Evaluation of performance of EUS-FNA in preoperative lymph node staging of cancers of esophagus, lung, and pancreas

We reviewed the cytologic and histologic diagnoses and EUS report of 77 consecutive patients who had undergone EUS-FNA preoperative staging for esophageal, lung, and pancreatic cancers at our institution. A total of 122 EUS-FNA lymph nodes were identified. Thirty of 77 cases had histologic follow-up. Using surgical node staging and/or surgical resection as the reference standard, the sensitivity, specificity, accuracy, and positive and negative predictive values were 75%, 95%, 89%, 86%, and 90%, respectively, for EUS-FNA node staging. We compared cytologically malignant and benign lymph node groups with eight EUS parameters including the total number of lymph nodes found by EUS, the shape, margin, long axis, short axis, echogenicity, location of the lymph node, and EUS tumor staging. We found that the short axis is the best EUS feature to predict malignancy. Lymph nodes found in an abdominal location in esophageal and lung cancer are likely malignant.     

Endoscopic ultrasound-guided fine-needle aspiration of lymph nodes: the Hennepin County Medical Center experience

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) allows for the sampling and diagnosis of lesions of the gastrointestinal system and adjacent tissues. It has also proved helpful with the sampling of lymphadenopathy both for the staging of malignancy and for the diagnosis of lymphadenopathy of other causes. We review our experience with EUS-guided FNA of lymph nodes. The cytology files were searched at Hennepin County Medical Center (HCMC) for all cases of lymph nodes sampled by EUS. Clinical history, biopsy site, diagnosis, and follow-up information (including ancillary testing) were reviewed. Between January 1, 2000 and December 5, 2002, 217 lymph nodes from 185 different patients were sampled by EUS at HCMC. Biopsy sites included 62 mediastinal, 9 paraesophageal, and 146 intra-abdominal lymph nodes. Diagnoses were as follows: metastatic non-small cell carcinoma (n = 69); benign, reactive lymph node (n = 76); granulomatous lymphadenopathy (n = 18); malignant lymphoma (n = 7); atypical-suspicious for malignancy (n = 5); metastatic small cell carcinoma (n = 2); necrotic debris (n = 4), and foreign material (n = 1); 35 cases were nondiagnostic (16.1%) in 22 of 185 patients (11.9%). Ancillary tests including flow cytometry, cytogenetics, and cultures were performed. EUS-guided FNA of mediastinal and intra-abdominal lymph nodes provides diagnostic material from which ancillary testing may be performed.     

Impact of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lymph nodal and mediastinal lesions: a multicenter experience

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established procedure in lung cancer (LC) staging and in the diagnosis of mediastinal masses. Most of the experiences reported refer to single specialized centers where dedicated teams of endoscopists and pathologists perform the procedure. We report the EUS-FNA experience of a cooperation group involving clinicians and cytopathologists from three hospitals. Fifty-seven consecutive EUS-FNA of mediastinal nodes in LC patients, eight mediastinal and two subdiaphragmatic masses were collected in 3 years. EUS-FNA was performed by two endoscopists and three experienced pathologists. On-site evaluation was performed in all cases by the three cytopathologists. Lymph node negative cases underwent surgery, which confirmed the cytological diagnoses but also detected two false negatives. Four of the 10 EUS cytological diagnoses of mediastinal and subdiaphragmatic masses were histologically confirmed. All EUS diagnoses were blindly reviewed by three pathologists to assess intra and interpersonal reproducibility. FNA-EUS diagnoses were: 10 inadequate (17%), 10 negative (17%), 4 suspicious (7%) and 33 positive (59%). Diagnoses of mediastinal and subdiaphragmatic masses were: relapse of lung carcinoma (3), mesenchimal tumor not otherwise specifiable (3), gastrointestinal stromal tumor (GIST) (1), esophageal carcinoma (2) and paraganglioma (1). The sensitivity attained was 85% and the specificity 100%; revision of the slides demonstrated a significant diagnostic reproducibility of the three cytopathologists (P < 0.5). The sensitivity and specificity attained were similar to those reported in the literature suggesting that experienced cytopathologists and endoscopists from different institutions can employ the same procedure reaching comparable results.     

Endoscopic ultrasound-guided fine-needle aspiration. A cytopathologist's perspective

Endoscopic ultrasound (EUS) is used to detect and delineate the extent of lesions in the gastrointestinal tract, periluminal lymph nodes, pancreas and hepatobiliary tree, left kidney, spleen, and adrenal glands. EUS-guided fine-needle aspiration (FNA) has added a new dimension to the capabilities of EUS because it permits characterization of the lesion, thereby enabling triage of patients for more efficient and effective management. This review focuses on the advantages and limitations of EUS-FNA, including a discussion of potential pitfalls in the diagnosis of commonly aspirated deep-seated lesions, such as those of the pancreas and lymph nodes. It also addresses the practical considerations associated with establishing an effective service and the importance of an integrated approach in which the cytopathologist undertakes a key role, interacting extensively with the endoscopist and the patient management team. EUS-FNA is a sensitive modality that enables specific and accurate diagnosis of deep-seated lesions. Samples can be obtained effectively from small lesions (< 25 mm), irrespective of the organ site. On-site assessment permits a highly accurate preliminary diagnosis of malignancy for samples obtained by EUS-FNA and provides an opportunity to increase the diagnostic yield of samples.     

Endoscopic ultrasound-guided real-time fine-needle aspiration: Clinicopathologic features of 60 patients

Diagnosis of lesions of the gastrointestinal tract and adjacent structures is possible using an imaging modality, endoscopic ultrasonography (EUS). Fine-needle aspiration (FNA) is a suitable and cost-effective technique for obtaining cytohistologic material to confirm the diagnosis. EUS is capable of both characterizing the lesion and then guiding the FNA under real-time (RT) ultrasound guidance using a through-the-scope needle aspiration system. The goal of this study was to determine the diagnostic accuracy of this technique and to describe the clinicopathologic features. Sixty patients underwent EUS-guided RTFNA of 64 lesions, including pancreas (n = 45), periluminal lymph nodes (n = 12), mediastinal and retroperitoneal masses (n = 4), and hepatobiliary masses (n = 3). Follow-up data were obtained by surgery, histopathology, or clinical course. Thirty-one lesions were malignant, eight were atypical/suspicious, 16 were non-neoplastic, and nine were non-diagnostic. Of the 55 lesions with sufficient material for interpretation, 54 had follow-up confirmation of the RTFNA diagnosis. The calculated sensitivity and specificity for malignancy was 90% and 100%, respectively. Diagnostic accuracy for malignancy was excellent for gastrointestinal associated lymph nodes (100%), mediastinal and retroperitoneal masses (100%), somewhat less so for pancreatic tumors (94%), and poor for hepatobiliary lesions (33%). EUS-guided RTFNA is accurate for sampling small gastrointestinal tract–associated lesions. EUS-guided RTFNA should be considered as a procedure of choice in selected patients when the results will influence management decisions. Diagn. Cytopathol. 1998; 18:98–109. © 1998 Wiley-Liss, Inc.     

Comparative leukocyte esterase-nitrite and BAC-T-SCREEN studies using single and multiple urine volumes

The Chemstrip LN and BAC-T-SCREEN filtration systems were used to evaluate 980 urine specimens rapidly for the presence of microorganisms. Multiple volumes of individual specimens were also tested using the BAC-T-SCREEN to determine whether this procedure enhanced test performance. Ninety-nine specimens (10%) could not be processed because of interfering substances or clogging of the BAC-T-SCREEN. Analysis of the remaining 881 samples showed these test results for the Chemstrip LN system: sensitivity, 48%; specificity, 93%; positive predictive value (PPU), 88%; and negative predictive value (NPV), 71%. The BAC-T-SCREEN results using multiple urine volumes were (for 1 mL) sensitivity, 88%; specificity, 98%; PPV, 97%; NPV, 92%; for 2 mL, sensitivity, 94%; specificity, 96%; PPV, 94%; NPV, 96%; for 3 mL, sensitivity, 98%; specificity, 95%; PPV, 93%; NPV, 98%. Analyzing multiple urine volumes permitted detection of 92% of urine samples with colony-forming units of 10(4) or less. The BAC-T-SCREEN system proved superior to Chemstrip LN for detecting microorganisms in urine specimens, and analyzing multiple urine volumes enhanced test sensitivity.     

Nodal stations and diagnostic performances of endobronchial ultrasound-guided transbronchial needle aspiration in patients with non-small cell lung cancer

There are no accurate data on the relationship between nodal station and diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). We evaluated the impact of nodal station and size on the diagnostic performance of EBUS-TBNA in patients with non-small cell lung cancer (NSCLC). Consecutive patients who underwent EBUS-TBNA of mediastinal or hilar lymph nodes for staging or diagnosis of NSCLC were included in this retrospective study. Between May 2009 and February 2010, EBUS-TBNA was performed in 373 mediastinal and hilar lymph nodes in 151 patients. The overall diagnostic sensitivity, specificity, accuracy and negative predictive value (NPV) of EBUS-TBNA were 91.6%, 98.6%, 93.8%, and 84.3%, respectively. NPV of the left side nodal group was significantly lower than those of the other groups (P = 0.047) and sensitivity of the left side nodal group tended to decrease (P = 0.096) compared with those of the other groups. Diagnostic sensitivity and NPV of 4L lymph node were 83.3% and 66.7%, respectively. However, diagnostic performances of EBUS-TBNA did not differ according to nodal size. Bronchoscopists should consider the impact of nodal stations on diagnostic performances of EBUS-TBNA.     

The role of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration in distinguishing pancreatic cystic lesions

Distinguishing mucinous from nonmucinous cystic lesions of the pancreas often constitutes a diagnostic dilemma. The clinical management differs between such lesions; therefore it is important to make an accurate preoperative diagnosis. Various centers have reported conflicting results regarding their ability to detect mucin-producing neoplastic cells and appropriately reach a diagnosis based on endoscopic ultrasound (EUS) guided FNA. The aim of this study is to assess the ability of EUS-FNA cytology to diagnose and differentiate mucinous from nonmucinous pancreatic cystic lesions. We reviewed records of patients who underwent EUS of pancreatic cystic lesions. If FNA was performed and mucinous neoplasm was suspected, aspirate was evaluated for cytomorphology and presence of mucin. FNA results were compared to final histologic diagnosis if surgery was performed.Cytologic diagnosis was provided for 28/30 (93%). By comparing EUS-FNA diagnoses with final surgical pathology, FNA accurately diagnosed in 10/11 cases with sensitivity and specificity for detection of malignancy of 100 and 89, respectively, while the accuracy for identification of mucinous cystic neoplasms was 100%. Our results indicate that in the appropriate clinical and imaging setting, EUS-FNA cytology with analysis for mucin production by tumor cells is an important test in distinguishing pancreatic cystic lesions and guiding further management.     

A comparative study of 200 head and neck FNAs performed by a cytopathologist with versus without ultrasound guidance: evidence for improved diagnostic value with ultrasound guidance

Our previous study showed that the sensitivity of head and neck fine-needle aspiration (FNA) procedures was significantly better in the cytopathologist-performed group than in the noncytopathologist-performed group (96 versus 67%). Recently, cytopathologists have learned to use ultrasound machines to assist them in performing FNA procedures. This study was designed to assess whether cytopathologist-performed FNAs with ultrasound guidance can improve diagnostic value in comparison to those done without ultrasound guidance. Two hundred consecutive head and neck FNA cases performed by the same cytopathologist with and without ultrasound guidance were reviewed. Cases consisted of 100 ultrasound-guided FNAs (USGFNAs) performed between July 2008 and March 2009 and 100 palpation-guided FNAs (PGFNAs) performed before July 2008. These cases were correlated with follow-up surgical diagnosis. The diagnostic, suspicious/atypical/suggestive, and nondiagnostic rates (%) for the head and neck FNAs were 83 versus 86, 10 versus 13, and 7 versus 1 in PGFNA group versus USGFNA group, respectively. Surgical follow-up specimens were found in 50 PGFNAs versus 35 USGFNAs. The true-positive, true-negative, false-positive, and false-negative rates (%) were 92, 2, 2, and 4 versus 80, 17, 3, and 0 in PGFNAs versus USGFNAs, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 96, 50, 98, 33, and 94% in PGFNAs versus 100, 86, 97, 100, and 97% in the USGFNA group, respectively. This study also shows increased FNAs of thyroid and salivary glands and other smaller nonpalpable lesions with ultrasound guidance. USGFNAs performed by a cytopathologist could significantly improve the specificity and NPV (P = 0.04) while preserving virtually the same excellent sensitivity and PPV as those of PGFNAs. With ultrasound guidance, a cytopathologist will be able to perform FNAs in smaller, nonpalpable lesions and target complex lesions with confidence and accuracy, thus achieving a better outcome.     

Hysterosalpingo contrast sonography (HyCoSy) with SH U 454 (Echovist) for the assessment of tubal patency

A total of 88 Fallopian tubes from 44 patients was examined with hysterosalpingo contrast sonography (HyCoSy), hysterosalpingogram (HSG), and laparoscopic chromopertubation (LC) in order to assess their relative accuracy for measuring tubal patency. HyCoSy was done by transvaginal ultrasound and the contrast was SH U 454 (Echovist). The flow of multiple fractions of the contrast medium through each Fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe. Compared with laparoscopic results, we found a sensitivity of 85.2%, a specificity of 85.2%, a positive predictive value (PPV) of 71.9%, a negative predictive value (NPV) of 92.9% and concordance (HyCoSy/LC) of 85.2%, while the corresponding values for HSG were sensitivity = 85.2%, specificity = 83.6%, PPV = 69.7%, NPV = 92.7% and concordance (HSG/LC) of 84.1%. Compared with HSG results, HyCoSy obtained a co-positivity of 66.7%, a co-negativity of 81.8% and a concordance of 76.1%. In conclusion, HyCoSy with SH U 454 proved to be a reliable and safe modality for evaluating tubal patency; it is suitable as an outpatient diagnostic procedure to be used before more invasive procedures.      

Evolution of transthoracic fine needle aspiration and core needle biopsy practice: A comparison of two time periods, 1996-1998 and 2003-2005

To examine the performance of our large pulmonary transthoracic fine needle aspiration/core biopsy (FNA/CB) practice over time, we performed a retrospective analysis of data from 333 consecutive procedures performed in 1996-1998 and 568 consecutive procedures performed in 2003-2005. Fluoroscopic guidance was performed more frequently in the earlier cohort, while a larger majority of procedures in the later cohort were by computed tomography (CT-guidance). A follow-up histologic diagnosis of cancer or clinical evidence of disease was considered the gold-standard. FNA/CB procedures during the later time period were performed on smaller lesions overall (3.60 cm versus 2.97 cm; P = 0.003) and malignant lesions also tended to be smaller (3.87 cm versus 3.14 cm; P = 0.006). Minimal improvements in sensitivity (94% versus 91%), specificity (99% versus 95%), diagnostic accuracy (95% versus 92%), negative predictive value (NPV) (80% versus 74%), and positive predictive value (PPV) (100% versus 99%) were noted during 2003-2005 when compared with 1996-1998 in all lesions. Larger improvements in sensitivity (94% versus 73%), diagnostic accuracy (95% versus 79%), and NPV (79% versus 50%) were identified in very small lesions (<1 cm) in the later patient cohort in comparison to the earlier patient cohort, as well as a significant decrease in total procedure complications. CT-guided transthoracic FNA/CB continues to be a very effective tool in our practice assessing lung lesions and performance has improved considerably at our institution for very small lesions.     

Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma

The prognostic and predictive value of Her2/neu and the hormone receptors in patient with primary or metastatic breast cancer is essential for a favorable outcome of treatment. We have been experiencing increasing requests to test cytologic specimens for these markers in patients with metastatic breast carcinoma. A recent study threw some doubts on the validity of such testing using cell blocks. In this study we compared our immunohistochemical Her2/neu, ER and PR testing performed on 42 formalin-fixed, paraffin-embedded cell blocks from 27 fine needle aspirations (FNA) and 15 serous effusions of 42 patients with metastatic (n = 38) and primary (n = 4) breast carcinoma to the test results obtained on tissue sections. In seven cases the Her2/neu immunohistochemistry (IHC) results on cell blocks were also compared with Her2/neu fluorescence in situ hybridization (FISH) on tissue or cell block. The study revealed 100% correlation for positive and negative Her2/neu results. For ER testing the results showed 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 85.7% negative predictive value (NPV). For PR testing the results showed 80% sensitivity, 100% specificity, 100% PPV, and 88.8% NPV respectively. In conclusion, IHC for Her2/neu, ER and PR performed on formalin-fixed, paraffin-embedded cell blocks prepared from fresh FNA and serous fluid is reliable in predicting the expression of these markers when correlated with IHC and FISH performed on the corresponding tumor tissue.     

Utility of endoscopic ultrasound‐guided fine‐needle aspiration in the diagnosis and staging of colorectal carcinoma

The objective of this study is to assess the utility of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) in the diagnosis and staging of colorectal cancer. The study includes patients who underwent EUS‐FNA at our institution for staging of colorectal carcinoma or for evaluation peri‐rectal masses or distal metastases from August 2000 to November 2010. We assessed the frequency with which EUS‐FNA procedure confirms the diagnosis of malignancy and the percent of cases in which it modifies staging of colorectal carcinoma. Using histology as a reference standard, we also assessed the diagnostic performance. We identified 79 cases of EUS‐FNA from 77 patients, mean (SD) age of 60 (12.5), 44 males. Twenty‐seven (34%) aspirates were from patients with primary rectal/peri‐rectal masses, 15 (19%) were from patients with suspected regional lymph node metastasis, and 37 (47%) were cases of suspected of distal metastasis. All lesions were clinically suspicious for primary or metastatic colorectal carcinoma. On cytologic examinations, 43 (54%) cases were confirmed as malignant, 6 (8%) were benign neoplasms, 4 (5%) were suspicious for malignant neoplasm, 2 (3%) showed atypical cells, and the rest 24 (30%) were negative for neoplasms. Fourteen of 27 (52%) of the local rectal masses were confirmed as colorectal carcinoma. Eleven of 15 (73%) regional lymph nodes were positive for metastasis—all, but two of these metastases, were of colorectal origin. Twenty of 37(54%) distal lesions were metastatic neoplasms and 15 of those were colorectal in origin. Diagnosis of primary colorectal carcinoma was confirmed in 52% of the clinically suspicious primary lesions and in 42% regional or distal metastatic lesions. Using histology as a reference standard in 27 of 79 (29%) cases, we calculated an overall sensitivity, specificity, and positive and negative predictive values (C.I) of EUS‐FNA of 89% (74–100%), 79% (50–100%) 89% (74–100%), and 79% (51–100%). EUS‐FNA is useful for assessing primary and metastatic colorectal lesion. This technique improves staging of suspected nodal or distant metastases. Diagn. Cytopathol. 2013;41:1031–1037. © 2011 Wiley Periodicals, Inc.     

Critical analysis and diagnostic usefulness of limited immunophenotyping of B-cell non-Hodgkin lymphomas by flow cytometry

We report the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of various immunophenotypes characteristic of each class of B-cell non-Hodgkin lymphoma (NHL) based on analysis of 352 morphologically well-characterized B-cell NHLs and 175 benign lymph nodes (LNs) using 2-color flow cytometry. All B-cell NHLs that exhibited a characteristic immunophenotype (except diffuse large B-cell lymphoma) had a high NPV. The immunophenotypes of small lymphocytic lymphoma and mantle cell lymphoma showed high specificity, but only small lymphocytic lymphoma also showed a high PPV. One third of follicular lymphomas coexpressed CD23 and CD10. Diffuse large B-cell NHL showed no consistent immunophenotype. About 90% of all benign LNs expressed no substantial amounts of CD5, CD10, or CD23. Most benign LNs also failed to express substantial amounts of immunoglobulin heavy chains. In contrast, about 90% of NHLs showed expression of 1 or 2 heavy chains. The expression pattern of immunoglobulin light chains was not found helpful in favoring one lymphoma type over another. The usefulness of each immunophenotype for each lymphoma group is of particular diagnostic importance in limited specimens, such as fine-needle aspiration biopsies, small core biopsies, body effusions, extranodal sites, and nodal tissues with various artifacts.     

Endoscopic ultrasound–guided fine needle aspiration as a diagnostic and staging tool for rectal and perirectal lesions—an institutional experience

The role of endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) in evaluating lesions adjacent to the upper gastrointestinal tract wall is well established. However, this tool is underused in evaluating rectal and perirectal lesions, possibly due to insufficient experience and underrecognized value of this procedure. In this study, we report our institutional experience with EUS-FNA as a diagnostic and staging tool for rectal and perirectal lesions. A retrospective chart review was performed and a cohort of 38 patients who underwent rectal EUS-FNA (41 specimens) at our institution between January 2002 and July 2012 was retrieved. The cytology diagnoses were compared with the concurrent or follow-up histologic and clinical diagnoses. Among the total 41 cases, rectal EUS-FNA was performed as a diagnostic procedure in 22 (54%) and a staging procedure in 19 (46%) cases. On cytology examination, 18 cases (44%) were diagnosed as malignant; 1 (2%), as atypical/suspicious for malignancy; 3 (7%), as benign neoplastic; 13 (32%), as nonneoplastic; and 6 (15%), as nondiagnostic cases. Concurrent or follow-up histologic diagnoses were available in 20 cases (48%), 19 of them had concordant cytological/histologic findings (10 benign, 9 malignant). One perirectal lymph node with negative cytology diagnosis was found to be positive on histologic examination, probably due to sampling error on cytology. The sensitivity and specificity of EUS-FNA for detecting malignant rectal/perirectal lesions in this study were 91% and 100%, respectively. Endoscopic ultrasound–guided fine needle aspiration is a useful diagnostic tool for rectal/perirectal lesions; it confirms or excludes malignancy for lesions with high or low clinical suspicions. It serves as a reliable staging method to identify patients for proper clinical management.     

Comparison of the Denka-Seiken INFLU A.B-Quick and BD Directigen Flu A+B kits with direct fluorescent-antibody staining and shell vial culture methods for rapid detection of influenza viruses

The INFLU A.B-Quick and Directigen Flu A+B enzyme immunoassays were compared with direct immunofluorescence and cell culture for detection of influenza A and B viruses in a total of 255 patient specimens. Both assays identified 23 of 42 influenza A viruses (sensitivity, 54.8%; specificity, 100%; positive predictive value [PPV], 100%; negative predictive value [NPV], 91.8%). The INFLU A.B-Quick assay identified 10 of 16 influenza B viruses (sensitivity, 62.5%; specificity, 99.6%; PPV, 90.9%; NPV, 97.5%), and the Directigen Flu A+B assay detected 9 of 16 influenza B viruses (sensitivity, 56.3%; specificity, 99.6%; PPV, 90%; NPV, 97.1%).     

Diagnostic usefulness and challenges in the diagnosis of mesothelioma by endoscopic ultrasound guided fine needle aspiration

Malignant mesothelioma is a rare neoplasm. It has been noted in the literature that fine needle aspiration (FNA) is a useful tool for the diagnosis of mesothelioma. However, the differential diagnosis may require use of a battery of immunohistochemical stains. Clinico-radiologic correlation is also crucial. Real time endoscopic ultrasound (EUS) combined with FNA has been shown to be a very sensitive technique to obtain samples from different organ sites, including mediastinal lesions. The use of EUS-FNA for the diagnosis of mesothelioma, reinforces the role of a cytopathologist as a cohesive team player along with a radiologist and a clinician during on-site assessment for the proper triage of additional specimens for ancillary studies leading to a better patient management.     

Detection of M2 antimitochondrial antibodies by dot blot assay is more specific than by enzyme linked immunosorbent assay

AIMS: The objective of our study was, in one hand, to determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ELISA and dot blot assay to investigate IgG M2 antimitochondrial antibodies (M2 AMA) and, on the other hand, to compare these results with those of indirect immunofluorescence technique (IIF). METHODS: Sera from patients suffering from primary biliary cirrhosis (PBC) (n=55), systemic lupus erythematosus (n=21), celiac disease (n=30) and blood donors (n=75) were analyzed. M2 AMA were detected by ELISA and dot blot using pyruvate dehydrogenase purified from porcine heart and by IIF on cryostat sections of rat liver-kidney-stomach. RESULTS: IIF was more sensitive (98%) than ELISA (93%) and dot blot (91%). The specificity of AMA for PBC using IIF, ELISA and dot blot reached 100%, 92% and 100%, respectively. The PPV of IIF, ELISA and dot blot was 100%, 93% and 100%, respectively. The NPV was 98% for IIF, 92% for ELISA and 91% for dot blot. CONCLUSION: Dot blot, using purified pyruvate dehydrogenase, had a higher specificity than ELISA and may be useful in confirming the specificity of AMA in cases of doubt with IIF.     

The usefulness of S100P,mesothelin, fascin,prostate stem cell antigen,and 14‐3‐3 sigma in diagnosing pancreatic adenocarcinoma in cytological specimens obtained by endoscopic ultrasound guided fine‐needle aspiration

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) of the pancreas is an efficient and minimally invasive procedure for the diagnosis and staging of pancreatic adenocarcinoma. Because of some limitations of EUS‐FNA in diagnosis of well‐differentiated or early stage cancers, the purpose of this study is to assess the added benefit of immunohistochemistry. We studied five proteins overexpressed in pancreatic adenocarcinoma, namely, prostate stem cell antigen, fascin, 14‐3‐3 sigma, mesothelin and S100P utilizing immunohistochemistry on paraffin sections from cellblocks obtained by EUS‐FNA. Sixty‐two cases of EUS‐FNA of the pancreas that had follow‐up histological and/or clinical diagnosis and sufficient material in cell blocks were included. Using histological diagnosis and/or clinical outcome as the reference standard, EUS‐FNA shows the highest sensitivity (95%) and specificity (91%) and is superior to any marker in this study. Among five antibodies, S100P reveals the best diagnostic characters showing 90% of sensitivity and 67% of specificity. Fascin shows high specificity (92%) but low sensitivity (38%). Mesothelin has a moderate sensitivity (74%) and low specificity (33%), PSCA and 14‐3‐3 show high sensitivity but zero specificity. S100P and mesothelin were useful in nine indeterminate cases. S100P correctly predicted six of seven cancers and one of one without cancer and mesothelin correctly diagnosed five of seven cancers and one of two noncancers in this group. EUS‐FNA cytomorphology is superior to any of the immunohistochemical markers used in this study. Use of S100P and mesothelin in cytologically borderline cases can increase the diagnostic accuracy in this group. Diagn. Cytopathol. 2014;42:193–199. © 2011 Wiley Periodicals, Inc.     

Prediction of recurrence and nucleolar features in node-negative breast carcinoma, ductal type, grade II

One-third of patients with node-negative breast carcinoma develop a local recurrence that will decisively influence their outcome. We conducted this quantitative ultrastructural study to determine the value of nucleolar features in predicting recurrence of node-negative breast carcinomas. Forty-three node-negative infiltrating duct carcinomas were examined by means of electron microscopy. The number of cells with three or more nucleoli (N3), percentage of nucleoli contacting the nuclear membrane (NC), patient age, tumor size, grading, treatment, follow-up time, development of recurrence, and status were recorded. There were no differences in patient age, tumor grade, or modality of surgical treatment. Significant differences were found among patients with and without recurrence for N3 ( P=0.02), NC ( P=0.01), and tumor size ( P=0.01). For N3, the positive predictive value (PPV) was 64.3, and the negative predictive value (NPV) was 72.4 (sensitivity=52.9%; specificity=80.8%; P=0.04). For NC, the PPV was 62.5, and the NPV was 74.1 (sensitivity=58.8%; specificity=76.9%; P=0.02). For tumor size, the PPV was 66.7, and the NPV was 64.9 (sensitivity=23.5%; specificity=92.3%; P not significant). Using logistic regression analysis, independent predictive value was shown for N3, NC, and tumor size. The number of nucleoli per cell and the number of cells with nucleoli in contact with the nuclear membrane have independent predictive value for the development of recurrence in lymph node-negative infiltrating duct carcinoma of the breast. Although electron microscopy is a highly accurate method, improving the precision of light microscopic techniques would allow more universal assessment of these nucleolar features.