Cystic pancreatic endocrine tumor

BACKGROUND.

Most cystic pancreatic neoplasms are currently evaluated by an endoscopic ultrasound‐guided fine‐needle aspiration biopsy (FNAB). In the authors' experience, FNAB of cystic pancreatic endocrine tumors (PETs) frequently causes diagnostic difficulties, partly because of unexpected overlapping features with cystic ductal adenocarcinomas.

METHODS.

The authors identified 5 histologically confirmed cystic PETs that were evaluated by FNAB and compared their cytomorphologic features to cystic ductal adenocarcinomas (n = 5) and solid PETs (n = 39) of the pancreas.

RESULTS.

Cytologically, 2 of the aspirates of cystic PETs were devoid of tumor cells whereas the other 3 were variably cellular and composed of cohesive aggregates of monomorphic cellular elements with variably coarse chromatin. Tumor necrosis and nuclear membrane irregularities were not identified in cystic PETs. Alternatively, in contrast to PETs, cystic ductal adenocarcinomas were characterized by nuclear pleomorphism, nuclear membrane irregularities, and tumor necrosis.

CONCLUSIONS.

Given the clinical implications, awareness of cystic PETs and their deceptive cytologic features would assist in distinguishing these lesions from cystic ductal adenocarcinomas. Cancer (Cancer Cytopathol) 2007 © 2006 American Cancer Society.     

Proliferative rate in endoscopic ultrasound fine‐needle aspiration of pancreatic endocrine tumors

BACKGROUND:

The objectives of this study were to evaluate the role of endoscopic ultrasonography (EUS)‐guided fine‐needle aspiration (FNA) in the preoperative diagnosis of pancreatic endocrine tumors (PETs) and to investigate whether the Ki‐67 index determined on cytologic material could help predict their behavior.

METHODS:

The study included 10 men and 5 women (ratio of men to women, 2:1) with a mean age of 62.4 years (range, 40‐79 years). Diff‐Quik‐ and Papanicolaou‐stained FNA samples were analyzed retrospectively, and immunocytochemical stains were performed for chromogranin A, synaptophysin, vimentin, α‐1‐antitrypsin, and Ki‐67 on cell block sections. The Ki‐67 index was evaluated by using digital image‐analysis software and was correlated with follow‐up (mean, 21.5 months; range, 2‐43 months).

RESULTS:

The overall survival was rate 86.7% (13 of 15 patients). Seven of 15 patients (46.7%) patients developed lymph node and/or hematogenous metastases. The Ki‐67 index in PETs with no metastases was lower (mean, 6.3%; range, 2%‐13%) than in clinically aggressive (metastatic) tumors (mean, 7.7%; range, 3%‐27%; P = .03). None of the tumors that had a Ki‐67 index ≤2% were metastatic. Both patients who died of disease had a Ki‐67 index of 4%.

CONCLUSIONS:

Although tumors with metastatic potential tended to exhibit a slightly higher Ki‐67 index, there was a significant overlap with nonmetastatic tumors, and PETs that had a very low proliferative rate still could behave aggressively; therefore, the authors concluded that the Ki‐67 index does not predict the risk of disease progression in patients with PETs. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Serous cystadenoma of the pancreas

BACKGROUND

Expectant management of serous cystadenoma (SCA) of the pancreas requires an accurate preoperative diagnosis. Previously published cytologic diagnostic sensitivities have ranged widely, from 10% to 100%. In the current study, the authors evaluated the diagnostic sensitivity of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration biopsy (FNAB) and cross‐sectional imaging for SCA.

METHODS

Group I consisted of 21 histologically confirmed SCAs. Group II (n = 7 lesions) lacked histologic confirmation and was defined by EUS findings that were consistent with SCA and a cyst fluid carcinoembryonic antigen (CEA) level <5 ng/mL. Group III was comprised of 2 nonserous and potentially malignant cysts of the pancreas for which a preoperative diagnosis of SCA was considered. Cross‐sectional imaging data were recorded. The smears were evaluated for the presence of serous lining epithelium, gastrointestinal‐contaminating epithelium, and inflammatory cells including hemosiderin‐laden macrophages. The authors also evaluated the presence of hemosiderin‐laden macrophages in a series of 110 FNA specimens from histologically confirmed neoplastic mucinous cysts of the pancreas and 45 pseudocysts of the pancreas.

RESULTS

Prospectively among Group I lesions, the appearance on computed tomography (CT) was considered definitive for SCA in 3 of 12 cases (25%). The histologically confirmed SCA cases had CEA levels of <5 ng/mL, except for 1 case for which the CEA level was 176.5 ng/mL. A cytologic diagnosis of SCA was made prospectively in only 1 CT‐guided case. Retrospectively, 3 intraoperative FNAs and 1 additional CT‐guided aspirate contained rare epithelial cells of a SCA. None of the EUS‐guided aspirates demonstrated serous epithelium. Among Group II aspiration specimens, only 1 contained serous epithelial cells. Approximately 52% of the EUS‐guided aspirates demonstrated gastrointestinal contamination. This glandular epithelium was categorized as atypical in 2 cases. Hemosiderin‐laden macrophages were identified in 43% of the SCAs. Conversely, only 2% of neoplastic mucinous cysts and 9% of pseudocysts produced hemosiderin‐laden macrophages in aspirate fluid.

CONCLUSIONS

In the current study, serous epithelial cells were identified in <20% of cases. Gastrointestinal‐contaminating epithelium, often observed in EUS‐guided aspirates, further contributes to difficulties in interpretation. The presence of hemosiderin‐laden macrophages as a surrogate marker for SCA requires further study. A preoperative diagnosis of SCA remains a challenge, and an EUS‐guided FNAB is unlikely to provide the high level of diagnostic accuracy necessary to permit a nonoperative approach. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

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). Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Large,clear cytoplasmic vacuolation

BACKGROUND.

Solid pseudopapillary neoplasm (SPN) and pancreatic endocrine neoplasm (PEN) are uncommon neoplasms that demonstrate characteristic cytologic features. It is also known that both these tumors may share similar morphologic changes. These features not uncommonly pose significant diagnostic challenge for unsuspecting cytopathologists. In the current study, the authors report that recognition of clear cytoplasmic vacuoles in endoscopic ultrasound–guided fine–needle aspiration (EUS‐FNA) samples from SPN serves as a useful clue that can distinguish this tumor from PEN.

METHODS.

The cytologic features from 5 SPN and 20 PEN cases were evaluated. Both Diff‐Quik and Papanicolaou stains from these cases were examined. A Fisher exact test of probability was performed to determine differences in the individual cytologic features noted in these 2 tumor types.

RESULTS.

The results demonstrated that pseudopapillary groups (P = .004); metachromatic matrix material (P = .004); nuclear membrane irregularity (P = .004); and large, clear cytoplasmic vacuoles (P = .001) are noted significantly more frequently in SPN. The authors also demonstrated that large, clear cytoplasmic vacuoles can serve as a powerful cytologic clue for the suspicion of SPN over PEN when there is a paucity of papillary groups within the smears. Large, clear cytoplasmic vacuoles, however, were noted only in Diff‐Quik–stained smears, but not in Papanicolaou‐;stained smears.

CONCLUSIONS.

The results of the current study highlight that large, clear cytoplasmic vacuoles can serve as a critical clue with which to distinguish SPN from PEN in diagnostically challenging cases. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

The role of cytomorphology and proliferative activity in predicting biologic behavior of pancreatic neuroendocrine tumors

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. © 2009 American Cancer Society.     

Role of ancillary studies in fine-needle aspiration from selected tumors

The routine use of ancillary studies is reshaping the practice of cytopathology. Currently, most cytopathologists recognize the importance of immunocytochemistry and molecular techniques as adjuncts to morphology to achieve a precise diagnosis. Cytopathologists also are expected to include specific prognostic and predictive information in their reports. The objective of this review was to address the use of immunocytochemistry and molecular techniques to refine the preoperative diagnosis and classification of lung cancer, thyroid cancer, kidney cancer, gastrointestinal cancer, and soft tissue tumors. Fine-needle aspiration also offers a suitable alternative to biopsy in a variety of clinical settings, in particular, when it may be useful to obtain material to study prognostic and predictive markers. This is particularly relevant to obtain material from metastatic sites. The study of KRAS in colon cancer, CKIT in gastrointestinal stromal tumors, and epidermal growth factor receptor mutational status in lung cancer also are addressed particularly in this report.     

Prospective analysis of atypical epithelial cells as a high‐risk cytologic feature for malignancy in pancreatic cysts

BACKGROUND:

Pancreatic cysts are aspirated to assess whether a cyst is mucinous on one hand and malignant on the other. The authors' retrospective data have indicated that high‐grade atypical epithelial cells (AECs) identified on cytology are a high‐risk feature and a better threshold than “positive” for detecting malignancy. The objective of the current study was to assess the accuracy of AECs in predicting malignancy in pancreatic cysts.

METHODS:

Cysts aspirated by endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (EUS‐FNAs) obtained between January 2006 and June 2011 were evaluated. Cytologic, histologic, imaging, and cyst fluid analysis data were recorded. AECs were defined as cells that had an increased nuclear‐to‐cytoplasmic ratio and nuclear hyperchromasia with or without membrane abnormalities and with or without cytoplasmic vacuoles, but of insufficient quality and quantity for a “positive” interpretation. Malignancy included mucinous cysts with high‐grade dysplasia and invasive carcinoma. Performance characteristics of cytology with AECs or worse (high‐grade atypia [HGA]) for predicting malignancy were assessed.

RESULTS:

There were 70 FNAs that had histologic confirmation from 404 EUS‐FNAs in 352 patients. Excluding 4 nondiagnostic FNAs, the study cohort consisted of 66 FNAs for analysis. There were 24 malignant cysts with 20 true‐positive, 4 false‐negative, 36 true‐negative, and 6 false‐positive results. For the detection of malignancy, HGA had 83% sensitivity, 86% specificity, a positive predictive value of 77%, a negative predictive value of 90%, and 85% overall accuracy. The lower threshold for malignancy with AECs resulted in a 12% increase in the detection of malignancy.

CONCLUSIONS:

A finding of AECs on cytology is a high‐risk feature for malignancy and is an accurate triage threshold for resection. Cancer (Cancer Cytopathol) 2013;121:29–36 © 2012 American Cancer Society.