Cytopathology of extramedullary plasmacytoma of the bladder: a case report

BACKGROUND: Plasmacytoma of the bladder is an extremely rare tumor, with all information concerning this neoplasm derived from case reports. It can be a major diagnostic pitfall on both histology and urine cytology. CASE: A 95-year-old woman presented with gross hematuria and a large bladder mass detected by ultrasound. The case was initially misdiagnosed as a high grade urothelial carcinoma. Since the urine cytology did not show the classical cytologic features of urothelial carcinoma, the histologic sections were reviewed and immunohistochemical staining performed. The final diagnosis was plasmacytoma of the bladder. Subsequently the patient underwent a skeletal survey and bone scan, which did not reveal any lesion suspicious for multiple myeloma. The patient was scheduled for radiotherapy. CONCLUSION: In this case of bladder plasmacytoma, urine cytology provided a clue to the diagnosis. Urine cytology can be a diagnostic tool to help make this diagnosis in the case of poorly differentiated bladder neoplasm, especially in a patient with a known history of multiple myeloma.     

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.     

Cytologic detection of urothelial cancer and other abnormalities in a cohort of workers exposed to aromatic amines

A total of 541 members of a cohort at increased risk for occupational bladder cancer underwent a 33-month program of screening with urine cytology. Selected workers received further urologic study with cystoscopy and bladder biopsies. Eight workers had positive or suspicious cytologic findings. Only one of the eight had a prior history of bladder cancer. Biopsies showed invasive carcinoma and/or nonpapillary carcinoma in situ in five workers in this group, severe atypia in one, and no significant abnormality in two. Of 56 workers who had atypical cytologic findings, 16 had bladder biopsies, which showed atypia of flat urothelium in 11, nonpapillary carcinoma in situ in one, noninfiltrating papillary carcinoma in one, and no significant abnormality in three. The cytologic detection of urothelial abnormalities often required more than a single specimen. Since the cohort in this study may develop more bladder cancers with the passage of time, continued follow-up is indicated.     

Plasmacytoma with involvement of the urinary bladder. Report of a case diagnosed by urine cytology

BACKGROUND: Plasmacytoma of the bladder is a rare but important entity. We report a case of plasmacytoma of the bladder that was diagnosed by urinary cytology. CASE: A 71-year-old male with a history of multiple myeloma presented in renal failure. Renal ultrasound revealed right-sided, moderate hydronephrosis with a 4 x 4-cm, posterolateral, obstructing mass. Magnetic resonance imaging demonstrated a bladder mass involving the bladder base, right lateral wall and dome with extension into the perivesical tissues on the right. The mass showed a moderate degree of enhancement following intravenous gadolinium administration. Urine cytology was performed to evaluate for bladder carcinoma or other malignancies besides plasmacytoma. The specimen was signed out as multiple myeloma of the bladder. Cystoscopy and biopsy were subsequently performed on the bladder mass. The diagnosis of plasmocytoma was made, confirming the urine cytology diagnosis. CONCLUSION: Urinary cytology can be a diagnostic tool for plasmocytoma involving the bladder.     

Use of cytomorphometry and cytology in the diagnosis of transitional-cell carcinoma of the upper urinary tract

Because of the rise in incidence of upper urinary tract tumors, there is a need for a simple and reliable method for diagnosing these tumors, especially in people in a "high-risk" group. This retrospective study showed the usefulness of cytology and cytomorphometry in making the diagnosis of transitional-cell carcinoma of the upper urinary tract. The study also emphasized that the methods of collection and processing are of the utmost importance: the cytologic evaluation of ureteral catheterized urine specimens gave 100% accuracy as compared with a 40% false-negative rate in the cytologic diagnosis of voided urine specimens. A higher accuracy of urinary cytology for the diagnosis of upper urinary tract lesions clearly requires selective catheterization of the ureter. Objective cytomorphologic grading of the urinary cytology specimens was shown to compare favorably with histologic grading. Cytomorphologic grading not only can offer important information in determining the prognosis and in planning treatment but can also assist in quality control of other diagnostic methods and can help to resolve apparent diagnostic discrepancies.     

Expression of vimentin and high‐molecular‐weight cytokeratin (clone 34ßE12) in differentiating reactive renal tubular cells from low‐grade urothelial carcinoma cells in voided urine

H. Ohsaki, E. Hirakawa, M. Nakamura, Y. Norimatsu, H. Kiyomoto and R. Haba Expression of vimentin and high‐molecular‐weight cytokeratin (clone 34ßE12) in differentiating reactive renal tubular cells from low‐grade urothelial carcinoma cells in voided urine Objective: Reactive renal tubular cells show features of an atypical repair reaction. Differentiation between reactive renal tubular cells and low‐grade urothelial carcinoma (LG‐UC) cells can therefore be a diagnostic challenge based on morphology alone. In this study, we evaluated the diagnostic utility of vimentin and a high‐molecular‐weight cytokeratin antibody (clone 34ßE12) in differentiating reactive renal tubular cells from LG‐UC. Methods: We evaluated voided urine cytology and surgical specimens from 40 patients with renal disease, and 17 patients with LG‐UC. All slides were stained with vimentin and 34ßE12. Results: In the reactive renal tubular cells in voided urine cytology, vimentin showed strong cytoplasmic staining in 39/40 (97.5%) cases, but all were negative for 34ßE12. LG‐UC cells showed positive staining for 34ßE12 in 3/17 (17.6%) cases, whereas none were positivity for vimentin. The reactive renal tubular cells of histological specimens in the renal disease group demonstrated positive for vimentin in all 40 cases and all were negative for 34ßE12. The LG‐UC group showed abnormal staining for 34ßE12 in 4/17 (23.5%) cases, whereas none were positive for vimentin. Conclusions: Vimentin expression in urine cytology can help to distinguish reactive renal tubular cells from LG‐UC. However, 34ßE12 does not appear to be a useful adjunct to distinguish these two groups in voided urine cytology.     

Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue

Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue We have evaluated the possibility of using the same specimen for both cytological diagnosis and multitarget multicolour FISH (MtMcFISH) analysis in order to determine whether the routinely processed specimens used for diagnosis were also suitable for this ancillary procedure. For this purpose 18 positive samples (11 voided urine and seven bladder washings) were selected, together with a representative section of the corresponding immediately previous or subsequent histological specimens. Two negative cytology slides were added as negative controls. FISH analysis revealed a normal pattern for each probe in the two negative controls and an abnormal pattern in the 18 positive cases. In the latter the same FISH alterations were found in the cytology samples and in the corresponding histological sections, and superimposable cytological/histological features were observed in two cases where two different histology samples were analyzed. The results clearly show that MtMcFISH may be successfully applied to destained routinely processed cytology slides.     

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? – experience at Kuwait University

Objectives:  This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology.
Methods:  Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls.
Results:  Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result.
Conclusion:  Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.     

Detection of bladder carcinoma in females by flow cytometry and cytology

The sensitivity of bladder wash flow cytometry (BWFCM), voided urinary cytology (VUC), and cytology of catheterized urine obtained at the time of cystoscopy (CUC) were reviewed on all women evaluated for bladder cancer at Memorial Sloan-Kettering Cancer Center between June 1985 and December 1986. This comprised sixty-four episodes of pathologically proven bladder cancer in 48 women. Considering positive and suspicious results jointly the sensitivities of BWFCM, CUC and 3 VUC were 75%, 64% and 56%, respectively. If only positive results were considered (i.e., suspicious results considered as negative), the sensitivities of BWFCM, CUC and 3 VUC were 64%, 31% and 32%, respectively. The sensitivities of these tests are less than for a predominantly male population, presumably related to the presence of squamous epithelium and greater frequency of pyuria. However, bladder wash flow cytometry and conventional cytology are still a very valuable addition to cystoscopic examination, and the combination of BWFCM with conventional cytology is more sensitive than either procedure alone.     

GLPp16/CSP17 探针在膀胱尿路上皮癌诊断中的应用

目的:探讨荧光原位杂交技术辅助诊断膀胱尿路上皮癌的可行性。方法:标记为17号染色体着丝粒及9号染色体p16位点9p21区带探针,采用荧光原位杂交技术(Fluorescence in Situ Hybridization FISH)对80例膀胱肿瘤患者尿液间期细胞核进行荧光原位杂交,以20例健康志愿者作为正常对照组,建立阈值。以术后病理结果作为诊断"金标准",对80例膀胱肿瘤患者同时行尿脱落细胞学检查,与FISH进行比较。结果:17号染色体和9p21的畸变率分别为57.5%和63.8%。17号染色体畸变率主要表现为多倍体,与膀胱癌的分级有显著相关性(P<0.01);9号染色体畸变率主要变现为染色体缺失,与膀胱癌分期分级均无相关性(P>0.05)。尿脱落细胞学灵敏度为12.2%,FTSH技术灵敏度为86.5%;两者差异有统计学意义(P<0.01)。结论:荧光原位杂交技术可以作为膀胱尿路上皮癌诊断的一项重要方法,并可能在预后判断中具有重要临床意义。     

Cell cannibalism and nucleus-fragmented cells in voided urine: useful parameters for cytologic diagnosis of low-grade urothelial carcinoma

OBJECTIVE: To clarify whether the 3 parameters of cell clusters, cell cannibalism and nucleus-fragmented cells could improve diagnostic accuracy for grade 1 urothelial carcinoma (G1UC). STUDY DESIGN: A total of 52 voided urine samples from 31 patients histologically diagnosed as having G1UC were reviewed. In addition, 10 voided urine samples from cases with grade 3 demonstration urothelial carcinoma (G3UC) and 30 voided urine samples from 25 patients with a histologic diagnosis of chronic inflammation of the bladder were evaluated for comparison. Areas of tumor cells with cannibalism were measured. RESULTS: Cell cannibalism was evident in 12 of 31 G1UC cases (38.7%), significantly less often than with G3UC, but never identified in the control group. Mean areas of tumor cells featuring cannibalism were significantly smaller in G1 UC than in G3UC cases. Nucleus-fragmented cells were also less frequent in G1UC than in G3UC, but more common than in the control group. CONCLUSION: Cell cannibalism and nucleus-fragmented cells in voided urine with special attention to areas of tumor cell with cannibalism could be applied as a parameter to improve diagnostic accuracy for G1UC.     

The diagnostic accuracy of sputum and urine cytology

The diagnostic accuracies of sputum and urinary cytology were examined in series spanning more than 20 years. The sensitivity and respiratory tract cytology in 1,289 patients with subsequently proven lung cancer was 69% while that or urine cytology in 860 patients with urinary tract cancer was 77%. The specificities were 96% for lung cancer and 97% for urinary tract cancer. Neither procedure was widely used for routine screening, but diagnostic cytology played an important part in providing a definite morphologic diagnosis in many of these cases. Urinary cytology was also very effective in the follow-up of patients with treated bladder cancer because of its high sensitivity for detecting carcinoma in situ.     

Significance of tissue fragments in voided urine specimens

OBJECTIVE: To determine the diagnostic significance of tissue fragments in voided urine specimens. STUDY DESIGN: We reviewed all the voided urine specimens collected and processed by the Millipore filter technique (Bedford, Massachusetts, U.S.A.) at our institution between January 1, 1997, and December 31, 1998, and the corresponding biopsies obtained within 120 days after urine examination. The type and number of tissue fragments were correlated with the histologic diagnosis and clinical features; the results were compared to those from a recently published study. RESULTS: Of the 2,553 voided urine specimens examined, 174 (7%) had corresponding biopsies. Cell groups (tissue fragments) consisting of either flat sheets or three-dimensional structures were significantly more common (57%) (chi 2 P < .005) in urine specimens with biopsies revealing urothelial malignancies than in negative biopsies (6%). Three-dimensional groups were also statistically more common in cases with invasive transitional cell carcinoma. Proper identification of tissue fragments was highly significant and correlated with urothelial neoplastic changes. CONCLUSION: The results of the present investigation using the Millipore filter technique for voided urine cytology processing, differed from those of a recently published study that employed cytocentrifugation. Tissue fragments, to be differentiated from groups, clumps or clusters that often result from centrifugation and other concentration artifacts, were strongly associated with urothelial neoplasia, uncommonly with nonneoplastic disease processes affecting the urinary tract but always with urothelial disease.     

Polyomavirus infection versus high-grade bladder carcinoma. The importance of cytologic and comparative morphometric studies of plastic-embedded voided urine sediments

The cytodiagnostic criteria of polyomavirus infection of the urinary tract versus high-grade bladder carcinoma in Cytospin and plastic-embedded preparations of voided urine samples are presented. In Cytospin preparations, the polyomavirus infection and the high-grade bladder carcinoma could not always be distinguished from each other. The diagnosis was facilitated when plastic-embedded specimens were used for cytologic study. On the basis of the comparison of morphometric data from the two types of specimens, it is postulated that the physical properties of the cancer cell nuclei differ from those of the virocytes.     

Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for the detection of bladder cancer

Bladder cancer is the fifth most common cancer in adults. Because of the high recurrence rate (up to 70%) new tumor markers for urine are necessary for monitoring patients. In this study, we investigated the value of M-FISH on cells from urine for the detection of bladder cancer. Urine samples from 141 patients suspicious of bladder cancer were analyzed in this study. Cells were isolated from urine before surgical therapy. For FISH analysis, a commercial kit (UroVysion) containing hybridization probes for chromosomes 3, 7, 9p21 and 17, was used. Twenty-five cells were analyzed in each case by two observers. A FISH result was obtained in 121 cases. Overall, sensitivity was 60% and specificity reached 82.6%. Sensitivity and specificity by cytology were 24.1% and 90.5%, respectively. Analyzing results concerning T-category, sensitivity of FISH and cytology was 36.1% and 15% in pTa, 65.2 and 25.7% in pT1, 100% and 66.7% in pT2-3 tumors, respectively. Concerning tumor grade, similar results were obtained: sensitivity was 37% and 14% in G1, 65.4% and 40% in G2, 91.7% and 50% in G3 tumors, for FISH and cytology, respectively. In conclusion, FISH on cells from urine has been shown in all studies to be highly sensitive and specific for detection of bladder cancer. Sensitivity of FISH is higher than conventional cytology and can be used in routine diagnosis additionally to conventional cytology especially in doubtful or negative cases. FISH can detect recurrence earlier than other methods like cytology, cystoscopy or biopsy histological examination.     

Size-Based Enrichment of Exfoliated Tumor Cells in Urine Increases the Sensitivity for DNA-Based Detection of Bladder Cancer

Bladder cancer is diagnosed by cystoscopy, a costly and invasive procedure that is associated with patient discomfort. Analysis of tumor-specific markers in DNA from sediments of voided urine has the potential for non-invasive detection of bladder cancer; however, the sensitivity is limited by low fractions and small numbers of tumor cells exfoliated into the urine from low-grade tumors. The purpose of this study was to improve the sensitivity for non-invasive detection of bladder cancer by size-based capture and enrichment of tumor cells in urine. In a split-sample set-up, urine from a consecutive series of patients with primary or recurrent bladder tumors (N = 189) was processed by microfiltration using a membrane filter with a defined pore-size, and sedimentation by centrifugation, respectively. DNA from the samples was analyzed for seven bladder tumor-associated methylation markers using MethyLight and pyrosequencing assays. The fraction of tumor-derived DNA was higher in the filter samples than in the corresponding sediments for all markers (p<0.000001). Across all tumor stages, the number of cases positive for one or more markers was 87% in filter samples compared to 80% in the corresponding sediments. The largest increase in sensitivity was achieved in low-grade Ta tumors, with 82 out of 98 cases positive in the filter samples (84%) versus 74 out of 98 in the sediments (75%). Our results show that pre-analytic processing of voided urine by size-based filtration can increase the sensitivity for DNA-based detection of bladder cancer.     

Urothelial neoplasms of the upper urinary tract. A correlation between cytologic and histologic findings in 43 patients with urothelial neoplasms of the renal pelvis or ureter.

The present study elucidates the possibilities to diagnose and classify urothelial tumors of the upper urinary tract by means of exfoliative cytology on voided urine using a membrane filter method. In a series of 30 patients with renal pelvic tumors and 13 patients with ureteral tumors an overall agreement between cytology and histopathology was obtained in 25 cases (58%). None of the Grade 1 tumors or of the non-invasive Grade 2 tumors were regarded as positive by cytology whilst two out of five invasive Grade 2 tumors had positive cytologic reports. The series included 24 patients with poorly differentiated or anaplastic tumors, 17 of whom had positive cytology (71%). By excluding from the series 13 patients with obstructed urinary passages or radiologically non-functioning kidneys on the tumor side an agreement between cytology and pathology was reached in 83 per cent of the cases, regardless of tumor grade, and in 17 out of 18 patients with Grade 3-4 tumors (94%).     

Free DNA in urine: a new marker for bladder cancer? Preliminary data

The aim of the present preliminary study was to investigate the presence of free DNA (FDNA) in urine as a possible marker for the diagnosis of bladder cancer. Naturally voided morning urine specimens were collected from 57 patients with suspected bladder cancer before cystoscopy. A standard urine test was performed; the specimens were then processed in order to obtain a quantitative evaluation of the presence of free DNA in the urine. Twenty-two patients were excluded from the study because they had leukocyturia and/or bacteriuria. Free DNA concentrations higher than 250 ng/mL were found in all 16 patients showing bladder cancer at cystoscopy and in seven (36.8%) of the 19 patients with negative cystoscopy. Urinary FDNA seems to have an excellent sensitivity: we observed no false negative cases and 36.8% false positive cases. By contrast, only 6.25% of the bladder cancer patients had positive urine cytology. Our results seem promising, although further studies and larger numbers are needed to define urinary free DNA as a reliable marker of bladder cancer.     

Primary malignant melanoma of the urinary bladder diagnosed by urine cytology: a case report

BACKGROUND: Primary melanoma of the urinary bladder is a rare neoplasm, and there have been no prior reports in which the initial diagnosis was made by urinary cytology. CASE: An 82-year-old woman presented with vaginal spotting, gross hematuria and dysuria. Voided urine cytology revealed malignant cells, several of which exhibited cytoplasmic melanin pigment and were accompanied by many macrophages also containing melanin. Cystoscopy revealed a darkly pigmented, polypoid mass at the bladder neck. Biopsy confirmed the diagnosis. CONCLUSION: Primary melanoma of the urinary bladder is rare. The diagnosis can be made on cytologic examination of voided urine if careful study of exfoliated malignant cells reveals cytoplasmic melanin pigment. Macrophages may also harbor melanin pigment, and their presence should alert the cytopathologist to search carefully for pigmented malignant cells. Clinical and radiologic studies are essential to rule out melanoma metastatic to the bladder.     

Urinary tract cytology

Tumors of the urinary tract are relatively inaccessible to direct biopsy and are often multifocal. Since urine is easily ortained and washes over the entire mucosal surface, urine cytology is, in theory, the perfect specimen to examine to detect a tumor. Unfortunately, interpretation of urine cytology is difficult, and both false-negative and false-positive results are very well known. Diagnostic accuracy increases with the grade of the tumor. Low-grade noninvasive papillary tumors are the sources of most false-negatives. Reactive and degenerative changes due to conditions such as inflammation, stones, prostatic hyperplasia, and therapy are responsible for most false-positives. This lecture will review basic urine cytology and give some pointers to help avoid diagnostic pitfalls.