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Pediatric surgical pathology: pitfalls and strategies for error prevention.

CONTEXT: Few data exist regarding quality measures for pediatric surgical pathology, types of errors, or how error-prone situations and diagnostic pitfalls can be minimized. OBJECTIVE: This review reports on survey findings regarding methodology for quality assurance and error detection measurement and classification in pediatric surgical pathology. It presents information regarding, and quality aspects of, intraoperative consultations in pediatric surgical pathology. General strategies for identifying diagnostic pitfalls in pediatric surgical pathology are briefly discussed. DATA SOURCES: A survey of children's hospitals based on a survey created by the Association of Directors of Anatomic and Surgical Pathology, literature review, and institutional quality assurance records provided information for this review. CONCLUSIONS: Approaches to quality assurance and error reduction in pediatric surgical pathology are similar to those used in general surgical pathology. The children's hospitals that were surveyed used a variety of standard quality assurance measures. Because of differences in data collection, classification, and reporting, it is not possible to provide a detailed analysis of the types of diagnostic error across institutions at this time. Intraoperative consultations are a potential source of error. Pediatric neoplasms and Hirschsprung disease account for the majority of intraoperative consultations in the pediatric setting. Further considerations include the unique aspects of pediatric medical and neoplastic disorders and special diagnostic criteria, classification, grading, and staging requirements.

Adolescent↗

Stage pT1 bladder carcinoma: diagnostic criteria, pitfalls and prognostic significance.

Recognition of early invasion (stage pT1) in urothelial neoplasia is one of the most challenging areas in bladder pathology, and reproducibility between pathologists is a major issue. This fact, together with the proposal by some urologists to treat early invasive tumours more aggressively, makes the accurate detection of pT1 lesions even more relevant in clinical practice. In recent years, the morphologic features and patterns of invasion of tumour into the lamina propria have been more accurately characterised and standardised, and although some of the features are subtle, they can be of great utility in the accurate assessment of pT1 staging. Histologic grade, changes at the stroma-epithelial interface, the characteristics of the invading epithelium, and the stroma-associated response are among the most important clues for appropriate pT1 staging and these are discussed in this review. Common problems in stage pT1 disease evaluation include, tangential sectioning--due to an inability to orient transurethral resection specimens--crush and cautery artefacts, and a streaking inflammatory infiltrate. With few exceptions, the criteria discussed in this review allow pathologists to separate superficial bladder tumours consistently and reproducibly into non-invasive (pTa) tumours and tumours that have invaded the lamina propria (pT1), the latter having a significantly poorer prognosis. This review is intended to assist the surgical pathologist by presenting appropriate diagnostic criteria, by describing common pitfalls and by outlining the different histologic patterns of invasion of urothelial carcinoma into the lamina propria. The value of pT1 tumour substaging, as a predictor of bladder cancer progression is also discussed.

Disease Progression↗

Pitfalls in diagnostic immunohistology.

The integration of immunostaining as an often-essential component of morphologic assessment makes it necessary that pathologists are familiar with the many technical and interpretive pitfalls that may arise because of the wide variety of factors that can significantly influence the ability to demonstrate relevant antigens in paraffin-embedded tissue sections. Pre-analytical variables that affect immunostaining include fixation, type of fixative, duration, temperature, and pH of fixation, variables in tissue processing, antigen loss resulting from delays in fixation, tissue necrosis, and levels of antigen expression. Analytical factors relate to the complex and sometimes capricious immunolabeling procedure that has as variables the specificity and sensitivity of the antibody clone, reagent dilution, detection system, and chromogen, and importantly, the method of antigen retrieval, which has its own set of variables such as time, temperature, method of heat generation, retrieval solution pH and molarity, and the synergistic action of proteolytic digestion. To obtain the highest diagnostic yield from immunostaining the correct questions must be asked and the pathologist must have familiarity with the characteristics of the antibody, its cross reactivity, if any, and localization of antigen in the cell to understand thresholds and cut-off levels and to recognize false-positive staining. Proper utilization of immunostaining requires that it is employed as a morphology-based technique and not interpreted in isolation.

Artifacts↗

Role of fine needle aspiration cytology in the diagnosis of goiter.

Enlargement of the thyroid gland is a common occurrence in most parts of the world especially in the iodine-deficient goiter belt areas. Vast majority of these lesions are benign but they invariably lead to a series of investigations among which FNAC plays a pivotal role. Although many studies have reported diagnostic accuracy of FNAC in detecting neoplasms, there have been few studies where the role of FNAC in the diagnosis of goiter along with their diagnostic pitfalls has been evaluated. The present study was undertaken to assess the accuracy of FNAC in diagnosis of goiter and to highlight its limitations and diagnostic pitfalls. 771 cases over a five-year period were retrieved from the files of Cytopathology Laboratory, Department of Pathology at the All India Institute of Medical Sciences, New Delhi. They included 733 cases where the cytological diagnosis was goiter or suggestive of goiter along with 38 cases in which the histological diagnosis was goiter while the cytological diagnosis was cystic change or neoplasm. FNAC with minimum of two passes were performed in each case and May Grünwald Giemsa and Papanicolaou stains were done. Histology was available in 192 cases. The cytological and histological concordance was determined and the FNAC smears and histological sections in cases showing discordance were reviewed. There was cytological and histological concordance 130/168 (77.38%) cases. In 34 cases (20.23%) no diagnosis could be offered because of cystic change. A false positive cytologic diagnosis of neoplasm was made in 4 cases. Presence of hurthle cell metaplasia, hyperplastic nodules and papillary hyperplasias were responsible for the false positive diagnoses. In 24 cases neoplasms were initially missed on FNAC of which 10 cases could be detected on review while 5 cases were considered unsatisfactory. Sampling errors were mainly responsible for these false negative diagnoses. FNAC is thus an accurate and reliable diagnostic tool for management of goiters provided strict adherence to adequacy criteria are maintained.

Adenoma↗

High-resolution MR cholangiopancreatography.

1. High-resolution MRCP is a noninvasive imaging modality for depicting the pancreatobiliary tree. The imaging quality of high-resolution MRCP is satisfactory. MRCP can demonstrate dilation, stenosis, and intraductal filling defects of both the biliary tract and the pancreatic duct, which meets the clinical demand for pancreatobiliary imaging. 2. MRCP was successful in almost all the patients. However, the causes of MRCP failure were patient motion, irregular respiratory rhythm, severe pneumobilia, and massive ascitic fluid. 3. When only MIP reconstructed images were used for interpretation, small intraductal filling defects such as a gallstone can be missed. In combination with coronal source images, the ability to detect intraductal stones can be increased. 4. Ferrite ammonium citrate (FAC) is useful in suppressing the background signal intensity of gastrointestinal contents so that the ducts can be clearly visualized. The other technique for decreasing the background signal intensity is target MIP postprocessing, which works well for better visualization of the ducts. 5. The degree of ductal narrowing tends to be overestimated with MRCP because of MIP reconstruction artifact and lower spatial resolution of MRCP than ERCP. 6. MRCP has a diagnostic pitfall of a pseudostenosis of extrahepatic ducts, which may lead to a false-positive diagnosis of ductal narrowing. This pitfall may be caused not only by MIP postprocessing artifacts but by gas, surgical metal, and vascular compression of right hepatic artery. There is another diagnostic pitfall that it is difficult to differentiate intraductal mucin from pancreatic fluid in dilate pancreatic ducts, although ERCP identifies mucin as intraductal filling defects.

Biliary Tract↗

Adenosine in wide complex tachycardia: potential pitfalls in diagnostic value.

Adenosine is an efficacious diagnostic and therapeutic agent in the acute management of wide complex tachycardias. Its potent negative dromotropic effect terminates supraventricular tachycardias involving the atrioventricular node, allowing differentiation from tachycardias of atrial and ventricular origin. Its extranodal actions, however, may lead to potential pitfalls in arrhythmia diagnosis. We report three unusual cases of patients with adenosine-sensitive tachycardias. One patient had idiopathic ventricular tachycardia originating from the right ventricular outflow tract, one had ectopic atrial tachycardia, and one had atrial fibrillation with rate-related intraventricular aberration. Recognition of the extranodal actions of adenosine and careful ECG evaluation before and after adenosine administration should maximize the diagnostic accuracy of adenosine in wide complex tachycardias.

Adenosine Triphosphate↗

Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells.

To identify the diagnostic pitfalls as well as the value of immunohistochemical studies in making a pathologic evaluation of a pediatric intestinal pseudo-obstruction (IPO), this study reassessed the pathology of 87 surgically resected intestines from 80 patients under the impression of IPO and 10 normal controls using immunohistochemical studies. The main diagnostic pitfall was the interpretation of the enteric nervous plexuses in the transitional zone and the detection of the indistinct or immature neurons indistinguishable from enteric glial cells or satellite cells. Immunohistochemical study was a very helpful diagnostic adjunct to delineating the immature neurons (bcl2), the size of the enteric ganglia and neuromuscular innervation (S-100 protein, synaptophysin, and CD56), and the interstitial cell of Cajal (c-Kit) and myopathy (SMA). With help of immunohistochemistry, our series of IPO could classify as neuropathy (92.5%), myopathy (2.5%), and the idiopathic forms (3.8%) more clearly. In terms of the types of neuropathy, Hirschsprung's disease (HD), pure hypoganglionosis, and intestinal neuronal dysplasia (IND-B) were diagnosed in 71.3%, 6.3%, and 48.8% of patients, respectively. IND-B was associated with other neuropathies, HD in 77.0% and hypoganglionosis in 7.7%, rather than being present in a pure form. Immature ganglion cells were found in 48.8%. Because a reduced number of interstitial cells of Cajal was commonly associated with HD in 84.2%, hypoganglionosis in 40%, and IND-B in 76.9% of cases, it might be a preceding or aggravating factor related to an IPO. In terms of detecting immature ganglion cells, we found bcl2 most helpful.

Biomarkers↗

MR imaging of soft-tissue masses of the extraperitoneal spaces.

Magnetic resonance (MR) imaging has an increasing role in evaluating soft-tissue masses of the extraperitoneal spaces. Since the MR imaging features of most soft-tissue masses are nonspecific, prediction of a specific histologic diagnosis remains a challenge for the radiologist. However, there are certain specific MR imaging appearances that are helpful for more accurate diagnosis. Some histologic components, such as myxoid stroma, collagen fibers, calcification, and fat, have characteristic MR imaging features. Recognition of these features can assist the radiologist in limiting the differential diagnosis. Dynamic enhancement patterns can reflect the vascularity of masses and may be useful in diagnosis, especially in differentiating benign from malignant soft-tissue masses. Familiarity with specific signs and knowledge of diagnostic pitfalls are also important for shortening the list of differential diagnoses. Specific signs are the target sign, the bowl of fruit sign, a whorled appearance, a flow void, speckled enhancement, associated lymphadenopathy, and extension into the intervertebral foramen. Diagnostic pitfalls are as follows: a myxoid stroma simulating cystic degeneration and necrosis, collagen fibers simulating hemorrhage, a fat component simulating extraperitoneal fat, extensive intratumoral hemorrhage simulating hematoma, benign masses mimicking malignant ones, malignant masses mimicking benign ones, and peritoneal lesions mimicking extraperitoneal masses.

Contrast Media↗

A practical approach to selected problematic melanocytic lesions.

Pigmented skin lesions are among the most common skin lesions. A majority can be diagnosed with ease; however, a minority of the cases are difficult and have the potential for error with catastrophic consequences for patients and the potential for litigation. Melanoma-related claims are second only to breast biopsy-related claims in surgical pathology. This review tries to highlight the problematic areas and diagnostic pitfalls in melanocytic lesions with emphasis on melanomas that might be underdiagnosed and benign melanocytic lesions that might be overdiagnosed and on practical approaches to deal with these lesions. Scanning power examination only is insufficient to avoid the potential diagnostic pitfalls in melanocytic lesions. We recommend examination of every melanocytic lesion in at least several high-power fields for cytologic atypia and mitotic activity. When dealing with problematic cases, it is important to see the entire lesion to determine whether lateral circumscription, nevoid maturation, and deep mitotic activity are present. Immunohistochemical analysis is useful, but it cannot replace careful examination of H&E-stained sections.

Female↗

Cytologic features of small-cell carcinoma on ThinPrep.

The use of ThinPrep (TP) technology for fine-needle aspiration (FNA) cytology has become widely accepted. However, some literature suggests that small-cell carcinoma may present a diagnostic pitfall due to morphologic alterations. In this study, we retrospectively compared 14 FNA of small-cell carcinoma prepared using TP with corresponding conventional smears (CS). We also examined the TP appearance of 23 other small round-cell lesions in order to determine if differential diagnostic features were preserved. TP and CS were evaluated semiquantitatively for background, architecture, chromatin quality, nuclear molding, nuclear smearing, nucleolar prominence, amount of cytoplasm, nuclear size, and single-cell necrosis. The data were analyzed using the McNemar chi(2) test. TP slides of small-cell carcinoma showed a cleaner background than CS (P < 0.005). Although some degree of nuclear molding was preserved, it was decreased in amount (P < 0.025) and subtler in quality. Similarly, nuclear smearing was present but decreased in amount (P < 0.05), and less prominent qualitatively. The amount of discernible cytoplasm was greater on TP (P < 0.005). No significant differences were found for any of the other parameters studied. The presence of nuclear molding was the single most useful feature in differentiating small-cell carcinoma from other small round-cell tumors on TP. Small-cell carcinoma may be diagnosed with confidence by FNA using TP. However, pathologists should be aware of certain morphologic alterations in order to avoid diagnostic pitfalls.

Biopsy, Fine-Needle↗

[False pancreatic pseudocyst during endoscopic retrograde cholangiopancreatography (ERCP) in a gastrectomized patient].

Endoscopic retrograde cholangiopancreatography (ERCP) is a very useful procedure for the diagnosis of biliopancreatic disorders. As a mixed endoscopic and radiologic procedure, its diagnostic yield depends heavily on the quality and skillful interpretation of radiological images. Diagnostic pitfalls must be kept in mind and avoided. We report on the case of a gastrectomized patient (Billroth II), in whom the observation during ERCP of two contrast-filled cavities, suggested the diagnosis of pancreatic pseudocysts. Other imaging procedures fully ruled out this diagnosis. The cause of this diagnostic pitfall was the accumulation of contrast in the blind end of the afferent loop. Additionally, we comment on other false cystic images in the ERCP.

Artifacts↗

Cytomorphologic spectrum of carcinoma ex pleomorphic adenoma.

OBJECTIVE: To delineate the cytomorphologic features of carcinoma ex pleomorphic adenoma (CPA) and identify the diagnostic pitfalls. STUDY DESIGN: Smears of 14 cases suspected as CPA on fine needle aspiration over a period of 15 years were reviewed. Cytohistologic correlation was done in 10 cases. RESULTS: All cases had a salivary gland mass of 1-16 years' duration, with a rapid increase in size in 10 cases. Epithelial cells predominated over stroma in 11 of 14 cases. Group I showed unequivocal malignant cells admixed with benign epithelial and stromal components of pleomorphic adenoma (PA), which were considered diagnostic of CPA on review. The cytologic differential diagnosis in these cases included mucoepidermoid carcinoma, carcinosarcoma and metastatic adenocarcinoma. Group II comprised 7 cases suspected to be cellular PA with atypia or CPA. These showed mild to moderate degrees of pleomorphism, absence of unequivocal malignant cells, and a variable proportion of benign epithelial and stromal components. Four of them were histologically confirmed as CPA. CONCLUSION: Sampling error is an important cause of diagnostic pitfalls. Correlation with clinical data is essential in diagnosis of CPA on cytology. In a proper clinical setting, extensive fine needle aspiration sampling should be done initially. Any degree of nuclear atypia in PA should be documented, alerting the clinician and histopathologist to the possibility of CPA.

Adenocarcinoma↗

[Possible errors in diagnosis of left atrial thrombosis in transesophageal echocardiography].

The detection of thrombi in the left atrium and left atrial appendage by transesophageal echocardiography has significant diagnostic and therapeutic value. However, it requires high method accuracy in routine evaluation. In order to record the percentage of false positive findings, a reevaluation was performed by two experienced examiners using the video recordings of 51 patients, in whom a thrombus has been diagnosed during the routine evaluation. From 1988 to 1994, these thrombi were diagnosed in 726 patients in whom we looked for a source of possible cardiac embolism. In the reevaluation of the 43 cases with sufficient video recordings, in 26 (60%) the diagnosis was classified as false-positive and in 5 patients (12%) as questionable. Thrombus diagnosis was confirmed in only 12 (28%) cases. The incidence of false-positive findings decreased over the course of years with 8.3% (1988-1990), 2.9% (1991-1992) and 0.4% (1993-1994), p = 0.0001. The agreement in the reevaluation between the two examiners was high (interobserver variability 7%), whereby completely divergent evaluations did not occur. Typical diagnostic pitfalls included a prominent trabecular structure in the left atrial appendage (n = 10), the membranous structure between the left atrial appendage and the upper left pulmonary vein (n = 7), transition of the lower left atrium/left atrial appendage (n = 3) and branches within the apex of the left atrial appendage (n = 2). When searching for thrombi in the left atrium and left atrial appendage, there is a high risk of false-positive findings, especially for the unexperienced investigator. Attention must be paid to the typical causes of diagnostic pitfalls in the case of complex and variable anatomy.

Adolescent↗

Hyalinizing trabecular adenoma--a case report with FNAC histologic, MIB-1 proliferative index and immunohistochemical findings.

Hyalinizing trabecular adenoma is a recently described benign thyroid tumor, almost exclusively occurring in females. The morphological features of this entity overlap with both papillary and medullary carcinoma to varying extent. This, in turn, creates a situation of serious diagnostic pitfall particularly for a false positive diagnosis of papillary carcinoma in fine needle aspiration (FNA) cytology. False consideration of medullary carcinoma is also possible by the unwary especially if staining for Congo red and/or immunostaining for calcitonin is not resorted to. At histologic level, the distinctive architectural pattern is however of great help and thus poses a much lesser danger of misdiagnosis. We relate here our experience in a recently encountered case of hyalinizing trabecular adenoma and describe detailed FNA cytologic and histologic findings along with immunohistochemical profile using a panel of eight monoclonal antibodies. The tumor proliferative potential has also been assessed using MIB-1 (Ki-67) immunostaining. The various pros and cons of diagnostic pitfalls are discussed.

Adenoma↗

Ultrasound-guided fine-needle aspiration biopsy of the thyroid bed.

BACKGROUND: Ultrasound (US) has been shown to be a sensitive technique for monitoring patients for recurrent thyroid carcinoma in the thyroid bed after total thyroidectomy. However, the role of US-guided fine-needle aspiration biopsy (FNAB) in the confirmation of sonographically indeterminate or suspicious masses has not been adequately addressed. The purposes of this study were to determine the sensitivity and specificity of US-guided FNAB of the thyroid bed for diagnosing recurrent carcinoma after total thyroidectomy and to highlight potential diagnostic pitfalls. METHODS: Twenty-one patients with a history of total thyroidectomy and histologically confirmed thyroid carcinoma who had undergone US-guided FNAB of hypoechoic lesions in the thyroid bed were included in this retrospective study. Fifteen of the 21 had papillary carcinoma (PC), 5 had medullary carcinoma (MC), and 1 had Hürthle cell carcinoma (HTC). The cytologic features of the aspirates were compared with histopathologic findings of pre- and post-FNA surgery. Immunohistochemical staining for thyroglobulin, calcitonin, and parathyroid hormone was performed in four cases. RESULTS: The cytologic diagnosis from the US-guided FNABs was conclusive in 20 of 21 cases. Fifteen cases were diagnosed as recurrent tumor (12 PC, 2 MC, and 1 HTC), and 13 of the 15 were confirmed subsequently by histology. Five cases were diagnosed as benign (two residual benign thyroid tissue, one parathyroid gland [PG] tissue, and two reparative changes) and hence were not resected. There was one false-positive diagnosis in which PG was misdiagnosed as PC. Immunohistochemical studies helped to confirm the diagnosis of PG tissue in two cases and of MC in two cases. The sensitivity of US-guided FNA for diagnosing recurrent carcinoma in the thyroid bed after total thyroidectomy was 100% and the specificity was 85.7%. CONCLUSIONS: US-guided FNAB was found to be a sensitive and specific test for diagnosing sonographically indeterminate lesions in the thyroid bed. One potential diagnostic pitfall was the misdiagnosis of normal residual thyroid or PG tissue as recurrent tumor. Careful attention to cytologic details and the use of selected immunohistochemical staining may help to prevent these misdiagnoses.

Adolescent↗

Pitfalls in diagnostic stereotactic brain surgery.

Some of the problems and dangers inherent to stereotaxis are discussed in a series of 243 procedures. Neurological deterioration, either due to haemorrhage or to traumatic oedema, was rare. One fatal accident occurred. Infections were not present although the patient's head was not shaved. Provided he can manipulate the proper instruments accurately stereotaxis can nowadays be performed by any surgeon who can make a burr hole and perform simple arithmetic calculations. This procedure can be considered to lie within the scope of any neurosurgeon.

Biopsy↗