Context.—:Prostatic acinar adenocarcinoma is the most common type of prostate cancer, while other types of cancer infrequently involve the prostate. In this review, we present an overview of contemporary updates on all types of cancers involving the prostate, with a focus on subtypes of prostatic adenocarcinoma. Unusual histological patterns and subtypes of acinar adenocarcinoma, and non-acinar forms of prostate cancers, and their prognostic and therapeutic relevance are discussed. The following summary of the contents presented in part at the 12th Princeton Integrated Pathology Symposium, Plainsboro, New Jersey, on May 10, 2025, supplemented with a relevant literature review, exemplifies the common diagnostic challenges and pitfalls for subtypes of prostate cancer, with emphasis on immunohistochemical and molecular updates when relevant. Objective.—:To describe the common lesions in the prostate, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant. Data Sources.—:Published peer-reviewed literature and personal experience are the sources for this study and presented at the course. Conclusions.—:Although most prostate cancers are acinar adenocarcinoma, other types of prostate cancer infrequently occur, which may pose diagnostic challenges. Pitfalls that arise in the pathologic assessment of prostate cancer should raise awareness. We summarize the course content, supplement it with a relevant literature review, and hope to provide a diagnostic framework for evaluating these lesions in routine clinical practice.

Patient selection for focal therapy (FT) of prostate cancer requires the assessment of MRI and biopsy results. However, there is currently little guidance for the utility of PSMA PET/CT in FT planning. We describe the case of a man originally considered an ideal candidate for FT based on biopsy and MRI who was found to have a contralateral lesion-harboring cancer detected only on PSMA PET/CT. Trial Registration: ClinicalTrials.gov identifier: NCT05852041.

e17001 Background: Computational analysis of digitized pathological images has been shown to have diagnostic and prognostic applications. Recent research suggests that molecular features, previously defined at the genomic level, might be additionally recognized. In prostate cancer, transcriptomic PAM50 molecular subtypes may correlate with patient response to systemic therapy. Here we investigate whether computational analysis of digital prostate biopsy slides can predict PAM50 category. Methods: Our study utilized digitized images of 704 prostate biopsy slides from 336 patients with prostate cancer at Northwestern Memorial Hospital with Decipher testing (Veracyte, Inc San Diego, CA). All slides analyzed contain carcinoma with the majority being primary Gleason pattern 3 (545 out of 704). Hematoxylin and eosin stained slides were scanned on a Leica GT450 scanner at 40x magnification. PAM50 subtypes were derived from the Decipher Genomic Resource Information Database (GRID). Data were split at the subject level using 80% for training, 10% for validation, and 10% for evaluation, facilitating model development and assessment. We devised a model comprising two decoupled parts: a multi-instance learning model that utilizes a multi-class attention mechanism to explore relevant class-specific information from slides, and a pre-trained network to extract high-dimensional semantic features from the tiles of WSIs. The model trained based on the WSIs of the training set to predict PAM50 subtypes (luminal A, luminal B, and basal). This attention-based training approach allowed the model to capture relevant patterns and information present in the WSIs. Following the training phase, the model was subsequently evaluated on the testing set. Results: Model AUC on the evaluation set was 0.78. Among evaluation set misclassifications, no luminal samples were misclassified as basal subtype. Conclusions: Our investigation provides preliminary results on the ability to predict RNA expression-based subtypes from prostate cancer biopsy histology. This approach may help to preserve tissue, minimize costs, and decrease turnaround time associated with molecular testing in prostate cancer while offering patients with prostate cancer opportunities for precision medicine.

Machine learning (ML) models are poised to transform surgical pathology practice. The most successful use attention mechanisms to examine whole slides, identify which areas of tissue are diagnostic, and use them to guide diagnosis. Tissue contaminants, such as floaters, represent unexpected tissue. While human pathologists are extensively trained to consider and detect tissue contaminants, we examined their impact on ML models. We trained 4 whole slide models. Three operate in placenta for 1) detection of decidual arteriopathy (DA), 2) estimation of gestational age (GA), and 3) classification of macroscopic placental lesions. We also developed a model to detect prostate cancer in needle biopsies. We designed experiments wherein patches of contaminant tissue are randomly sampled from known slides and digitally added to patient slides and measured model performance. We measured the proportion of attention given to contaminants and examined the impact of contaminants in T-distributed Stochastic Neighbor Embedding (tSNE) feature space. Every model showed performance degradation in response to one or more tissue contaminants. DA detection balanced accuracy decreased from 0.74 to 0.69 +/- 0.01 with addition of 1 patch of prostate tissue for every 100 patches of placenta (1% contaminant). Bladder, added at 10% contaminant raised the mean absolute error in estimating gestation age from 1.626 weeks to 2.371 +/ 0.003 weeks. Blood, incorporated into placental sections, induced false negative diagnoses of intervillous thrombi. Addition of bladder to prostate cancer needle biopsies induced false positives, a selection of high-attention patches, representing 0.033mm2, resulted in a 97% false positive rate when added to needle biopsies. Contaminant patches received attention at or above the rate of the average patch of patient tissue. Tissue contaminants induce errors in modern ML models. The high level of attention given to contaminants indicates a failure to encode biological phenomena. Practitioners should move to quantify and ameliorate this problem.

IntroductionRenal cell neoplasms are known to be associated with paraneoplastic syndromes, and the association with Castleman-like regional lymphadenopathy has been rarely reported. We aim to characterize the association between renal neoplasms and Castleman-like lymphadenopathy.MethodsA search for renal neoplasms with concurrent Castleman-like lymphadenopathy in one single medical institution from 2000 to 2023 resulted in 4 specimens. A literature search for "Castleman" and "renal neoplasm" resulted in 8 reports. Patients' demographics, clinical presentation, gross and histologic features, results of ancillary studies, treatment, and follow-up were evaluated.ResultsOur patients included 3 men and 1 woman, with a mean age of 60 years. Four different subtypes of renal neoplasms were diagnosed, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, and mucinous cystadenoma of the renal pelvis. For Castleman-like regional lymphadenopathy, 2 were plasma-cell predominant, and 2 were hyaline-vascular. After a median follow-up of 84 months, all patients were alive with no recurrence or progression of Castleman-like features following nephrectomies.ConclusionCastleman-like regional lymphadenopathy should be considered in patients with renal tumors and lymphadenopathy. Although more prevalent in clear cell RCC, it can be also associated with other renal neoplasms. The concurrent lymphadenopathy was remitted following the renal tumor resections.

Introduction: Sarcomatoid differentiation has been reported in approximately 8% of chromophobe renal cell carcinoma (RCC) and is associated with a worse prognosis. We aim to describe the clinicopathologic and molecular findings of chromophobe RCC with sarcomatoid differentiation. Methods: Surgical pathology database was searched to identify chromophobe RCC with sarcomatoid differentiation from January 2015 to December 2021. Results: Five patients were diagnosed with chromophobe RCC with sarcomatoid differentiation. The median age at the time of diagnosis was 57 years (range 51-61 years). Three patients died after median follow-up of 12.1 months (range 1.6-18.2 months). The median tumor size was 10.7 cm (range 5.6-13.6 cm). The median percentage of sarcomatoid component was 60% (range 10-90%), and the median percentage of necrosis was 30% (range 10-50%). One tumor demonstrated osteoid formation. PAX8, keratin 7, KIT (CD117), and Hale colloidal iron were positive in the epithelial component, whereas the sarcomatoid component was positive for vimentin, CD10, and high Ki67 proliferative index. Molecular testing was performed in three specimens: all were TP53 mutated and microsatellite stable. One aggressive tumor had RB1 frameshift mutation and copy number gains for TERT and CUL4A. Conclusion: Chromophobe RCC with sarcomatoid differentiation is a rare entity with aggressive behavior. Percentage of sarcomatoid component, necrosis, and the occurrence of metastasis is associated with worse prognosis. Molecular profiling reveals frequent TP53 mutation. While TERT promoter mutation has no prognostic implication, FLCN inactivation may be associated with a less aggressive course. The clinical significance of RB1 loss is unclear.

Context.— Controversies and uncertainty persist in prostate cancer grading. Objective.— To update grading recommendations. Data Sources.— Critical review of the literature along with pathology and clinician surveys. Conclusions.— Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace “tertiary grade pattern” in radical prostatectomy (RP) with “minor tertiary pattern 5 (TP5),” and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) “atypical intraductal proliferation (AIP)” is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

Abstract Introduction: The incidence of brain metastasis complicated with breast cancer (BCBM) is approximately 10-15%. Given that the survival status of the BC patients is not optimistic, the choice of clinical treatments should be based on individualized clinical characteristics of the BC patients. Thus understanding of the patient clinical characteristics is critical for patient management and forecasting the prognoses of the patients. Methods: The trial was designed as a real-world observational study. The BCBM patients who were enrolled in the clinics from 2012 to 2017 were recruited and the study data on the patient demographic, tumor biological characteristics, and clinical treatments were retrospectively collected for evaluating overall survival (OS), and the OS impact factors. The Kaplan-Meier and Log-rank tests were performed to assess patient survivals. The Cox regression analyses were applied to explore the OS impact factors. All the statistical significance was set as α=0.05 except as other specified. Results: A total of 117 female BCBM patients (mean age: 48.28±9.49 years) were enrolled in this study including 32 patients (27.4%) with extracranial metastases and 85 patients (72.6%) without extracranial metastases. Of all the subjects, by classification of the molecular types, 13.3% of the patients were diagnosed with luminal A tumor and 45.8% were observed with luminal B tumor. The patients with HER2 positive accounted for 19.3% of all the subjects and 21.7% of the subjects were triple-negative BC patients. In the clinical treatments, 65.8% of the patients were administered with chemotherapies, 14.5% with target therapies, and 11.1% with radiotherapies. The median of the OS duration was approximately 38.57 months. The OS rates were decreased along with the observation period: The 18-month OS rate was 73.6% (95% confidential interval, CI 0.558, 0.852) and the 48-month OS rate was 24.9% (95% CI 0.045, 0.537), respectively. In the patients with >3 metastatic brain tumors, the median of the OS duration was 20.27 months and the median of the OS duration was 38.57 months in the patients with ≤3 metastatic brain tumors. The OS durations in the patients with ≤3 metastatic brain tumors were longer than the durations in the patients with >3 metastatic brain tumors from 12 month- to 36 month- observation period. In the patients with Ki-67≤14%, the OS durations were longer than the durations of the patients with Ki-67>14%. In the 18 month-observation period, the OS duration was longer in the patients with HER2 positive as compared with that of the patients with HER2 negative. In the univariate and multivariate analyses, those patients with chemotherapies were significantly associated with longer OS durations (p<0.05). The multivariate analyses showed that the menopausal patients were related to shorter OS durations (p<0.05). Conclusions: The real-world study offered the clinical evidences on the clinical characteristics of the BCBM patients, patient management, and patient survivals. The patient survivals improved significantly after clinical treatments with BCBM. The tumor biological characteristics and chemotherapies were predictive for the status of patient survivals. Citation Format: Ouyang Q, Tang Y, Hu Z, Tian C, Xie N, Liu L, Xiao H, Li J, Wu H, Yang X, Yang C. A single-center real-world observational study to explore clinical treatments and prognoses of the Chinese patients with breast cancer complicated with brain metastases [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-65.

Aims Special AT-rich sequence-binding protein 2 (SATB2) is a novel immunomarker that is expressed in glandular cells of the lower gastrointestinal tract with retained expression in the majority of primary and metastatic colorectal adenocarcinomas (CRCs). Because of its tissue specificity, SATB2 has been shown to be a clinically useful marker to distinguish CRC from non-CRC. In this study, we investigated whether or not SATB2 can help differentiate CRC from small intestinal adenocarcinoma (SIA), a practical diagnostic challenge due to their morphological and immunophenotypic similarities.Methods Fifty surgically resected primary SIAs and 50 CRCs were immunohistochemically examined for the expression of SATB2. Positive staining was graded as 1+ (5-25% of the tumour cells stained), 2+ (26-50%), 3+ (51-75%) or 4+ (> 75%), as well as weak, intermediate or strong for staining intensity.Results Positive SATB2 immunoreactivity was observed in 23 (46%) SIAs in contrast to 48 (96%) CRCs (p< 0.0001). Among these, only 4 (8%) SIAs showed strong and diffuse (4+) SATB2 staining compared with 38 (76%) of CRCs (p< 0.0001).Conclusions SATB2 is not entirely CRC-specific and is expressed in a subset of SIAs. Unlike CRC, however, SIA infrequently shows a strong and diffuse staining pattern, which still makes SATB2 a useful immunomarker to distinguish SIA from CRC.

Condyloma acuminata (CA) is a common sexually transmitted disease caused by Human Papilloma Virus (HPV) infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC) arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

Glypican 3 (GPC3), a heparan sulfate proteoglycan, plays a role in cell growth and differentiation. Mutations of the GPC3 gene are responsible for Simpson-Golabi-Behmel syndrome, which is characterized by anomalies of postnatal overgrowth and an increased risk of developing pediatric malignancies, mostly Wilms tumor and liver cancer. In order to understand the possible role of GPC3 in renal development and Wilms tumor formation, we analyzed messenger RNA (mRNA) and protein levels of GPC3 in sporadic Wilms tumors and compared it to normal kidneys and other common renal epithelial tumors. By using Affymetrix HGU133 oligonucleotide gene expression microarray data from 191 renal tumors and 12 normal kidneys, we found significant overexpression of GPC3 in Wilms tumors (p < 0.01), with 3.5-fold higher expression in comparison to normal kidneys and 6.5-fold higher than any type of renal tumors. The GPC3 gene product in Wilms tumor was further evaluated by immunohistochemistry and quantified by an automated image analysis. Cytoplasmic and membranous GPC3 immunoreactivity was present in 77 % of primary Wilms tumors (23/30), 93 % of metastatic Wilms tumors (13/14), 50 % of metanephric adenomas (4/8), 33 % of congenital mesoblastic nephromas (2/6), 100 % of nephrogenic rests (11/11), and 100 % of fetal kidneys (5/5). GPC3 staining was predominantly identified in blastemal and epithelial components of Wilms tumors, similar to that of fetal non-neoplastic kidney. All adult renal tumors (n = 60) and normal kidneys (n = 15) were GPC3 negative. These findings suggest the utility of GPC3 in differential diagnosis and follow-up of Wilms tumors. Our data also indicate that GPC3 is an oncofetal protein with a potential therapeutic value.

Though rare, renal transplantation into a bowel containing urinary diversion is necessary in select clinical situations. Compared to renal transplant patients with functional native bladders, patients with urinary diversion have comparable long-term graft and patient survival rates. However, compounding the increased risk of malignancy in those on chronic immunosuppression are the inherent risks of urinary diversion. We present a case report of a high grade adenocarcinoma with neuroendocrine differentiation arising in an ileal conduit and discussion on the pathophysiology, management, and screening of this highly select population.