross-sectional study to evaluate twenty-six CNBs results of suspicious malignant thyroid nodules with nondiagnostic repeated fine needle aspiration. 25 from 26 CNBs were diagnostic. Twenty-one needle biopsy reports were papillary thyroid carcinoma, three CNB samples diagnosed medullary thyroid carcinoma and one of them had anaplastic results. All diagnostic needle biopsies results were compatible with final pathology. Our study would suggest CNB a safe and efficient method for investigating thyroid nodules while repeated FNA yielded nondiagnostic results.

Enhancing the Critical Role of Core Needle Biopsy in Breast Cancer

The aim of this literature review is to derive detailed information on the significance of core needle biopsy in the diagnosis and effective treatment of breast cancer, according to current evidence, in an era of targeted therapy dependent on breast cancer stage and subtype. Preoperative diagnosis by core biopsy is rendered obligatory due to its crucial role not only in precise surgical management but also in segregating patients that often present with complete pathologic response (pCR) after neoadjuvant chemotherapy (NAC). Even in the absence of pCR, proper therapeutic management of these patients show significantly better prognosis in progression free survival (PFS) and overall survival (OS).

A challenging case of Mesenchymal Chondrosarcoma involving the thyroid and special considerations for diagnosis

BackgroundThyroid ultrasound is usually used to risk-stratify incidental thyroid nodules. Nodules with high risk sonographic features for malignancy are evaluated by fine-needle aspiration. The role of core needle biopsy for thyroid nodules is limited to cases where the fine needle aspiration is inconclusive.Case presentationWe describe a rare case of mesenchymal chondrosarcoma of the thyroid gland with uncertain primary origin. Thyroid ultrasound showed right sided large, solid, hypoechoic nodule with calcifications and peripheral vascularity and unremarkable isthmus and left thyroid lobe. Fine needle aspiration of the right nodule suggested lymphocytic thyroiditis. The sonographic findings contradicted the typical bilateral clinical and sonographic picture of lymphocytic thyroiditis. A core needle biopsy showed mesenchymal chondrosarcoma.ConclusionThis case highlights the importance of correlating pathologic diagnosis with sonographic findings, the appropriate utilization of fine needle aspiration and core needle biopsy to evaluate thyroid nodules and the rare incidence of mesenchymal chondrosarcoma involving the thyroid.

Rendimiento diagnóstico de la biopsia por punción en tumor filodes de la mama

ObjectiveTo evaluate the role of core needle biopsy (CNB) in the diagnosis of phyllodes tumour (PT) of the breast. Material and methodsAll pathological diagnoses of PT in both CNB and surgical biopsy (SB) were reviewed. The clinical, imaging and pathological characteristics of the cases and the diagnostic agreement between CNB and SB were analysed. ResultA total of 87 cases with a diagnosis of PT, 16 in CNB and 71 in SB, were studied. In 18 cases, CNB and SB were available. Benign PT diagnosed in CNB consisted of: 7 fibroadenomas (one of them cellular), 2 benign PT, 1 borderline PT, 2 malignant PT, and 1 hamartoma. Two cases of benign PT in SB had been diagnosed with CNB as fibrosis and hyperplasia. One PT diagnosed as malignant in CNB was diagnosed as a borderline PT in SB. There was diagnostic agreement in 1 borderline PT and 1 malignant PT. We detected 5 (27%) false negatives and 8 false positives (38%). ConclusionsThe efficiency of CNB in the diagnosis of PT is low, with a high rate of false negatives and false positives. Therefore, it is advisable to suggest a diagnosis of fibroepithelial lesion with cellular stroma in CNB, reserving definitive diagnosis to SB.

Role of core needle biopsy in the diagnosis of lymphoma: looking through the keyhole

Objective The aim was to evaluate the diagnostic value of core needle biopsy (CNB) for lymphoma-suspected cases.Materials and methods A total of 186 cases of lymph nodes and extranodal CNB were received at the pathology lab of MUST University and from private practice of authors between January 2016 and December 2018 with clinical suspicion of lymphoma. CNB specimens were examined and reviewed by two pathologists using hematoxylin and eosin and immunohistochemical (IHC) staining. Clinical data and sites of CNB were recorded. Adequacy and good integrity of tissues, confident pathologic diagnosis, subtyping, staging, and therapy effects were assessed.Results Of the 186 cases examined, 85% of CNB were adequate, providing confident diagnosis utilizing hematoxylin and eosin and IHC techniques. Reactive/non-neoplastic hyperplasia was the highest diagnostic entity of 27%, followed by small B-cell lymphomas (22%), Hodgkin lymphoma 18%, large B-cell lymphoma 10%, follicular lymphoma 2%, lymphoblastic lymphoma 1.5%, T-cell lymphoma 1.5%, and other lymphomas 3%. The remaining 15% of CNB were inadequate and excisional biopsy was performed. Bone marrow and liver CNB were positive in stage IV small B-cell lymphoma. CNB for follow-up showed residual or necrotic lymphoma cells in 9.1% of cases.Conclusion CNB is a highly reliable procedure for the diagnosis, subtyping, staging, and therapy follow-up of lymphoma. Sufficient tissue cores, pathologist experience, and IHC are essential requirements for confident diagnosis.

The Role of Core Needle Biopsy for the Evaluation of Thyroid Nodules with Suspicious Ultrasound Features.

ObjectiveRecent studies demonstrated that core needle biopsy (CNB) can effectively reduce the possibility of inconclusive results and prevent unnecessary diagnostic surgery. However, the effectiveness of CNB in patients with suspicious thyroid nodules has not been fully evaluated. This prospective study aimed to determine the potential of CNB to assess thyroid nodules with suspicious ultrasound (US) features.Materials and MethodsPatients undergoing CNB for thyroid nodules with suspicious features on US were enrolled between May and August 2016. Diagnostic performance and the incidence of non-diagnostic results, inconclusive results, conclusive results, malignancy, unnecessary surgery, and complications were analyzed. Subgroup analysis according to nodule size was performed. The risk factors associated with inconclusive results were evaluated using multivariate logistic regression analysis.ResultsA total of 93 patients (102 thyroid nodules) were evaluated. All samples obtained from CNB were adequate for diagnosis. Inconclusive results were seen in 12.7% of cases. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis of malignancy were 93.8%, 100%, 100%, 78.9%, and 95%, respectively. None of the patients underwent unnecessary surgery. The diagnostic performance was not significantly different according to nodule size. On multivariate logistic regression analysis, larger nodule size and shorter needle length were independent risk factors associated with inconclusive results.ConclusionSamples obtained by CNB were sufficient for diagnosis in all cases and resulted in high diagnostic values and conclusive results in the evaluation of suspicious thyroid nodules. These findings indicated that CNB is a promising diagnostic tool for suspicious thyroid nodules.

The role of core needle biopsy in the diagnosis of initially detected thyroid nodules: a systematic review and meta-analysis.

To systematically review the published literature and evaluate the efficacy and safety of core needle biopsy (CNB) for initially detected thyroid nodules. The Ovid-MEDLINE and Embase databases were searched for studies evaluating CNB for the diagnosis of initially detected thyroid nodules. A meta-analysis was performed to evaluate non-diagnostic results, inconclusive results and diagnostic accuracy for a diagnosis of malignancy with CNB. To overcome heterogeneity, multiple subgroup analyses were performed. The complication rate was also evaluated. Thirteen eligible studies, which included a total sample size of 9,166 patients with 13,585 nodules, were included. The pooled proportions were 3.5% (95% CI 2.4-5.1) for non-diagnostic results and 13.8% (95% CI 9.1-20.3) for inconclusive results. Considerable heterogeneity was observed among the studies in terms of the pooled proportions for CNB (I2=92.9%, 97%). With regard to the diagnostic performance for malignancy, the sensitivity was 80% (95% CI 75-85) and the specificity was 100% (95% CI 93-100). Only two major complications of CNB were observed. CNB demonstrates a low non-diagnostic result rate and high diagnostic accuracy for initially detected thyroid nodules and a low major complication rate. These findings indicate that CNB may be a feasible diagnostic tool for patients with initially detected thyroid nodules. CNB demonstrates high diagnostic accuracy for initially detected thyroid nodules. CNB demonstrates a low major complication rate. CNB may be a feasible diagnostic tool for patients with initially detected thyroid nodules.

A Case Report of Diffuse Large B-cell Lymphoma Masquerading as Necrotizing Lymph Nodes: The Role of Core Needle Biopsy for Early Diagnosis

Introduction: Complete lymph node necrosis is a rare condition. Excisional biopsy of infarcted lymph node could wrongly lead physicians to benign diagnoses such as Kikuchi-Fujimoto disease, while malignant lymphoma progresses. Case Presentation: A 33-year-old man was referred with gradual enlargement of a left submandibular mass which had recently become painful. The patient had no dysphagia, odynophagia, dysphonia, dyspnea, coughing, nasal obstruction, tooth ache or epistaxis. Three masses were detected by physical examination and computed tomography. There were no signs of malignancy in fine needle aspiration and excisional biopsy. The patient was finally diagnosed by core needle biopsy under ultrasonography guidance and a second excisional biopsy. Conclusions: The core needle biopsy under ultrasonography guidance could help choosing the optimal lymph node among multiple necrotizing lymph nodes and would prevent more invasive procedures. We emphasize that physicians should keep a high clinical suspicion for lymphoma even if the initial excisional biopsy of an infarcted lymph node is negative.

Role of core needle biopsy as a first-line diagnostic tool for thyroid nodules: a retrospective cohort study.

PurposeThe purpose of this study was to evaluate the diagnostic efficacy of fine-needle aspiration (FNA), core needle biopsy (CNB), and combined FNA/CNB for the first-line diagnosis of thyroid nodules.MethodsA total of 782 consecutive nodules that underwent simultaneous FNA and CNB were analyzed in this study. We compared the rate of inconclusive results and the diagnostic values for malignancy among FNA, CNB, and combined FNA/CNB.ResultsCNB showed a lower rate (10.2%) of inconclusive results than FNA (23.7%) (P<0.001). Combined FNA/CNB showed a lower rate (6.5%) of inconclusive results than FNA (all nodules, P<0.001; macronodules, P<0.001; and micronodules, P<0.001, respectively) or CNB (all nodules, P<0.001; macronodules, P<0.001; and micronodules, P=0.003, respectively). Combined FNA/CNB and CNB showed significantly higher sensitivity, accuracy, and diagnostic performance for malignancy as defined by criterion 1 (Bethesda category VI) or criterion 2 (Bethesda categories IV/V/VI) than FNA (P<0.001). However, there was no significant difference in the sensitivity, accuracy, or diagnostic performance between combined FNA/CNB and CNB (with criterion 1, P=0.063, P=0.063, and P=0.412, respectively; with criterion 2, P=0.500, P=0.500, and P=0.348, respectively).ConclusionCNB was found to be more effective than FNA for the diagnosis of thyroid nodules, and its sensitivity and diagnostic performance for malignancy were similar to those of combined FNA/CNB. CNB has the potential to be an effective alternative first-line diagnostic tool for thyroid nodules when performed by an experienced operator.

The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the accurate pathologic diagnosis of epithelial ovarian cancer.

The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the accurate pathologic diagnosis of epithelial ovarian cancer.

Role of core needle biopsy in primary breast lymphoma.

Primary breast lymphoma (PBL) may mimic carcinoma clinically and also mammographic and ecographic distinction is subtle. Despite its rarity, incidence of PBLs has increased over the last four decades and continues to increase for younger women and for some subtypes, and for this reason it is increasingly important to achieve a preoperative pathological diagnosis using core needle biopsy (CNB) or fine-needle aspiration cytology (FNA). The aim of this retrospective study was to report our single-center experience in CNBs performed for histological diagnosis of PBL compared to FNA. From a total of 10,500 CNBs we found seven patients affected by PBL diagnosed at Careggi Florence University Hospital, between January 2000 and December 2016. Diffuse large B cell lymphoma (DLBCL) was the most frequent PBLs and on CNBs specimens was possible do the fluorescent in situ hybridization analysis to evaluate the presence of chromosomal translocation. CNB is an effective method for the assessment of PBLs, especially for DLBCL, in which a correct and fast classification could change the therapeutic approach and the prognosis.

The Role of Core Needle Biopsy for Thyroid Nodules with Initially Indeterminate Results on Previous Fine-Needle Aspiration: A Systematic Review and Meta-Analysis.

Sonography-guided fine-needle aspiration leads to relatively frequent cases of indeterminate cytology for the diagnosis of thyroid nodules. Our aim was to evaluate the efficacy and safety of core needle biopsy for the examination of thyroid nodules with initially indeterminate results on fine-needle aspiration. A computerized search of the MEDLINE and Embase databases was performed to identify relevant original articles. Studies investigating the use of core needle biopsy for thyroid nodules with initially indeterminate results on previous fine-needle aspiration were eligible for inclusion. The pooled proportions for nondiagnostic results, inconclusive results, malignancy on core needle biopsy, the ability of core needle biopsy to diagnose malignancy, and the related complications of the procedure were analyzed. The meta-analytic pooling was based on a random-effects model. Nine eligible studies, involving 2240 patients with 2245 thyroid nodules, were included. The pooled proportion for nondiagnostic results was 1.8% (95% CI, 0.4%-3.2%), and the pooled proportion for inconclusive results was 25.1% (95% CI, 15.4%-34.9%). The pooled proportion for malignancy was 18.9% (95% CI, 8.4%-29.5%). With regard to the diagnostic performance for malignancy, the sensitivity of core needle biopsy varied, ranging from 44.7% to 85.0%, but the specificity was 100% in all cases. No major complications of core needle biopsy were observed. The relatively small number of included studies and retrospective nature were limitations. Core needle biopsy has low nondiagnostic result rates and high specificity for the diagnosis of malignancy. It is a safe diagnostic technique with a higher diagnostic yield, especially when molecular testing is not available or fine-needle aspiration did not yield enough cells for molecular testing.

First-Line Use of Core Needle Biopsy for High-Yield Preliminary Diagnosis of Thyroid Nodules.

Although core needle biopsy was introduced as a diagnostic alternative to fine-needle aspiration, the utility and safety of core needle biopsy for thyroid nodules in a large population has yet to be studied comprehensively. We evaluate core needle biopsy yields on a large-scale basis to investigate its potential in the preliminary diagnosis of thyroid nodules. Between March 2005 and December 2013, 2448 initially detected thyroid nodules from 2120 consecutive patients who underwent core needle biopsy were retrospectively evaluated. Of these, 72 thyroid nodules from 63 patients were excluded due to prior fine-needle aspiration attempts. The inconclusive and conclusive result rates, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and unnecessary surgery rate of core needle biopsy were evaluated. With core needle biopsy as the first-line method, the inconclusive result rate was 11.9% (283/2376) and the conclusive result rate was 88.1% (2093/2376). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of core needle biopsy for the diagnosis of malignancy were 96.7% (1160/1200), 89.7% (347/387), 100% (813/813), 100% (347/347), and 95.3% (813/853), respectively. There were no major complications and 12 minor complications. We have demonstrated that first-line use of core needle biopsy may well improve diagnostic accuracy in thyroid nodules, reducing inconclusive or false-negative results and unnecessary operations. Such benefits underscore the promising role of core needle biopsy in managing thyroid nodules and optimizing related surgical decision-making.

Metastatic renal cell carcinoma in the thyroid gland: ultrasonographic features and the diagnostic role of core needle biopsy.

PurposeThe aims of this study were to present the ultrasonographic (US) features of metastatic renal cell carcinoma (RCC) in the thyroid gland and to evaluate the diagnostic utility of fineneedle aspiration (FNA) and core needle biopsy (CNB).MethodsEight patients with nine metastatic RCC nodules in the thyroid glands who were treated from January 2002 to March 2015 in a single tertiary hospital were consecutively selected and retrospectively reviewed. US features and clinical history were obtained from the institution’s medical database. FNA was performed nine times on eight nodules and CNB was performed six times on six nodules. The diagnostic utility of FNA and CNB was evaluated.ResultsAll nine nodules showed mass formation without diffuse thyroid involvement. On ultrasonography, metastatic RCC nodules were solid (100%), hypoechoic (100%), and ovalshaped nodules with a well-defined smooth margin (88.9%) and increased vascularity (100%, with 55% showing extensive vascularity). No calcifications were noted in any nodules. Lymph node metastasis and direct extension to nearby structures beyond the thyroid gland were not found. One FNA (11%) was able to confirm metastatic RCC, whereas all six CNBs confirmed metastatic RCC.ConclusionMetastatic RCC appears as oval-shaped hypoechoic solid nodules with well-defined smooth margins, no calcifications, and increased vascularity on ultrasonography. Characteristic US features along with a previous history of RCC should raise clinical suspicion, and CNB should be performed to make an accurate diagnosis.