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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.--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 [...]

Background:In recent years, anatomic pathology laboratories have been struck by new revenue policies secondary to the Affordable Care Act. In particular, modifications to compensation for processing prostatic core needle biopsies (PCNBs) have led to important reimbursement cuts. Herein, we explore a hypothetical reduction in the costs for the processing of PCNBs using three simple, hypothetical methods while maintaining high-standard patient care. Materials and methods:We determined the number of blocks and slides used per case on all PCNBs performed at our institution from August 2013 to September 2014 and calculated the total procedural cost for each case and for the total number of cases processed during the study period based on a published estimated procedural cost. We then estimated the procedural cost of three different proposed hypothetical scenarios that consisted in reducing the number of blocks used per case. A Student t test was used to assess the difference between real and hypothetical costs. Results:A total of 4,406 paraffin blocks were used to process 363 PCNBs with a total annual procedural cost of $26,303. By implementing any of the hypothetical scenarios, the annual procedural cost was significantly reduced; the reduction could potentially be as low as $8,978 (P

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 [...]

Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends an upper limit of 10% for atypia of undetermined significance (AUS). Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, the AUS and positive call rates for this facility's cytology laboratory and each cytopathologist (CP) were calculated. Methods: A retrospective analysis of all thyroid cytology cases in a 4.5‐year period was performed. Cases were stratified by TBSRTC, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each CP and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition of currently negative to the positive results obtained from the ThyroSeq report. Results: A total of 7535 cases were classified as nondiagnostic, 7.6%; benign, 69%; AUS, 17.5%; follicular neoplasm/suspicious for follicular neoplasm, 1.4%; suspicious for malignancy, 0.7%; and malignant, 3.8%. The AUS rate for each CP ranged from 9.9% to 36.8%. The overall PCR was 24% (range, 13%–35.6% per CP). When including cases with currently negative results, the PCR increased to 35.5% for the cytology laboratory (range, 13%–42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, undercalling of higher TBSRTC category cases. Conclusions: The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists' performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology. Assessing the atypia of undetermined significance rate in the context of positive call rate and time serves as a valuable metric for evaluating cytopathologists proficiency and overall laboratory performance and helps identify trends to provide valuable feedback. [ABSTRACT FROM AUTHOR]

Background: The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be ≤10%. Although this recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular‐derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM. Methods: Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed. Results: A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors. Conclusion: The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback. Quality metric tools in thyroid cytology can offer valuable feedback to individual cytopathologists and laboratories, contributing to improving diagnostic practices. [ABSTRACT FROM AUTHOR]

The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body's physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO), we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm.

Background: Basaloid salivary gland neoplasm of uncertain malignant potential (B‐SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid‐based cytology (LBC) specimens. Methods: In total, 45 B‐SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative. Results: PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1‐positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex‐PA. PLAG1‐equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%. Conclusions: PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1‐positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1‐negative/equivocal tumors should remain in the B‐SUMP category. PLAG1 immunocytochemistry is useful for the diagnosis of pleomorphic adenoma when strong/diffusely positive and can be reliably performed directly on alcohol‐fixed conventional smears and liquid‐based cytology specimens. It may help enhance diagnostic accuracy in challenging cases and reduce indeterminate diagnoses. [ABSTRACT FROM AUTHOR]