Cytology of lleal conduit urine in bladder cancer patients: diagnostic utility and pitfalls

OBJECTIVE: To study the cytomorphology of urine obtained from the ileal conduit and to determine its utility and identify the pitfalls. STUDY DESIGN: Urine specimens from 469 cases of suspected or proven bladder cancer received over a period of 5 years were analyzed in the cytology laboratory. In 35 cases, total bladder resection was followed by ileal conduit reconstruction. The follow-up cytologic analysis of these 35 ileal conduit cases formed the basis of this study. RESULTS: There was absence of urothelial cells in all but 2 cases. The smear predominantly showed small, scattered intestinal mucosal cells with pyknotic nuclei, extensive karyorrhexis and numerous bacteria. In 2 cases, cytology proved superior to endoscopy and radiology in detecting recurrent disease. We had 2 false negative cases, and the negativity was attributed to sampling errors. There was 1 false positive case in which 3-dimensional clusters of intestinal columnar cells were erroneously diagnosed as adenocarcinoma. CONCLUSION: Urine obtained from ileal conduit specimens shows a smear picture that is different from that of specimens from the bladder. Thus, it is imperative to understand the difference between the cytomorphology of bladder urine and ileal conduit urine, to minimize the pitfalls and increase diagnostic utility.     

Small cell carcinoma of the bladder. Two cases diagnosed by urinary cytology

BACKGROUND: Primary small cell carcinoma (SCC) of the bladder is a rare but important entity. We report two cases of SCC of the bladder diagnosed by urinary cytology. CASES: A 71-year-old male (case 1) and a 79-year-old female (case 2) presented with asymptomatic gross hematuria. Urinary cytology in case 1 showed the presence of a few undifferentiated malignant small cells and many transitional cell carcinoma (TCC) cells with a bloody and necrotic background. The former cells were small and round, with naked, hyperchromatic nuclei and finely granular chromatin. Pathologic diagnosis after total cystectomy was TCC > SCC > adenocarcinoma, T2M0N0. Urinary cytology of case 2 showed the presence of many undifferentiated malignant small cells and many TCC cells with or without squamous metaplasia. Cytologic features of the former cells were almost the same as those in case 1. Moreover, these cells were neuroendocrine marker positive by immunocytochemistry. Pathologic diagnosis after tumor resection was SCC and TCC > squamous cell carcinoma, T1b. CONCLUSION: The prognosis of primary SCC of the bladder is usually poor. Because our cases were found by urinary cytology at a relatively early stage, both have been well, without any evidence of recurrence, 30 and 25 months after surgery even without adjuvant therapy.     

Nephrogenic adenoma of the urinary bladder. Histologic and cytologic observations in a case

The histologic and cytologic features of multiple tissue and voided urine specimens from a man with nephrogenic adenoma of the urinary bladder are described. The urinary cytology showed papillary fragments, with cells showing palisade formation. The cells were round to oval, with a centrally placed nucleus with a fine chromatin pattern. These cells were identical to those seen in a low-grade papillary transitional-cell carcinoma. Tissue biopsy is needed to separate these two very different pathologic conditions.     

Comparison of three types of continent urinary diversions in a single center

The results including the complication and continence rates for 3 types of continent urinary diversion were evaluated. From 1992 to 1998 we performed 58 continent urinary diversions after radical cystectomy for invasive transitional cell carcinoma (TCC) of the urinary bladder. All three types of continent diversions and ileal loop procedures were discussed and patient preferences were determined. The patient preference rate for continent urinary diversion was 96.6%, and half of these patients wanted to be completely dry. Mean age of the patients was 58.2 years. Of the 58 patients, 9 (15.5%) had a Kock pouch, 15 (25.8%) had a Kock neobladder and 34 (58.6%) had sigmoidorectal pouch (Mainz-II pouch). Early and late complication rates of the three different continent diversions were evaluated. The number of complications, such as urine leakage, pyelonephritis, hydronephrosis, reflux and stone formation, were similar in all three types of diversions. Two (5.9%) Mainz pouch II patients who had stopped oral alkalinization demonstrated severe hyperchloremic acidosis. Spontaneous pouch rupture occurred in 1 of the Kock pouches. Reoperation rates were higher with the Kock pouch and Kock neobladder cases. Daytime continence rates for the Kock pouch, Kock neobladder and Mainz II pouch were 77.7%, 86.7% and 100% respectively. Even though complete dryness may not be achieved in every patient, orthotopic bladder substitution appears to be the best choice after radical cystectomy. Although it carries the risk of life-long oral alkalinization therapy, the Mainz pouch II is associated with an excellent continence rate and may be a good alternative for patients who desire to be dry.     

Adenocarcinoma with a neuroendocrine component arising in the urachus. A case report

The clinical, cytologic, histologic and ultrastructural findings in a mixed adenocarcinoma and neuroendocrine carcinoma of the urinary bladder urachus, an extremely rare tumor only recently described, are presented for a 31-year-old woman who died of widespread metastatic disease six months following the initial diagnosis and treatment. Cytologic study of voided urine and bladder washings disclosed the presence of malignant cells with the features of a small cell carcinoma; retrospectively, scarce adenocarcinoma cells were also identified in those specimens. Histologic study of resection specimens, including the use of special stains and electron microscopy, confirmed the presence of a small cell component, consistent with the poor prognosis in this case. Image analysis measurements of the malignant cells suggested a high proliferation rate.     

Immunocytochemistry of collagenase expression in transitional cell carcinoma of the bladder

OBJECTIVE: To evaluate the usefulness of collagenase immunocytochemistry as well as its immunohistochemistry in assessing the correlation with prognostic factors in transitional cell carcinoma (TCC) of the urinary bladder. STUDY DESIGN: We investigated the expression of collagenase in catheterized urine and histologic specimens from 38 patients with TCC and 20 cases with benign lesions of the urinary tract. RESULTS: Thirteen (34.2%) and 17 (44.7%) patients with TCC showed positive expression of collagenase on cytologic and histologic specimens, respectively, whereas in no cases with benign lesions was such expression found (P < .01). Invasive and nonpapillary TCC had higher positive rates than noninvasive and papillary TCC. Grade 3 TCC was positive at a higher rate than was grade 2, whereas there were no positive cases with grade 1. Collagenase expression did not correlate significantly with stage. CONCLUSION: Collagenase expression in urinary TCC correlated well with tumor growth pattern, pathologic grade and invasiveness of the carcinoma; all are known to be prognostic factors. The application of collagenase immunostaining to urinary cytology is very useful for assessing prognosis in TCC.     

The use of hierarchic classification in the image analysis of a complex cell population. Experience with the sediment of voided urine

Microscopic analysis of cells in the sediment of voided urine is the principal noninvasive method of diagnosing and detecting cancer of the lower urinary tract, mainly the bladder. The sediments contain several populations of cells of unequal diagnostic value. By applying a system of hierarchic classification to the computer analysis of digitized cell images, we were able to eliminate from diagnostic consideration cells that are difficult to classify, such as degenerated cells, multinucleated cells, cell clusters, renal tubular cells and cells infected by the human polyomavirus. When this method of triage was applied to the images of sequentially encountered epithelial cells and clusters, the cell images accepted for final analysis by the computer were sufficient in number and quality to automatically construct cytologic profiles of documented diagnostic value in 15 patients with bladder cancer. The method proved to be applicable to smears and quantitative cytocentrifuge preparations processed by methods developed in our laboratory. This work clearly documents the feasibility of automated analysis of cells in voided urine for the purpose of diagnosing bladder cancer. It also confirms prior observations suggesting that a relatively small sample of sequential images of epithelial cells (200 to 300) is sufficient to establish a diagnostic profile of clinical value on patients with high-grade cancer of the urinary bladder.     

Cytologic diagnosis of mesonephric adenocarcinoma of the urinary bladder

Mesonephric adenocarcinoma is a rare primary neoplasm of the urinary bladder, composed of papillary and glandular structures with clear-cell features. A case is reported in which cytologic examination of urine specimens showed the distinctive dimorphic cell population of small cells in papillary formations and larger cells with features of a clear-cell adenocarcinoma, permitting a specific diagnosis.     

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.     

Fine needle aspiration diagnosis of transitional cell carcinoma metastatic to the brain. A case report

BACKGROUND: Transitional cell carcinoma (TCC) rarely metastasizes to the brain. In this case, aspiration of a cystic brain lesion was performed and a cytologic diagnosis made. To the best of our knowledge, this is the first reported case of TCC metastatic to the brain diagnosed by fine needle aspiration. CASE: A 72-year-old male with a past medical history of invasive TCC, colonic adenocarcinoma and prostatic adenocarcinoma presented with a large, right, temporal, cystic mass. Fine needle aspiration was performed intraoperatively, and a cytologic diagnosis of metastatic TCC was rendered and confirmed by subsequent tissue examination. CONCLUSION: Intraoperative fine needle aspiration of cystic tumors can be useful in identifying the primary site. The cytologic features of intracerebral metastatic TCC can differ significantly from those observed in urinary tract specimens of high grade TCC. A predominance of large fragments of malignant cells with numerous mitotic figures and apoptotic bodies was seen in the former. The background showed high grade, single transitional cells similar to those observed in urinary tract samples of TCC.     

Metastatic transitional cell carcinoma causing a unilateral pleural effusion: a case report

BACKGROUND: Transitional cell carcinoma (TCC) is a common neoplasm, but it is only rarely associated with serous effusions. The cytologic features of metastatic TCC in pleural effusions have been described only in occasional studies. One feature that raises the possibility of metastatic TCC in this setting is the presence of eosinophilic cytoplasmic inclusions (ECIs). CASE: Metastatic TCC was diagnosed in a pleural fluid from a 50-year-old man with a unilateral effusion. Two years previously he had been diagnosed with a poorly differentiated TCC of the urinary bladder (WHO grade 3, stage pT2 at least), and more recently he had also been diagnosed with an omental metastasis. Cytologic examination of the pleural fluid sample revealed numerous pleomorphic malignant cells, many of which were vacuolated. Numerous eosinophilic inclusions were identified within the malignant cells in the liquid based cytology (ThinPrep) preparation. Examination of the omental cake biopsy revealed similar appearances. CONCLUSION: ECIs within malignant pleural effusion fluid specimens should, if detected, raise the possibility of metastatic transitional cell carcinoma.     

Urine cytology evaluation in cases of uretero-ileal cutaneous diversion

Cytological examination of urine from the ileal conduit in cases of bladder cancer treated by radical surgery can be an important and effective follow-up procedure. A total of 19 patients (18 males and one female) on whom radical cystectomy for cancer was performed were studied. Three urine specimens were examined in each case using routine cytological methods. Three cases of recurrent carcinoma (mainly of papillary type) were diagnosed cytologically before any clinical evidence of disease. the cytological examination of urine at 3-6 month intervals after cystectomy for bladder carcinoma is considered advisable in all cases, since the recurrence rate of transitional cell neoplasms in the upper urinary tract after cystectomy for transitional carcinoma is quite high.     

Microglandular hyperplasia of the uterine cervix. Cytologic diagnosis in cervical smears

OBJECTIVE: To identify cytomorphologic features specific to microglandular hyperplasia (MGH) in cervical cytologic smears. STUDY DESIGN: Twenty-four cervical smears from 24 patients obtained before the histologic diagnosis of MGH made on colposcopically directed biopsies during a period of two years (1995-1997) were evaluated. RESULTS: Of cases with MGH, 13/24 (54%) showed the presence of bidimensional or tridimensional cellular clusters made up of cubic or cylindrical glandular cells with vacuolated cytoplasm; cells with dense cytoplasm, basaloid in appearance, corresponding to immature squamous metaplasia; and subcylindrical reserve cells with small, round nuclei and scant cytoplasm. Clusters showed microlumina or fenestrated spaces, preserved polarity and absence of nuclear peripheral dispersion. In the control group these cellular clusters were found in 6/100 (6%). Statistical analysis (chi 2) showed a strong, highly significant association (P < 0.001) of the cytologic parameters selected and the histologic diagnosis of MGH. CONCLUSION: Until now, no specific cytologic parameters were described for MGH. This study underscored the value of cytomorphologic parameters described for typical cellular clusters showing microlumina or fenestrated spaces with shared party walls and an admixture of glandular cells, and immature squamous metaplastic and subcylindrical reserve cells in the cytologic diagnosis of MGH.     

Cytologic features of subependymal giant cell astrocytom: a review of 7 cases

OBJECTIVE: To describe the cytologic features of subependymal giant cell astrocytoma (SEGA) on smears and analyze cytomorphologic parameters that may help in reaching the diagnosis of SEGA. STUDY DESIGN: Cytologic smears of 7 cases of SEGA were reviewed and graded semi-quantitatively for 11 cytologic features: clustering, cytoplasmic fibrillary processes (fibrillarity), cellularity, small prominent nudcleoli, binucleation or multinucleation, "strap cells", spindle-shaped cells, mitoses, intranuclear inclusions, nuclear atypia and perivascular palisading/pseudorosettes. Corresponding histologic sections were also reviewed. RESULTS: The study included 5 male and 2 female patients with an average age of 8.3 years (range, 3-16) at surgery. Cytologic examination revealed loosely cohesive clusters of large cells possessing round to oval nuclei with no or minimal atypia; fine, evenly distributed chromatin; and abundant eosinophilic cytoplasm enmeshed in abundant thin, hairlike processes. Predominant features included hypercellularity, cell clustering, and fibrillarity. Binucleation or multinucleation; small, prominent nucleoli; and strap cells were often seen. Although common in histologic sections, perivascular palisading/pseudorosettes and spindled astrocytic cells were rarely noted on smears. CONCLUSION: The cytologic features of SEGA are highly characteristic and thus are of great use in supporting a diagnosis of SEGA and in excluding mimics, primarily gemistocytic astrocytoma and ependymoma.     

Cytology of bladder papilloma

Eighty-four urinary cytology specimens from 51 patients known to have bladder papilloma were reviewed and compared with 30 specimens from patients without neoplastic urologic disease, 12 specimens from patients later found to have papillomas that were unsuspected at the time of examination and 6 specimens from patients with a history of papilloma but no present evidence of the disease. No specific findings were identified that could be used to make a cytologic diagnosis of papilloma. However, the specimens from patients with papilloma were likely to contain an increased number of exfoliated epithelial cells, including atypically shaped cells that were small and round or, less frequently, elongated; they were also likely to contain a small number of red blood cells. This combination of cytologic findings yielded a pattern that can be described as consistent with or suggestive of papilloma in the appropriate clinical setting. It is not diagnostic since the absence of this cytologic pattern does not rule out papilloma, and the same cytologic features can be found (less frequently) in patients with other urologic diseases.     

Cytologic evaluation of low grade transitional cell carcinoma and instrument artifact in bladder washings

OBJECTIVE: To identify key cytologic features for the separation of low grade transitional cell carcinomas (TCCs) from nonneoplastic lesions in bladder washings. STUDY DESIGN: The cytomorphologic features of 95 bladder washing specimens showing papillary fragments, which included 50 low grade TCCs and 45 nonneoplastic lesions, were reviewed retrospectively. RESULTS: Bladder washings from low grade TCCs showed papillary and irregular groups of cells with ragged borders, cytoplasmic homogeneity and subtle nuclear changes, such as increased nuclear/cytoplasmic ratio and irregular nuclear border. Bladder washings after instrumentation from nonneoplastic lesions of the bladder showed cellular specimens with cohesive, ball-shaped and papillary clusters with smooth borders lined with a denser-staining cytoplasmic collar. Reactive urothelial cells often displayed loose aggregates with irregular borders but no cytoplasmic collar. CONCLUSION: In bladder washing cytology, nuclear changes and cytoplasmic homogeneity play a major role in the diagnosis of carcinoma.     

Expression of cytokeratin 20 in urine cytology smears: a potential marker for the detection of urothelial carcinoma

BACKGROUND: Urine cytomorphology is one of the oldest methods for screening and monitoring patients with transitional cell carcinoma (TCC). Sensitivity of urine cytology is relatively low. Ancillary techniques on urine sample may increase the sensitivity. AIM: To explore the utility of cytokeratin 20 (CK20) immunostaining in identifying malignant cells in urine cytology smears. MATERIALS AND METHODS: Fourteen cases each of confirmed TCC and benign urinary cytology along with five cases of atypical cells in urine were immunostained with a monoclonal CK20 antibody. Of 14 cases of TCC, 12 showed strong positive staining with the antibody. All benign cases were negative except for a few cases in which the umbrella cells were weakly to moderately positive. In all five cases of atypical urine cytology the atypical cells stained positive with the antibody. These cases were later confirmed as TCC on histopathology of bladder wall biopsy. CONCLUSION: CK20 is an important biomarker that can be used to identify TCC in urine cytology smears. It is particularly useful in those cases where malignancy cannot be confirmed by morphology alone.     

Cytologic diagnosis of small cell anaplastic hepatoblastoma: a case report

BACKGROUND: Small cell anaplastic hepatoblastoma (HB) is the least common subtype of HB. There are few articles in the literature describing the cytologic characteristics of this rare subtype. CASE: A 5-year-old girl present with a progressively enlarging abdominal mass. Ultrasound examination revealed the mass to be arising within the right lobe of the liver. Fine needle aspiration (FNA) of the mass revealed primitive cells with a high nuclear/cytoplasmic ratio and hyperchromatic, ovoid nuclei in poorly cohesive clusters as well as dispersed singly. These cells closely resembled those of small round cell tumors of childhood. CONCLUSION: The cytologic differential diagnosis of undifferentiated HB must include small round cell tumors of childhood. With knowledge of the typical cytomorphologic appearance of HB in association with clinical and radiologic information, one can offer a reliable preoperative diagnosis on FNA.     

Thin-layer cytology findings of small cell carcinoma of the lower female genital tract. Review of three cases with molecular analysis

OBJECTIVE: To describe the thin-layer cytology findings of small cell carcinoma of the low female genital tract, with histologic correlation and human papillomavirus (HPV) genotyping. STUDY DESIGN: The authors reviewed the clinical findings, thin-layer cytology and histologic features of small cell carcinoma of the lower female genital tract (cervix or vagina) occurring in three postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, over a four-year period, from January 1998 to December 2001. Molecular techniques for HPV screening and genotyping using the polymerase chain reaction and restriction fragment length polymorphism were employed on the cytologic specimens. RESULTS: The thin-layer preparations were of moderate to high cellularity. There were loose aggregates of or isolated small round cells with a high nuclear/cytoplasmic ratio, thin but irregular nuclear membrane, hyperchromatic nuclei, inconspicuous nucleoli and scanty cytoplasm. Tumor cell cannibalism was commonly found. Small groups of tumor cells with nuclear molding were noted. There was also obvious tumor diathesis in the background. The necrotic debris was admixed with isolated small round cells, apoptotic bodies and nuclear dust. Associated koilocytosis or squamous intraepithelial lesions were not seen. Histologic examination of the tumor biopsies showed classic features of small cell carcinoma associated with squashing artifacts and vascularized stroma. Molecular analysis revealed the presence of HPV DNA (either type 18 or 16) in all the three liquid-based cytology samples. CONCLUSION: While the cytomorphologic features of small cell carcinoma of the cervix or vagina in thin-layer preparations are slightly different from those in conventional smears, due mainly to the absence of smearing effect, recognition of the subtle but characteristic appearance can enhance the accuracy of the cytologic diagnosis. The association between HPV and primary small cell carcinoma of the lower female genital tract was confirmed by this study.