Search Results (78)

Background/Objectives: The aim of this study was to investigate the relationship between the PRIMARY score derived from [⁶⁸Ga]Ga-PSMA PET/CT and key clinical and pathological parameters of prostate cancer aggressiveness, including the PSA level, ISUP Grade Group, and D’Amico risk classification, in patients with biopsy-proven prostate cancer. A secondary aim was to evaluate the interobserver agreement of the PRIMARY score in routine clinical practice. Methods: This retrospective analysis included 51 patients with histopathologically confirmed prostate adenocarcinoma who underwent [⁶⁸Ga]Ga-PSMA PET/CT imaging for staging. PRIMARY scores were determined based on the intraprostatic uptake pattern, intensity, and zonal localization. These scores were compared with PSA levels, ISUP GG, D’Amico risk classification, and histopathological features such as the cribriform pattern, intraductal carcinoma, perineural invasion, extraprostatic extension, and lymphovascular invasion. The PRIMARY scores were independently assigned by a total of three nuclear medicine physicians, and interobserver agreement was calculated using Fleiss’ kappa analysis. Results: Significant associations were found between the PRIMARY scores and the PSA level, ISUP Grade Group, and D’Amico risk classification. The most prevalent score was PRIMARY 5 (54.9%), which was significantly associated with ISUP GG 5 and the high-risk category in D’Amico classification. Among patients with PRIMARY Score 2, a substantial proportion (64.7%) had ISUP GG ≥ 3, and 58.8% were in the high-risk group, highlighting the limitations of binary PRIMARY classification. No statistically significant correlations were found between the PRIMARY scores and specific histopathologic features. Interobserver agreement was excellent (κ = 0.833). Conclusions: The PRIMARY score demonstrates high reproducibility and clinical relevance in stratifying prostate cancer aggressiveness. However, the findings challenge the reliability of binary classifications, particularly for patients with Score 2, who may still harbor high-grade disease. Integrating imaging-based scores with clinical and histopathological data is essential, particularly for accurate staging and decision-making regarding active surveillance. Full article

Background and Aims: An appropriate surveillance system must be established to efficiently identify cases of intraductal papillary mucinous neoplasm (IPMN)-related malignant transformation. We analyzed the initial clinical background that affects long-term prognosis and narrowed the population for whom continued evaluation is inevitable. Methods: We included 1645 patients with IPMN treated at our hospital since 2010. We examined the types and timing of malignant transformation in terms of the worrisome features (WFs). The chi-squared test, log-rank test, and Cox proportional hazards model were used for the analysis (statistical significance at α = 0.05). Results: In total, 123 (7.5%) and 41 patients (2.5%) had IPMN-derived carcinoma (IPMN-DC) and concomitant pancreatic ductal adenocarcinoma (c-PDAC), respectively. Compared with IPMN-DC, a significantly higher proportion of c-PDAC patients were diagnosed with an advanced disease stage that developed earlier. The factors with significantly shorter time for IPMN-DC development were maximum cyst diameter (MCD) ≥ 30 mm, nonbranched type, main pancreatic duct (MPD) diameter ≥ 5 mm, and septal nodal structure (SNS) for IPMN-DC, and MCD ≥ 30 mm, main duct type, MPD ≥ 5 mm, SNS, cyst enlargement (≥2.5 mm/year), and abnormal CA19-9 levels for c-PDAC. Both groups could be significantly stratified by the number of WFs. A relative risk analysis revealed that SNS, MCD ≥ 30 mm, and MPD ≥ 5 mm were significant factors for IPMN-DC, whereas abnormal CA19-9 and SNS were significant for c-PDAC. Conversely, significantly more patients exhibiting these factors initially later developed IPMN-DC or c-PDAC. Conclusions: Ten percent of IPMN cases will develop IPMN-DC or c-PDAC, thereby requiring careful follow-up, especially in cases with SNS, abnormal CA19-9, and MCD ≥ 30 mm. Full article

Background/Objectives: Pathological factors are integral in the risk stratification and management of localized prostate cancer. In recent years, there has been an upsurge of studies that uncovered novel approaches and have refined prognostic factors for prostate cancer in needle biopsy and radical prostatectomy (RP) specimens. Methods: We conducted a review of literature and summarized the significant recent updates on pathological factors for localized prostate cancer. Results: Innovative factors derived from the traditional Gleason grading, such as the extent of Gleason pattern 4 and presence of cribriform pattern are now recognized to significantly improve discrimination of outcome. The components and rules of Gleason grading themselves underwent modifications, and the subsequent prognostic grouping of the different grades (Grade group) have resulted in enhanced stratification of behavior more meaningful in management decision. The approaches for grade reporting in systematic or targeted needle biopsies and in RP with multifocal cancers are also being optimized. Newer tumor growth pattern-based factors such as intraductal carcinoma and atypical intraductal proliferation can have ramifications in management, especially in the background of low to intermediate risk prostate cancers. Gleason grade considerations in the different post-treatment settings and for de novo and residual prostate cancers with varying treatment effects have also been explicated. Likewise, the application of more traditional factors in tumor extent and perineural invasion in biopsy, or positive surgical margin in RP, have also evolved. Conclusions: Some of these newer pathological factors are now officially recommended in standardized pathology reporting protocols and are applied in the management decision for localized prostate cancer. Full article

Mammary tumors occur in female and male guinea pigs. However, published data on their histology and sex predispositions are limited. Histologically, we examined proliferative mammary lesions of 69 female and 48 male pet guinea pigs. Lobular hyperplasia was observed only in females (n = 50). Benign tumors included simple adenomas (n = 20), adenolipomas (n = 3) and intraductal papillary adenomas (n = 5). All except two intraductal papillary adenomas occurred in females. Most malignancies were tubulopapillary and solid carcinomas (n = 54), and intraductal papillary carcinomas (n = 13). These were diagnosed more frequently in male (n = 41) than in female (n = 26) guinea pigs. The carcinomas of males had higher mitotic counts than those of females (p = 0.05). Three carcinosarcomas developed in adenolipoma, and one arose in adenoma. Results show that the mammary tumor classification of dogs and cats can be applied to guinea pigs. However, some tumors (adenolipoma, metaplastic carcinoma) are unique to guinea pigs and shared with laboratory rodents and humans, respectively. Benign tumors may undergo malignant progression. Male guinea pigs appear predisposed to ductal-associated and malignant tumors. Data suggest that male guinea pigs represent an animal model for human male breast cancer. Full article

Cancerization of lobules (COL) is defined as the involvement of lobular acini by ductal carcinoma in situ (DCIS). Whether it represents a morphological variation in DCIS or a secondary extension of DCIS into lobules is debatable. The relation between COL and the probability of invasion is conflicting among different studies. We assessed if COL is a predictor of adverse pathological outcomes in mastectomy specimens. We reviewed the clinicopathological data of patients who underwent partial or total mastectomy for DCIS during a 3-year period (January 2015 until December 2017). Pathological parameters and follow-up data were collected. Whole-tissue hematoxylin and eosin (H&E) slides were reviewed and re-evaluated for COL. Cases with COL were stained immunohistochemically for E-cadherin and p120 to confirm the ductal phenotype of the neoplasms. In total, 171 mastectomies were identified including 65 specimens with pure DCIS and 106 specimens with DCIS with invasive carcinoma. COL was identified in 73 specimens. COL was significantly associated with adverse pathological outcomes including higher DCIS nuclear grade (p-value = 0.006), central (expansive “comedo”) necrosis (p-value = 0.008), presence of DCIS within or less than 2 mm from the surgical resection margin(s) (p-value = 0.004), higher percentage of blocks/slides with DCIS (p-value < 0.001), and extensive intraductal component (EIC) (applicable in cases with invasion) (p-value < 0.001). Invasion was seen in approximately two-thirds of the cases regardless of the presence of COL, with no statistical significance. Ninety-eight patients achieved 60 months of follow-up, of which only one patient developed local DCIS recurrence and had COL and EIC. Four other patients developed metastatic disease related to the invasive component. While other studies have previously hypothesized that COL may be associated with a worse pathological outcome at mastectomy, our results show that it may indeed be a measure of a higher disease burden representing EIC; however, it is not associated with an increased risk of detecting invasive carcinoma. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic databases were used for mutational correlation analysis. p-value ≤ 0.05 was considered as significant. Results: A total of thirty-nine patients with resected IPMN with complete clinical and sequencing data were identified and included in the final cohort. The male-to-female distribution was 21:18, and the mean age was 70.1 ± 9.1 years. GNAS mutations occurred in 23.1% of patients, and 89.7% of patients had iIPMN. In iIPMN patients, GNAS mutation was strongly associated with improved disease-free survival: all GNAS-mutant patients survived to follow-up with significantly fewer recurrences than in GNAS wild-type (WT) patients (p = 0.013). Mutated GNAS closely co-occurred with wild-type KRAS (p < 0.001), and further analysis of large genomic PDAC datasets validated this finding (OR 3.47, p < 0.0001). Conclusions: Our study suggests prognostic value of mutational status in malignant resected IPMNs. WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations. Full article

Mammary intraductal macrophages (foam cells) in humans are the most commonly encountered cells in spontaneous breast nipple discharge, nipple aspirate fluid, and ductal lavage, yet their origin remains unproven. These cells, in both humans and murine model systems, increase in pregnancy, pseudopregnancy, and other conditions like proliferative fibrocystic disease and intraductal neoplasia, ductal carcinoma in situ (DCIS), where there is intraductal ectasia and obstruction. Previous immunocytochemical studies with macrophage (CD68, lysozyme), epithelial (cytokeratin, estrogen receptor), and myoepithelial (smooth muscle actin, CALLA, maspin) markers have indicated that intraductal foam cells are of macrophage lineage. These foam cells engage in phagocytosis of both endogenous and exogenous substances present within the ducts and are not proliferative. Although it has been suggested that foam cells could derive from tissue-specific and niche-specific precursors or circulating monocytes, to date no experimental nor clinical studies have provided direct proof of their origin. In this study, we provide evidence in both human and murine bone marrow transplant studies that intraductal foam cells are bone marrow-derived. We first studied a registry of sex-mismatched bone marrow transplant recipients who later in life had undergone breast biopsies for either proliferative fibrocystic disease, DCIS, or gynecomastia, and studied these biopsies by XY chromosome fluorescence in situ hybridization (FISH) and informative microsatellite polymorphic markers. The intraductal foam cells were of bone marrow donor-origin. Then, in the experimental bone marrow transplant murine studies, donor marrow from female ROSA26 containing the lacZ reporter were transplanted into either irradiated female recipient transgenic mice carrying the highly penetrant MMTV-pymT or FVB/N background mice, where induced pluripotent stem (iPS) cells derived from tail vein fibroblasts of FVB/N-Tg(MMTV-PyVT)634Mul/J mice were subsequently injected into their mammary fat pads. In all of the transplanted recipient mice, the intraductal foam cells expressed the β-galactosidase (lacZ) reporter and also co-expressed markers of myeloid–macrophage lineage. The number of donor-derived intraductal foam cells increased in pseudopregnancy 5-fold and in intraductal neoplasia 10-fold. Although macrophages of different origins and lineages are undoubtedly present within both the murine and human breasts, those macrophages that qualify as phagocytic intraductal foam cells are bone marrow-derived. Full article

There are several types of microvasculature supplying neoplasms: “newly formed blood vessels” (neoangiogenesis), which are a component of the tumor microenvironment (TME) of invasive carcinoma with wound healing-like reaction; and “pre-existing blood vessels”, which are used as tumor-supplying vessels by neoplasms (co-option vessels) and are likely to develop in hypervascularized organs. We herein review the microvasculature of neoplasms of biliary tract with reference to pre-existing vessels and vessel co-options. In the hepatobiliary system, intrahepatic large and extrahepatic bile ducts (large bile ducts) and the gallbladder as well as hepatic lobules are highly vascularized regions. In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia–PCP alignment, whereas the hepatocyte–sinusoid alignment composes hepatic lobules. Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are the main biliary tract carcinomas. CCA is subdivided into distal (d/CCA), perihilar (pCCA), and intrahepatic (iCCA), and iCCA is subdivided into small duct type (SD-iCCA) and large duct type (LD-iCCA). High-grade biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of LD-iCCA, p/dCCA, and GBC. In the large bile ducts and gallbladder, all cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while p/dCCA, LD-iCCA, and GBC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma, a unique microvasculature different from that of co-option or neoangiogenesis. Regarding iCCA showing invasion into the hepatic lobules, some SD-iCCAs replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of malignant progression and of vascular supply in CCAs and its precursors. Full article

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change the intestinal flora, increasing intestinal permeability and allowing gut microbes to enter the bloodstream, leading to chronic inflammation. High dietary lipids can increase BA secretion into the duodenum and fecal BA levels. BAs can cause genetic mutations, mitochondrial dysfunction, abnormal activation of intracellular trypsin, cytoskeletal damage, activation of NF-κB, acute pancreatitis, cell injury, and cell necrosis. They can act on different types of pancreatic cells and receptors, altering Ca²⁺ and iron levels, and related signals. Elevated levels of Ca²⁺ and iron are associated with cell necrosis and ferroptosis. Bile reflux into the pancreatic ducts can speed up the kinetics of epithelial cells, promoting the development of pancreatic intraductal papillary carcinoma. BAs can cause the enormous secretion of Glucagon-like peptide-1 (GLP-1), leading to the proliferation of pancreatic β-cells. Using Glucagon-like peptide-1 receptor agonist (GLP-1RA) increases the risk of pancreatitis and PC. Therefore, our objective was to explore various studies and thoroughly examine the role of BAs in PC. Full article

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series. Full article

This study addresses the critical need for the accurate diagnosis and management of intraductal papillary mucinous neoplasms (IPMNs), which are pancreatic cystic neoplasm types holding a substantial potential for malignancy. It evaluates the diagnostic effectiveness of the Fukuoka consensus guidelines and the European evidence-based guidelines in detecting high-grade dysplasia/invasive carcinoma in IPMNs, utilizing a retrospective analysis of 113 patients from two European medical centers. The methods include a comparative analysis of clinical, radiological, and endoscopic ultrasonography data, alongside an assessment of guideline-driven diagnostic performance. The results demonstrate that both guidelines offer similar accuracy in identifying severe disease stages in IPMNs, with certain clinical markers—such as jaundice, solid mass presence, and an increase in CA 19-9 levels—being pivotal in predicting the need for surgical intervention. This study concludes that while both guidelines provide valuable frameworks for IPMN management, there is an inherent need for further research to refine these protocols and improve patient-specific treatment strategies. This research contributes to the ongoing discourse on optimizing diagnostic and treatment paradigms for pancreatic cystic neoplasms, aiming to enhance clinical outcomes and patient care in this challenging medical field. Full article

Over the years, our understanding of cribriform and intraductal prostate cancer (PCa) has evolved significantly, leading to substantial changes in their classification and clinical management. This review discusses the histopathological disparities between intraductal and cribriform PCa from a diagnostic perspective, aiming to aid pathologists in achieving accurate diagnoses. Furthermore, it discusses the ongoing debate surrounding the different recommendations between ISUP and GUPS, which pose challenges for practicing pathologists and complicates consensus among them. Recent studies have shown promising results in integrating these pathological features into clinical decision-making tools, improving predictions of PCa recurrence, cancer spread, and mortality. Future research efforts should focus on further unraveling the biological backgrounds of these entities and their implications for clinical management to ultimately improve PCa patient outcomes. Full article

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer. Full article

Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P. While the diagnosis of IDC-P relies on specific morphological criteria, its detection remains challenging due to inter-observer variability. Emerging evidence underscores the association of IDC-P with aggressive disease and poor clinical outcomes across various PCa stages. However, standardized management guidelines for IDC-P are lacking. Recent studies suggest considering adjuvant and neoadjuvant therapies in specific patient cohorts to improve outcomes and tailor treatment strategies based on the IDC-P status. However, the current level of evidence regarding this is low. Moving forward, a deeper understanding of the pathogenesis of IDC-P and its interaction with conventional PCa subtypes is crucial for refining risk stratification and therapeutic interventions. Full article

Despite its first recognition even longer ago, in the past nearly 20 years, intraductal carcinoma of the prostate has become a standard histopathologic reporting parameter conveying a strong negative prognostic factor for prostatic adenocarcinoma. When seen at biopsy, intraductal carcinoma of the prostate is associated with risk for aggressive prostatectomy outcomes, including frequently high-grade, high-stage, high-volume disease, with increased risk for recurrence and progression. Multiple organizations, including the uropathology subspecialty societies to the World Health Organization, recognize and recommend reporting the presence of intraductal carcinoma, whether sampled in “pure” form or present with concomitant invasive adenocarcinoma. Moreover, emerging scholarship relates intraductal carcinoma to higher prevalence of homologous recombination repair deficiency mutations in prostatic adenocarcinoma, whether somatic or germline, which serve as indications for approved targeted therapies. Taken together, this is a diagnosis for the histopathologist not to miss. In view of these elevated stakes and the opportunity to further precision medicine, this review details neoplastic and non-neoplastic simulants in the differential diagnosis of intraductal carcinoma of the prostate. Full article