Renal Pelvic Urothelial Carcinoma With Invasion Into Renal Medulla Can Be Redefined as pT2 to Improve Correlation With Survival.

According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest pT category, with notable survival heterogeneity. Anatomical landmarks within the renal pelvis can be difficult to discern. Using glomeruli as a boundary to differentiate renal medulla invasion from renal cortex invasion, this study aimed to compare patient survival of pT3 renal pelvic urothelial carcinoma on the basis of the extent of renal parenchyma invasion and, thereafter, determine whether redefining pT2 and pT3 improves pT correlation with survival. Cases with primary renal pelvic urothelial carcinoma were identified through a review of pathology reports from nephroureterectomies completed at our institution from 2010 to 2019 (n = 145). Tumors were stratified by pT, pN, lymphovascular invasion, and invasion of the renal medulla versus invasion of the renal cortex and/or peripelvic fat. Overall survival between groups was compared using Kaplan-Meier survival models and Cox regression multivariate analysis. pT2 and pT3 tumors had similar 5-year overall survival, with multivariate analysis demonstrating an overlap between hazard ratios (HRs) for pT2 (HR, 2.20; 95% CI, 0.70-6.95) and pT3 (HR, 3.15; 95% CI, 1.63-6.09). pT3 tumors with peripelvic fat and/or renal cortex invasion had a 3.25-fold worse prognosis than pT3 tumors with renal medulla invasion alone. Furthermore, pT2 and pT3 tumors with only renal medulla invasion had similar overall survival, whereas pT3 tumors with peripelvic fat and/or renal cortex invasion had a worse prognosis (P = .00036). Reclassifying pT3 tumors with only renal medulla invasion as pT2 yielded greater separation between survival curves and HR. Thus, we recommend redefining pT2 renal pelvic carcinoma to include renal medulla invasion and restricting pT3 to peripelvic fat and/or renal cortex invasion to improve the prognostic accuracy of pT classification.

Impact of prostate biopsy secondary pathology review on radiotherapy management.

BACKGROUND: The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation. We sought to address the impact a secondary pathology review had on radiation therapy treatment recommendations in men with prostate cancer at our institution. METHODS: We retrospectively collected patient data on 342 patients seen at our institution from January 2012 to December 2018. Clinicopathologic data were used to subdivide patients into risk groups and available treatment options per NCCN criteria. Cases reviewed by our genitourinary pathologist (GUP) were compared with reports from outside pathologists. Inter-rater reliability between pathologists was assessed with weighted Cohen's kappa statistic and agreement of treatment options was determined by McNemar's exact tests. RESULTS: GUP scored more cores positive in 16.47% of cases on secondary review. Primary Gleason score was changed in 12.28% of patients and secondary score in 26.02% of cases. Total Gleason score was different in 29.24% of cases, 19.01% were downgraded and 10.23% upgraded. The weighted kappa statistic was 0.759 (95% confidence interval [CI]: 0.711, 0.807). 18.77% of patients were assigned to a different NCCN risk group following secondary review. The weighted kappa statistic comparing NCCN risk stratification was 0.802 (95% CI: 0.754, 0.850). Secondary review influenced radiation therapy recommendations pertaining to brachytherapy boost and androgen deprivation therapy in men with high risk disease (χ2 = 5.33, p = 0.0386; χ2 = 8.05, p = 0.0072, respectively). Kappa statistic was found to be highest when GUP assessed high-risk disease versus all other categories (κ = 0.823, 95% CI: 0.750, 0.895). CONCLUSIONS: We found nearly one in five men (18.7%) was assigned a different NCCN risk group and thus offered potentially different treatment options after a secondary pathology review at our institution. Given the inherent nature of prostate cancer and lung disease-specific survival associated with modern therapies, our study demonstrates the importance of a secondary pathology review and its potential impact on radiation therapy recommendations.

Testicular Germ-Cell Tumors with Spermatic Cord Involvement: A Retrospective International Multi-Institutional Experience.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.

Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.

Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitation-exonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles.

HER2 equivocal breast cancer that is positive by alternative probe HER2 FISH are classified as HER2 negative by Oncotype DX.

In breast cancer, human epidermal growth factor receptor 2 (HER2) status is determined by immunohistochemistry (IHC) and/or in situ hybridization. Oncotype DX also reports HER2 status by an rt-PCR-based assay. Assay concordance between IHC and fluorescent in situ hybridization (FISH) (including alternative probe HER2 FISH) vs Oncotype DX HER2 rt-PCR has not been described in the post-2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guideline revision setting. We performed a retrospective review of HER2 equivocal invasive breast carcinoma from 2014 to 2016 with the Oncotype DX HER2 result. Fifteen patients with HER2 equivocal invasive breast cancer had Oncotype DX performed. Of these, 13 underwent alternative probe HER2 FISH yielding 4 negative, 6 equivocal and 3 positive results. All 15 cases were classified as HER2 negative by Oncotype DX rt-PCR, including the three cases which were positive by alternative probe HER2 FISH, yielding a discordance rate for Oncotype DX rt-PCR HER2 of 20% (3/15). All three patients with HER2-positive breast cancer on the basis of alternative probe HER2 FISH received anti-HER2-targeted therapy. Treatment decisions based on HER2 status should utilize the IHC/FISH result as Oncotype DX results may incorrectly disqualify some patients from being eligible for anti-HER2 therapy based on the current 2013 ASCO/CAP HER2 Guidelines.

Utility of GATA3 in the differential diagnosis of pheochromocytoma.

AIMS: GATA3 is a relatively new immunohistochemical marker which shows consistent nuclear expression in a variety of tumours, including breast and urothelial carcinoma. The staining pattern of GATA3 in adrenal lesions is not well established. We aim to describe the expression of GATA3 in adrenal tumours and determine if there is differential staining between pheochromocytoma and adrenal cortical carcinoma. METHODS AND RESULTS: A retrospective search was performed to identify 74 adrenal lesions which were tested immunohistochemically for GATA3 expression. GATA3 was negative in 90% of adrenal cortical carcinoma. In contrast, pheochromocytomas were frequently positive (71%), including benign pheochromocytoma, pheochromocytoma with features concerning for malignancy, malignant (metastatic) pheochromocytoma and composite pheochromocytoma with ganglioneuroma. Metastatic lung adenocarcinoma in the adrenal gland had occasional (36%) expression, while metastatic clear cell renal cell carcinoma in the adrenal gland did not express GATA3. CONCLUSION: As the most common pitfall in diagnosing adrenal cortical carcinoma is mistaking it for pheochromocytoma or vice versa, GATA3 may be useful in narrowing the differential diagnosis as a part of a panel of immunohistochemical markers. However, occasional GATA3 expression in the most common source of metastases within the adrenal gland, metastatic pulmonary adenocarcinoma, may confound the diagnosis due to the overlapping expression with pheochromocytoma and other carcinomas.

Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

OBJECTIVES: To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. METHODS: Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. RESULTS: Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. CONCLUSIONS: The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. KEY POINTS: • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.

Prediction of chemotherapeutic response in bladder cancer using K-means clustering of dynamic contrast-enhanced (DCE)-MRI pharmacokinetic parameters.

PURPOSE: To apply k-means clustering of two pharmacokinetic parameters derived from 3T dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the chemotherapeutic response in bladder cancer at the mid-cycle timepoint. MATERIALS AND METHODS: With the predetermined number of three clusters, k-means clustering was performed on nondimensionalized Amp and kep estimates of each bladder tumor. Three cluster volume fractions (VFs) were calculated for each tumor at baseline and mid-cycle. The changes of three cluster VFs from baseline to mid-cycle were correlated with the tumor's chemotherapeutic response. Receiver-operating-characteristics curve analysis was used to evaluate the performance of each cluster VF change as a biomarker of chemotherapeutic response in bladder cancer. RESULTS: The k-means clustering partitioned each bladder tumor into cluster 1 (low kep and low Amp), cluster 2 (low kep and high Amp), cluster 3 (high kep and low Amp). The changes of all three cluster VFs were found to be associated with bladder tumor response to chemotherapy. The VF change of cluster 2 presented with the highest area-under-the-curve value (0.96) and the highest sensitivity/specificity/accuracy (96%/100%/97%) with a selected cutoff value. CONCLUSION: The k-means clustering of the two DCE-MRI pharmacokinetic parameters can characterize the complex microcirculatory changes within a bladder tumor to enable early prediction of the tumor's chemotherapeutic response.

Discovery and diagnostic value of a novel oncofetal protein: glypican 3.

Glypican 3 is a membrane-bound heparan sulfate proteoglycan, which has recently been identified as a marker for liver cancer and germ cell malignancies. Individuals with loss-of-function mutations for the glypican 3 gene exhibit Simpson-Golabi-Behmel syndrome, a rare X-linked overgrowth disorder. Expression of glypican 3 mRNA and protein is normally silenced in most adult organs and may reappear during malignant transformation. In the past few years, immunohistochemical and molecular characteristics of glypican 3 in hepatocellular carcinoma have been elucidated. More recently, glypican 3 has been emerging as a new diagnostic marker for germ cell tumors and especially testicular and ovarian yolk sac tumors. However, in other tumors such as renal cell carcinomas, squamous cell carcinomas, and melanomas, studies disagree on the level of glypican 3 expression. Finally, there is the controversial notion of glypican 3 as a tumor suppressor gene. In this review article, we update current knowledge on glypican 3 expression in normal and neoplastic tissues, evaluate its utility as a tumor marker in clinical practice, and explore its role as a novel oncofetal protein with clinical implications. Our focus is on the diagnostic value of glypican 3 in germ cell tumors and other neoplasms in addition to hepatocellular carcinoma. In conclusion, glypican 3 has been proven to be a useful immunohistochemical marker in distinguishing yolk sac tumors, choriocarcinomas, and Wilms tumors from other malignancies histologically mimicking these primitive tumors. Clinically, we recommend that glypican 3 be used as part of a panel of markers in subtyping testicular germ cell tumors.

Do robotic prostatectomy positive surgical margins occur in the same location as extraprostatic extension?

PURPOSE: Positive surgical margins (PSMs) may reflect incomplete surgical resection, while extraprostatic extension (EPE) could suggest that complete tumor resection is more difficult. This study evaluated cases with both EPE and PSMs in robotic-assisted radical prostatectomy (RARP) specimens to determine the respective locations of each. METHODS: A single institutional retrospective review of RARP performed between 2007 and 2009 was conducted to identify cases with both EPE and PSM. Prostates were entirely submitted and processed in whole mount format. All locations of EPE and PSM were recorded as was the size of the largest focus of EPE and PSM. RESULTS: About 8.5 % (112/1,315) of RARP had both EPE and PSM. Analysis of cases with concurrent EPE and PSM revealed that EPE occurred most commonly in the mid-gland, particularly in the posterolateral mid-prostate. In contrast, PSM was most frequent at the base (bladder neck), specifically the anterior base. 51.8 % of the cases had EPE and PSM in discordant locations, 19.6 % had EPE and PSM in the same location, and 28.6 % had areas of EPE and PSM both in the same location as well as in different locations. Cases with both concordant and discordant locations of EPE and PSM had significantly more high-risk features including higher tumor volume, more frequent positive nodes, and more frequent Gleason score ≥ 8 compared to concordant or discordant subgroups. CONCLUSION: PSMs frequently did not occur in the same location as EPE. A better understanding of where EPE and PSMs occur may help guide surgical technique to decrease residual tumor.

ER and PR immunohistochemistry and HER2 FISH versus oncotype DX: implications for breast cancer treatment.

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT-PCR-based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2-amplified cases, two were negative and one was equivocal, and all FISH HER2-equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2-amplified, Oncotype DX HER2-negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2-positive breast carcinomas. The preferential use of Oncotype DX biomarker results over IHC and FISH is discouraged.

Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.

What's new in genitourinary pathology 2023: WHO 5th edition updates for urinary tract, prostate, testis, and penis.

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduced many significant changes relevant to urologic daily practice, mainly to renal tumors which was covered in the What's New newsletter in September 2022. In this newsletter, we summarize the notable changes to bladder, prostate, testis, and penis based on the 5th edition of the WHO.

Adenoid cystic carcinoma metastatic to the kidney: a series of 10 patients emphasizing unilateral presentation and long time interval from primary diagnosis.

Adenoid cystic carcinoma (AdCC) metastasis to kidney is rare. We identified 10 patients with metastatic AdCC in multi-institutional collaboration. Core needle biopsy was the most common specimen (n = 6). Patients were predominately female (n = 7) with a median age of 48 years (35-62 years). The most common primary location of the AdCC was head and neck (n = 6, among them parotid gland = 4), followed by lung (n = 2), breast (n = 1), and vulva (n = 1). Median lapse between primary AdCC and renal metastasis was almost 13 years (154 months, range 1-336 months). Moreover, all but one patient had unilateral kidney metastasis. The majority of metastatic AdCC within the kidney demonstrated mixed growth patterns, frequently cribriform, and tubular morphology. Follow-up available for 8 patients showed 6 alive with disease and 2 died of disease (the longest survival was 4 years past the diagnosis of renal metastasis). A systematic literature review including 29 patients revealed that kidney metastasis by AdCC is usually a late event, is typically unilateral, and is usually composed of one to three foci, and thus has clinical features which mimic a primary renal tumor.

Alterations of histone H1 phosphorylation during bladder carcinogenesis.

There is a crucial need for development of prognostic and predictive biomarkers in human bladder carcinogenesis in order to personalize preventive and therapeutic strategies and improve outcomes. Epigenetic alterations, such as histone modifications, are implicated in the genetic dysregulation that is fundamental to carcinogenesis. Here we focus on profiling the histone modifications during the progression of bladder cancer. Histones were extracted from normal human bladder epithelial cells, an immortalized human bladder epithelial cell line (hTERT), and four human bladder cancer cell lines (RT4, J82, T24, and UMUC3) ranging from superficial low-grade to invasive high-grade cancers. Liquid chromatography-mass spectrometry (LC-MS) profiling revealed a statistically significant increase in phosphorylation of H1 linker histones from normal human bladder epithelial cells to low-grade superficial to high-grade invasive bladder cancer cells. This finding was further validated by immunohistochemical staining of the normal epithelium and transitional cell cancer from human bladders. Cell cycle analysis of histone H1 phosphorylation by Western blotting showed an increase of phosphorylation from G0/G1 phase to M phase, again supporting this as a proliferative marker. Changes in histone H1 phosphorylation status may further clarify epigenetic changes during bladder carcinogenesis and provide diagnostic and prognostic biomarkers or targets for future therapeutic interventions.

Whole-mount evaluation of penectomies for penile cancer: feasibility, cost and comparison to routine sectioning.

AIMS: Pathological staging in penectomies may be difficult due to the anatomical complexity of penile anatomy, and may be additionally challenging due to the low volume at most institutions. Our study aimed to assess the feasibility of whole-mount processing for penectomy specimens. METHODS AND RESULTS: A 7-year retrospective search for partial or radical penectomies identified 55 specimens, which were processed routinely (n = 31) from 2006 to 2009 and whole-mounted (n = 24) from 2010 to 2012. Routine cases used more slides per case compared to whole mounts (mean 10.4 versus 7.2). Recuts occurred more often in routine cases (12.9% versus 0%). More routine cases had additional blocks grossed (19.4% versus 4.2%). Upon review, five discrepancies that impacted pT staging were identified in the routine group, with none in the whole-mount group. The average estimated additional cost for each whole-mount case compared to routine processing was $40.74, with an increased turnaround time of 1 day. CONCLUSIONS: Whole-mounting is a feasible technique for penectomy that can be utilized with minimal increased cost and turnaround time, and may improve staging. Institutions in which whole-mounting is already established for other organs, such as prostate, may wish to consider utilizing this format for penectomy specimens.

The stratification of positive lymph nodes into pN1 and pN2 for upper urinary tract carcinoma is not prognostically significant.

The 3rd-7th edition of the American Joint Committee on Cancer had 3 categories for positive lymph nodes (pN1-3) in upper urinary tract carcinomas. The 8th edition removed pN3, defining pN1 as one lymph node with a tumor deposit ≤2 cm and pN2 as a node with a tumor deposit >2 cm or metastases in multiple nodes. The aim of this study was to assess if the current pN categories impact survival in renal pelvic and ureteral carcinomas. Nephroureterectomies performed at our institution for primary upper urinary tract carcinomas between 2010 and 2019 were reviewed. Lymphadenectomy was performed in 73.3% of cases (151/206, median = 9 nodes). Eighty-one (53.6%) patients were deceased at the last review (pN0, 53 [44.5%]; pN1-2, 28 [87.5%]). There was no difference in overall or recurrence-free survival between pN1 and pN2 with 5-year overall survival (95% confidence interval) of pN0, 60.7% (52.0-70.8%); pN1, 15.4% (4.3-35.2%); and pN2, 21.1% (8.8-40.3%). The metastatic deposit size threshold of 2 cm, the number of positive lymph nodes, as well as extranodal extension did not correlate with overall or recurrence-free survival. As such, pN1 and pN2 were grouped together with a 5-year overall survival of 18.8% (9.12-28.6%). The current stratification of upper urinary tract carcinomas into pN1 and pN2 does not provide prognostic information, and both yield a stage IV classification, regardless of pT or pM category. Therefore, we recommend further simplification of pN classification into one category for regional lymph node metastasis, irrespective of the lymph node deposit size or number of positive lymph nodes.

Ultrastructural findings in adrenal cortical adenomas clinically mimicking pheochromocytoma: a comparison with other adrenal tumors and tissue preparation techniques.

Adrenal cortical tumors clinically mimicking pheochromocytomas are extremely rare, with 14 cases in the literature. The authors describe 2 patients with adrenal cortical adenoma (ACA) and catecholamine elevations. The impact of tissue preparation methods on electron microscopy (EM) images was assessed in ACA mimicking pheochromocytoma, pheochromocytoma, and ACA lacking pheochromocytoma-like symptoms. Ten adrenal cortical tumors were examined using EM after a variety of tissue preparation techniques, including fixation with glutaraldehyde, formalin for varying lengths of time followed by glutaraldehyde, and/or formalin followed by paraffin embedding. Electron micrographs were assessed for image quality and the presence of dense secretory granules and eccentric, norepinephrine (NE)-type granules. Images created from tissue fixed in glutaraldehyde and/or formalin and embedded in resin were of good quality, while those derived from paraffin-embedded specimens were poor with disrupted cellular architecture. When pheochromocytoma was fixed in glutaraldehyde for 24 h or in formalin for 8 days, eccentric granules were identified. These granules were absent when tissue was fixed in formalin for 20 days or was obtained from a paraffin block. ACA without pheochromocytoma-like symptoms and ACA mimicking pheochromocytoma both had noneccentric dense-core granules on EM regardless of tissue preparation, and eccentric NE-type granules were absent. ACA is a rare cause of pheochromocytoma-like symptoms. These tumors lack eccentric, NE-type dense-core granules present in pheochromocytoma. Glutaraldehyde alone or formalin fixation followed by glutaraldehyde produces electron micrographs that may aid in the diagnosis of adrenal cortical tumors, whereas formalin-fixed, paraffin-embedded tissue results in images that are inadequate.

Reclassifying pT3 renal pelvic urothelial carcinoma with renal parenchyma invasion to pT2 improves correlation with overall survival.

The American Joint Cancer Committee pT categorization in renal pelvic carcinoma defines pT3 as invasion of renal parenchyma, invasion of peripelvic fat, or both. However, survival heterogeneity within the pT3 category has been demonstrated. This investigation sought to compare survival between pT categories of renal pelvic urothelial carcinoma and identify modifications to improve correlation with survival. Pathology reports from nephroureterectomies performed at our institution from 2010 to 2019 were analyzed to identify primary renal pelvic urothelial carcinoma (n = 146). Tumors were stratified based on pT, pN, and invasion of renal parenchyma vs invasion of peripelvic fat with or without renal parenchyma invasion. Kaplan-Meier survival curves and Cox regression multivariate analysis were used to compare overall survival between groups. Similar survival curves were observed for pT2 and pT3 tumors. Multivariate analysis confirmed overlapping hazard ratios (HRs) for pT2 (HR = 2.64, 95% confidence interval [CI] = 0.69, 10.06) and pT3 (HR = 4.42, 95% CI = 2.08, 9.37). pT3 tumors with peripelvic fat invasion, regardless of renal parenchyma involvement, had a 3.3-fold worse overall survival than pT3 tumors with only renal parenchyma involvement. Additionally, pT3 tumors with only renal parenchyma invasion had similar survival compared to pT2, while pT3 tumors with peripelvic fat invasion had worse overall survival (p = 0.00091). Reclassifying renal parenchyma invasion as pT2 yielded greater survival curve separation and greater difference in HRs. For renal pelvic urothelial carcinoma, modifying the pT3 category to only include tumors with peripelvic fat invasion and expanding the pT2 category to include renal parenchyma invasion may improve pT correlation with overall survival.

Clinicopathologic features of scrotal leiomyosarcoma: single institutional experience of ten cases.

Scrotal leiomyosarcoma arises from the subcutaneous smooth muscle layer and is an exceptionally rare disease process, with only six patients in the largest reported case series. This rarity creates uncertainties regarding diagnosis, surgical management, and clinical outcomes. Our purpose was to retrospectively describe our institutional experience with scrotal leiomyosarcoma from 2010 to 2022. Slides were reviewed with case inclusion requiring both nuclear atypia and mitotic activity. Ten patients with scrotal leiomyosarcoma were identified. Clinical impression included scrotal cyst in nine cases. The median age at diagnosis was 52 years (range: 29-75 years). The mean tumor size was 1.6 cm (range: 0.4-3.7 cm). Margins were positive in three cases and close in one case, prompting four re-excisions. The mean mitotic rate was 2.3 per 10 high-power field (range: 1-11), with mean Ki67 of 4.6% (range: 1-15%). Nine of the tumors were grade 1, while 1 was grade 2. Four patients had disease-specific follow-up. The remaining six patients have not had disease-specific surveillance. None of the ten patients have shown evidence of recurrence (median follow-up: 75 months, range: 0-116 months). Our series demonstrates that scrotal leiomyosarcoma has a deceptive clinical presentation with a wide age range and small tumor size. With complete surgical resection, scrotal leiomyosarcoma has an excellent prognosis and rigorous follow-up or adjuvant treatment is not likely to be necessary. Cases with unusual clinical or pathologic findings, such as large tumor size or high mitotic rate, may merit more intensive disease-specific surveillance.