Low-grade Papillary Transitional Cell Carcinoma Research Articles

Ovarian Brenner Tumors Revisited: Do We Have Space for Malignant Tumorsvand Methanol

Summary We present a case of a 75-year-old female who underwent a total abdominal hysterectomy with bilateral salpingooophorectomy for an ovarian tumor. Hematoxylin-eosin- stained slides from tumor specimen revealed 1) focci of benign Brenner tumor; 2) mucinous cysts and 3) intracystic papillary projections resembling low-grade papillary transitional cell carcinoma (Grade 1-2) with squamous differentiation and comedo-type necrosis; 4) focal areas resembling noninvasive papillary transitional cell carcinoma Grade 3. Immunohistochemical investigation with a panel of antibodies (p63, p53, Ki-67, Wilms Tumor 1 - WT1, pi 6) was initiated. Areas resembling urothelial carcinoma showed diffuse nuclear positive reaction for p63 and wild-type expression of p53. Ki-67-nuclear positivity varied from less than 5% up to 30% in areas resembling high-grade urothelial carcinoma. WT1 expression was not seen. Weak but still exceeding background staining was observed in predominantly cytoplasmic fashion with few scattered positive nuclei in transitional cell nest of the benign component. No reactivity, however, was seen within the proliferative component. The histopathological diagnosis was a borderline/atypical proliferative Brenner tumor. The patient has been regularly followed up and is at present disease-free 5 years after diagnosis. In this paper, the authors describe the morphological characteristics of Brenner tumors and address some debatable issues in the light of recent immunohistochemical and molecular studies.

Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer

There is substantial evidence for the existence of mutually exclusive molecular pathways to tumorigenesis, in the formation of papillary and invasive carcinomas, respectively. The most common genetic alterations in low grade papillary transitional-cell carcinoma (TCC) are loss of heterozygosity of part or all of chromosome 9 and activating mutations of the fibroblast growth factor receptor 3 (FGFR3). The pathway to development of invasive TCC seems to start with dysplasia, progress to carcinoma in situ, followed by invasion of the lamina propria. The most frequent genetic alteration in dysplasia and carcinoma in situ is mutation of TP53, followed by loss of heterozygosity of chromosome 9. A marker for progression in TCC is loss of chromosome 8p, which occurs in approximately 60% of bladder tumors. Global trends of increased genomic instability and aberrant methylation of cytosine residues in DNA correlate with increased tumor invasion and progression. When researching markers of bladder cancer for clinical use, it is important that biomedical pathways and their alterations are measured in the same tumor populations. This review examines the published data and proposes a model for the mechanisms behind bladder cancer development.

Unusual Cytologic Findings in Low Grade Papillary Transitional Cell Carcinoma

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. 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. 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. Some LG-pTCCs show many single, atypical transitional cells.

Comparison of the WHO/ISUP Classification and Cytokeratin 20 Expression in Predicting the Behavior of Low-Grade Papillary Urothelial Tumors

It has not been possible to identify those low-grade papillary transitional cell bladder tumors that will recur based on conventional histopathologic assessment. Both the new World Health Organization/International Society of Urologic Pathology (WHO/ISUP) classification of transitional cell papillary neoplasms and the pattern of tumor cytokeratin 20 (CK20) immunostaining have been suggested as means of improving prognostication in low-grade transitional cell tumors. Forty-nine low-grade, noninvasive papillary transitional cell tumors were identified for the period between 1984 and 1993. The recently described WHO/ISUP classification was applied, and the tumors were classified histologically as papilloma, papillary neoplasm of low malignant potential (LMP) or low-grade papillary carcinoma. After CK20 immunostaining, the expression pattern in the tumor was classified as normal (superficial) or abnormal. Of 49 tumors, 20 were classified as papillary neoplasms of LMP and five of these patients (25%) experienced a recurrence. Of 29 tumors classified as low-grade papillary carcinoma, 14 (48.2%) recurred. In 46 of 49 cases, the CK20 immunostaining could be evaluated. Sixteen tumors showed normal (superficial) pattern of CK20 expression, and four (25%) of these patients experienced a recurrence. In contrast, of 30 patients with abnormal CK20 staining of their tumors, 15 (50%) patients had one or more recurrences. In this study, papillary neoplasms of LMP (as per the WHO/ISUP classification system) had a lower recurrence rate than low-grade papillary transitional cell carcinoma. Similarly low-grade urothelial tumors showing a normal CK20 expression pattern recurred less frequently than tumors with an abnormal pattern of CK20 staining. Neither of these differences was statistically significant, and recurrences were observed in 20% of patients whose tumors were both classified as papillary neoplasms of LMP and showed normal CK20 immunostaining; thus they do not allow a change in our current management of patients with low-grade papillary urothelial tumors, with close follow-up for all patients.

Papillary Tumour of the Vagina Resembling Transitional Cell Carcinoma

A case of a peculiar papillary neoplasia of the vagina resembling a urothelial tumour is presented. Four vaginal tumours were excised from a 76-year-old woman. Five years before this patient had undergone a uretero-nephrectomy for a non-invasive papillary transitional cell carcinoma of the renal pelvis. The four vaginal tumours demonstrated gross and microscopic similarities to low-grade papillary transitional cell carcinoma of the urinary tract. This observation indicates that multicentric, non-invasive, papillary tumours may affect the whole uro-genital area. The vaginal wall was not overlaid by a normal squamous epithelium, but by a peculiar "transitional-like" epithelium. Variegated endocrine cells were documented within this lining, using immunohistochemical and ultrastructural techniques. The eventuality of a histogenetic link between the tumour and the adjacent epithelial lining remains unresolved.

Nephrogenic adenoma of the urinary bladder: A comparison of its cytologic and histopathologic features in ten cases

We studied the cytologic features of ten cases of nephrogenic adenoma, a benign proliferative lesion of urothelium that is typically associated with prior trauma or urothelial irritation. The typical cytologic features consisted of numerous vacuolated polygonal cells, including signet-ring-like cells, that were isolated or formed papillae or loose groups. Columnar cells and occasional glandular structures were also seen. The cells typically exhibited no or only mild nuclear atypia. There was often a background of acute inflammation. The differential diagnosis of urinary cytologic specimens with these features includes degenerative changes, changes induced by instrumentation, and, most importantly, adenocarcinoma and low-grade papillary transitional-cell carcinoma.

Ureteral intussusception by papillary transitional cell carcinoma

A case of ureteral intussusception caused by a low-grade papillary transitional cell carcinoma of the ureter is described. This is the first case of ureteral intussusception resulting from a malignant tumor of the ureter. The patient presented with weight loss and vague pain in the right lower abdominal quadrant. Right ureterovesical junction obstruction was seen in the retrograde pyeloureterogram. Right nephroureterectomy including a cuff of adjacent bladder wall was performed.

Inverted papillomas of the urinary bladder.

Study of 20 patients with inverted papilloma of the urinary bladder and urethra revealed that the lesion is a true neoplasm, benign in its histologic morphology and clinical behavior. The lesion is believed to arise from the trigone and bladder outlet as a result of chronic proliferative cystitis. It occurs predominantly in men who are past middle age. The most commonly associated clinical symptoms are hematuria and those of urinary obstruction. The lesion may be easily mistaken for a low-grade papillary transitional cell carcinoma, although the histologic appearance is distinctly different, as is its subsequent behavior.