Daniel A. Fajardo

Non-invasive papillary urothelial neoplasms: The 2004 WHO/ISUP classification system

The classification and grading of papillary urothelial neoplasms has been a long‐standing subject of controversy. Previously, numerous diverse grading schemes for bladder tumor, including the 1973 World Health Organization (WHO) classification, existed whereby one of the major limitations was poor inter‐observer reproducibility among pathologists. The WHO/International Society of Urological Pathology (ISUP) consensus classification system of urothelial neoplasms of the urinary bladder was developed in 1998 and was revised most recently in 2003 (published in 2004). Importantly, the current classification system provides detailed histological criteria for papillary urothelial lesions and allows for designation of a lesion (papillary urothelial neoplasm of low malignant potential) with a negligible risk of progression. Thus, the latest system is designed to be a universally acceptable one for bladder tumors that not only could be effectively used by pathologists, urologists, and oncologists, but also stratifies the tumors into prognostically significant categories. This article outlines the 2004 WHO/ISUP classification system regarding the specific histological criteria for non‐invasive papillary urothelial neoplasms and the clinical significance of each category.

Small Endoscopic Biopsies of the Ureter and Renal Pelvis: Pathologic Pitfalls

Technical advances in endoscopic equipment have led to increased ureteroscopic biopsies of the upper urinary tract, resulting in limited biopsy material. We retrospectively reviewed 76 consecutive mid-upper ureter and renal pelvis biopsies submitted for consultation from January 2004 to January 2009, where follow-up was obtainable. There were 49 (64.5%) males and 27 (35.5%) females. Thirty-nine (51.3%) of the biopsies were from the ureter with the remaining 37 (48.7%) from the renal pelvis. The mean age was 70 years for males and 71 for females (range: 24 to 89). At consultation, the most common diagnoses were benign urothelium (n=25, 32.9%); atypical (n=17, 22.4%); low-grade noninvasive papillary urothelial carcinoma (n=10, 13.2%); and high-grade noninvasive papillary urothelial carcinoma (n=8, 10.5%). In cases where a definitive diagnosis could not be reached on expert review, it was mainly because of the limited size of the biopsy, absence of papillary fronds, crush artifact, and distorted architecture. There were 7 major discrepancies between the outside and second opinion diagnosis, where all of the cases were initially diagnosed as an urothelial neoplasm, yet was non-neoplastic upon review. Strips of urothelium without well-developed fibrovascular cores, polypoid ureteritis/pyelitis, and reactive urothelium mimicked urothelial neoplasms. In 5 of these 7 cases, there was no gross lesion suspicious of a tumor present according to the urologist. Overall, 33 of the 44 (75%) cases with a mass noted by the urologist or by radiography was found to have a neoplasm at follow-up. Conversely, 24 of the 32 (75%) cases without a grossly suspected tumor had no neoplasm at follow-up. The association between the histologic presence of a neoplasm at follow-up and the presence of a clinically suspected tumor was highly significant (P<0.0001). Pathologists need to recognize that in almost 1 of the 4 renal pelvic/ureteral biopsies a definitive diagnosis cannot be made because of the inadequate tissue. Caution must be exercised in the evaluation of these limited specimens, especially in the absence of a clinically suspected tumor.

Low-grade papillary urothelial carcinoma of the urinary bladder: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center.

CONTEXT Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. OBJECTIVE To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. DESIGN Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. RESULTS A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2-113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n = 5; metastatic carcinoma, n = 2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P = .04). CONCLUSIONS A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.

Identification of gleason pattern 5 on prostatic needle core biopsy: Frequency of underdiagnosis and relation to morphology

The presence of a Gleason pattern 5 prostatic adenocarcinoma is associated with a worse outcome. This study assesses the accuracy of grading a tumor as having Gleason pattern 5 and the potential factors contributing to its undergrading. From the consultation service of one of the authors, we identified 59 consecutive needle biopsy cases comprising 138 parts that, upon review, were graded as having Gleason pattern 5. All cases were reported as the final diagnosis by the outside pathologist. They were sent for a second opinion at the behest of clinicians or patients and not because the pathologist was seeking a second opinion. Considering the highest Gleason score in a given multicore specimen as the overall Gleason score, Gleason pattern 5 was missed in 34 of 59 (57.6%) cases by the outside pathologist. Compared with the outside pathologist’s diagnosis, the Gleason score rendered at the second opinion was increased in 101 of 138 (73.2%) parts, was decreased in 5 of 138 (3.6%) parts, and remained unchanged in 32 of 138 (23.2%) parts. Gleason pattern 5 was not identified by the initiating pathologist in 67 of 138 (48.6%) of the evaluated parts. The architectural patterns of pattern 5 were as follows: single cells (n=104, 75.3%); solid sheets (n=69, 50%); cords (n=62, 44.9%); and comedonecrosis (n=3, 2.2%). Pattern 5 was missed more frequently when it was not the primary pattern. The most common Gleason pattern 5 architectural type was single cells and the least common was comedonecrosis. None of the architectural patterns appeared to be more correctly identified than the others; however, the most accurate grading was when the primary pattern was 5 and was composed mostly of solid sheets. Owing to the important prognostic and therapeutic implications of Gleason pattern 5, pathologists must be attuned to its varied patterns and to the fact that it may often represent a secondary or tertiary component of the carcinoma.

Fragmentation of prostatic needle biopsy cores containing adenocarcinoma: the role of specimen submission

Study Type – Diagnostic (case series)
Level of Evidence 4

Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center

Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted.

High-grade papillary urothelial carcinoma of the urinary tract: a clinicopathologic analysis of a post–World Health Organization/International Society of Urological Pathology classification cohort from a single academic center ☆ ☆☆

About one half of all bladder neoplasms are noninvasive, and in those, the histologic grade is a crucial prognosticator. Few single-center studies have assessed the recurrence, progression, and cancer-related mortality rates of noninvasive high-grade papillary urothelial carcinomas. With this aim, we evaluated the clinicopathologic and outcome features of 85 patients with high-grade papillary urothelial carcinoma. Median age was 68 years, and 80.5% were men. Tumor size ranged from 0.3 to 13.0 cm (median, 1.6 cm). Recurrence was found in 36.5% of the patients, whereas tumor progression, defined as invasion of lamina propria or beyond, was identified in 40% of all cases. When present, lesion reappearance involved mostly 1 to 2 episodes. Metastasis appeared in 20% of the patients, and 15% died of disseminated bladder cancer. All cancer-related deaths occurred in the group of patients with progression, whereas patients with recurrence showed similar outcomes to those with no recurrence. For patients with tumor progression, clinical stage was significantly associated with outcome (P = .002). As for prognosis, tumor size was strongly associated with progression (P < .01). In conclusion, recurrence, progression, and cancer-specific mortality rates were 36.5%, 40%, and 15%, respectively. All the patients who died of cancer had a history of tumor progression. Patients with recurrences showed similar outcomes to those with no recurrence. Tumor size was strongly associated with tumor progression and cancer-specific survival, whereas clinical stage was significantly associated with outcome in the progression group. In light of the high recurrence and progression rates of high-grade papillary urothelial carcinoma, strict clinical surveillance aimed to detect early recurrent lesions, especially in patients with larger tumors, is warranted.

High-grade prostatic adenocarcinoma present in a single biopsy core is associated with increased extraprostatic extension, seminal vesicle invasion, and positive surgical margins at prostatectomy.

OBJECTIVE To evaluate the pathologic outcome of prostate-specific antigen-screened patients with high-grade (Gleason score ≥ 8) prostate cancer limited to 1 biopsy core, without clinical evidence of disease. METHODS Ninety-two patients with only 1 biopsy core with cancer and treated by radical prostatectomy were divided into 4 groups according to the biopsy Gleason score: 3 + 3 = 6 (23 cases), 3 + 4 = 7 (25 cases), 4 + 3 = 7 (20 cases), and ≥ 8 (24 cases). RESULTS Cases with Gleason score ≥ 8 showed a significantly higher proportion of extraprostatic extension (50%), positive surgical margins (21%), and seminal vesicle invasion (12%) when compared with the other groups. Patients with Gleason score ≥ 8 in the biopsy had a 25-fold increased in the odds ratio for extraprostatic extension in the prostatectomy. The incidence of extraprostatic extension was higher in those with prostatic cancer involving ≥ 50% of one core (88%) compared with cases involving <50% (32%). CONCLUSION In patients with prostate cancer limited to 1 biopsy core, the presence of Gleason score ≥ 8 significantly increased the incidence of extraprostatic extension, positive surgical margins, and seminal vesicle invasion. The odds ratio was substantially higher in patients with ≥ 50% of Gleason ≥ 8 in the biopsy core. These data might be taken into account for proper clinical management of this set of patients.