A limited immunocytochemical panel for the distinction of subepithelial gastrointestinal mesenchymal neoplasms sampled by endoscopic ultrasound-guided fine-needle aspiration.

We studied the use of immunocytochemical analysis with material procured by endoscopic ultrasound-guided fine-needle aspiration (EUS-guided FNA) for the diagnosis of subepithelial intramural gastrointestinal (GI) mesenchymal neoplasms (SIGIMNs). We identified all EUS-guided FNA specimens of SIGIMNs that had undergone immunocytochemical analysis. Results were compared with follow-up histologic diagnoses. There were 95 aspirates that were diagnosed as GI mesenchymal tumors (GI stromal tumors [GISTs], n = 46), leiomyomas (n = 38), peripheral nerve sheath tumors (n = 5), and other neoplasms by cytologic examination. Immunoreactivity with antibodies to CD117 always predicted GIST at follow-up; 15 of 16 cases immunoreactive with antibodies to CD34 were found to be GISTs at follow-up. Strong immunoreactivity with antibodies to smooth muscle actin or desmin usually predicted a leiomyoma at follow-up aside from a single glomus tumor and a case with apparent nonneoplastic smooth muscle contaminant. When sufficient material is present, immunocytochemical analysis used with material obtained by EUS-guided FNA is highly predictive of final pathologic diagnosis.

Rapid assessment of fine needle aspiration and the final diagnosis--how often and why the diagnoses are changed.

BACKGROUND: On-site rapid interpretation (RI) of fine needle aspiration (FNA) has been shown to increase the diagnostic yield of FNA and decrease the need for repeat diagnostic procedures. Because the pathologist interprets only a fraction of the sample and has limited resources available at such times, an occasional RI diagnosis will be changed at the time of the final diagnosis. We investigated how often these changes in diagnoses occur and the possible reasons for the changes. METHODS: All cytology reports from 1/1/02 to 12/31/03 from a single institution were reviewed. Cases with RI with discrepant final diagnoses were noted. The discrepant diagnoses were categorized depending on how they were changed. Possible sources for changed diagnoses were noted. RESULTS: Between 1/1/02 and 12/31/03 there were 1368 RIs of FNAs. Of these 80 (5.8%) had discrepancies between the RIs and final diagnoses. Seventy-eight cases had additional slides and/or cell block at time of final diagnosis. 16 cases had ancillary studies available at final diagnosis. Consultant pathologists were used in 7 cases. Different pathologists interpreted the RI and final diagnosis in 31 cases. CONCLUSION: Although uncommon, discrepancies between RIs and final diagnoses occur 5.8% of the time at our institution. Most commonly, this involves a change of diagnosis from either "non-diagnostic" or "benign" to "malignancy". Although much of this is likely due to the presence of additional material and information at the time of final diagnosis, the number of cases that had different pathologists involved in the RI and final diagnosis suggests that inter-observer variability may also play some role.

Fine-needle aspiration cytology of pancreatic lymphoepithelial cysts.

BACKGROUND: Lymphoepithelial cysts (LECs) of the pancreas are extremely rare, benign, nonneoplastic cysts that can mimic pseudocysts or cystic neoplasms clinically and radiographically. The cytologic features of LECs have been described only in a handful of case reports and may overlap with both benign and malignant pancreatic tumors. METHODS: The authors conducted a 5-year, retrospective, computerized review of the cytopathology files of 2 institutions for all diagnoses of pancreatic LECs. Clinical, radiographic, cytologic, and chemical findings were reviewed. RESULTS: Four patients were identified. The study group consisted of 3 men and 1 woman who ranged in age from 33 years to 63 years. The masses were located throughout the pancreas. Tumor sizes ranged from 1.8 cm to 5.7 cm in greatest dimension. Smears from all patients revealed numerous anucleated squamous cells, rare benign nucleated cells, amorphous debris, and an absence of lymphocytes. Mildly atypical mucinous glandular and parakeratotic epithelium were identified in 2 patients, leading to diagnoses of atypical and suspicious for malignancy. Subsequent surgical follow-up of 3 patients revealed pancreatic LECs. CONCLUSIONS: Pancreatic LECs are extremely rare, and certain cytologic pitfalls may hinder a correct prospective diagnosis. Familiarity with the lesion's clinical and cytologic features may help clinicians arrive at the appropriate prospective diagnosis and, thus, permit conservative management. Cancer

Interobserver variability with the interpretation of thyroid FNA specimens showing predominantly Hürthle cells.

Fine-needle aspiration (FNA) is used for the diagnosis and triaging of thyroid lesions. Recently, it has been shown that the pathologic interpretation of selected thyroid specimens can show a high degree of interobserver variability (IV). Because Hürthle cells may be seen in neoplastic and nonneoplastic disease, we investigated whether pathologists consistently interpret FNA specimens from these lesions. In the present study, 22 FNA specimens that showed Hürthle cells as the predominant cell type were reviewed by 7 pathologists. Cytologic features were assessed semiquantitatively. IV was calculated, and individual case diagnoses were compared with cytologic features. IV was high before diagnoses were collapsed into like diagnoses and triage recommendations (k = 0.17, 0.44, and 0.51, respectively). Overall cellularity, number of Hürthle cells, and number of lymphocytes all correlated with collapsed diagnostic agreement, and the number of air-dried rapid Romanowsky-stained slides, overall cellularity, number of Hürthle cells, and number of lymphocytes all correlated with collapsed triage recommendations.

Cytology of pancreatic acinar cell carcinoma.

Acinar cell carcinoma (ACC) of the pancreas is extremely uncommon and its cytologic features have rarely been described. We describe the cytologic features of cases we have seen, review the literature regarding its cytologic features and discuss the pitfalls that may be encountered and the use of immunohistochemistry for its diagnosis. We searched our databases for all cases of histologically confirmed pancreatic ACC which had undergone prior fine needle aspiration (FNA) of the primary pancreatic lesion. The clinical histories, radiographic and sonographic findings, cytologic features, original cytologic diagnoses, and final histologic diagnoses were reviewed. Four cases of pancreatic ACC were found that had undergone FNA prior to histologic confirmation of the diagnoses. They were from 2 men and 2 women aged 50-75 yr. All masses were in the head of the pancreas, 2 had apparent peri-pancreatic adenopathy and 1 had an apparent liver metastasis. On review, all 4 had had diagnostic material on cytology samples. Original cytologic diagnoses included "acinar cell carcinoma," "pancreatic endocrine tumor," "favor neuroendocrine tumor, low-grade" and "non-diagnostic specimen." The cytologic features included small to moderate-sized loose groups with numerous single cells, prominent acinar formation, little anisonucleosis and prominent nucleoli. The cytologic features showed significant overlap with those of pancreatic endocrine tumors.

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.

Esophageal carcinoma with a rhabdoid phenotype: a case report of diagnosis by endoscopic ultrasound-guided fine-needle aspiration.

Malignant extra renal tumors with rhabdoid phenotype are aggressive neoplasms associated with a poor prognosis. These tumors have been reported in soft tissue and various organs including the gastrointestinal tract. We report one of such tumors arising in the esophagus and discuss the cytopathologic, immunohistochemical, and ultrastructural features. Endoscopic ultrasound-guided fine-needle aspiration (FNA) cytology revealed a highly cellular tumor, consisting of polygonal poorly cohesive cells with prominent eosinophilic paranuclear cytoplasmic inclusions. Immunohistochemical staining showed strong cytoplasmic positivity for vimentin and cytokeratin. Electron microscopy revealed presence of numerous intermediate filaments. To the best of our knowledge, this is the first example of carcinoma with rhabdoid phenotype of the esophagus diagnosed by FNA cytology.

A case report of anthracosilicotic spindle-cell pseudotumor of mediastinal lymph node: cytologic diagnosis by endoscopic ultrasound-guided fine-needle aspiration.

Pigmented spindle-cell tumors of the lymph nodes have a broad differential diagnosis, including both benign and malignant neoplasms. Here, we report a case of a pigmented spindle-cell lesion in a mediastinal lymph node mimicking a spindle-cell melanoma on fine-needle aspiration cytology. Smears showed atypical polygonal and spindle cells with bland nuclear features and abundant cytoplasmic anthracotic pigment. Immunohistochemistry was negative for melanoma markers, but showed positivity for histiocyte markers. Polarization microscopy revealed minute birefringent intracellular crystals consistent with silica. Electron microscopy was confirmatory and a diagnosis of anthracosilicotic spindle-cell pseudotumor was made. To the best of our knowledge, fine-needle aspiration cytology findings of this lesion have not been reported.

Interobserver variability in thyroid fine-needle aspiration interpretation of lesions showing predominantly colloid and follicular groups.

We studied interobserver variability (IV) in the assessment of thyroid fine-needle aspiration (FNA). We limited our cases to those showing predominantly colloid and follicular cell groups. Twenty cases of thyroid FNA diagnosed by 1 experienced cytopathologist were reviewed by 4 other cytopathologists who made their own diagnoses while unaware of the original diagnoses. Two cytopathologists then assessed the cytologic features of the 20 cases. IV was calculated for noncollapsed and collapsed diagnoses. Diagnoses and observer agreement were compared with cytologic features. There was little correlation among observers regarding the diagnosis of follicular "lesion" vs "neoplasm." IV was somewhat poor before data were collapsed to treatment recommendations (kappa = 0.35) but was relatively good when data were collapsed (kappa = 0.65). Cellularity, cyst change, and amount of colloid correlated with treatment recommendations; no specific features correlated with poor performance. Thyroid FNA shows good interobserver agreement in the diagnoses of lesions showing predominantly colloid or follicular cells (when collapsed). We speculate that IV is poor in some cases owing to difficulty assessing thin colloid, some lack of agreement regarding criteria for adequacy, and a possible "gray zone" that might exist with lesions showing colloid and abundant follicular cells.

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms.

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.

Sampling of the adrenal glands by endoscopic ultrasound-guided fine-needle aspiration.

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven to be a valuable modality for the primary diagnosis and staging of gastrointestinal, and perigastrointestinal malignancy. Aside from assessing thoracic and abdominal lymph nodes and the liver for metastases, EUS can assess and sample the adrenal glands, which are frequently involved by metastatic disease, but can also harbor benign primary neoplasms. The cytology files at our institution were reviewed for all cases of EUS-guided FNA of the adrenal glands. Clinical histories, sonographic findings, and cytologic findings of all cases were reviewed. Results were compared with overall EUS-guided FNA performance and the performance of non-EUS-guided FNA of the adrenal. The utility of cell block immunohistochemistry (IHC) in these cases was reviewed. Between 1/1/00 and 5/15/04 there were 24 cases of EUS-guided FNA of the adrenal gland from 22 different patients (13 men; 9 women) at our institution. This represented 1.4% of overall EUS-guided FNA and 77% of adrenal gland FNA. Patient ages ranged from 37 to 86 yr (mean 69 +/- 11 yr). Most patients had other cancers or mass lesions and were being staged at the time of the procedure (19 of 22). Almost all FNAs were of the left adrenal gland (23 of 24). Lesion size ranged from 0.9 to 7.9 cm (mean 2.5 +/- 1.6 cm). Diagnostic material was present in all cases when compared with an overall EUS-guided FNA diagnostic rate of 88%. Material for cell block was present in 21 cases, and IHC was used in 3 cases. Final diagnoses were as follows: cortical tissue consistent with cortical adenoma (19), metastatic adenocarcinoma (3), pheochromocytoma (1), and adrenal cortical carcinoma (1). EUS-guided FNA of the adrenal gland is primarily used in the staging of other malignancies when lesions of the left adrenal are recognized sonographically. Diagnostic tissue is easily obtained, including material for cell block IHC, which allows definitive diagnosis in cases that present difficult differential diagnoses.

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.

The cytological spectrum of chronic pancreatitis.

Chronic pancreatitis (CP) refers to a spectrum of changes generally seen after repeated injury that ranges histologically from mild fibrosis to extensive fibroinflammatory replacement of acinar tissue with accumulation of calcific debris. Because CP can share clinical and radiological features with malignancy, it often is sampled by fine-needle aspiration (FNA). The cytology files at Hennepin County Medical Center (HCMC) were searched for 20 consecutive cases of CP sampled by FNA. Clinical data and cytological findings were recorded. A spectrum of cytological findings typifies aspirates of CP. In most cases, mixed inflammation with debris and calcific material is present. Often, ductal cells are present and at most show mild atypia but generally appear organized. Often, fibrotic acinar tissue also is present while definitive islets are identified only rarely. Although these cytological findings were consistent with CP, 3 of 17 patients with follow-up were found to have pancreatic ductal adenocarcinoma.

Short term cyclin D1 overexpression induces centrosome amplification, mitotic spindle abnormalities, and aneuploidy.

In normal cells, cyclin D1 is induced by growth factors and promotes progression through the G(1) phase of the cell cycle. Cyclin D1 is also an oncogene that is thought to act primarily by bypassing the requirement for mitogens during the G(1) phase. Studies of clinical tumors have found that cyclin D1 overexpression is associated with chromosome abnormalities, although a causal effect has not been established in experimental systems. In this study, we found that transient expression of cyclin D1 in normal hepatocytes in vivo triggered dysplastic mitoses, accumulation of supernumerary centrosomes, abnormalities of the mitotic spindle, and marked chromosome changes within several days. This was associated with up-regulation of checkpoint genes p53 and p21 as well as hepatocyte apoptosis in the liver. Transient transfection of cyclin D1 also induced centrosome and mitotic spindle abnormalities in breast epithelial cells, suggesting that this may be a generalized effect. These results indicate that cyclin D1 can induce deregulation of the mitotic apparatus and aneuploidy, effects that could contribute to the role of this oncogene in malignancy.

Diagnosis of nonprimary pancreatic neoplasms by endoscopic ultrasound-guided fine-needle aspiration.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a proven modality for the diagnosis of primary pancreatic neoplasms. We describe our experience in diagnosing nonprimary pancreatic tumors by EUS-FNA. Cytology files were searched for all EUS-FNA of the pancreas for the period 2000-2002. All cases diagnosed as neoplasms were selected and those diagnosed as nonprimary pancreatic tumors were reviewed and analyzed. One hundred ninety-one of 468 cases were diagnosed as neoplasms. Eleven of these cases were diagnosed as nonprimary pancreatic tumors (2.4% of all diagnoses and 5.7% of all neoplasms). The diagnoses were supported by clinical history (n = 7), cytological findings (n = 11), cell block histology (n = 11), cell block immunohistochemistry (n = 6), and flow cytometry (n = 1). EUS-FNA is a safe and minimally invasive method for the diagnosis of nonprimary pancreatic neoplasms. Evaluation of clinical history, cytomorphology, and ancillary techniques, especially those applied to cell block material, are essential for accurate diagnoses.

The cytology of pancreatic foamy gland adenocarcinoma.

All cell block specimens from pancreatic fine-needle aspirations (FNAs) obtained between January 1, 2002, and June 30, 2003, were reviewed for foamy gland adenocarcinoma (FGA). All smears from these cases were reviewed for cytologic features, including those previously noted in conventional pancreatic adenocarcinoma. Fifty-two cell block specimens showed adenocarcinoma. Of these, 12 (23%) showed histologic features of FGA. This pattern predominated in 6 cases and was present focally in 6 cases. Although there were relatively low nuclear/cytoplasmic (N/C) ratios, other features of adenocarcinoma were present universally, including loss of cohesiveness, nuclear overlap or loss of "honeycomb" architecture, anisonucleosis (> 4 to 1), irregular nuclear contours, prominent nucleoli, and atypical chromatin. Background necrosis was present in 8 cases. Distinct cell borders were present in 9 cases, and foamy cytoplasm was present in all cases. Pancreatic FGA is a recently described histologic pattern of pancreatic adenocarcinoma. It is not uncommon, and we identified the pattern, at least focally, in 23% of our FNA cell blocks. Although cytologic samples show low N/C ratios, most cytologic features of conventional pancreatic adenocarcinoma are present, and the diagnosis presents little additional difficulty.

Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solid-pseudopapillary tumor of the pancreas: a rare neoplasm of elusive origin but characteristic cytomorphologic features.

Clinical histories, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) material, and immunohistochemical stains performed on cell block samples of 6 solid-pseudopapillary tumors of the pancreas (SPTPs) were reviewed in the cases of 5 females (13-58 years) and 1 man (57 years); all had abdominal pain. Preliminary cytologic diagnoses at endoscopy included 1 SPTP 2 low-grade neoplasms, and 3 pancreatic endocrine tumors. Variable numbers of branching fragments with central capillaries and myxoid stroma were seen in the smears of 5 of 6 cases but were more apparent in the cell block material of all cases. The cells had bland nuclear features and rare grooves. Extensive necrosis was noted in 1 case and rare mitotic figures in 1. SPTPs showed strong cellular immunoreactivity for vimentin and focal weak keratin reactivity. Neuron-specific enolase, alpha1-antitrypsin, and alpha1-antichymotrypsin stains performed in 2 cases were strongly positive. Subsequent surgical resection confirmed all diagnoses. EUS-guided FNA diagnosis of SPTP is accurate. The characteristic branching papillae with myxoid stroma are best seen in cell block slides. Clinical setting, cytomorphologic features, and immunostains of the cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma, and papillary mucinous carcinoma.

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

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

Endoscopic ultrasound-guided fine-needle aspiration cytology of peripheral nerve-sheath tumors.

Endoscopic ultrasound (EUS) has allowed for the fine-needle aspiration and diagnosis of many different gastrointestinal neoplasms, including mesenchymal tumors. Although most mesenchymal tumors of the gastrointestinal tract are gastrointestinal stromal tumors (GISTs), other mesenchymal tumors, including neural tumors, do occur. Proper diagnosis and differentiation of these tumors from GISTs are important because of their different prognoses and treatment regimens. We encountered three peripheral nerve-sheath tumors of the gastrointestinal tract aspirated by EUS (two schwannomas and a granular-cell tumor). We report on the endoscopic ultrasound, cytologic, histologic, and immunohistochemical findings of these cases.