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* Context.-Metastatic pleomorphic lobular carcinoma (MPLC) to the bladder is rare and has considerable histologic and immunohistochemical overlap with plasmacytoid urothelial carcinoma (PUC). Objective.-To distinguish MPLC from PUC morphologically and immunohistochemically, including a newer marker, TRPS1. Design.-Ten MPLCs to the bladder were reassessed and stained with estrogen, progesterone, and androgen receptors; GATA3; keratin 5/6; HMWK; GCDFP-15; and TRPSl. Sixteen PUCs constituted controls. Results.-We studied 4 transurethral resections of bladder tumors and 6 biopsies from 10 women (median age, 69 years) who had breast cancer on average 15 years prior. Microscopic patterns included single cells and cords of cells (n = 4), nests/sheets of dyscohesive cells (n = 2), or both (n = 4). All tumors had cells with voluminous eosinophilic cytoplasm and eccentric nuclei mimicking PUC, and 7 of 10 tumors had signet ring cells. MPLCs were positive for estrogen (8 of 10), progesterone (3 of 7), and androgen (4 of 10) receptors; GCDFP-15 (7 of 10); GATA3 (9 of 10); HMWK (7 of 8); and TRPS1 (7 of 10). No MPLCs stained for keratin 5/6 (n = 9). Of 16 PUCs, 2 showed faint and 2 demonstrated strong TRSP1 staining; 7 of 16 were negative for p63. Conclusions.-MPLC to bladder often presents in patients with a remote history of breast cancer, exhibiting significant histologic and immunohistochemical overlap with PUC. Based on prior works and the current study, estrogen receptor (particularly SP-1), mammaglobin, and p63 help differentiate MPLC from PUC. Keratin 5/6 may aid in distinguishing a less frequent basal-type PUC because it is typically negative in MPLC. Some PUCs express TRPS1. Caution should be exercised because immunophenotypes of these tumors greatly overlap, and ramifications of misclassification are major. (Arch Pathol Lab Med. 2024;148:1110-1118; doi: 10.5858/arpa.2023-0379-OA), Conventional invasive lobular carcinoma of the breast accounts for 10% to 15% of all breast carcinomas and is the second most common histologic subtype of breast cancer. (1,2) It is [...]

* Context.--Retraction artifact, paradoxic maturation/ differentiation, desmoplasia, and complex irregular growth are morphologic criteria of invasion in urothelial carcinoma. Objective.--To describe changes mimicking invasion in noninvasive papillary urothelial carcinoma (NPUC). Design.--We reviewed 159 consecutive in-house patients with NPUC for either the presence of pseudoinvasion (irregular carcinoma nests within dense hyalinized stroma in the absence of other criteria of invasion) or precursor findings (stromal hyalinization not yet associated with epithelial architectural alteration). We assessed the correlation of these findings with age, sex, evidence of peripheral vascular disease, tumor grade, tumor infarction, and tumor size. We then followed up the patients clinically for tumor recurrence or progression. Results.--We identified 233 separate NPUCs (136 high grade and 97 low grade) in 125 men and 34 women. Of the 233 tumors, 26 (11.2%) had pseudoinvasion and 24 of 233 tumors (10.3%) had precursor findings. Except for complex irregular growth, no other criteria for invasion were seen. Pseudoinvasion and precursor findings were more common in men (47 of 183 [26%] versus 3 of 50 [6%]; P = .003), larger tumors (mean size, 2.6 versus 1.2 cm; P < .001), and tumors with infarction (33 of 50 [66%] versus 29 of 183 [15.8%]; P Conclusions.--Given the correlation with size and presence of infarcted papillae, we suggest the possibility of tumor ischemia/infarction as a plausible etiology of pseudoinvasion. Awareness of this phenomenon is important for the accurate diagnosis of invasion in papillary urothelial carcinoma. (Arch Pathol Lab Med. 2024;148:1007-1013; doi: 10.5858/arpa.2023-0185-OA), The histologic criteria for invasion in pT1 bladder cancer are well established and include desmoplastic stromal response, retraction artifact, paradoxic epithelial maturation (differentiation), and irregular complex epithelial architecture that cannot [...]

* Context.--There is limited literature describing gynecologic adenocarcinomas involving the urinary bladder and potential diagnostic pitfalls. Objective.--To describe key features distinguishing metastatic (or extension of) gynecologic adenocarcinomas from urothelial carcinomas with glandular differentiation. Design.--Retrospective review of surgical pathology cases of gynecologic adenocarcinomas involving the bladder from 2 different institutions, retrieved from surgical pathology archives, was performed. Morphologic features were recorded, along with immunohistochemistry results when available. Electronic medical records were reviewed for clinical and radiographic information. Results.--Sixteen cases of gynecologic adenocarcinomas (9 endometrial endometrioid adenocarcinomas, 4 endometrial serous carcinomas, 2 high-grade tubo-ovarian serous carcinomas, and 1 cervical adenosquamous carcinoma) involving the bladder were identified. All included cases had mucosal involvement potentially mimicking primary bladder neoplasms, including 4 cases originally diagnosed as urinary carcinomas. Tumors expressed keratin 7 (12 of 13; 92%), PAX8 (11 of 12; 92%), estrogen receptor (11 of 15; 73%), p16 (8 of 11; 73%), progesterone receptor (8 of 14; 57%), GATA3 (5 of 12; 42%), and p63 (3 of 11; 27%); all tumors were negative for keratin 20 (0 of 12). Features supportive of Mullerian origin included prior history of gynecologic malignancy, lack of morphologic heterogeneity in nonendometrioid tumors, and immunophenotypic coexpression of PAX8 and estrogen receptor with absent GATA3. Potential pitfalls seen in a subset of cases included misleading radiologic and cystoscopic findings, replacement of the overlying urothelial mucosa by tumor mimicking precursor lesions, focal GATA3 and/or p63 positivity, and areas of squamous differentiation in tumors of endometrioid histology. Conclusions.--A combination of clinical history, certain morphologic features, and proper selection of immunohistochemical stains is key for the correct diagnosis of secondary gynecologic adenocarcinomas involving the urinary bladder. (Arch Pathol Lab Med. 2024;148:705-714; doi: 10.5858/arpa.2022-0469-OA), Secondary involvement of the urinary bladder by cancer is uncommon, occurring in approximately 2% of all resected bladder specimens. (1) Most cases with direct extension originate from the prostate or [...]

Context.--Pseudocarcinomatous urothelial hyperplasia (PCUH) architecturally and cytologically mimics cancer. The urine cytology features of PCUH have not been described. Objective.--To describe PCUH features in urine cytology. Design.--We reviewed urine cytology cases with concurrent PCUH tissue specimens from 5 academic institutions and classified them by using The Paris System criteria. Results.--Thirty-nine patients included 31 men and 8 women with a mean age of 67 years (range, 39-87 years). All patients had prior pelvic irradiation, and most presented with hematuria (n = 27). The specimens included voided urine (n = 16); bladder washing (n = 11); and urine, not otherwise specified (n = 12). The specimen preparation included cytospin (n = 29) and ThinPrep (n = 10). Original interpretations were negative for high-grade urothelial carcinoma (n = 28), atypical urothelial cells (AUCs; n = 10), and high-grade urothelial carcinoma (HGUC; n = 1). Twenty-five urine specimens (64%) had findings of PCUH. These specimens were moderately cellular and composed of sheets, cohesive groups, or isolated urothelial cells. Nucleoli were present in 23 cases. The nuclear membrane was smooth to irregular (n = 9), smooth (n = 8), and irregular (n = 8). The chromatin was glassy (n = 8), vesicular (n = 7), hyperchromatic (n = 7), and vesicular to finely granular (n = 3). The cytoplasm varied from dense squamoid, to finely vacuolated, to vacuolated. Nucleomegaly was observed in all 25 specimens, and nuclearcytoplasmic ratio greater than 0.5 was seen in 11 of 25 cases (44%). The background contained acute inflammation (n = 14), was clean (n = 9), and contained red blood cells (n = 2). All cases originally interpreted as AUCs and HGUC had PCUH features. Conclusions.--PCUH urine features can overlap with AUCs, HGUC, and other nonurothelial malignancies. In our cohort, 44% (11 of 25) of urine specimens with PCUH changes were initially misclassified. Recognition of cytologic features of PCUH is important to avoid overcalling reactive changes. (Arch Pathol Lab Med. 2023;147:716-721; doi: 10.5858/arpa.2022-0125-OA), Pseudocarcinomatous urothelial hyperplasia (PCUH) was first described by Baker and Young in 2000. (1) In 4 cases following radiation therapy, the authors described an inverted proliferation of urothelial nests within [...]

* Context.--Nephrogenic adenoma (NA) is a common urinary tract lesion typically associated with urothelial disruption, leading to implantation of shed renal tubular cells. NA may demonstrate a spectrum of architectural and cytologic features mimicking urothelial carcinoma (UC), adenocarcinoma (including clear cell adenocarcinoma and prostatic adenocarcinoma), and invasion. However, admixed UC and NA has not been described. Objective.--To describe cases where the NA was intimately intermixed with UC, potentially mimicking variant differentiation or invasion. Design.--In 3 health care systems we identified specimens of NA and UC intimately intermixed with each other to the extent that they could mimic a spectrum of one lesion. We assessed patterns of NA and clinical implications of misdiagnosing NA as glandular differentiation of UC. Results.--There were 4 women and 29 men (median age, 72 years; range, 31-89 years). Twenty-four patients had transurethral resections, 3 had biopsies, and 6 had major resections. Fourteen had noninvasive high-grade papillary UC, 6 had carcinoma in situ, and 11 had invasive high-grade UC. In 2 patients, NA developed in a papillary urothelial neoplasm with extensive denudation. Three patients had fibromyxoid NA infiltrated by invasive UC. Classical NA (n = 30) had tubulopapillary (n = 18), pure tubular (n = 7), or pure papillary architecture (n = 5). In 1 lesion, NA was present in muscularis propria, and 2 lesions involved adventitia. NA could have been misdiagnosed as invasion in 17 of 22 (77%) noninvasive tumors or higher stage in 19 of 33 (58%). Conclusions.--NA can be intermingled with highgrade UC, expanding the spectrum of entities that must be considered in the differential diagnosis, as it may mimic glandular or tubular differentiation, invasion, and a higher stage of disease. Misinterpretation of NA in such a setting may incorrectly convey a more aggressive biological potential of cancer to clinicians. doi: 10.5858/arpa.2021-0620-OA, Nephrogenic adenoma (nephrogenic metaplasia) is a lesion not infrequently seen in urologie surgical pathology. (1,2) Although originally it was thought to represent a metaplastic process, Mazal et al (3) demonstrated [...]

Context.--Multifocal prostate cancer at radical prostatectomy (RP) may be graded with assessment of each individual tumor nodule (TN) or global grading of all TNs in aggregate. Objective.--To assess case-level grade variability between these 2 grading approaches. Design.--We reviewed 776 RPs with multifocal prostate cancer with 2 or more separate TNs of different Grade Groups (GGs). Two separate grades were assigned to each RP: one based on the TN with the highest grade and a global grade based on the Gleason pattern volumes for all TNs. We then compared the results of these 2 methods. Results.--The case-level grade changed by 1 or more GGs between the 2 grading methods in 35% (132 of 374) of GG3 through GG5 cases. Twelve percent (37 of 309) of GG2 cases with Gleason pattern 4 of more than 5% based on individual TN grading decreased their Gleason pattern 4 to less than 5% based on the global approach. Minor tertiary pattern 5 (Gleason pattern 5 Conclusions.--The global grading approach resulted in a lower grade in 35% of GG3 through GG5 cases compared with grading based on the highest-grade TN. Two significant risk factors for this discrepancy with a global grading approach occur when the highest-grade TN has a relatively small tumor volume and with a higher number of TNs per RP. The observed grade variability between the 2 grading schemes most likely limits the interchangeability of post-RP multi-institutional databases if those institutions use different grading approaches. (Arch Pathol Lab Med. 2022;146:1032-1036; doi: 10.5858/arpa.2021-0279-OA), The Grade Group (GG)/Gleason score (GS) of prostate cancer assigned at radical prostatectomy (RP) predicts the likelihood of biochemical recurrence and prostate cancer-specific mortality. (1-3) Currently, there are 2 major [...]

Context.--Prostatic ductal adenocarcinoma (PDA) has historically been considered to be an aggressive subtype of prostate cancer. Objective.--To investigate if PDA is independently associated with worse biochemical recurrence (BCR)-free survival after radical prostatectomy. Design.--A review of 1584 radical prostatectomies was performed to grade, stage, and assess margin status in each tumor nodule. Radical prostatectomies with localized PDA (ie, those lacking metastasis) in the tumor nodule with the highest grade and stage and worst margin status were matched with prostatic acinar adenocarcinoma according to grade, stage, and margin status. The effect of PDA on BCR was assessed by multivariable Cox regression and Kaplan-Meier analyses. Results.--Prostatic ductal adenocarcinoma was present in 171 cases. We excluded 24 cases because of lymph node metastasis (n = 13), PDA not in the highest-grade tumor nodule (n = 9), and positive surgical margin in a lower-grade tumor nodule (n = 2). The remaining 147 cases included 26 Grade Group (GG) 2, 44 GG3, 6 GG4, and 71 GG5 cancers. Seventy-six cases had extraprostatic extension, 33 had seminal vesicle invasion, and 65 had positive margins. Follow-up was available for 113 PDA and 109 prostatic acinar adenocarcinoma cases. Prostate-specific antigen density (odds ratio, 3.7; P = .001), cancer grade (odds ratio, 3.3-4.3; P = .02), positive surgical margin (odds ratio, 1.7; P = .02), and tumor volume (odds ratio, 1.3; P = .02) were associated with BCR in multivariable analysis. Prostatic ductal adenocarcinoma, its percentage, intraductal carcinoma, and cribriform Gleason pattern 4 were not significant independent predictors of BCR. Conclusions.--Advanced locoregional stage, higher tumor grade, and positive surgical margin status rather than the mere presence of PDA are more predictive of worse BCR-free survival outcomes following radical prostatectomy in men with a component of PDA. (Arch Pathol Lab Med. 2022;146:1012-1017; doi: 10.5858/arpa.2021-0048-OA), Melicow and Pachter (1) first described prostatic ductal adenocarcinoma (PDA) in 1967 as an 'endometrial carcinoma of prostatic utricle (uterus masculinus),' and in so doing suggested it had a Mullerian [...]

Context.--Effect of tumor nodule (TN) location in the prostate on adverse radical prostatectomy (RP) outcomes is not well studied in contemporary cohorts. Objective.--To investigate the significance of TN location with respect to extraprostatic extension (EPE), seminal vesicle invasion (SVI), and positive surgical margin (SM+) in 1388 RPs. Design.--Each TN at RP was independently graded, staged, and volumetrically assessed. TNs with at least 80% of their volume occupying either the anterior or posterior part of the prostate were categorized accordingly and included in our study, while all other TNs were excluded. Results.--A total of 3570 separate TNs (median = 3 per RP; range = 1-7 per RP) were scored. There were 1320 of 3570 (37%) anterior TNs and 2250 of 3570 (63%) posterior TNs. Posterior TNs were more likely to be higher grade, and exhibit EPE (18% versus 9.4%) and SVI (4% versus 0.15%), all P Conclusions.--These associations may be useful in preoperative surgical planning, particularly with respect to improving radiographic analysis of prostate cancer., Prostate cancer is a major cause of morbidity and mortality in men around the world. According to The American Cancer Society, there were approximately 191 930 new cases of prostate [...]

We described two patients diagnosed with rare bladder metastasis (BM) from pancreatic adenocarcinoma, a prevalent neoplastic disease primarily associated with ductal adenocarcinoma. The overall prognosis for those patients with metastasis is very poor, with a 5‐year survival rate of < 3%. The scarcity of cases in the literature makes this series a significant contribution as it presents the first documented instance of BM originating from pancreatobiliary ampullary cancer and a rare case associated with the Krukenberg tumor. Additionally, we extensively reviewed the literature on the infrequent metastasis of pancreatic cancer to the bladder and provided details of those nine previously reported cases. Given its unusual nature, this report highlights the importance of considering BM in patients with a history of pancreatic carcinoma who present with new‐onset hematuria or upper tract obstruction, stressing the need for comprehensive evaluation and timely management. [ABSTRACT FROM AUTHOR]

Objectives There are 2 grading approaches to radical prostatectomy (RP) in multifocal cancer: Grade Group (GG) and percentage of Gleason pattern 4 (GP4%). We investigated whether RP GG and GP4% generated by global vs individual tumor grading correlate differently with biochemical recurrence. Methods We reviewed 531 RP specimens with GG2 or GG3 cancer. Each tumor was scored separately with assessment of tumor volume and GP4%. Global grade and GP4% were assigned by combining Gleason pattern 3 and 4 volumes for all tumors. Correlation of GG and GP4% generated by 2 methods with biochemical recurrence was assessed by Cox proportional hazard regression and receiver operating characteristic curves, with optimism adjustment using a bootstrap analysis. Results Median age was 63 (range, 42-79) years. Median prostate-specific antigen was 6.3 (range, 0.3-62.9) ng/mL. In total, the highest-grade tumor in 371 (36.9%) men was GG2 and in 160 (30.1%) men was GG3. Global grading was downgraded from GG3 to GG2 in 37 of 121 (30.6%) specimens with multifocal disease, and 145 of 404 (35.9%) specimens had GP4% decreased by at least 10%. Ninety-eight men experienced biochemical recurrence within a median of 13 (range, 3-119) months. Men without biochemical recurrence were followed up for a median of 47 (range, 12-205) months. Grade Group, GP4%, and margin status correlated with the risk of biochemical recurrence using highest-grade tumor and global grading, but the degrees of these correlations varied and were statistically significantly different between the 2 grading approaches. Conclusions Grade Group, GP4%, and margin status derived by global vs individual tumor grading predict postoperative biochemical recurrence statistically significantly differently. This difference has important implications if results derived from cohorts graded using different methods are compared. [ABSTRACT FROM AUTHOR]