Diagnosis of deep‐seated lymphomas by endoscopic ultrasound‐guided fine needle aspiration combined with flow cytometry

A. Stacchini, P. Carucci, D. Pacchioni, G. Accinelli, A. Demurtas, S. Aliberti, M. Bosco, M. Bruno, A. Balbo Mussetto, M. Rizzetto, G. Bussolati and C. De Angelis
Diagnosis of deep‐seated lymphomas by endoscopic ultrasound‐guided fine needle aspiration combined with flow cytometry Objective: Although endoscopic ultrasound combined with fine needle aspiration (EUS‐FNA) is rapidly becoming the preferred diagnostic approach for the sampling and diagnosis of gastrointestinal and mediastinal malignancies, there are limited data as to its use in the diagnosis of lymphoproliferative disorders. Therefore, we carried out a retrospective evaluation of the performance of EUS‐guided FNA combined with flow cytometry (FC) as a tool to improve overall sensitivity and specificity in the diagnosis of lymphoma. Methods: Of 1560 patients having EUS‐guided FNA during the period of the study, a total of 56 patients were evaluated by cytology with FC after EUS‐FNA. There was adequate material to perform FC analysis for all but one case. Results: EUS‐FNA‐FC gave a diagnosis of lymphoma in 11 cases and of reactive lymphadenopathy in 20. A specific histological type was defined by FC alone in eight cases. The remaining cases were diagnosed later by cytology and cell block sections: 13 carcinomas, nine granulomatous lymphadenopathies and one mediastinal extramedullary haematopoiesis. One case was considered only suspicious for lymphoma on cytology and FC but was not confirmed on molecular analysis and one had insufficient material for FC. Conclusions: Our results show that a combination of EUS‐FNA‐FC is a feasible and highly accurate method, which may be used for the diagnosis and subtyping of deep‐seated lymphoma, providing a significant improvement to cytomorphology alone both for diagnosis and treatment planning, as long as immunocytochemistry is available for non‐lymphoma cases.     

Outcomes of endoscopic ultrasound‐guided pancreatic FNAC diagnosis for solid and cystic lesions at Manchester Royal Infirmary based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme

Objective

To compare endoscopic ultrasound (EUS)‐FNAC diagnosis of pancreatic lesions with patient outcome based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme diagnostic categories: Panc 1 (non‐diagnostic); Panc 2 (negative for malignancy/neoplasia); Panc 3 (atypical); Panc 4B (neoplastic, benign); Panc 4O (neoplastic, other); Panc 5 (suspicious of malignancy); and Panc 6 (positive/malignant).

Methods

All EUS‐FNA pancreas specimens taken at Manchester Royal Infirmary in 2015 were prospectively classified according to the above scheme at the time of cytology reporting and data recorded prospectively. Subsequently, outcomes based on clinical follow‐up or histopathology diagnosis were compared with the cytology diagnosis.

Results

120 EUS‐FNA pancreas specimens from 111 patients were received, of which 112 (93.3%) specimens had follow‐up data. There were 79 and 41 EUS‐FNA pancreas specimens from solid and cystic lesions, respectively. Based on the cytology diagnosis the specimens were classified as Panc 1 (7.5%), Panc 2 (33.3%), Panc 3 (2.5%), Panc 4B (2.5%), Panc 4O (15.0%), Panc 5 (3.3%) and Panc 6 (35.9%). The performance indicators for diagnosis of malignancy or neoplasia with malignant potential, included sensitivity (95.4%), specificity (100%), positive predictive value (100%), negative predictive value (92.3%), false positive rate (0%) and false negative rate (4.6%).

Conclusions

The Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme is a logical system that can easily be introduced in a diagnostic cytopathology service. This classification scheme acts as an aid to diagnostic reporting, clear communication of significant results including risk of neoplasia/malignancy to clinicians, clinical audit and comparison of results with other centres.     

Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours

Y. Kopelman, S. Marmor, I. Ashkenazi and Z. Fireman
Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours Objective: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is performed in order to achieve a definite tissue diagnosis of pancreatic lesions. This in turn is a guide to the appropriate treatment for the patient. Tissue samples collected by the same needle for cytological preparations and cell block histological sections (often referred to as FNA‐cytology and FNA–biopsy, respectively) are handled differently. The specific contribution of each of these tests was evaluated. Methods: One hundred and two consecutive patients underwent EUS‐FNA while being investigated for pancreatic solid lesions. Diagnosis was made by cytology, cell block sections or both. The diagnosis was confirmed by clinical outcome. Results: Male/female ratio was 61/41. Mean age was 65 ± 12 years (range, 22–94). Mean lesion size was 3.1 ± 1.8 cm (range, 0.6–10 cm); 68% were >2 cm and 75% were located in the pancreatic head. The average number of needle passes was two (range, 1–4 passes). Final tissue diagnosis was malignant in 66 (65%) patients. Sensitivity, specificity and accuracy were 73%, 94% and 81%, respectively, for cytology alone, and 63%, 100% and 78%, for cell blocks alone. Eighty‐two patients (80%) had cytology and cell blocks, which matched in 64 (78%) patients. EUS‐FNA results that relied on both techniques had 84% sensitivity, 94% specificity and 88% accuracy. Cytology revealed 13 malignancies not diagnosed on cell blocks, while cell blocks revealed five malignancies not diagnosed by cytology. Malignant lesions were more common in men; they were larger in size and located in the pancreatic head. Conclusion: EUS‐FNA cytology was more sensitive than cell blocks but less specific for the diagnosis of solid pancreatic lesions. The two methods are complementary and implementing both improves the diagnostic value of EUS‐FNA.     

Lymphangioma of the pancreas: a multimodal approach to pre‐operative diagnosis

Background: Lymphangioma of the pancreas is an extremely rare benign tumour of lymphatic origin, with only four cases diagnosed by EUS‐FNA reported to date. Methods and materials: Five cases of either cytologically or histologically diagnosed pancreatic lymphangioma with pre‐operative cytological analysis by EUS‐FNAC were reviewed. Results: All patients were female, with a mean age of 56.4 years. By imaging, the cystic lesions ranged in size from 2 to 7 cm (mean 4.5 cm) and were mainly located in the head of the pancreas. All cysts had thin walls and no cyst demonstrated a mural nodule. Diagnosis based on imaging features was benign in all cases due to the absence of high‐risk features. Four samples were sent for biochemical analysis, which showed low CEA levels (range, <0.5–19.4 ng/ml; mean, 5.45 ng/ml) and CA 19.9 and CA 72.4 levels within normal range. All cyst fluids showed numerous small lymphocytes with no atypia; no epithelial cells were present, including no gastrointestinal contamination. Flow cytometry in two cases showed T lymphocytes with a mature phenotype. Surgical resection in two patients confirmed the cytological diagnosis. Benign clinical follow‐up was available in three patients at 2, 3 and 3.5 years. Conclusion: A multimodal approach to cytological diagnosis (combining clinical, radiological and cyst fluid gross, biochemical and cytological characteristics) can lead to the diagnosis of this cystic neoplasm and distinguish it from other more common cysts in the pancreas, potentially avoiding the need for unnecessary surgery.     

Endoscopic ultrasound‐guided fine needle aspiration of the pancreas: cytomorphological evaluation with emphasis on adequacy assessment,diagnostic criteria and contamination from the gastrointestinal tract1

Objective: Endoscopic ultrasound (EUS)‐guided fine needle aspiration (FNA) has been proved to be safe, efficient and reliable in the diagnosis of pancreatic lesions. This study evaluated specimen adequacy, diagnostic criteria of various pancreatic neoplasms and contamination from the gastrointestinal (GI) tract. Methods: EUS‐guided FNA of the pancreas and subsequent surgical resections performed at the University of California Irvine Medical Center during February 1996–October 2000 were retrospectively selected. Modified Papanicolaou staining method was used for immediate evaluation and cell block prepared. Results: A total of 267 cases were available for review, including 147 (55.1%) positive/suspicious, 10 (3.7%) atypical, 96 (36.0%) negative and 14 (5.2%) unsatisfactory cases. Eighty‐six (58.5%) positive/suspicious cases had histological confirmation and 12 (8.3%) had lymph node or distant metastases by cytology. Three atypical, two negative, and two unsatisfactory cases proved to have adenocarcinoma. Contamination from duodenum, stomach or pancreas was found in 77 positive/suspicious, three atypical and 90 negative cases. The sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were 94.6%, 100%, 95.6%, 100%, 82% respectively. Conclusions: EUS FNA is efficient and accurate in the diagnosis of pancreatic neoplasms in adequate samples. Contamination from the GI tract should be well recognized to avoid misinterpretation.     

Role and accuracy of rapid on‐site evaluation of CT‐guided fine needle aspiration cytology of lung nodules

A. Fassina, M. Corradin, D. Zardo, R. Cappellesso, F. Corbetti and M. Fassan
Role and accuracy of rapid on‐site evaluation of CT‐guided fine needle aspiration cytology of lung nodules Objective: To prospectively investigate the role of trans‐thoracic fine needle aspiration cytology (FNA) and the value of rapid on‐site evaluation (ROSE) in the clinical management of patients with pulmonary nodules/masses. Computed tomography (CT)‐guided FNA is commonly employed for the diagnosis of lung lesions although its position in the diagnostic work‐up is still a matter of debate. Methods: We reviewed 311 patients (211 males and 100 females, mean age 69.5 years) admitted to the University of Padova from 2004 to 2008, correlating the results of cytology with the available histological findings obtained from biopsies, surgery or autopsy. Results: Smears were adequate in 305 cases (98%) and inadequate in six (2%); a diagnosis of malignancy was achieved in 263 cases (86.2%); 39 cases (12.8%) were classified as non‐malignant; and three cases (1%) were classified as suspect for malignancy. When correlated with histology, FNA with ROSE discriminated malignant versus non‐malignant lesions (Cohen’s kappa 0.78), with three false negatives (sensitivity 96.3%, specificity 100%). Moreover, a satisfactory overall agreement of 71.4% was achieved in differentiating the cancer histological types. Pneumothorax occurred in 13 cases, haemoptysis in four, and chest pain in three. A single aspiration was sufficient in 79.6% of patients; two aspirations were needed in 17.4% and three in 3%. The low complication rate was related to the limited number of aspirations needed due to ROSE. Conclusions: FNA with ROSE is a safe and useful tool in the diagnostic work‐up of lung cancer patients, with no contraindications to its use as the first diagnostic procedure for all patients with peripheral lung lesions. FNA with ROSE should be reconsidered in the guidelines for diagnosing and managing lung cancer.     

Optimizing specimen collection and laboratory procedures reduces the non‐diagnostic rate for endoscopic ultrasound‐guided fine‐needle aspiration of solid lesions of the pancreas

Objectives: Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is a routine technique to assess solid pancreatic lesions. The aim of this study was to analyse the effect of optimizing laboratory procedures for specimen preparation on the rate and accuracy of the procedure. Methods: All EUS‐FNAs of solid pancreatic lesions performed during the year 2000 (Period 1) and from May 2003 to May 2004 (Period 2) were analysed. During Period 1, one experienced gastroenterologist performed all EUS‐FNAs, making direct smears and retrieving small fragments if present on the smear for histology. In Period 2, two endoscopists performed the EUS‐FNAs and all the material was emptied into a vial containing a fixative. Slide preparation was carried out in the pathology laboratory: one slide was processed using cytocentrifugation and cell blocks were made from left‐over material. Neither period utilized rapid on‐site evaluation. Results: During the two periods, 67 and 102 FNAs were analysed and showed significantly different (P < 0.001) non‐diagnostic rates of 22.8% and 4.2%, respectively. The increased diagnostic yield can be explained by the modified laboratory procedures and to a lesser extent by the increased experience of the gastroenterologists. Sensitivity, specificity, PPV, NPV and accuracy in the second time period were, respectively, 90.6%, 100%, 100%, 81.8% and 93.4%, not significantly different from the first time period. Conclusion: This study shows that accurate EUS‐FNA results may be obtained with a low non‐diagnostic rate comparable to those reported for rapid on‐site evaluation by optimizing laboratory specimen processing in a setting of solid pancreatic lesions.     

Fatal primary diffuse large B‐cell lymphoma of the maxillary sinus initially treated as an infectious disease in an elderly patient: A clinicopathologic report

Objective

To report a case of primary diffuse large B‐cell lymphoma (DLBCL) of the maxillary sinus in an 82‐year‐old Caucasian woman.

Background

Diffuse large B‐cell lymphoma of the maxillary sinus has non‐specific signs and symptoms that may be confused with benign inflammatory conditions and upper respiratory infections.

Methods

An incisional biopsy was performed. CD20⁺/CD3^–/Ki‐67: 95% cells were observed.

Conclusion

A good medical history, clinical and imaging evaluations and immunohistochemical reactions are crucial to establish a correct and early diagnosis of DLBCL.     

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA): experience of an academic centre in the USA

S. Zhang, D. V. S. DeFrias, R. Alasadi and R. Nayar
Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA): experience of an academic centre in the USA Objectives: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) has become widely accepted as an effective modality for obtaining tissue for primary diagnosis and staging. We have been using EUS‐FNA since July 2001 and herein we summarize our experience over a 5‐year period. Methods: A computer‐based search for in‐house EUS‐FNA was performed in the pathology database from July 2001 to October 2006. To calculate the sensitivity, specificity and accuracy of EUS‐FNA, the cytology diagnosis was compared with the surgical follow‐up. Results: A total of 951 EUS‐FNAs were performed during the study period and included 279 pancreatic solid lesions, 186 pancreatic cyst lesions, 249 lymph node aspirations, 111 gastrointestinal (GI) tract submucosal lesions, and 126 miscellaneous lesions. EUS‐FNA had a very high sensitivity and accuracy for solid pancreatic lesions (94.7 and 97.7%, respectively), low sensitivity and accuracy but high specificity (47, 64.8 and 95%, respectively) for cystic lesions. Cyst fluid carcinoembryonic (CEA) levels were significantly higher in mucinous neoplasms than non‐neoplastic cysts. EUS‐FNA also had very high sensitivity and specificity for detecting metastatic carcinoma in lymph nodes (95 and 100%, respectively). GI submucosal spindle cell tumours were further classified with immunohistochemical stains performed either on a cell block or a core biopsy obtained via EUS guidance. Conclusions: EUS‐FNA has a very high sensitivity and accuracy for pancreatic solid lesions, but the sensitivity for cystic lesions is generally low. Cyst fluid chemical analysis for CEA is helpful, but the overlap between mucinous neoplasm and non‐neoplastic cysts is significant. Recognizing GI contamination is important and immunohistochemical stains are useful for GI submucosal spindle cell lesions.     

Pre‐operative features of non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features: An analysis of their cytological,Gene Expression Classifier and sonographic findings

Objective

To investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features (NIFTP), as well as any coexisting pathology.

Methods

We performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1^st April 2016 and 1^st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in‐house vs outside hospital) and any additional pathology identified in the resection specimen.

Results

The case cohort included 87 nodules diagnosed as NIFTP (size range: 1‐7 cm, mean: 2.5 cm) from 82 patients (age range: 22‐82, mean age: 50.4, M:F—1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non‐calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases.

Conclusions

The majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.

     

An algorithmic approach to diagnose haematolymphoid neoplasms in effusion by combining morphology,immunohistochemistry and molecular cytogenetics

Objective

There are limited studies of cytology diagnosis of haematopoietic and lymphoid tumours in serosal effusion except for occasional case reports. We would like to demonstrate an algorithmic approach for accurate diagnosis, especially in patients without previous history.

Methods

We reviewed 36 cases of lymphoma diagnosed in serosal effusion following an algorithmic approach. Suspected tumour cells were classified into small, intermediate and large sizes and two characteristic forms of plasmacytoid and Reed Sternberg‐like on smears (step 1), followed by utilising panels of immunohistochemical markers and Epstein‐Barr encoding region in situ hybridisation on cell blocks (step 2). A panel of CD3, CD20 and Ki‐67 formed the basic workup, followed by pertinent batteries of immunostaining. Molecular tests were applied in 22 selected cases by fluorescence in situ hybridisation (step 3).

Results

There were 15 diffuse large B‐cell lymphomas; 12 plasma cell myelomas; two mantle cell lymphomas; one anaplastic large cell lymphoma ALK +; one small lymphocytic lymphoma; one plasmablastic lymphoma; one peripheral T‐cell lymphoma, not otherwise specified, one extranodal NK/T‐cell lymphoma, nasal type and two T‐cell lymphoblastic lymphomas. 14 cases with previous history had complete concordance in immunophenotype between cytology and histology. Another 14 cases were primarily diagnosed in patients with initial symptom of effusion based on immunophenotyping and cytogenetic test in selected cases. Eight cases were diagnosed based on morphology alone.

Conclusion

An algorithmic approach based on morphology and immunohistochemistry is the key to making an accurate diagnosis of haematopoietic and lymphoid tumours in effusion. A molecular test is also important for confirmation and prognostic prediction. We reviewed 36 haematolymphoid neoplasms diagnosed in effusion including 14 cases primarily diagnosed in patients without previous history following an algorithmic approach by combining morphology, immunohistochemistry and molecular cytogenetics.     

Anti‐Helicobacter pylori therapy in localized gastric mucosa‐associated lymphoid tissue lymphoma: A prospective,nationwide, multicenter study in Japan

Background

Helicobacter pylori eradication therapy was approved in Japan for the first‐line, standard treatment of H. pylori‐positive gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small‐scale single‐center studies have been reported, a prospective, large‐scale, nationwide, multicenter study has not been reported from Japan.

Materials and Methods

We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole‐based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice‐based clinical trial. A total of 108 H. pylori‐positive patients with stage I/II₁ gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS).

Results

CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0‐44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4‐53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow‐up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma.

Conclusions

Rabeprazole‐based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice‐based, multicenter study.     

The impact of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature terminology in the routine diagnosis of thyroid tumours

Background

Due to the recent proposal of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice.

Methods and results

A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically‐treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III‐IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC‐like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1).

Conclusions

In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC‐like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low‐risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations.

     

The role of fine needle aspiration cytology in the diagnosis of lymphoma

The accuracy of fine needle aspiration (FNA) cytology for the diagnosis of lymphoma and other hematolymphoid malignancies was investigated by a review of 158 FNA specimens from 143 patients. Patients included in the study had either a diagnosis of a hematolymphoid malignancy by FNA cytology or a biopsy diagnosis of lymphoma that was preceded by FNA cytology. Biopsy specimens were obtained from 85% of the patients. Of the 158 needle aspirates, 118 (75%) were diagnosed as lymphoma, 13 (8%) as suspicious of lymphoma, 8 (5%) as myelomas, 3 (2%) as leukemias, 12 (8%) as positive for malignancy and 4 (2%) as negative for malignancy. Two of the 118 needle aspirates diagnosed as lymphoma were false positives while 3 of 13 diagnosed as suspicious for lymphoma were found to be benign. Overall, there were four false negatives. Morphologic subclassification of the lymphomas, originally attempted for 60 needle aspirates, was identical to the histologic subclassification in 51 cases (85%). FNA cytology provided the initial diagnosis of a hematolymphoid malignancy in 51% of the cases and allowed the documentation of recurrent disease in 49%. The results demonstrate the usefulness of FNA cytology for the diagnosis and management of patients with lymphoma.     

Contrast-Enhanced Harmonic Endoscopic Ultrasound-Guided Fine-Needle Aspiration in the Diagnosis of Solid Pancreatic Lesions: A Retrospective Study

Background

The negative predictive value of endoscopic ultrasonography-guided fine needle aspiration for the diagnosis of solid pancreatic lesions remains low, and the biopsy specimens are sometimes inadequate for appropriate pathological diagnosis.

Aims

To evaluate the usefulness of a novel method of contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for the differential diagnosis and adequate sampling of solid pancreatic lesions.

Methods

Patients with a diagnosis of solid pancreatic lesions who underwent fine-needle aspiration guided by contrast-enhanced harmonic endoscopic ultrasonography or by endoscopic ultrasonography from October 2010 to July 2013 were retrospectively identified and classified into the CH-EUS or EUS group, respectively. Surgical pathology and/or follow-up results were defined as the final diagnosis. Operating characteristics and adequacy of biopsy specimens by fine-needle aspiration were compared between the two groups.

Results

Operating characteristics for contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration in solid pancreatic lesions were as follows: area under the curve = 0.908, sensitivity = 81.6%, specificity = 100%, positive predictive value = 100%, negative predictive value = 74.1%, and accuracy = 87.9%. The percentage of adequate biopsy specimens in the CH-EUS group (96.6%) was greater than that in the EUS group (86.7%).

Conclusion

Simultaneous contrast-enhanced harmonic endoscopic ultrasonography during fine-needle aspiration is useful for improving the diagnostic yield and adequate sampling of solid pancreatic lesions.     

Fine needle aspiration of the liver and pancreas with ultrasound guidance

The experience of the Institut Gustave-Roussy in the diagnosis of hepatic and pancreatic lesions by fine needle aspiration (FNA) is reported. Totals of 116 consecutive percutaneous ultrasound-guided FNAs of the liver and 27 of the pancreas were performed without complication in patients with ultrasonically suspected neoplastic lesions. In 12 cases, the material was not suitable for diagnosis. In the liver, 97 cases were correctly diagnosed and confirmed by follow-up. Immunohistologic studies were helpful in distinguishing primary liver tumors from other malignancies. One false-positive result was reported. In the pancreas, malignancy was detected in 17 cases. Cytology alone provided the correct tumor diagnosis in 15 cases: 10 primary carcinomas, 2 endocrine tumors and 3 metastases. The sensitivities of FNA in this study were 87.6% for the liver and 85% for the pancreas, similar to those reported in other series.     

Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas

Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series.     

Cumulative sum procedure in evaluation of EUS-guided FNA cytology: the learning curve and diagnostic performance beyond sensitivity and specificity

Background: Using cumulative sum (CUSUM) chart, we address two questions: (i) Over time, how will an EUS‐FNA (endoscopic ultrasound guided fine needle aspiration) service maintain an acceptable non‐diagnostic rate defined as technical failures, unsatisfactory specimens and atypical and suspicious diagnoses? (ii) Over time, how will EUS‐FNA maintain acceptable diagnostic errors (false‐positives plus false‐negative diagnosis)? Methods: The study included all consecutive patients who underwent EUS‐FNA at our institution from July 2000 to October 2003 and were followed up until December 2004. Using a simple spread sheet, we designed CUSUM charts and used them to track trends and assess performance at a preset acceptable rate of 10% and a preset unacceptable rate of 15% for non‐diagnostic rate and diagnostic errors. We assessed all cases collectively and then in groups defined by site, size and cytopathologist. Results: Of 876 patients undergoing EUS‐FNA, 83 (9.5%) had non‐diagnostic results: 43 (51%) of these diagnoses were ‘atypical’, 27(33%) were ‘suspicious for malignancy’, eight (10%) were ‘insufficient material for diagnosis’ and five (6%) were ‘technical failure’. In 585 cases with adequate follow up, there were 26 (6.3%) diagnostic errors: three (0.5%) were false positive and 23 (3.1) were false negative. The overall CUSUM charts for both non‐diagnostic rate and for diagnostic error rate start with a small period of learning then cross to a significantly acceptable level at case numbers 121 and 97 respectively. Our diagnostic performance was better in lymph nodes than in the pancreas and other organs and was not significantly different for lesions ≤25 mm compared with lesion >25 mm in diameter. Performance was better for pathologists with prior experience than for pathologists without experience. Conclusion: In the current climate of proficiency testing, error tracking and competence evaluation, there is a great potential for the use of CUSUM charts to assess procedure failure and error tracking in quality control programs, particularly when a new procedure such as EUS‐FNA is introduced in the laboratory. Additionally, the method can be used to assess trainee competency and to track the proficiency of practicing cytologists.     

Pancreatobiliary cytology in the multidisciplinary setting

This review article discusses the role of endoscopic ultrasound‐guided fine needle aspiration (EUS FNA) cytology in the clinical management of patients with pancreatic tumours in the setting of a multidisciplinary team (MDT). The commonest diagnosis encountered is pancreatic adenocarcinoma, which is seldom diagnosed early enough for surgical resection. Thus, cytology is likely to be the only form of diagnosis in the majority of cases. Nevertheless, about half the lesions discussed at the MDT meeting are lesions other than primary adenocarcinoma and a wide differential diagnosis must be considered in order to identify tumours, including neuroendocrine tumours, that are amenable to surgical resection. Cytology is not always definitive and the diagnosis may be helped by categorizing results according to whether they are malignant, suspicious, atypical/indeterminate, benign or inadequate. Discussion at MDT meetings and correlation with clinical and imaging findings along with review of cytology slides may allow equivocal results to be clarified before treatment is decided. Inadequate cytology results are avoided by rapid on‐site evaluation of slides; although this is cost‐effective in terms of overall patient care, attendance of cytopathologists on‐site may not be feasible. At Imperial College NHS Trust, specially trained biomedical scientists successfully carry out rapid on‐site evaluation.     

Patterns of Lymph Node Pathology; Fine Needle Aspiration Biopsy as an Evaluation Tool for Lymphadenopathy: A Retrospective Descriptive Study Conducted at the Largest Hospital in Africa

Background

Lymphadenopathy is a common clinical presentation of disease in South Africa (SA), particularly in the era of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) co-infection.

Methods

Data from 560 lymph node biopsy reports of specimens from patients older than 12 years at Chris Hani Baragwanath Academic Hospital (CHBAH) between 1 January 2010 and 31 December 2012 was extracted from the National Health Laboratory Service (NHLS), division of Anatomical Pathology. Cytology reports of lymph node fine needle aspirates (FNAs) performed prior to lymph node biopsy in 203 patients were also extracted from the NHLS. Consent was not obtained from participants for their records to be used as patient information was anonymized and de-identified prior to analysis.

Results

The majority of patients were female (55%) and of the African/black racial group (90%). The median age of patients was 40 years (range12–94). The most common indication for biopsy was an uncertain diagnosis (more than two differential diagnoses entertained), followed by a suspicion for lymphoma, carcinoma and TB. Overall, malignancy constituted the largest biopsy pathology group (39%), with 36% of this group being carcinoma and 27% non-Hodgkin lymphoma. 22% of the total sampled nodes displayed necrotizing granulomatous inflammation (including histopathology and cytology demonstrating definite, and suspicious for mycobacterial infection), 8% comprised HIV reactive nodes; in the remainder no specific pathology was identified (nonspecific reactive lymphoid hyperplasia). Kaposi sarcoma (KS) accounted for 2.5% of lymph node pathology in this sample. Concomitant lymph node pathology was diagnosed in four cases of nodal KS (29% of the subset). The co-existing pathologies were TB and Castleman disease. HIV positive patients constituted 49% of this study sample and the majority (64%) of this subset had CD4 counts less than 350 cells/ul. 27% were HIV negative and in the remaining nodes, the HIV status of patients was unknown. The most common lymph node pathologies in HIV positive patients were Mycobacterial infection (31%), HIV reactive nodes (15%), non-Hodgkin lymphoma (15%) and nonspecific reactive lymphoid hyperplasia (15%). Only 8.7% were of Hodgkin lymphoma. In contrast, the most common lymph node pathologies in HIV negative patients were nonspecific reactive lymphoid hyperplasia (45%), carcinoma (25%) and Mycobacterial infection (11%). In this group, non-Hodgkin lymphoma and Hodgkin lymphoma constituted 9% and 8%, respectively. There were more cases of high-grade non-Hodgkin lymphoma in the HIV positive group compared to the HIV negative group. FNA and lymph node biopsy had statistically significant good agreement with regard to Hodgkin lymphoma (K 0.774, SE 0.07, 95% CI 0.606-0.882, p=0.001), non-Hodgkin lymphoma (K 0.640, SE 0.07, 95% CI 0.472-0.807, p=0.001), carcinoma (K 0.723, SE 0.069, 95% CI 0.528-0.918, p=0.001), and mycobacterial infection (K 0.726, SE 0.07, 95% CI 0.618-0.833, p=0.001).

Conclusions

The most common lymph node pathologies in CHBAH are malignancies, nonspecific reactive lymphoid hyperplasia, necrotizing granulomatous inflammation and HIV reactive nodes. The distribution of disease differs in HIV positive patients. Overall, adequate FNA samples of lymph nodes have been found to have good correlation with lymph node biopsy findings in our setting.