Thin-layer cytology in urinary diagnosis

To evaluate the thin-layer method in urinary cytology we have compared cytospin smears, filter and thin layer. Cellularity, cellular morphology and background were evaluated. Thin layer method in urinary cytology improve cell recovery and cell preservation, reducing background artefact. Cytohistologic correlations with thin layer method were better than with filter and cytospin; an higher capacity to detect low grade transitional cell carcinomas, frequently undiscovered by cytology, was demonstrated.     

Comparison of liquid-liquid extraction-thin layer chromatography with solid-phase extraction-high-performance thin layer chromatography in detection of urinary morphine

Liquid-liquid extraction-thin layer chromatography (LLE-TLC) has been a common and routine combined method for detection of drugs in biological materials.Solid-phase extraction (SPE) is gradually replacing the traditional LLE method.High performance thin layer chromatography (HPTLC) has several advantages over TLC.The present work studied the higher efficiency of a new SPE-HPTLC method over that of a routine LLE-TLC method,in extraction and detection of urinary morphine.Fifty-eight urine samples,primarily identified as morphine-positive samples by a strip test,were re-screened by LLE-TLC and SPE-HPTLC.The results of LLE-TLC and SPE-HPTLC were then compared with each other.The results showed that the SPE-HPTLC detected 74% of total samples as morphine-positive samples whereas the LLE-TLC detected 48% of the same samples.We further discussed the effect of codeine abuse on TLC analysis of urinary morphine.Regarding the importance of morphine detection in urine,the present combined SPE-HPTLC method is suggested as a replacement method for detection of urinary morphine by many reference laboratories.     

Prostatic adenocarcinoma diagnosed by urinary cytology

Prostatic adenocarcinoma rarely may involve the urinary bladder. Prostatic adenocarcinoma and high-grade transitional cell carcinoma (TCC) may coexist and account for the malignant cells seen in urinary cytology. Differentiating prostatic adenocarcinoma cells from those of TCC is important for therapy but remains difficult. A 10-year retrospective search identified 250 patients with high-grade carcinoma in urinary cytology. Among them, 6 cases of tissue-documented prostate adenocarcinoma were identified. The cytologic features of these cases were compared with those of 15 similarly documented cases of high-grade TCC. By using these criteria, 2 additional cases of prostatic adenocarcinoma were diagnosed prospectively. An oval nucleus with smooth borders; fine, powdery, evenly distributed nuclear chromatin and a large prominent nucleolus when present; and lack of significant pleomorphism are most helpful to differentiate prostatic adenocarcinoma from high-grade TCC. Recognizing these cells may be the first clue for the diagnosis of prostate adenocarcinoma.     

Cytological significance of abnormal squamous cells in urinary cytology

The aim of this study was to evaluate the significance of abnormal squamous cells (ASCs) in urinary cytology to clarify whether finding of ASCs could improve diagnostic accuracy. A total of 3,812 urine specimens were reviewed. We focused on three parameters of ASCs, necrotic debris, and ASC clusters, and linked them to histological diagnosis and clinical information. ASCs were identified in 34 (0.9%) specimens from 21 different patients. The incidence of ASCs was higher in females than in males. The 34 urine specimens were categorized as voided urine (16 cases), bladder-catheterized urine (17 cases), and bladder-washed fluid (1 case). Six (28.6%) of 21 patients were histologically diagnosed as having combined urothelial carcinoma and squamous cell carcinoma (SCC). Eight patients (38.1%) were histologically diagnosed as having SCC originating from sites other than the urinary tract; those urine specimens showed ASCs that were likely to have been exfoliated from malignant lesions. Necrotic debris and ASC clusters were identified in 12 specimens (35.3%) from 11 patients and 4 specimens (11.8%) from 4 patients, respectively, from a total of 34 specimens. Our results indicate that a great amount of care is needed for cytological diagnosis when attempting to recognize ASCs in urine specimens because ASCs were identified in not only SCC of the bladder but also in carcinoma or nonmalignant lesions of nonurinary tracts. Necrotic debris was found not only in patients who had malignant bladder tumors but also in those who had malignant lesions in locations other than the bladder.     

尿路上皮癌诊断中 DNA倍体分析和尿脱落细胞学检查的临床价值

目的：探讨DNA倍体分析和尿脱落细胞学检查对尿路上皮癌诊断的临床价值,寻找早期诊断尿路上皮癌的理想方法。方法随机收集121例尿路上皮癌患者的尿液标本作为实验组,另取95例良性血尿非肿瘤患者的尿液标本作为对照组,分别进行尿脱落细胞学检查和DNA倍体分析。结果尿脱落细胞学检查的敏感性高于DNA倍体分析,但特异性低于DNA倍体分析。尿脱落细胞学检查敏感性为85.10%,特异性为76.80%;DNA倍体分析敏感性为81.80%,特异性为81.10%。121例中,膀胱癌103例,上尿路上皮癌18例。对于不同分型的尿路上皮癌,两种方法在高级别肿瘤中均有较好的敏感性,尤其是DNA倍体分析在浸润性膀胱癌和上尿路上皮癌的诊断中具有极好的敏感性,均>94%。结论 DNA倍体分析结合尿脱落细胞学检查,可大大提高尿路上皮癌检测的特异性,以及增加对浸润性膀胱癌及上尿路上皮癌诊断的灵敏度,是对尿路上皮癌检测方法的有利补充。     

Koilocytes in urinary cytology in a patient with kidney transplant

We are reporting the case of a 17-year-old girl with kidney transplant under immunosuppressive treatment. Evidences of transplant malfunction led to urinary cytology to rule out BKV infection. The smears showed the presence of koilocytes. Gynecologic examination revealed numerous condylomatous lesions in the vulva, vagina, and cervix. PAP smears showed cells with moderate to severe koilocytic dysplasia. PCR performed on material retrieved from both the smears showed HPV18 DNA sequences. Koilocytes have rarely been documented in urinary cytologic examination. Since post-transplant immunosuppressed patients are prone to develop florid and extensive HPV infections, urinary cytology may prove useful for routine search of cells with this virus cytopathic effect.     

FISH检测子宫颈病变脱落细胞中EGFR基因扩增及临床应用价值

目的 探讨表皮生长因子受体(epithelial growth factor receptor,EGFR)在子宫颈鳞状上皮内病变中基因扩增及临床意义.方法 在液基细胞学基础上应用荧光原位杂交(FISH)技术检测78例子宫颈各种病变组织[正常组28例、低度鳞状上皮内病变(LSIL)26例和高度鳞状上皮内病变(HSIL)24例]中的EGFR基因扩增情况.结果 EGFR基因扩增阳性率在正常组、LSILs和HSILs中分别是7.14%、23.08%和62.50%,HSILs的阳性率与LSILs及正常组相比均有差异.同时,LSILs随访阳性病例的EGFR基因扩增阳性率与随访阴性病例之间也有差异.另外,比较了部分病例中EGFR基因扩增与HPV的病毒负荷量.结论 EGFR基因扩增在HSILs与随访阳性LSILs中明显增高,提示EGFR基因扩增与子宫颈严重细胞学病变密切相关.因此,EGFR基因扩增可作为巴氏试验中筛查HSILs与预测持续或进展性LSILs的客观遗传学监测指标.     

Evaluation of upper urinary tract tumors by FISH in Chinese patients

Upper urinary tract tumor (UUTT) usually presents a high grade and stage, and recurs frequently. The aim of this study was to evaluate the utility of a fluorescence in situ hybridization (FISH) assay on chromosomes 3, 7, 9, and 17 as a reliable and noninvasive method for the diagnosis of Chinese patients with UUTT. Urine specimens from 50 patients with UUTT and 25 donors without evidence of urothelial tumors were analyzed by cytology and FISH. Voided urine samples from 20 normal individuals were used to establish the cut-off values for FISH assay. The McNemar test was applied for sensitivity and specificity. The overall sensitivity of FISH was statistically significantly greater than that of cytology (84.0 vs. 40.0%, P=0.000). The overall specificities of FISH and urine cytology were all 96.0% (P=1.000). Polysomy in chromosomes 3, 7, and 17 were 38, 42, and 30%, respectively. Heterozygous and homozygous loss of the p16 locus was found in 36 and 32%, respectively. FISH analysis performed on cells collected from voided urine is feasible, and FISH could prove to be a reliable and less invasive ancillary test and improve the sensitivity of urine cytology in the diagnosis of UUTT.     

Atypical squamous cells in exfoliative urinary cytology: clinicopathologic correlates

Presence of atypical squamous cells (ASC) in voided urine is an uncommon finding that may be the harbinger of an underlying malignant process. ASCs in urine may precede a de novo histologic diagnosis of malignancy or be the first sign of a recurrence in the lower urinary tract, or the gynecologic tract (in women). This study analyzed all urine cytology specimens with such diagnoses, with reference to their final histologic outcome. All urine cytology cases (n = 17,446) that included ASCs, evaluated at The Johns Hopkins Hospital between 1989 and 2003 (14 yr), were reviewed for diagnoses. ASCs as defined in this study are keratinizing cells with large and hyperchromatic smudgy nuclei, high N/C ratio, abnormal nuclear or cytoplasmic shapes, and densely orangeophilic cytoplasm. These cases lacked the qualitative and quantitative criteria for malignancy. The final reference outcome was determined by subsequent histologic and clinical follow-up. Of these 17,446 urine specimens, 55 cases (0.3%) from 47 patients had ASCs present. Thirty-two of the 47 patients had adequate follow-up. In 8 of these 32 patients (25%), a diagnosis of squamous-cell carcinoma (SCC) of the urinary bladder or urothelial carcinoma (UC) with squamous differentiation was made on subsequent histologic examination. In two cases (6%) a diagnosis of high-grade cervical SCC was established on subsequent follow-up. Twenty two of 32 cases (69%) remained benign on histologic and prolonged clinical follow-up. We conclude that ASCs in urine are rare (0.3% in this series). An interpretation of ASCs in a urine specimen is made when there is insufficient qualitative/quantitative evidence for a carcinoma diagnosis. ASCs in urine are a clinically valid diagnostic category (31% were later diagnosed with SCC). Most patients with urinary ASCs do not develop malignancy and, therefore, these cells may represent a reactive/inflammatory process most commonly due to vaginal contamination (in women) or exfoliation from the distal urethra (in men). Rarely, ASCs may exfoliate from a uterine cervical SCC and, therefore, a pelvic examination should be considered in such patients.     

Spindling artifact of urothelial cells in post-laser treatment urinary cytology

We reviewed 22 post-laser (Nd:YAG laser) coagulation bladder washes collected immediately after treatment. All washes demonstrated a striking artifact of cellular spindling. These spindled cells occurred singly, in loose clusters, and in lamellar stacks and had elongated nuclei with dense chromatin and bipolar cytoplasm that was fused in the stacks. Concurrent biopsies demonstrated similar cytologic changes. The spindling is a nonspecific epithelial response to heat. Conventionally electrocauterized epithelia show this artifact in biopsies, but since only the base of the lesion and surrounding urothelium are subjected to heat with electrocautery, the relatively few spindled epithelial cells created presumably go undetected in cytology specimens. With laser treatment, however, the whole urothelial surface of the lesion is coagulated, producing a much greater number of spindled cells. It is important to avoid misinterpreting the spindled cells as cells from a mesenchymal neoplasm or a sarcomatoid carcinoma, mistakes that were made in some of our initial cases. Malignancy cannot be evaluated when cells exhibit spindling artifact; this judgement should be made on undistorted cells. Thus, pre-laser and post-laser washes should be submitted for evaluation of malignancy.     

Urinary cytology for carcinoma of the urinary bladder]

Cytologic examinations of voided urine were reviewed for 82 cases of invasive or noninvasive papillary carcinoma and 25 cases of carcinoma in situ of the urinary bladder. Five of the 82 cases of invasive or noninvasive papillary carcinoma and 3 of the 25 cases of carcinoma in situ were asymptomatic, and malignancy was detected only by urinary cytology. Urinary cytology was positive in 18.5% of the Grade 1, 33.3% of the Grade 2, 75% of the Grade 3 noninvasive carcinomas and in 77.8% of the invasive carcinomas. However, all 25 cases of carcinoma in situ gave positive cytologic results. Malignant cells found in Grade 1 noninvasive papillary carcinoma were slightly atypic in shape. Their nuclei were small but showed mild to moderate hyperchromasia. These malignant cells appeared in small clusters but the number of clusters were few. In Grade 2 or 3 noninvasive papillary carcinoma, malignant cells appeared in small clusters or isolated single cells. Their nuclei were irregular in shape and showed moderate to marked hyperchromasia. In invasive carcinoma and carcinoma in situ, many malignant cells with marked atypia were observed, but in carcinoma in situ, the background of the specimens was clean.