Pancreatic fine‐needle aspiration cytology in patients < 35‐years of age: A retrospective review of 174 cases spanning a 17‐year period

Pancreatic lesions in young patients are relatively rare and, to our knowledge, the clinical value of pancreatic fine needle aspiration (FNA) in patients < 35 years of age has not been previously established by any other large retrospective studies. All pancreatic endoscopic ultrasound‐guided FNA (EUS‐FNA) cases performed on patients < 35 years of age were identified for a 17‐year period (1994–2010). All FNAs and all available correlating surgical pathology reports were reviewed. There were a total of 174 cases of pancreatic FNA performed on 109 females and 65 males under the age of 35 (range: 8–34, mean: 27 years). The FNA diagnoses included 37 malignant, 114 negative, nine atypia/suspicious, and 14 cases that were nondiagnostic. Of the 37 malignant FNA cases, the diagnoses included 18 pancreatic neuroendocrine tumors (PanNeT), 11 solid pseudopapillary neoplasms (SPN), five adenocarcinomas and three metastatic neoplasms. Histologic follow‐up was available in 22 of the 37 malignant cases diagnosed by FNA, and the diagnosis was confirmed in 21 cases. One pancreatoblastoma was misclassified as SPN on EUS‐FNA. False negative diagnoses were noted in three cases of low‐grade mucinous cystic neoplasm and one case of PanNeT. The most common type of neoplasms diagnosed by EUS‐FNA in patients < 35‐year old is PanNeT, followed by SPN with both tumors accounting for 75% of all the neoplasms encountered in this age group. The sensitivity and specificity for positive cytology in EUS‐FNA of the pancreas to identify malignancy and mucinous neoplasms were 90% and 100%, respectively. Diagn. Cytopathol. 2014;42:297–301. © 2013 Wiley Periodicals, Inc.     

Pitfalls in endoscopic ultrasound-guided fine-needle aspiration and how to avoid them

Although a broad range of pancreatic, gastrointestinal, thoracic, and abdominal pathology may be sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA), certain difficulties tend to recur because of the frequency of certain sample types and because of the nature of their individual cytomorphologic profiles. With this in mind, we review certain pitfalls that may befall cytopathologists with EUS-guided FNA. We discuss the diagnosis of pancreatic ductal adenocarcinoma and of other pancreatic epithelioid tumors including pancreatic endocrine neoplasms, solid pseudopapillary tumors, and acinar cell carcinomas. We also discuss the diagnosis of pancreatic cystic neoplasia including intraductal papillary mucinous neoplasms and mucinous cystic neoplasms and the diagnosis of gastrointestinal mesenchymal neoplasia with particular attention to gastrointestinal stromal tumors. Finally, we discuss the interpretation of lymph node aspirates.     

Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation

The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples.A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation.The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions.     

Primary pancreatic leiomyosarcoma with metastasis to the liver diagnosed by endoscopic ultrasound‐guided fine needle aspiration and fine needle biopsy

Primary pancreatic leiomyosarcomas are rare tumors of the pancreas that are usually diagnosed after resection or by biopsy. One case in the literature has utilized endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) cytology. We report a second case of a primary pancreatic leiomyosarcoma that yielded diagnostic material on EUS‐FNA cytology. A 72‐year‐old female presented with 3–4 months of abdominal pain. A CT scan showed a large heterogeneous, lobulated pancreatic head and uncinate mass and multiple hypoattenuating liver lesions. An EUS‐FNA was performed on one of the liver lesions with a 25‐gauge needle, yielding an adequate sample with lesional cells. The initial read was a spindle cell neoplasm. A subsequent endoscopic ultrasound‐guided fine needle biopsy with a 22‐gauge needle was performed on the pancreatic head mass to rule out two primaries and to provide tissue for a mitotic index in the case of gastrointestinal tumor. Both the cell block of the EUS‐FNA and the core biopsy were equally cellular and showed interlacing spindle cells that stained positive for SMA and negative for DOG‐1, CD 117, and CD34. In addition, the core biopsy of the pancreas stained positive for Desmin. A diagnosis of a primary pancreatic leiomyosarcoma was made and the patient was started on systemic chemotherapy. Primary pancreatic leiomyosarcomas are rare pancreatic tumors that may yield diagnostic material by EUS‐FNA with a 25‐gauge needle. Diagn. Cytopathol. 2016;44:1070–1073. © 2016 Wiley Periodicals, Inc.     

Cyst fluid analysis for the differential diagnosis of pancreatic cysts

Pancreatic cystic neoplasms comprise a pathologically heterogeneous group with many shared clinical features. We assessed the reliability of cyst fluid analysis for the differential diagnosis of pancreatic cysts. Cyst fluid was obtained by fine-needle aspiration from 78 pancreatic cysts. The lesions studied consisted of 17 mucinous cystic tumors (MCTs), 13 serous cystadenomas (SCAs), 5 solid pseudopapillary tumors (SPTs), 8 intraductal papillary mucinous tumors (IPMTs), 6 ductal adenocarcinomas (ACAs) with cystic degeneration, and 29 pseudocysts (PCs). Epithelial cells were observed in 27 (81%) of 33 successful aspirates of cystic neoplasms. Cytologic diagnosis was possible in 5 (31%) out of 16 MCTs. Mucicarmine staining was positive in five out of nine MCTs, one out of one ACA, and one out of two IPMTs, but in none of the SCAs, SPTs, or PCs. Cyst fluid carcinoembryonic antigen (CEA) levels of more than 467 ng/mL had a 87% sensitivity and a 98% specificity for detecting MCTs, and amylase levels of more than 479 U/L had a 73% sensitivity and a 90% specificity for detecting PCs. In conclusion, cyst fluid analysis for cytology, mucin staining, CEA, and amylase levels are useful in the differential diagnosis of pancreatic cysts.     

EUS‐guided 22‐gauge fine‐needle aspiration versus core biopsy needle in the evaluation of solid pancreatic neoplasms

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is widely used for diagnosis of pancreatic lesions. The Echotip Procore Needle (Wilson‐Cook Medical) is a new 22G fine biopsy needle (FNB) for obtaining core biopsy material at time of EUS. This study aimed to compare the technical and diagnostic performance of conventional FNA and FNB. Thirty‐two patients met the design criteria for this prospective paired cohort study. All lesions sampled were solid (non‐cystic) pancreatic masses by EUS appearance. Patients were randomized to receive FNA or FNB by first attempt. A cytopathologist performed on‐site evaluations. Samples were assessed for accuracy of diagnosis, cellularity, contamination, and sufficiency for ancillary studies. Technical and diagnostic performances were compared. Compared to FNA, there was a statistically significant decreased ability of FNB to achieve a diagnosis (FNA 93.8%, FNB 28.1%, P < 0.001). FNB was diagnostically superior to FNA in 1 of 32 cases. Technical failures were observed in five cases due to resistance to advancement of the FNB needle. Regarding operator perceived ease‐of‐use, FNA outperformed FNB (P < 0.001). Eight cases had insufficient FNB material to survive tissue processing. There was no significant difference in mean specimen cellularity between devices. FNA samples showed an increased amount of contaminant (P = 0.036) but were more sufficient for ancillary studies (P = 0.502). Although deemed comparable to FNA when providing material for cytology, the pledged advantage of FNB acting like a core biopsy needle was not apparent in our series. Additional studies are needed before routine adoption of 22G FNB can be recommended. Diagn. Cytopathol. 2014;42:751–758. © 2014 Wiley Periodicals, Inc.     

Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of intraductal papillary mucinous neoplasm of the pancreas is highly predictive of pancreatic neoplasia

Intraductal papillary mucinous neoplasms (IPMN) have been considered difficult to diagnose by fine-needle aspiration (FNA) cytology. We identified 57 cases diagnosed as IPMN or consistent with IPMN by endoscopic ultrasound (EUS)-guided FNA over a 9-yr period. Histologic follow-up was available for 20 patients (35%). Pancreatic neoplasia was demonstrated in 18 of these cases (90%). The histologic diagnoses were IPMN (16 cases), pancreatic intraductal neoplasia (grade 1b, 1 case), invasive mucin-producing adenocarcinoma (1 case), and chronic pancreatitis with a pseudocyst (2 cases). Sixty-two cases of IPMN without coexisting adenocarcinoma were diagnosed by histology during this time period. Of these, 35 (56%) had a preceding EUS-guided FNA. The diagnosis made by EUS-guided FNA in these 35 cases was negative or nondiagnostic (6 cases), benign cyst (1 case), chronic pancreatitis (2 cases), atypical ductal cells (2 cases), adenocarcinoma or suspicious for adenocarcinoma (3 cases), consistent with mucinous cystic neoplasm (4 cases), and IPMN or consistent with IPMN (16 cases). An EUS FNA diagnosis of probable or definite neoplasia was, therefore, made in 71% of cases of histologically proven IPMN.     

Fine‐needle aspiration of cystic pancreatic mucinous tumor: Oncotic cell as an aiding diagnostic feature in paucicellular specimens

In juxtaposition with imaging studies, endoscopic ultrasound‐guided fine‐needle aspiration has gained popularity in the initial evaluation of pancreatic masses, especially cystic lesions of pancreas. Cystic pancreatic mucinous tumors include mucinous cystic neoplasm and intraductal papillary mucinous tumor, both of which have been known to have a low malignant potential and a high rate of association with invasive adenocarcinoma. As such, preoperative diagnosis is of great significance in guiding patient management. Although fine‐needle aspiration cytological diagnosis of pancreatic tumor in cellular specimens has been well described, as with other cystic lesions, the yield of diagnostic cells from needle aspiration of cystic pancreatic mucinous tumors is typically low. Cytological diagnosis from these paucicellular specimens remains challenging. An additional compounding problem is the high frequency of gastrointestinal mucin and epithelial contamination. The diagnostic morphology and criteria in these paucicellular specimens have not been well addressed in the literature. The cytopathologists' ongoing efforts tend to improve the diagnostic accuracy. In this current study, oncotic cells, characterized by cytoplasmic swelling and karyolysis, were analyzed from 17 cases of cystic pancreatic mucinous tumor, of which the diagnosis was either confirmed by surgical resection or supported by cell block and/or increased CEA. Oncotic cells were found in variable amounts in almost all the cystic pancreatic mucinous tumors in this series. None of the five fine‐needle aspirations intended for aspirations of hypoechoic nonlesional pancreas, which yielded either gastrointestinal tract material only or admixture of gastrointestinal and normal pancreatic components, was found to contain oncotic cells, evidencing the utility of oncotic cell as a surrogate morphologic marker in aiding the diagnosis of cystic pancreatic mucinous tumor as well as its differentiation from gastrointestinal contaminant, particularly in paucicellular specimens. Diagn. Cytopathol. 2009. © 2008 Wiley‐Liss, Inc.     

BCL10 as a useful marker for pancreatic acinar cell carcinoma,especially using endoscopic ultrasound cytology specimens

Acinar cell carcinomas (ACCs) of the pancreas are characterized by the histological and immunohistochemical features of acinar cell differentiation. Recently, BCL10, originally identified as a recurrent t(1;14)(p22;q32) translocation in MALT B‐cell lymphoma, was found to be immunohistochemically positive in some solid tumors, including ACC. To evaluate its diagnostic efficacy, we performed BCL10 immunohistochemistry and evaluated molecular markers correlated to pancreatic tumor lineages (neuroendocrine markers and a mutation analysis of KRAS and GNAS) using samples from 126 pancreatic tumors (17 ACCs, 24 pancreatic ductal adenocarcinomas, 4 adenosquamous carcinomas, 9 intraductal papillary mucinous neoplasms, 10 mucinous cystic neoplasms, 44 neuroendocrine tumors, 9 serous cystic tumors and 10 solid‐pseudopapillary neoplasms). BCL10 was exclusively expressed in normal acini. In pancreatic tumors, 14 of 17 (82%) ACCs and 2 of 4 (50%) adenosquamous carcinomas were positive, while the other subtypes were almost negative. We subsequently examined the diagnostic utility of BCL10 in endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) specimens using 57 pancreatic tumors. BLC10 correctly identified ACCs (9/13) and adenosquamous carcinomas (2/4) but none of the other subtypes (n = 41). Therefore, we suggested that BCL10 expression is a useful marker for acinar cell differentiation, particularly in the diagnosis of EUS‐FNA specimens.     

Review of endoscopic ultrasound-guided fine-needle aspiration cytology

This review, based on the Hennepin County Medical Center experience and review of the literature, vastly covers the up-to-date role of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (FNA) in evaluating tumorous lesions of the gastrointestinal tract and adjacent organs. Emphasis is given to the tumoral and nodal staging of esophageal, pulmonary, and pancreatic cancer. This review also discusses technical, pathological, and gastroenterologic aspects and the role of the pathologist and endosonographer in the evaluation of these lesions, as well as the corresponding FNA cytology and differential diagnosis.     

Ciliated foregut cyst of pancreas: cytologic findings on endoscopic ultrasound-guided fine-needle aspiration

The cytologic findings of a ciliated foregut cyst of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (FNA) are described. Cytologic features of ciliated foregut cysts include the presence of ciliated columnar cells and detached ciliary tufts in a cystic fluid background with amorphous debris and rare macrophages. These cytologic findings are clearly distinct from those of cystic mucinous neoplasms and other pancreatic cysts with which the ciliated foregut cyst may be confused. To the best of our knowledge, this is the first case reporting the cytologic findings of a pancreatic ciliated foregut cyst sampled by endoscopic ultrasound-guided FNA. We believe that the distinctive and characteristic cytologic features can allow a preoperative cytologic diagnosis of this highly unusual pancreatic cystic lesion.     

A correlation study on diagnostic endoscopic ultrasound-guided fine-needle aspiration of lymph nodes with histological and clinical diagnoses, the UCLA Medical Center experience

Endoscopic ultrasound guided (EUS) FNA procedure has two aspects, the endoscopic sampling and the FNA interpretation. The two aspects of the procedure are performed in two different disciplines; gastroenterology (EUS) and pathology (FNA). The aim of this study was to evaluate the concordance, sensitivity, specificity, positive predictive (PPV), and negative predictive values (NPV).Sixty-one EUS-FNA procedures of the lymph nodes were analyzed by correlating the FNA results with histological or clinical diagnoses. The lymph nodes were divided in five groups; mediastinal, gastrohepatic, peripancreatic, portal, and perirectal.The study showed a concordance of 92% in mediastinal, 80% in gastrohepatic, 81% in peripancreatic, 95% in portal, and 100% in perirectal lymph nodes with an overall sensitivity of 84%, specificity of 92%, PPV of 88%, and NPV of 89%. In conclusion, EUS-FNA offers an invaluable approach for diagnostic examination of the internal lymph nodes where percutaneous FNA is either difficult or impossible. impossible.     

Adenoid cystic carcinoma of the breast diagnosed by fine-needle aspiration

Fine-needle aspiration cytology remains a useful tool for preoperative diagnosis of breast lesions. We describe a case of adenoid cystic carcinoma (ACC) of the breast detected by ultrasound-guided fine-needle aspiration (FNA). Subsequent histopathology corroborated the diagnosis. ACC is a rare but distinctive neoplasm of the breast that can be accurately diagnosed by FNA. Its infrequent presentation, favorable prognosis, and relatively conservative management in the breast prompt us to reinforce its features.     

Intrapancreatic schwannoma diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration cytology

Schwannoma is a tumor of neuro‐ectodermal origin, usually occuring in the head and neck and extremities. A retroperitoneal, and particularly intra‐pancreatic presentation is very rare, and poses a clinical and diagnostic challenge. We report a case of a male patient who underwent an Endoscopic Ultrasound‐guided Fine Needle Aspiration (EUS‐FNA) biopsy of a hypoechoic, intra‐pancreatic mass. The onsite cytological evaluation was consistent with a spindle cell neoplasm. Further evaluation, aided by immunohistochemical stains, defined the mass as a Schwannoma. The patient then underwent a pancreaticoduodenectomy and the histopathological diagnosis of the surgical specimen confirmed the cytological diagnosis. To our knowledge, this is the first report of intra‐pancreatic Schwannoma diagnosed preoperatively by EUS‐FNA cytology. Diagn. Cytopathol. 2009. © 2008 Wiley‐Liss, Inc.     

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.     

Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS‐guided FNA

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound‐guided fine needle aspiration biopsy (EUS‐FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS‐FNA during evaluation of pancreatic cystic lesion.     

Clinical evaluation,imaging studies,indications for cytologic study,and preprocedural requirements for duct brushing studies and pancreatic FNA: The papanicolaou society of cytopathology recommendations for pancreatic and biliary cytology

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreaticobiliary cytology including indications for endoscopic ultrasound (EUS) and fine‐needle aspiration (FNA) biopsy, techniques for EUS‐FNA, terminology and nomenclature to be used for pancreaticobiliary disease, ancillary testing, and post‐biopsy management. All documents are based on expertise of the authors, literature review, discussions of the draft document at national and international meetings, and synthesis of online comments of the draft document. This document selectively presents the results of these discussions. This document summarizes recommendations for the clinical and imaging work‐up of pancreatic and biliary tract lesions along with indications for cytologic study of these lesions. Prebrushing and FNA requirements are also discussed. Diagn. Cytopathol. 2014;42:325–332. © 2014 Wiley Periodicals, Inc.     

Indeterminate diagnosis in fine-needle aspiration of the pancreas: reasons and clinical implications

An indeterminate diagnosis made on fine-needle aspiration (FNA) samples of the pancreatic lesions can cause dilemmas in clinical management. We retrospectively analyzed FNA features of such lesions in 65 consecutive pancreatic FNAs from 56 lesions to learn more about the sources of uncertainty and their clinical implications. A definitive diagnosis based on follow-up information was available in 50 lesions. Radiologically, 39% of the lesions showed a cystic component, and 25% of the lesions were ill-defined. Cytologically, contributing factors included scant atypical cells, coexistence of gastrointestinal epithelium, pancreatitis, poor cellular preservation, and interpretation error. Repeat sampling, as requested by clinicians prior to treatment, was performed in 33 (66%) of the 50 lesions, leading to a definitive pathologic diagnosis in 20 (61%) lesions. Seventeen lesions were eventually resected, of which a definitive preoperative diagnosis was attempted in 12 lesions via repeat sampling and was successful in seven. We concluded that indeterminate cytologic diagnosis of a pancreatic lesion often needs to be pursued for optimal management. Although intrinsic natures of a lesion such as cystic component may contribute to insufficient sampling, diagnostic certainty can be improved by proper specimen handling, interpretation, and clinical and/or radiographic correlation.