Calculus artifact. A challenge in urinary cytology.

OBJECTIVE: To retrospectively review calculus artifact and compare it with instrument artifact and papillary transitional cell carcinoma (TCC). STUDY DESIGN: Voided urine specimens from patients with calculi (65), TCC (low grade, 10, high grade, 34) and history of prior instrumentation (12) were studied. RESULTS: Nineteen specimens of calculus artifact had unremarkable cytology. Forty-six specimens had abnormal single cells or papillary clusters and cell balls or a mixture of both. The papillary groups had smooth as well as irregular borders, a cytoplasmic collar and cells with occasional cytoplasmic vacuoles, slightly increased nuclear/cytoplasmic (N/C) ratio and inconspicuous nucleoli. Squamous preponderance and birefringent crystals were seen. In instrumentation artifact, papillary clusters or three-dimensional cell balls had smooth borders, cytoplasmic collars, an occasional cytoplasmic vacuole, normal N/C ratio, regular nuclear membrane and finely granular nuclear chromatin. In TCC, papillary clusters with loss of polarity and irregular borders were present in both grades but were predominant in low grade TCC. No cytoplasmic collar was noted. In high grade TCC, single cells and nuclear alterations were more pronounced, with increased N/C ratio, hyperchromasia, coarse chromatin, irregular nuclear envelopes, prominent nucleoli and rare mitosis. CONCLUSION: Calculus artifact can produce papillary clusters masquerading as papillary TCC. Unlike instrument artifact, there may be significant nuclear atypia, which could be reversible. To avoid diagnostic pitfalls, further investigation is suggested after removal of calculus.     

Differential immunocytochemical staining patterns of uroplakin observed on neoplastic and nonneoplastic tissue fragments obtained from upper urinary tract brush specimens

OBJECTIVE: To discern any differences in the distribution of uroplakin expression on neoplastic and nonneoplastic upper urinary tract lesions. STUDY DESIGN: Thirty-seven representative 95% ethanol-fixed direct smears of brush specimens, which were subsequently diagnosed histologically as 10 reactive and 27 transitional cell carcinomas (TCCs), were stained with polyclonal uroplakin antibodies utilizing the avidin-biotin-peroxidase method. In order to ascertain any differences in diagnostic accuracy between conventional cytomorphology and uroplakin immunocytochemical staining, the results were compared to the original final cytologic diagnoses for all 37 cases. RESULTS: The linear staining pattern on the luminal surface of umbrella cells was the dominant pattern expressed on tissue fragments from all 10 reactive lesions. Tissue fragments from low grade TCC demonstrated a weaker and less continuous superficial membrane staining pattern along with a variably intense, diffuse, membranous staining pattern throughout the tumor cell groups. This staining pattern was seen in all 17 (sensitivity = 100%) histologically confirmed low grade TCCs, of which only 13 of the 17 (sensitivity = 76.5%) were diagnosed as TCC on the original final cytology report. Tissue fragments from 10 high grade TCCs lacked the superficial linear staining pattern seen in reactive cell groups. Instead, all 10 high grade TCCs displayed a strong diffuse membrane staining pattern in all the cells in the fragment and also demonstrated microluminal structures within the tumor cell groups. CONCLUSION: The distinctive patterns of uroplakin antigen expression observed in nonneoplastic and neoplastic upper urinary tract lesions in the present study can greatly enhance the accuracy of diagnostic interpretation of upper urinary tract lesions in conventional cytologic specimens.     

Comparative image analysis of cells in voided and catheterized urine

OBJECTIVE: To objectively evaluate the difference in cytologic findings between specimens of voided and catheterized urine by using a comparative image analysis device, CAS200. STUDY DESIGN: Cells in voided and catheterized urine from 13 patients with transitional cell carcinoma (TCC), including 3 with grade 1, 6 with grade 2 and 4 with grade 3, were compared cytologically. The cellular area, nuclear area, nuclear/cytoplasmic ratio and nuclear density of both types of cytologic specimen were measured using CAS200. RESULTS: Cell area and nuclear area of grade 1 TCCs were significantly greater in voided urine than in catheterized urine. In contrast, cell area and nuclear area of grade 3 TCCs were significantly smaller in voided urine than in catheterized urine (P < .01), and nuclear density of grade 3 TCCs was higher in the latter than in the former. CONCLUSION: The cellular findings in voided urine were different from those in catheterized urine from the same patient. Thus, the method selected for obtaining urine specimens will affect the findings in urinary cytology.     

Micropapillary variant of transitional cell carcinoma of the urinary bladder: a report of three cases with cytologic diagnosis in urine specimens

BACKGROUND: Micropapillary transitional cell carcinoma is a recently described, aggressive variant of bladder cancer. Its cytologic features in urine have not been previously characterized. CASES: Three cases illustrate the urinary cytologic features of this high grade urothelial carcinoma and its concurrent biopsy findings. This tumor is similar to low. grade urothelial lesions of the bladder, tends to present as micropapillary clusters in urine and yet has high grade nuclear features within these clusters that help with the differential diagnosis of a flat, high grade urothelial carcinoma. CONCLUSION: The micropapillary type of transitional cell carcinoma is a distinct morphologic entity with an aggressive clinical course. Recognizing its presence in urinary cytology, albeit a rare occurrence, is important in distinguishing this lesion from the more indolent, low grade papillary lesions and high grade urothelial carcinomas, which continuously shed single malignant urothelial cells.     

Cytologic features of urothelial carcinoma in catheterized urine with cellular fragments

OBJECTIVE: To identify architectural and cytomorphologic differences that might help distinguish urothelial neoplasms from instrumentation artifact. STUDY DESIGN: We examined 73 cytologic smears of catheterized urine containing urothelial cell clusters between 1998 and 2004. All patients had at least 1 follow-up biopsy. Smears were reviewed for several morphologic features blindly, without knowledge of the follow-up diagnosis. RESULTS: Of the 73 smears, 39 had a benign diagnosis on follow-up biopsy, and 34 had urothelial carcinoma. Cytoplasmic collar, regular and rounded fragment borders, and fine nuclear chromatin were statistically more common in benign smears than those with urothelial carcinoma (p < 0.0001). No significant differences were identified with regard to the presence of background inflammation or nucleoli in the urine specimens. Of the 17 smears that had a cytoplasmic collar, regular fragment borders and fine nuclear chromatin, only 1 (6%) was found to have urothelial carcinoma on follow-up biopsy. All 20 smears in which all 3 features were absent were proven malignant on biopsy. CONCLUSION: Certain architectural and nuclear features can help differentiate urothelial neoplasms from instrumentation artifact in urine cytologic smears.     

Cytologic features of ovarian tumors of low malignant potential in peritoneal fluids

The distinction of ovarian tumors of low malignant potential (OTLMP) from invasive ovarian carcinomas has significant therapeutic and prognostic implications. This study was undertaken to define the cytologic features of OTLMP in peritoneal fluids and to compare them with the cytologic features of invasive carcinomas. Peritoneal fluids from 13 patients with OTLMP and 10 patients with invasive ovarian carcinoma contained neoplastic cells and were reviewed with attention to papillary fragment morphology, cellular pleomorphism and cytoplasmic and nuclear characteristics. Cytologic preparations from patients with OTLMP contained large, cohesive papillary fragments with smooth borders. The neoplastic cells were relatively small and uniform, with high nuclear-cytoplasmic (N/C) ratios (greater than 1:2), few intracytoplasmic vacuoles and inconspicuous nucleoli. Mitotic figures were rare. Peritoneal fluids from patients with invasive ovarian carcinoma contained smaller discohesive papillary fragments with irregular borders. The neoplastic cells were relatively large and pleomorphic, with low N/C ratios (less than or equal to 1:2), abundant intracytoplasmic vacuoles and prominent nucleoli; most preparations contained many single cells and mitotic figures.     

Papillary clusters as a diagnostic pitfall in urinary cytology of pseudosarcomatous fibromyxoid tumor of the bladder. A case report

BACKGROUND: Pseudosarcomatous fibromyxoid tumor (PFT) of the urinary bladder is an uncommon benign lesion that can involve any site in the bladder. Cellular features of PFT of the bladder are exceedingly rare. We describe the urinary cytology in a PFT patient who displayed numerous papillary fragments that suggested a malignant tumor. CASE: A 52-year-old man was seen at the hospital for evaluation of gross hematuria. At cystoscopy, the urologist observed a 3-cm, smooth, polypoid and ulcerated mass extending from the trigone to the bladder neck. Urinary cytology showed many papillary clusters with irregular nuclear margins in the bloody cell background. No spindle cells were noted. Cytology was interpreted as papillary growth, factor transitional cell carcinoma, grade 2-3. A laparotomy with partial resection of the urinary bladder was carried out, and histologically the tumor was composed of spindle, stellate, fibroblastic cells embedded in myxoid stroma with little collagen. Immunohistochemical and ultrastructural studies revealed the fibroblastic nature of the lesion. The final diagnosis was PFT of the bladder on the basis of histologic examination of the resected material. CONCLUSION: Papillary fragments are a diagnostic pitfall in urinary cytology of PFT lesions.     

Benign squamous cells with pleomorphic microvilli in urine or bladder washings

Exfoliated cells in catheterized urine or bladder washings from 40 patients were observed by light microscopy (LM) and by scanning electron microscopy (SEM). The specimens from seven of these patients (six postmenopausal females and one 85-year-old male) contained squamous cells with pleomorphic microvilli (PMV) on their surfaces. Four of these cases had no bladder lesions by cystoscopic examination. Three patients had recurrent papillary transitional-cell carcinoma of the bladder, and the cytologic specimens from two of them contained transitional cells with PMV. The distinction between squamous and transitional cell is readily made by SEM, based primarily on cell shape and thickness. The presence of PMV on otherwise-benign-appearing squamous cells in urine or bladder washing specimens may be a source of confusion in the interpretation of SEM findings. The presence of PMV on exfoliated squamous cells in cytologic material from the human urinary tract does not seem to have the same diagnostic and prognostic significance as the presence of PMV on transitional cells.     

Proliferating cell nuclear antigen in normal urothelium and urothelial lesions of the urinary bladder: a quantitative assessment using a true color image analysis system

To evaluate proliferating cell nuclear antigen (PCNA) staining for assessing proliferative activity in routine pathology specimens of urinary bladder, the bladder carcinoma cell line J82 and a total of 122 specimens of normal bladder and urothelial lesions were stained with the antibody clone PC10 against proliferating cell nuclear antigen. In in vitro plateau cultures the proportion of PCNA-positive cells exceeded that of Ki-67-positive cells, and only very few cells were negative. In formalin-fixed tissues, the PCNA staining pattern, which should be confined to replicon units in the nucleus, was optimized by 1 h postfixation in an organic solvent (methacarn). Sections showed positive nuclear staining confined to basal and some suprabasal cells in normal urothelium and grade 1 dysplasias, but more generalized nuclear staining in all other neoplastic lesions. In addition, stromal cells adjacent to invasive tumors showed nuclear positivity in some instances. Using quantitative true color image analysis of sections counterstained with hemalum, the degree of brown staining of the PCNA reaction product is contrasted with the blue staining of the nuclear area. With this method low contrast specific staining not appreciated optically can be reliably detected. Image analysis data confirmed observations made on noncounterstained sections and showed significant differences between grade 1 and 2 dysplasias as well as between grade 1 dysplasia and all grades of papillary tumor. Furthermore, a significant difference in PCNA staining indices was found between grade 1 and 3 bladder carcinomas. The results indicate that PCNA staining using the PC10 antibody is not confined to the proliferative fraction of neoplastic urothelium. In contrast with data from normal tissue and malignant hematological neoplasms, the amount of PCNA is regulated differently in urothelial neoplasms, emphasizing the biological differences between the following two sets: mild dysplasia and moderate dysplasia; mild dysplasia and papillary carcinomas. The use of image analysis to standardize the detection process after controlled staining conditions is advisable in order to provide reliable data. Supported by the DFG project: Knuechel/Urothelcarcinom 263     

Usefulness of diagnostic criteria for aspiration cytology of hepatocellular carcinoma.

OBJECTIVE: To establish new criteria for cytodiagnosis of hepatocellular carcinoma by comparing cytologic findings of hepatocellular carcinoma with those of liver cirrhosis. STUDY DESIGN: Review of cytologic findings of hepatocellular carcinoma on preoperative aspiration biopsy of 31 lesions from 27 patients who underwent surgical resection and comparison of these findings with those of liver cirrhosis in 17 patients. RESULTS: In the 11 lesions of moderately and poorly differentiated hepatocellular carcinoma, significant cytologic findings included monotonous and abundant cytoplasm, thick cytoplasm, increased nuclear/cytoplasmic ratio, irregular nuclear contours, increased chromatin density, intranuclear vacuoles and naked nuclei. In the 20 lesions demonstrating well-differentiated hepatocellular carcinoma, significant cytologic findings included monotonous and scant cytoplasm, well-defined cytoplasmic borders, thick cytoplasm, eccentric nuclei, increased nuclear/cytoplasmic ratio, thick nuclear membranes and increased chromatin density. We established the criteria for moderately and poorly differentiated hepatocellular carcinoma as including three cytologic parameters: increased nuclear/cytoplasmic ratio, irregular nuclear contours and increased chromatin density. We also established the criteria for well-differentiated hepatocellular carcinoma as including six cytologic parameters: monotonous cytoplasm, scant cytoplasm, well-defined cytoplasmic borders, thick cytoplasm, eccentric nuclei and increased nuclear/cytoplasmic ratio. For all 31 hepatocellular carcinoma lesions, including 27 lesions that were < or = 2 cm in diameter, both sensitivity and specificity were 100% by concurrently employing both criteria. CONCLUSION: The new criteria for cytodiagnosis we established were useful for differentiating hepatocellular carcinoma from liver cirrhosis. In particular, our criteria ensured appropriate diagnostic accuracy for well-differentiated hepatocellular carcinoma.     

Evaluating the diagnostic significance of nuclear grooves in thyroid fine needle aspirates with a semiquantitative approach

OBJECTIVE: To clarify the diagnostic significance of nuclear grooves in thyroid fine needle aspirates, to search for other associated nuclear features and to identify possible diagnostic pitfalls. STUDY DESIGN: In total, 67 fine needle aspiration cases were retrospectively reviewed for selected nuclear features, including grooves, intranuclear cytoplasmic invaginations, enlargement, pleomorphism and status of nucleoli. A semiquantitative method was used to estimate the percentage of nuclear grooves in 5 high-power fields with the most frequent nuclear grooves. RESULTS: Unequivocal intranuclear cytoplasmic invaginations were a specific diagnostic feature of papillary carcinoma. In the absence of intranuclear cytoplasmic invaginations, the presence of > or = 20% nuclear grooves was virtually diagnostic of thyroid neoplasms, predominantly papillary carcinoma. Less than 10% of nuclear grooves virtually eliminated the possibility of papillary carcinoma. However, 10-19% of nuclear grooves may be seen in papillary carcinoma and benign lesions; therefore, such cases fell into the diagnostic category of "atypical cytology" or "indeterminate" cytology. Nuclear enlargement with elongation was a readily identifiable feature usually associated with nuclear grooves. Significant pleomorphism was more commonly seen in papillary carcinoma than in benign lesions. CONCLUSION: A semiquantitative method is helpful when nuclear grooves are encountered in thyroid cytology in the absence of other diagnostic features. It can significantly improve the diagnostic specificity of nuclear grooves for papillary carcinoma.     

Papillary breast lesions diagnosed on cytology. Profile of 65 cases

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features. STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases. RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last. CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.     

Cytologic diagnosis of florid peritoneal endosalpingiosis. A case report

The cytologic findings in a case of endosalpingiosis presenting in peritoneal washings taken at the time of staging laparotomy for endocervical adenocarcinoma are described. Dense papillary epithelial clusters with distinct ciliated cell borders were found in the cytologic specimens. Cell nuclei were oval, with finely dispersed chromatin and uniform nuclear membranes. These findings, in conjunction with the discovery of tubal-type epithelial inclusions in pelvic and periaortic lymph nodes, established a diagnosis of endosalpingiosis or benign glandular inclusions involving the pelvic peritoneum and lymph nodes.     

Exfoliative cytology of a primary adenocarcinoma of the renal pelvis. A case report

The cytologic features of a primary adenocarcinoma of the renal pelvis in a 64-year-old woman are reported. Cytologic examination of voided urine revealed an ordinary papillary pattern, characterized by clumping of cells with nuclear overlapping, eccentric position of nuclei and cytoplasmic vacuolization due to mucus production. Leukocytes and micro-organisms were also present. Multiple lesions of papillary adenocarcinoma were subsequently found in the right renal pelvis and ureter. The histogenesis of the primary adenocarcinoma seemed to be closely related to columnar-cell metaplasia of lining of the renal pelvis of this patient, who had previously been treated for tuberculosis of the urinary bladder.     

Müllerian inclusions in peritoneal washings. Potential source of error in cytologic diagnosis

Müllerian inclusions in peritoneal washings from female patients may be mistaken for adenocarcinoma. Such findings were studied in the peritoneal washing cytology specimens from eight cases. The inclusions usually presented as tubular or papillary structures, often forming a single layer of epithelium surrounding psammoma bodies. The cells forming these structures often displayed some degree of atypia. Recognition of this entity in peritoneal fluids is important to avoid a misdiagnosis of disseminated cancer. A general outline is proposed for interpreting such findings in peritoneal washings, based on the cytomorphology of these structures as well as the microscopic features of the primary neoplasms.     

Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial

Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis.     

Stereological estimates of nuclear volume in normal mucosa and carcinoma in situ of the human urinary bladder

The nuclear volume of the epithelial cells in the human urinary bladder mucosa has been estimated using point sampled intercepts in vertical sections (local vertical windows). The study included 27 specimens: ten from normal bladder mucosa, five from inflamed mucosa, seven from mucosa with flat grade II lesions and five from mucosa with flat grade III lesions. After standard fixation, embedding, sectioning and haematoxylin-eosin staining an unbiased estimate of the mean volume of nuclei sampled with a chance proportion to the volume = vV = pi/3 x (l0)3 was calculated using a frame for orientating the linear test probe in vertical sections. Here l0 is the length of the intercept through a test point hitting a nucleus measured in a random direction through the test point. The weighted mean nuclear volume of bladder mucosa with grade II and grade III lesions (537 microns 3 and 494 microns 3 respectively) was significantly larger than the weighted mean nuclear volume of normal (133 microns 3) and inflamed bladder mucosa (182 microns 3). This simple and fast estimation of nuclear volume seems to provide objective data useful in discriminating between neoplastic and non-neoplastic lesions of the bladder mucosa.     

Postoperative bladder washing cytology after transurethral resection. Can it predict the recurrence of urothelial carcinoma?

OBJECTIVE: To assess the ability of postoperative bladder washing cytology, performed immediately after transurethral resection of mostly stage Ta or T1 papillary urothelial carcinoma, to predict early recurrence. STUDY DESIGN: In a 1-year period, preoperative and postoperative bladder washing cytology specimens were sampled from patients undergoing transurethral resections in which all visible tumor was removed. There were 38 resections in 32 patients. RESULTS: Postoperative cytology was satisfactory in 35 of 38 cases and positive in 17 (49%) after a mean of 6.9 months. Follow-up of these 35 transurethral resections disclosed a 15/17 (88%) recurrence rate after positive cytology and a 4/18 (22%) recurrence rate after negative cytology (P < .001). Postoperative cytology demonstrated a sensitivity for recurrence of 79%, specificity of 88%, positive predictive value of 88% and negative predictive value of 77%. In contrast, tumor in the transurethral resection specimen had a positive predictive value of 54% for recurrence, and its grade and stage were inferior to cytology in predicting recurrence. CONCLUSION: Postoperative bladder washing cytology is a useful adjunct to the management of papillary urothelial carcinoma. A positive result, signifying residual tumor, should encourage prompt follow-up and possibly repeat transurethral resection.     

Unusual cytologic findings in low grade papillary transitional cell carcinoma

OBJECTIVE: To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. STUDY DESIGN: We defined the following unusual cytologic findings as "isolated, single cell pattern": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. RESULTS: Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. CONCLUSION: Some LG-pTCCs show many single, atypical transitional cells.     

Cytologic study of noninvasive intraductal papillary-mucinous carcinoma of the pancreas

OBJECTIVE: To examine the cytologic features of noninvasive intraductal papillary-mucinous carcinoma (IPMC) in an attempt to differentiate it cytologically from hyperplasia, invasive IPMC and invasive ductal adenocarcinoma (IDA). STUDY DESIGN: Tumor samples from 23 patients clinically diagnosed with a mucin-producing tumor of the pancreas, including 10 cases of hyperplasia, 10 noninvasive IPMCs and 3 invasive IPMCs, and tumor samples from 21 patients with IDA, were examined cytologically. Cytologic specimens were obtained in various ways, such as by fine needle aspiration, imprint, brushing, vinyl tube aspiration and aspiration from a cannula at endoscopic retrograde cholangiopancreatography. RESULTS: Cytologically, all 10 noninvasive IPMCs exhibited clearly defined cytoplasmic boundaries (+1, ++4, ++ and mainly small nuclei (++7, +++3), with nuclear size and cytoplasm similar to those of hyperplastic cells, and irregular chromatin distribution (+2, ++8) and prominent nucleoli (-2, +4, ++3, +++1), all atypical nuclear features similar to those of invasive IPMC or IDA. There also were small papillary cohesive clusters (-1, +2, ++4, +++3) and euchromatin (+1, ++1, +++8), which were found only in IPMCs. CONCLUSION: The cytologic features of small, malignant nuclei and small papillary cohesive clusters are suggestive of noninvasive IPMC. Furthermore, the addition of clearly defined cell borders and euchromatin and the presence of some goblet cells are more strongly suggestive of noninvasive IPMC.