Prostatic Acinar Adenocarcinoma Research Articles

Extra-Skeletal Osteosarcoma of the Prostate After Treated Prostatic Acinar Adenocarcinoma: A Case Report and Review of the Literature.

Extra-skeletal osteosarcoma is a rare form of malignant soft tissue sarcoma. Its occurrence in the prostate gland is particularly uncommon. In this case report, we present a patient diagnosed with osteosarcoma arising within the prostatic gland. A 58-year-old man was initially diagnosed with Gleason 8 prostate acinar adenocarcinoma following a transurethral resection (TUR) of the prostate. This diagnosis was accompanied by locoregional involvement and multiple bone metastases. The patient underwent a treatment regimen including complete androgen blockade, chemotherapy, greenlight laser prostate vaporization, and palliative radiotherapy. After treatment, he achieved a complete biochemical response, and his bone metastases remained stable. However, at 16 months post-diagnosis, clinical follow-up by means of radiological examinations revealed an increase in the size of the prostatic lesion, along with additional infiltration of the tumor into the rectum and bladder walls. Remarkably, a mesenchymal tumor proliferation with intratumor calcifications was observed. A subsequent TUR biopsy of the prostate showed a malignant tumor spindle and ovoid cell proliferation with high-grade nuclear atypia, necrosis, and islets of osteoid formation, leading to a final diagnosis of high-grade prostatic extra-skeletal osteosarcoma. Despite undergoing chemotherapy, the patient's condition progressed with the development of pulmonary and liver metastases, culminating in his demise.

Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

68Ga-PSMA PET/CT and 18F-FDG PET/CT in the diagnosis of prostatic ductal cancer

PurposesTo explore the characteristics of PSMA PET/CT and FDG PET/CT images in prostatic ductal adenocarcinoma (DA) patients. MethodsWe retrospectively enrolled prostatic DA patients with PET/CT scans at Tongji Hospital from 2018 to 2022. Patients with prostatic acinar adenocarcinoma (AA) and benign pathology (BP) were enrolled by 1:1 matching. Differences in the uptake of primary and metastatic foci on PET among the groups were analyzed. ResultsA total of 42 patients were enrolled: 14 in each group. In primary foci, the mean PSMA uptake in the DA group was lower than that in the AA group (14.2 ± 9.6 vs. 27.1 ± 14.3, P = 0.009) and greater than that in the BP group (14.2 ± 9.6 vs. 4.7 ± 1.3, P = 0.003). The AUCs of the DA-AA ROC curve and DA-BP ROC curve were 0.781 and 0.872, respectively. The median PSMA uptake of metastatic lymph nodes in the DA group was lower than that in the AA group (5.6 vs. 14.2, P = 0.033), with no significant difference in metastatic bone lesions (9.5 vs 19.1, P = 0.485). No significant difference was found in the FDG uptake of primary and metastatic foci between the DA and AA groups (P > 0.05). ConclusionProstatic DA has greater PSMA uptake than BP diseases, but lower uptake in both primary foci and metastatic lymph nodes than AA on PSMA PET/CT, aiding in the differential diagnosis of DA, AA and BP diseases. Clinicians should combine traditional imaging with PSMA PET/CT to avoid underestimating the clinical stage of DA patients.

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

NTRK3-Rearranged Prostatic Acinar Adenocarcinoma: Report of a Patient and Review of the Literature.

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1::NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can be oncogenic drivers or develop as resistance mechanisms. The tumor-agnostic approvals of TRK inhibitors by the FDA provide additional rationale for molecular investigations of aggressive prostatic adenocarcinomas. This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion.

Amplifiation of the c-MYC gene in acinar prostate adenocarcinoma. Morphogenic comparisons

The purpose of this work was to evaluate c-MYC gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor. The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe. In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (p<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (p<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (p<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (p<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (p<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (p<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (p<0.05). Amplification of the c-MYC gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the c-MYC gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.

Molecular complexity of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis

BackgroundWe compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). MethodsWe performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan–Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. ResultsKaplan–Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). ConclusionAmongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Differential expression of LLGL2 in prostate ductal adenocarcinoma and acinar adenocarcinoma and its significance

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.

Immunohistochemical study of mismatch repair and programmed death ligand-1 protein expression in prostatic acinar adenocarcinoma in correlation with patient clinicopathological parameters

Background Castrate-resistant prostate cancer (CRPC) is the main challenge among prostate cancer patients; most are metastatic and eventually resist any treatment. No cure yet exists for them. Aim Investigate the immunohistochemical expression of mismatch repair genes (MMR) protein products for loss of expression and programmed death ligand-1 (PDL-1) overexpression in prostatic acinar adenocarcinoma cases as a trial to find benefit from using immune checkpoint inhibitor drugs as a new therapeutic modality, especially in CRPC. Patients and methods This study included 166 cases of prostatic acinar adenocarcinoma of different grades and stages along with different responses to therapy including 57% being classified as CRPC. Tissue microarray was applied using mostly three cores from each donor case, resulting in the formation of six new recipient blocks. Immunohistochemical staining for MSH2, MSH6, MLH1, PMS2, and PDL-1 was done. Interpretation of the results, their correlation with all collected clinical and pathological parameters, and statistical analysis of the results were done. Results Most of the studied cases showed retained nuclear stain for all MMR genes (MSH2, MSH6, MLH1, PMS2), with total loss of the nuclear stain found in few cases ranging from one (0.7%) case in MLH1 to six (4.2%) cases in MSH2. PDL-1 was expressed in about seven (4.8%) cases. No significant correlation was found between MMR protein loss or PDL-1 expression and the different clinicopathological parameters including CRPC. Conclusion The limited cases that showed MMR protein loss or PDL-1 expression may suggest that the immune checkpoint inhibitors are of limited value in CRPC but can be used as the last option after investigations of these markers as still few cases can show these changes. Patchy loss of MMR proteins is suggested to be further investigated by molecular studies.

Association of high-grade prostatic intraepithelial neoplasia immunohistochemical profile with acinar adenocarcinoma of the prostate.

Prostate carcinoma is the second leading cause of cancer and the fifth cause of cancer death in men worldwide. To know high-grade prostatic intraepithelial neoplasia and prostate acinar adenocarcinoma immunohistochemical profiles. Observational, analytical, cross-sectional, retrospective study of specimens obtained by cutting needle biopsy and prostate resection from subjects diagnosed with acinar adenocarcinoma of the prostate and high-grade prostatic intraepithelial neoplasia between January 2015 and December 2020. Tissue microarrays were performed and, subsequently, immunohistochemical studies for BCL2, EGFR, p53, Her2/neu and Ki67. Descriptive statistics were used to analyze clinicopathological factors. Qualitative variables were compared with Fisher's exact test. Twenty-three patients were studied; eight (34%) with angiolymphatic invasion, 14 (60.8%) with perineural invasion, five (21.2%) with prostatitis, and four (17.3%) with fibroadenomatous hyperplasia. HER2/neu (p = 0.1023), p53 (p = 1) and BCL2 expression (p = 0.4136) was observed. HER2/neu increased expression was identified in high-grade prostatic intraepithelial neoplasia and acinar adenocarcinoma of the prostate.

Association of high-grade prostatic intraepithelial neoplasia immunohistochemical profile with acinar adenocarcinoma of the prostate

Prostate carcinoma is the second leading cause of cancer and the fifth cause of cancer death in men worldwide. To know high-grade prostatic intraepithelial neoplasia and prostate acinar adenocarcinoma immunohistochemical profiles. Observational, analytical, cross-sectional, retrospective study of specimens obtained by cutting needle biopsy and prostate resection from subjects diagnosed with acinar adenocarcinoma of the prostate and high-grade prostatic intraepithelial neoplasia between January 2015 and December 2020. Tissue microarrays were performed and, subsequently, immunohistochemical studies for BCL2, EGFR, p53, Her2/neu and Ki67. Descriptive statistics were used to analyze clinicopathological factors. Qualitative variables were compared with Fisher's exact test. Twenty-three patients were studied; eight (34%) with angiolymphatic invasion, 14 (60.8%) with perineural invasion, five (21.2%) with prostatitis, and four (17.3%) with fibroadenomatous hyperplasia. HER2/neu (p = 0.1023), p53 (p = 1) and BCL2 expression (p = 0.4136) was observed. HER2/neu increased expression was identified in high-grade prostatic intraepithelial neoplasia and acinar adenocarcinoma of the prostate.

Distinct genomic features and evolutionary relationships between concurrent intraductal carcinoma and adenocarcinoma of the prostate.

215 Background: Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally co-exists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared to concomitant adenocarcinoma. Till now, the genomic characteristics of IDC-P remain largely unknown. Methods: To explore the genomic features and evolutionary relationships between concurrent IDC-P and PAC, we isolated IDC-P, concurrent invasive high-grade PAC lesions, and adjuvant normal prostate tissues from 22 radical prostatectomy specimens. Whole-exome, RNA, and DNA-methylation sequencing were performed on the acquired tumoral and normal samples. The biological characteristics of IDC-P and concurrent PAC were compared at different molecular levels. Results: Three evolutionary patterns between concurrent IDC-P and PAC were identified. Tumors with clonally distant and early divergent evolutionary patterns showed higher genomic and pathological heterogeneities between concurrent IDC-P and PAC than those with the late-divergent pattern. Compared to co-existing PAC, increased adverse prognosis-associated genes were overexpressed in IDC-P. Besides, IDC-P was similar to Gleason pattern 5 PAC on the transcriptome profile. Survival analysis based on an independent cohort supported IDC-P resembled Gleason pattern 5 tumors. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Conclusions: Our findings provide a molecular groundwork for the aggressive behavior of IDC-P and contribute to developing potential therapies for tumors with IDC-P.

Nomogram Models for Distinguishing Intraductal Carcinoma of the Prostate From Prostatic Acinar Adenocarcinoma Based on Multiparametric Magnetic Resonance Imaging.

To compare multiparametric magnetic resonance imaging (MRI) features of intraductal carcinoma of the prostate (IDC-P) with those of prostatic acinar adenocarcinoma (PAC) and develop prediction models to distinguish IDC-P from PAC and IDC-P with a high proportion (IDC ≥ 10%, hpIDC-P) from IDC-P with a low proportion (IDC < 10%, lpIDC-P) and PAC. One hundred and six patients with hpIDC-P, 105 with lpIDC-P and 168 with PAC, who underwent pretreatment multiparametric MRI between January 2015 and December 2020 were included in this study. Imaging parameters, including invasiveness and metastasis, were evaluated and compared between the PAC and IDC-P groups as well as between the hpIDC-P and lpIDC-P subgroups. Nomograms for distinguishing IDC-P from PAC, and hpIDC-P from lpIDC-P and PAC, were made using multivariable logistic regression analysis. The discrimination performance of the models was assessed using the receiver operating characteristic area under the curve (ROC-AUC) in the sample, where the models were derived from without an independent validation sample. The tumor diameter was larger and invasive and metastatic features were more common in the IDC-P than in the PAC group (P < 0.001). The distribution of extraprostatic extension (EPE) and pelvic lymphadenopathy was even greater, and the apparent diffusion coefficient (ADC) ratio was lower in the hpIDC-P than in the lpIDC-P group (P < 0.05). The ROC-AUCs of the stepwise models based solely on imaging features for distinguishing IDC-P from PAC and hpIDC-P from lpIDC-P and PAC were 0.797 (95% confidence interval, 0.750-0.843) and 0.777 (0.727-0.827), respectively. IDC-P was more likely to be larger, more invasive, and more metastatic, with obviously restricted diffusion. EPE, pelvic lymphadenopathy, and a lower ADC ratio were more likely to occur in hpIDC-P, and were also the most useful variables in both nomograms for predicting IDC-P and hpIDC-P.

Expression of ERG in Prostatic Acinar Adenocarcinoma Diagnosed on TRUS-guided Biopsy and its Association with WHO Grade Group- A Prospective Observational Study

Introduction: Prostate cancer is a common malignancy affecting men and the second leading cause of cancer related death in India. Numerous molecular biomarkers have been evaluated for their potential role in predicting disease progression, their response to therapy and survival. Erythroblast Transformation Specific (ETS) related Gene (ERG) is one of the newest addition in the existing list of biomarkers of prostate cancer. Aim: To analyse the expression of ERG in prostatic adenocarcinoma and to evaluate its association with World Health Organisation (WHO) grade group. Materials and Methods: This was a prospective observational study was conducted in the Department of Pathology in association with Department of Urology, IPGME&amp;R, SSKM Hospital, Kolkata, West Bengal, India. The duration of the study was 1.5 years, from January 2019 to June 2020. A total of 267 cases of Transrectal Ultrasound (TRUS) guided tru-cut biopsy was included. Clinical data including preoperative Prostate Specific Antigen (PSA) level, Digital Rectal Examination (DRE) were obtained. Histopathological reports were prepared by two pathologists along with Gleason scoring and WHO grading as per 2014 International Society of Urological Pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma. Formalin Fixed Paraffin Embedded (FFPE) sections of representative blocks of each tumour was selected for Immunohistochemistry (IHC) study. Only the cases which had more than 10% nuclear staining were considered as positive. Statistical analysis was performed with help of Epi Info (TM) 7.2.2.2 and Chi-square test was used to test the association of different study variables. Results: The mean age of the study participants was 65.55 years, and the age range was 45-93 years. Among the 80 malignant cases where, ERG immunostaining was assessed, 28 cases (35%) showed positive expression. Among these positive cases, 50% cases were weakly positive, 28.57% showed moderate positivity and 21.43% had strong positive expression. Highest positivity was observed in WHO grade group V (44.83%). The intensity of ERG expression was also higher in high grade group (13) than low grade group cancer patients. Conclusion: ERG expression in the prostate cancer can be a prognostic factor as the expression and intensity of expression both increases with higher grade group of cancer.

Prostate Pathology: What is New in the 2022 WHO Classification of Urinary and Male Genital Tumors?

In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male Genital Tumors, which provides a comprehensive update on tumor classification of the genitourinary system. This review article focuses on prostate carcinoma and underscores changes in the prostate chapter as well as those made across the entire series of the 5th edition of WHO Blue Books. Although no major alterations were made to this chapter, some of the most notable updates include restructure of contents and introduction of a new format; standardization of mitotic counts, genomic nomenclatures, and units of length; refined definition for the terms "variant", "subtype", and "histologic pattern"; reclassification of prostatic intraepithelial neoplasia (PIN)-like adenocarcinoma as a subtype of prostatic acinar adenocarcinoma; and recognition of treatment-related neuroendocrine prostatic carcinoma as a distinct tumor type. Evolving and unsettled issues related to grading of intraductal carcinoma of the prostate and reporting of tertiary Gleason pattern, the definition and prognostic significance of cribriform growth pattern, and molecular pathology of prostate cancer will also be covered in this review.

An Immunohistochemical Study for Mammalian Target of Rapamycin Signaling Pathway Including Interacting PTEN in Prostatic Acinar Adenocarcinoma and Correlation with the Patient Clinicopathological Parameters

Background: The activation of AKT-mTOR-PTEN pathway may promote prostate cancer progression and affects response to targeted therapies. The full extent of this activation remains to be determined. Our aim: was to assess the expression of inactive mTOR, phosphor-mTOR, phosphor-AKT and loss of PTEN in prostatic adenocarcinomas then correlate their expression with the clinicopathological parameters.&#x0D; Methods: The study included 166 prostatic adenocarcinoma tissues using immunohistochemistry on tissue microarrays. Statistical analysis considering markers expression and correlation with the clinicopathologic parameters was done using appropriate tests.&#x0D; Result: The mean age was 72.63 and 75.9% were clinically high risk. Gleason score 7 and WHO grade group 5 were the commonest (31.3% and 31.9% respectively). Most patient (73.1%) were stage T2 or higher. Expression of inactive mTOR, phospho-mTOR and phosphor-AKT was seen in 96.1%, 93.5% and 95.9% respectively. The loss of PTEN expression was noted in 55.3%. There were significant correlations between Gleason pattern 4 and the expression of inactive mTOR (p value &lt;0.001 and 0.004 respectively) and phospho-mTOR (p value 0.003 and 0.001 respectively). Gleason score 7 was significantly correlated to inactive mTOR expression (p value &lt;0.001). There was also significant correlation between phosphor-AKT and phospho- mTOR expression with p value 0.004.&#x0D; Conclusion: The immunohistochemical expression of inactive mTOR, phosphor-mTOR and phosphor-AKT and loss of PTEN was appreciated in most prostate cancer cases, suggesting that activation of this pathway occur early during prostate tumorigenesis. This may indicate that targeting mTOR pathway may have a promising therapeutic role in the management of prostatic adenocarcinoma.

Hepar-1 Positive Prostatic Adenocarcinoma: A Case Report and Review of Literature

Abstract Introduction/Objective Poorly differentiated metastatic malignancy in patients with a history of more than one known primary tumor, such as a history of both hepatocellular and prostatic carcinoma as seen in our case, can be challenging. Both tumors are CK7/CK20 positive, and both can be reactive for hepar-1, as has been demonstrated in the current case, and rarely described in the literature. Methods/Case Report Herein we present a sixty-three-year-old male who presented for follow-up of his lower back pain in the setting of hepatocellular carcinoma. MRI of the spine was suggestive of an expansile metastatic lesion in the C2 vertebral body with extraosseous soft tissue extension resulting in moderate to severe central canal and left foraminal narrowing at C2-3. Multiple additional metastatic lesions were visualized throughout the cervical upper thoracic spine as detailed above. Vertebral body biopsy showed metastatic adenocarcinoma with sheets of neoplastic cells infiltrating the medullary spaces. The patient’s history of hepatocellular carcinoma was noted, and immunohistochemical staining for HepPar1 with appropriate control was performed and found to be diffusely reactive in the tumor cells. However, tumor cells were also positive for PSA, PSAP, and NKX3.1 (Fig-1-A-D, H&amp;E, Hepar-1, PSAP, PAP). This immunoprofile is consistent with a prostatic origin of the tumor cells, and a diagnosis of metastatic prostatic adenocarcinoma was given. Results (if a Case Study enter NA) NA. Conclusion Hepar-1 and even arginase-1 have been observed in rare subsets of prostatic acinar adenocarcinoma. Even in the setting of PSA and PSAP negative metastatic disease in patients with a history of hepatocellular carcinoma, we suggest utilizing additional stains suggestive of a prostatic origin, such as NKX3.1, and even molecular studies. This could be useful diagnostic approach to help differentiate between the two neoplasms in such patients.

Exceptional Response of Rare Plasmacytoid Variant Prostate Cancer Post 177Lu-PSMA Therapy Seen on 68Ga-PSMA PET/CT.

Plasmacytoid is a rare variant of acinar prostatic adenocarcinoma. The aggressive type is characterized by an aggressive clinical course, lack of responsiveness to hormonal therapies, and an overall poor prognosis. Here we present pretherapy and posttherapy 68Ga-PSMA PET/CT images showing an exceptional response to 177Lu-PSMA therapy. This case demonstrates the usefulness of both 68Ga-PSMA PET/CT in assessing the tumor PSMA avidity and the potential of 177Lu-PSMA therapy in these patients.