Preoperative Diagnosis of Abdominal Extra-Adrenal Paragangliomas with Fine-Needle Biopsy.

Paragangliomas are rare, non-epithelial neuroendocrine neoplasms originating in paraganglia, for instance the adrenal medulla, or at extra-adrenal locations. The aim of this study was to review the literature regarding abdominal extra-adrenal paragangliomas diagnosed pre-operatively with fine-needle biopsy (FNA and/or FNB). The PubMed database was searched to identify such cases, using a specific algorithm and inclusion/exclusion criteria. An unpublished case from our practice was also added to the rest of the data, resulting in a total of 36 cases for analysis. Overall, 24 (67%) lesions were found in females, whereas 12 (33%) in males. Most (21/36; 58.33%) were identified around and/or within the pancreatic parenchyma. FNA and/or FNB reached or suggested a paraganglioma diagnosis in 17/36 cases (47.22%). Of the preoperative misdiagnoses, the most common was an epithelial neuroendocrine tumor (NET). Regarding follow-up, most patients were alive with no reported recurrence; however, 5/36 patients exhibited a recurrence or a widespread disease, whereas one patient died 48 months following her diagnosis. In two patients, transient hypertension was reported during the EUS-FNA procedure. In conclusion, this study showed that the preoperative diagnosis of these lesions is feasible and, while diagnostic pitfalls exist, they could significantly be avoided with the application of immunochemistry.

EUS-FNA Diagnosis of a Metastatic Adult Granulosa Cell Tumor in the Stomach.

Granulosa cell tumors are uncommon ovarian neoplasms, predominantly of the adult type (AGCT). In this report, we present a rare case of a patient with metastatic AGCT to the stomach diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 61-year-old woman without a history of AGCT underwent both a vaginal and an abdominal ultrasound that showed a solid and cystic ovarian mass along with a solid mass in the gastric antral wall. Subsequently, an EUS-FNA was performed to assess the gastric lesion. Cytologic findings showed high cellularity, and the groups of neoplastic cells invaded the muscle layer of the stomach. Notably, these cells formed Call-Exner bodies, whereas some nuclei exhibited nuclear grooves. Immunohistochemistry was performed, revealing positivity for α-inhibin, calretinin, and CD56 in the neoplastic cells, whereas chromogranin, synaptophysin, CD117, and DOG1 were negative. The combination of clinical presentation, radiology, cytomorphology, and immunohistochemistry could facilitate the diagnosis of metastatic AGCT and the management of such patients.

Portal-mesenteric vein resection for pancreatic cancer: Results in par with the defined benchmark outcomes.

Background: Patients with pancreatic cancer (PC), which may involve major peripancreatic vessels, have been generally excluded from surgery, as resection was deemed futile. The purpose of this study was to analyze the results of portomesenteric vein resection in borderline resectable or locally advanced PC. This study comprises the largest series of such patients in Greece. Materials and Methods: Investigator-initiated, retrospective, noncomparative study of patients with borderline resectable or locally advanced adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2014 and October 2021. Follow-up was complete up to December 2021. Operative and outcome measures were determined. Results: Forty patients were included. Neoadjuvant therapy was administered to only 58% and was associated with smaller tumor size (median: 2.9 cm vs. 4.2 cm, p = 0.004), but not with increased survival. Though venous wall infiltration was present in 55%, it was not associated with tumor size, or Eastern Cooperative Oncology Group (ECOG) status. Resection was extensive: a median of 27 LNs were retrieved, R0 resection rate (≥1 mm) was 87%, and median length of resected vein segments was 3 cm, requiring interposition grafts in 40% (polytetrafluoroethylene). Median ICU stay was 0 days and length of hospitalization 9 days. Postoperative mortality was 2.5%. Median follow-up was 46 months and median overall survival (OS) was 24 months. Two-, 3- and 5-year OS rates were 49%, 33%, and 22% respectively. All outcomes exceeded benchmark cutoffs. Lower ECOG status was positively correlated with longer survival (ECOG-0: 32 months, ECOG-1: 24 months, ECOG-2: 12 months, p = 0.02). Conclusion: This series of portomesenteric resection in borderline resectable or locally advanced PC demonstrated a median survival of 2 years, extending to 32 months in patients with good performance status, which meet or exceed current outcome benchmarks.

EUS-FNA diagnosis of pancreatic serous cystadenoma with the aid of cell blocks and α-inhibin immunochemistry: A case series.

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow-up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine-needle aspiration (EUS-FNA). In this brief report, we describe six EUS-FNA cases from five patients that were reported as "benign, consistent with serous cystadenoma". Samples were hypocellular, composed of loose clusters and single cuboidal, bland-looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α-inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS-FNAs of SCA commonly result in non-diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.

Evaluation of metastases to the pancreas with fine needle aspiration: A case series from a single centre with review of the literature.

OBJECTIVE: Fine needle aspiration (FNA) is a minimally invasive albeit highly effective modality used to detect solid and cystic pancreatic lesions. This manuscript aims to present our experience in diagnosing metastases to the pancreas and highlight the importance of immunocytochemistry in the diagnostic process. It also aims to provide a brief review of the literature on this topic. METHODS: We retrospectively searched our archives for cases of metastatic deposits to the pancreas diagnosed with FNA over a 5-year period. We also reviewed the literature for such cases. RESULTS: We describe seven cases from our archives that metastasised to the pancreas. Three of them (43%) represented metastatic renal cell carcinoma while the rest four comprised deposits from a lung adenocarcinoma, a colon adenocarcinoma, an adrenal leiomyosarcoma, and a small cell carcinoma of the urinary bladder, respectively. History of primary malignancy was available for all seven patients. All diagnoses were confirmed with the use of immunostains. In our literature review, similar to our case series, renal cell carcinoma was the most common metastasis to the pancreas managed with FNA (around one out of three patients; 35%). Of interest, our endoscopic ultrasound-FNA case of pancreatic metastasis from urinary bladder small cell carcinoma is the first reported. CONCLUSIONS: As metastases to the pancreas are commonly accompanied by diverse prognostic signatures and management strategies compared to primary pancreatic malignancies, their accurate identification is imperative. Pancreatic FNA is a diagnostic modality that can confirm or exclude metastasis to the organ, especially when immunocytochemistry is applied.

Portal-Mesenteric Vein Resection in Borderline Pancreatic Cancer; 33 Month-Survival in Patients with Good Performance Status.

Background: Patients with pancreatic cancer (PC), which is not upfront resectable, but borderline, involving major peripancreatic vessels, have not been generally considered for surgery, considering that resection in such a setting may be futile. Materials and Methods: Retrospective analysis of prospectively collected data on patients with borderline pancreatic adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2012 and February 2017. Follow-up was complete up to January 2018. Results: Twenty-four patients were included. Neoadjuvant therapy (NAT) was administered to only 38%, but more commonly in the second half of the group (58% vs. 17%, p = 0.035). It was associated with smaller tumor size (median: 2.5 vs. 4.2 cm, p < 0.001), fewer positive lymph nodes (LNs) in the resected specimen (median: 2 vs. 5, p = 0.04), and higher likelihood of adjuvant therapy (78% vs. 40%, p = 0.01), but not with survival. Resection was extensive: a median of 26 LNs were retrieved, R0 resection rate (≥1 mm) was 79%, and median length of vein segments was 4 cm, requiring interposition grafts in 58% (mostly polytetrafluoroethylene). Median intensive care unit stay was 0 days and length of hospital stay was 9 days. Post-operative mortality was 12.5%. Median overall survival was 24 months. Eastern Cooperative Oncology Group (ECOG) status was significantly associated with survival (p < 0.001) with ECOG-0: 33 months, ECOG-1: 12 months, and ECOG-2: 6 months. Conclusion: This first Greek national series of portomesenteric vein resection in borderline PC demonstrates that it results to 2 years of median survival, extending to 33 months in patients with good performance status, especially if NAT is uniformly administered.

Dissecting the presence of malignant squamous cells in pancreatic cytopathology: A case series.

The presence of malignant squamous cells in pancreatic cytopathology is a rare phenomenon that results either from a primary or a metastatic process. Pancreatic adenosquamous carcinoma (PASC) represents the most common variant of pancreatic ductal adenocarcinoma and is associated with a dismal prognosis. Within the period of 2013-2018, the archives of "Hygeia and Mitera Hospital" were searched for pancreatic cytopathology-related diagnoses that included the interpretation of "malignant squamous cells present." All fine needle aspirations (FNAs) of pancreatic lesions, including liver metastases in patients with known pancreatic primaries, were retrieved along with their relevant clinical information. Five pancreatic and two liver FNAs acquired from a total of six patients were reexamined. None of these patients had any documented history of primary squamous malignancy elsewhere. All pancreatic and one of the two liver FNAs showed malignant squamous cells, identified based on either morphology or immunochemistry. The other liver FNA represented a metastatic deposit which comprised of only a glandular component, whereas the associated pancreatic FNA exhibited both squamous and glandular counterparts. Most cases characteristically showed necrosis and keratinization. Of interest, two cases revealed the presence of tumor-associated giant cells. In conclusion, the presence of malignant squamous cells in pancreatic FNAs could mean the presence of PASC, especially when there is no documented history of a primary malignancy and a complete clinical and imaging workup has been performed. Immunochemistry on cell block material could help to confirm squamous differentiation in the absence of overt keratinization.

Imaging and Cytopathological Criteria Indicating Malignancy in Mucin-Producing Pancreatic Neoplasms: A Series of 68 Histopathologically Confirmed Cases.

OBJECTIVES: This study aims to evaluate the performance of clinical, imaging, and cytopathological criteria in the identification of high-grade dysplasia/carcinoma (HGD/Ca) in pancreatic mucin-producing cystic neoplasms. METHODS: Sixty-eight consecutive, histopathologically confirmed mucin-producing cystic neoplasms, evaluated by endoscopic ultrasound-guided fine-needle aspiration, were enrolled; specifically, 39 branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), 21 main duct IPMNs, and 8 mucinous cystic neoplasms. The associations between HGD/Ca in histopathology and findings of endoscopic ultrasound and cytology, demographic, lifestyle, and clinical parameters were evaluated, separately in IPMNs and mucinous cystic neoplasms. RESULTS: Age 65 years or more was associated with HGD/Ca in IPMNs. In BD-IPMNs, cyst diameter 3 cm or greater (sensitivity, 68.8%; specificity, 65.2%), a mural nodule (sensitivity, 56.3%; specificity, 78.3%), main pancreatic duct diameter 5 to 9 mm (sensitivity, 50.0%; specificity, 87.0%), and suspicious cytology (sensitivity, 81.3%; specificity, 100%) signaled the presence of HGD/Ca. Similarly, in main duct IPMNs, suspicious cytology predicted HGD/Ca with high sensitivity (88.9%) and excellent specificity (100%). Regarding cytopathological criteria, in BD-IPMNs, HGD/Ca was associated with a high nuclear/cytoplasmic ratio, background necrosis, presence of papillary structures, hypochromatic nuclei, hyperchromatic nuclei, and major nuclear membrane irregularities (thickening and/or indentations). CONCLUSIONS: Clinical, imaging, and cytopathological criteria are useful in the identification of HGD/Ca in IPMNs.

Clear cell "sugar tumor" of the lung: Diagnostic features of a rare pulmonary tumor.

Clear cell tumor of the lung (CCTL) is an extremely rare neoplasm with about 50 cases reported in the literature so far. CCTL belongs to a family arising from putative perivascular epithelioid cells and is otherwise named as "sugar tumor" due to its high cellular glycogen concentration. Due to its rarity, diagnostic features of this entity are not widely known and this usually leads to misdiagnosis. Herein, we report a case of benign CCTL, which was primarily evaluated intraoperatively by FNA cytology and then by a pathological examination of the resected tumor. The cytologic preparations were moderately cellular and showed multiple large, irregular, cohesive clusters of ovoid or spindle tumor cells. Cells had clear cytoplasm, showing positivity with the periodic acid-Schiff (PAS) staining method owing to the glycogen (sugar) content. The rapid cytologic report excluded the possibility of malignancy and a middle lobectomy along with an anterior upper segmentectomy was performed. Immunochemistry revealed a diffuse positivity for HMB45, MART-1, SMA and focally for desmin, while specimen was negative for pancytokeratin cocktail AE1/AE3, cytokeratin7, cytokeratin20 and EMA. These findings confirmed the diagnosis of a benign CCTL. Due to its rarity and similarity with other clear cell tumors of the lung, awareness of this entity, recognition of the cytomorphologic features and familiarity with the associated clinical features can help clinicians avoid certain pitfalls in the diagnostic process. Considering its benign course, unnecessary extensive lung resections may also be avoided thus permitting conservative management of these patients.

Combined Use of Mammography and FNA Eliminates Pitfalls in the Management of Metaplastic Breast Carcinoma.

BACKGROUND: Due to its heterogeneity, metaplastic breast carcinoma (MBC) poses diagnostic dilemmas, leading to delayed treatment, thereby aggravating the prognosis. Over the years, there has been controversy regarding the role of fine-needle aspiration (FNA) cytology in timely diagnosis. CASE REPORT: A 54-year-old woman presented with a palpable mass in the upper outer quadrant of her right breast with corresponding mammographic findings and FNA was performed. The smears revealed small- and medium-sized cohesive clusters of malignant cells with atypical nuclei. Sporadically, there was a pleomorphic population of notably large mononuclear cells, with disturbance of nuclear/cytoplasmic ratio, and binucleated or multinucleated malignant cells. The presence of chondromyxoid substance with focally embedded cells in a magenta-colored substrate was predominant in the background. These features, along with the corresponding mammographic findings, allowed for high preoperative suspicion of MBC. Surgical resection followed immediately without neoadjuvant chemotherapy; the pathology report led to the definite diagnosis of MBC. DISCUSSION: MBC is a rare clinical entity with unfavorable prognosis, thus early diagnosis is imperative regarding its management. The effectiveness of FNA in the diagnostic algorithm has been questioned, with data from literature being rather contradictory. FNA seems to provide valuable information, which should always be interpreted in correlation with the clinical and mammographic findings. CONCLUSION: High preoperative suspicion of MBC with the combination of mammography and FNA cytology necessitated the surgical excision of the lesion as the principal treatment approach. Although the role of FNA in the diagnosis of MBC is debatable, its combination with clinical presentation and corresponding mammographic findings may prevent the administration of neoadjuvant chemotherapy in patients with ambiguous indications, given the poor response rate of this cancer subtype.

Squamous cell carcinoma of the pancreas: A systematic review and pooled survival analysis.

The diagnosis and treatment of squamous cell carcinoma of the pancreas pose dilemmas in the clinical practice. The present study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to 30th April 2016. A pooled Cox regression analysis was performed to evaluate factors potentially associated with overall survival (OS) and relapse-free survival (RFS). Fifty-four cases of pure squamous cell pancreatic carcinomas were identified in total. The mean age was 61.9 years, and most patients were males (61.1%). The median OS was 7 months. Resectability (p = 0.003) and more recent publication year (p < 0.001) were associated with better OS, as was low/intermediate tumour grade (p = 0.032) with RFS. Despite its poor prognosis, survival rates of pancreatic squamous cell carcinoma seem improved during the recent years; resectability and low/intermediate grade emerged as favourable prognostic factors. Collaborative epidemiological studies are deemed necessary to further validate the results stemming from the published case reports of this rare entity.

Challenging differential diagnosis of an extra-adrenal paraganglioma; the role of fine needle aspiration cytology.

Paragangliomas are rare neoplasms that arise from neural crest cells of the autonomous system. Herein, we present a case of a 37-year-old patient with a history of retroperitoneal paraganglioma and tuberculous infection presenting with a paraganglioma of the neck that was initially misdiagnosed as metastatic tumor originating from the lungs. Cytological features from fine needle aspiration and immunocytochemistry pointed to the right diagnosis. However, distinguishing between primary and metastatic site of a paraganglioma can be very challenging due to the overlapping features of these entities. Furthermore, this case underlines the value of a detailed medical history in the era of modern diagnostic modalities. Diagn. Cytopathol. 2017;45:565-568. © 2017 Wiley Periodicals, Inc.

Intraductal papilloma of the breast in an 11-year-old male patient: a case report.

Intraductal papilloma (IP) constitutes a rare benign neoplasm among male population with only few reports on childhood patients. Herein, we describe an 11-year-old IP male patient who presented with spontaneous nipple discharge of his right breast.

Endoscopic ultrasound staging and guided fine needle aspiration biopsy in patients with resectable pancreatic malignancies: a single-center prospective experience.

BACKGROUND: Endoscopic ultrasound staging and guided fine needle aspiration biopsy (EUS-FNA) is a highly accurate diagnostic method, useful in characterizing pancreatic lesions, obtaining definitive tissue diagnosis in patients with suspected pancreatic lesions, and providing accurate locoregional staging that enhances diagnostic certainty and evaluation of appropriateness of surgical intervention. The aims of this study were to evaluate the preoperative contribution of EUS staging and EUS-FNA in patients with suspected resectable pancreatic malignancies. PATIENTS AND METHODS: A prospective study was conducted in a tertiary referral center. During a 54-month period, a total of 103 consecutive patients were prospectively evaluated with EUS and EUS-FNA. Enrolled in the study were patients with resectable pancreatic lesions, who underwent surgery. RESULTS: The overall operating characteristics of EUSFNA were sensitivity 96.7%, specificity 90.0%, positive predictive value 98.9%, negative predictive value 75.0%, and diagnostic accuracy 96.1%. CONCLUSION: EUS and EUS-FNA have a high accuracy and positive predictive value in the preoperative determination of resectability in pancreatic cancer.

Endoscopic ultrasound-guided fine needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas: a report of 3 cases.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is an exceedingly rare pancreatic tumor. We present the clinical, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytologic features and immunohistochemical findings performed on cell blocks of 3 SPTPs. CASES: Three females (17-32 years old) were admitted to our hospital due to unexplained episodic abdominal pain. EUS confirmed the presence of a mass in the body and tail of the pancreas (2 cases) and in the head (1 case), with distinct borders and occassional dilation of the peripheral part of the pancreatic duct. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform polyhedral cells, forming branching papillary clusters with delicate fibrovascular cores and nuclear overlapping (2 cases) and glandlike structures (1 case). Variable hyaline, myxoid stromal elements and naked capillaries were also seen. The cells had bland nuclear features, small nucleoli, nuclear grooves in some of them and focally cytoplasmic projections. Mitoses and necrosis were not observed. The immunohistochemistry on cell blocks revealed: vimentin+ (3 cases), CA19.9+ (2 cases), cytokeratin 7+ (focal, intensive, 1 case), synaptophysin+ (1 case), MUC1+ (focal, intensive, 1 case), EMA+ (diffuse weak, 1 case), a1-antitrypsin and a1-antichymotrypsin+ (focal intensive, 2 cases), progesterone+ (1 case), chromogranin-A- (3 cases) and NSE- (3 cases). CONCLUSION: Cytologic and immunohistochemical findings were strongly suggestive of SPTP. Surgical resection confirmed the diagnosis in all cases. EUS-FNA cytology features and immunohistochemistry provide the diagnosis of SPTP with accuracy.

Fine needle aspiration cytology diagnosis of primary renal lymphoma involving the pleura: a case report.

BACKGROUND: Primary renal lymphoma is a rare disease (< 1% of kidney lesions). We present a case of renal large B-cell type non-Hodgkin's lymphoma (NHL) with right sided pleural involvement. CASE: A 70-year-old man was admitted with persistent, painless, macroscopic hematuria for 1 month. Ultrasound examination, abdominal computed tomography and magnetic resonance imaging techniques revealed a large tumor in the right kidney extending in the perirenal area. The patient underwent a radical nephrectomy for suggested renal cell carcinoma. He developed thoracic pain and pleural effusion in the 10 days after surgery. The pleural fluid was cytologically processed using conventional and ThinPrep (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) cytopreparatory techniques, slides were Papanicolaou and Giemsa stained, and immunocytochemistry was performed on the ThinPrep slides. The cytologic examination of the fluid specimen revealed a highly cellular smear composed of dispersed neoplastic cells of intermediate and large size. Immunocytochemically, the neoplastic cells were: CD45 (LCA) (+), CD20 (+), CK7 (-), CK20 (-), NSE (-), CD45 RO (UCHL-1) (-) and CD30 (-). On cytomorphologic and immunocytologic examination, the specimen fulfilled the criteria of a large B-cell type NHL. Histologic evaluation of the nephrectomy specimen revealed an infiltrating, diffuse large cell renal NHL, B-cell type, of immunoblastic and centroblastic morphology. This NHL was considered a renal primary because no peripheral lymphadenopathy or hepatosplenomegaly was revealed by the imaging techniques. CONCLUSION: Cytomorphologic and immunocytologic examination revealed the typical features of a renal large B-cell type NHL in a case with pleural involvement.

CK19 and CD10 expression in pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound-guided fine-needle aspiration cytology.

BACKGROUND: CK19 and CD10 are useful markers in the differential diagnosis of pancreatic tumors. The authors evaluated CK19 and CD10 expression in pancreatic neuroendocrine tumors (NETs) obtained by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). METHODS: Twenty-eight patients diagnosed with pancreatic NETs based on EUS-FNA cytology were studied retrospectively (2004-2007) for immunohistochemical expression of CK19 and CD10. Immunohistochemistry was performed on cell blocks for each case. The pattern of expression for CD10 (cytoplasmic or membranous) and its intensity (0-2) were noted. The staining of the stromal elements for CD10 was recorded as negative. Cytoplasmic staining in tumor cells and percentage distribution (1+ to 4+) for CK19 were regarded as positive. RESULTS: Twenty-three of 28 (82.14%) NETs showed positive cytoplasmic and/or membranous staining for CD10, and 25 of 28 (89.29%) cases were positive for CK19. CONCLUSIONS: The findings demonstrate the high expression of CD10 and CK19 in pancreatic NETs. This indicates that CD10 and CK19 cannot reliably differentiate NETs from other tumors with similar cytomorphologic features (solid pseudopapillary tumors, which frequently stain with CD10, and pancreatic adenocarcinoma, which stains with CK19).

The role of cytomorphology and proliferative activity in predicting biologic behavior of pancreatic neuroendocrine tumors: a study by endoscopic ultrasound-guided fine-needle aspiration cytology.

BACKGROUND: The biologic behavior of pancreatic neuroendocrine tumors (NETs) is difficult to predict in the absence of metastases or invasion into adjacent organs. In this study, the authors retrospectively evaluated the cytopathology and proliferative activity in cytology specimens obtained by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). METHODS: Thirty-five patients who were diagnosed with pancreatic NET based on EUS-guided FNA were studied retrospectively (2002-2007). Cytopathology and proliferative activity (Ki-67) in cytology specimens were reviewed. Patients were divided into 2 groups: Group A (all patients with simultaneous, suspicious, metastatic masses [unresectable tumors]) and Group B (patients with final histopathologic diagnosis). Moreover, the patients in Group B were classified into 4 risk subgroups according to the 2004 World Health Organization (WHO) classification (Subgroups 1a, 1b, 2, and 3). RESULTS: Thirteen of 35 patients who were diagnosed with unequivocally malignant tumors were placed in Group A (unresectable tumors), and 22 of 35 patients were placed in Group B. In Group A, >2% Ki-67-positive cells were present in 12 of 13 patients (92.3%). In Group B, >2% Ki-67-positive cells were present in 0 of 6 patients in WHO Subgroup 1a (0%), in 3 of 7 patients in WHO Subgroup 1b (42.86%), in 7 of 7 patients in WHO Subgroup 2 (100%), and in 2 of 2 patients in WHO Subgroup 3 (100%). In Group A, nuclear pleomorphism/multinucleation was observed in 8 or 13 patients (61.53%). In Group B, nuclear pleomorphism/multinucleation was observed in 4 of 7 patients in WHO Subgroup 2 (57.14%) and in 2 of 2 patients in WHO Subgroup 3 (100%). In Group A, nucleoli were present in 7 of 13 patients (53.85%); whereas, in Group B, nucleoli were present in 6 of 7 patients in WHO Subgroup 2 (85.7%) and in 2 of 2 patients in WHO Subgroup 3 (100%). None of the remaining cytologic features that were evaluated (necrosis, mitoses, spindle cells, and molding/crush artifact) were observed consistently in malignant NETs. CONCLUSIONS: The current results indicated that Ki-67 evaluation in routine EUS-FNA cytology specimens can be used as a potential prognostic marker in pancreatic NETs. Nuclear pleomorphism/multinucleation and the presence of nucleoli also are reliable for predicting malignant pancreatic NETs. Cancer (Cancer Cytopathol) 2009. (c) 2009 American Cancer Society.