Single-cell and bulk RNA-sequencing reveals mitosis-involved gene HAUS1 is a promising indicator for predicting prognosis and immune responses in prostate adenocarcinoma (PRAD).

It was imperative to identify latent biomarkers pertinent to malignancies, given the pivotal role targeted molecular therapies play in tumor treatment investigations. This study aimed to assess the validity of HAUS1 as an indicator for survival prognosis and immune responses in prostate adenocarcinoma (PRAD) via single-cell and bulk RNA-sequencing. Related data on HAUS1 expression in PRAD were obtained from online databases, followed by comprehensive analyses to delineate its associations with survival prognosis, implicated pathways, and immune responses. Besides, the expression pattern of HAUS1 in PRAD was also verified in vitro, by using qRT-PCR, Western blot analysis, and immunohistochemistry. We found HAUS1 was downregulated in PRAD compared with normal tissues, as verified in vitro by qRT-PCR, Western blot, and immunohistochemistry (p < 0.05). Single-cell RNA-sequencing analysis indicated that HAUS1 had relatively higher expressions in B cells, Mono/Macro cells, and Endothelial cells compared with other cell types. Cox regression analysis revealed HAUS1 could serve as an independent indicator for the overall survival prognosis of PRAD (p < 0.05). Spearman correlation analyses revealed HAUS1 was closely related to the tumor microenvironment, immune cell infiltration levels, immune checkpoints, and immune cell pathways (p < 0.05). Furthermore, HAUS1 expression was found to be closely related to the immunotherapeutic response of patients receiving clinical intervention (p < 0.05). Collectively, our findings underscored the significant role of HAUS1 in PRAD prognosis and immune response, thereby presenting a novel and promising avenue for investigating the clinical utility of immunotherapy in PRAD.

Anti-nuclear matrix protein 2 antibody-positive amyopathic dermatomyositis presenting in a patient with prostate cancer: A case report.

Nuclear matrix protein (NXP-2) positive amyopathic dermatomyositis (DM) may present without classic symptoms like muscle weakness, dysphagia, and edema, and mimic conditions like cutaneous lupus. Given DM's association with malignancy and interstitial lung disease, prompt and accurate diagnosis is important. Testing for myositis-specific antibodies aids diagnosis in ambiguous cases.

Cytopathological Features of Extensive Bilateral Pleural Effusions in Metastatic Prostate Cancer: Report of a Rare Case.

We report a rare case of a 59-year-old male with a history of metastatic prostate cancer presenting with acute onset dyspnea due to extensive bilateral pleural effusions. This case highlights the rarity of metastatic prostate cancer with pleural involvement and underscores the importance of accurate diagnosis using cytopathology and immunohistochemical staining.

Epigenetic-related gene-based prognostic model construction and validation in prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.

Unusual initial presentation of prostate adenocarcinoma with inguinal lymph nodes metastases: a case report.

The presence of lymph node metastases in prostate adenocarcinoma is a poor prognostic sign, and mortality rates are often high. Inguinal lymph node metastases are an unusual presentation of advanced disease, and they can be easily misinterpreted with other diseases. We present a case of a 63-year-old patient with no previous symptoms and signs of prostate disorder with a right-sided inguinal lump and abdominal pain. The CT scan showed right inguinal and retroperitoneal lymphadenopathy. Elevated PSA serum levels, digital rectal examination, and skeletal scintigraphy with 99mTc-MDP favored the diagnosis of metastatic prostate adenocarcinoma. Since the patient denied prostate biopsy, a dissection of the right inguinal nodes was performed. Histopathological findings confirmed metastatic prostate adenocarcinoma. The treatment was hormonal and bisphosphonate therapy, with objective posttreatment improvement. Based on this case, it can be concluded that inguinal and generalized lymphadenopathy are potential initial manifestations of metastatic prostate adenocarcinoma in male patients.

Use of approved Lu-177 radiopharmaceuticals in patients with end-stage renal disease: A review of the literature and proposed treatment algorithm.

Peptide receptor radionuclide therapy (PRRT) can be a very useful treatment for patients with neuroendocrine neoplasms and metastatic castration-resistant prostate cancer but it is routinely avoided in those with advanced kidney disease because it can adversely affect the renal function. Accordingly, no clear guidelines exist on the use of PRRT for patients on hemodialysis (HD). We performed a literature review to identify publications on HD patients who received PRRT with Lutetium-177 (Lu177) Dotatate and Y-90 and obtained information on Lu177 pharmacokinetics and early testing data from the manufacturer. We also perused the most recent North American Neuroendocrine Tumor Society (NANETS)/European Neuroendocrine Tumor Society (ENETS) recommendations. Seven relevant publications with a total of 15 patients were included. Patients received dose-adjusted fractions of PRRT with HD occurring usually within 24 h. There were no immediate or long-term serious adverse events attributed to the radioligand, although data was limited. Using available evidence and input from a multidisciplinary group, we have created an institutional workflow. Dose-adjusted PRRT can be offered to patients undergoing HD under careful, multidisciplinary supervision.

Gamut of Urological Diseases in a Tertiary Hospital in North Central Nigeria.

Context: Worldwide, urological disorders vary from one topography to another. An in-depth understanding of their distribution in each region could serve as a basis for the distribution of manpower, equipment's alongside determine policy formulation and training. Aims: This study enumerates the annual frequency and distribution of urological disorders at the Federal Medical Centre, Keffi. Settings and Design: A cross-sectional retrospective study from November 2021 to November 2022 of all new patients who attended the urology outpatient clinic, emergency department as well as those who had surgical interventions at the Federal Medical Centre, Keffi, Nasarawa State. Materials and Methods: The pertinent records were extracted from the patient's electronic medical records (EMR) and entered into a semistructured questionnaire. Statistical Analysis Used: Data were analyzed using the SPSS software version 20. Results: A total of 452 new patients were seen over the study period. There were 428 (94.5%) males and 24 (5.3%) females, with a male-to-female ratio of 17.8:1. The median age was 58 years, with the age range of 2-97 years. Urological emergencies were seen in 13.5% patients. Ninety-eight percent of cases were acquired, whereas 1.8% were of congenital etiology. Overall, the most commonly diagnosed urologic diseases among new patients in order of decreasing frequency were benign prostatic enlargement (BPE) (54.7%), urethral stricture disease (11.0%), upper tract urinary calculi (6.3%), prostate adenocarcinoma (5.9%), and male infertility (4.3%). Conclusions: BPE, urethral stricture disease, upper tract urinary calculi, prostate adenocarcinoma, and male infertility are common in our environment. An understanding of the urological disease distribution will enhance policy-making and drive manpower needs inspiring core areas of subspecialization with a view at improving the standard of urological care and promoting collaboration with international organizations and funding agencies.

Concomitant Bilateral Inferior Gluteal Lymph Node Involvement in Metastatic Prostate Adenocarcinoma Detected on 68 Gallium-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

An unusual and unique case of prostate adenocarcinoma with involvement of bilateral inferior gluteal lymph nodes is reported. The patient was a 42-year-old male, with conventional prostatic adenocarcinoma (Gleason score: 5 + 4 = 9), who, during disease progression with rising serum prostate specific antigen levels following medical androgen deprivation therapy, demonstrated new prostate-specific membrane antigen expressing metastatic intermuscular deposits in the bilateral gluteal region, subsequently proven to be bilateral inferior gluteal nodal metastasis. A therapeutic implication to this may be that these nodes usually fall beyond the range covered by the therapeutic radiation field coverage where external radiotherapy is the advocated modality of choice and are not easily reachable through standard surgical procedures. As a result, they could have an impact on the way patients are clinically treated and on their prognosis.

Post-therapeutic squamous cell transformation of a metastatic prostate adenocarcinoma with comparison of molecular profiles: a case report and review of the literature.

Transformation of primary prostate adenocarcinoma to squamous cell carcinoma after initial treatment with chemotherapy and hormonal therapy is extremely rare and typically results in rapid treatment-refractory disease progression and death. Here, we present a case of a 64-year-old man who was initially diagnosed with metastatic prostate adenocarcinoma (positive PSA and NKX3.1 stains, total PSA 747.2 ng/ml) to the thoracic spine (T8) in 2019. The patient received androgen deprivation therapy and chemotherapy with good response (PSA 2.53 ng/ml). In 2022, the patient had a tumor resection from the left humerus with a consequent fracture. Pathology showed pure squamous carcinoma without any adenocarcinoma component (PSA and NKX3.1 stains negative and weak p504s stain, PSA 19.82 ng/ml). Given the patient's history of metastatic prostate adenocarcinoma and no history of any other malignancies, a diagnosis of squamous carcinoma transformed from prostate adenocarcinoma was rendered. The patient passed away in 2023. Molecular profiling identified the same TP53 mutation and two variants of uncertain significance in both specimens, suggesting the same primary. However, there was CCND3 amplification and absence of the TMPRSS2::ETV4 fusion in the 2022 specimen, which may be associated with squamous transformation and poor prognosis. A microarray might be beneficial to confirm loss of the TMPRSS2::ETV4 fusion. This case illustrates the rare occurrence of squamous transformation in prostate adenocarcinoma and the aggressive clinical course, and need for more therapy guidance and prognostic studies. It also highlights the importance of molecular profiling to provide insights into the pathogenesis of histologic transformation.

Identification of Molecular Subtype and Prognostic Signature for Prostate Adenocarcinoma based on Neutrophil Extracellular Traps.

Background: Prostate adenocarcinoma (PRAD) is one of the most common cancers in male. Increasing evidences pointed out that Neutrophil Extracellular Traps (NETs) play an important role in tumor angiogenesis, tumor metastasis and drug resistance. However, limited systematic studies regarding the role of NETs in PRAD have been performed. Identification of biomarkers based on NETs might facilitate risk stratification which help optimizing the clinical strategies. Methods: NETs-related genes with differential expressions were identified between PRAD and adjacent normal tissues in TCGA-PRAD dataset. Consensus cluster analysis was performed to determine the PRAD subtypes based on the different-expressed NETs-related genes. The difference of pathway enrichment, infiltrating immune cell and genomic mutation were also evaluated between subtypes. LASSO cox regression analysis was conducted to construct a NETs-related prognostic signature. Result: We identified 19 NETs related genes with differential expressions between PRAD and adjacent normal tissue in TCGA-PRAD dataset. Two significant subtypes were identified based on these 19 genes by consensus cluster analysis, namely subtype 1 and subtype 2. Significant differences in prognosis, immune infiltration and tumor mutation burden were observed in subtypes. LASSO Cox regression analysis identified a NETs-associated prognostic signature including 13 genes, and this signature had a good performance in predicting the progression-free survival of PRAD patients. Further integrated analysis indicated that MMP9 mostly expressed in Mono/Macrophage cells might play a role in regulating NETs formation via neutrophil activation in PRAD. Conclusion: To sum up, the current study identified two NETs-related molecular subtypes and based on which constructed a prognostic signature for PRAD.

Complementary comments on metastatic liver lesions with exceptional and rare cases.

Liver metastases can appear in different forms in magnetic resonance imaging. Contrary to popular belief, while radiologists report hypovascular or hypervascular metastatic lesions, exceptional examples may be detected in various tumors. The aim of this article is to improve this review by presenting rare and atypical examples of liver metastasis, as well as cases that might potentially be misdiagnosed as metastases during the process of differential diagnosis.

CD44 and CD133 protein expression might serve as a prognostic factor for early occurrence castration-resistant prostate cancer.

BACKGROUND: The occurrence of castration-resistant prostate cancer (CRPC) varies in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). The rate of occurrence of CRPC may be related to the presence of prostate cancer stem cells (CSC). Thus, this study aims to evaluate the presence of CSC markers (CD44 and CD133) in histopathology tissue at the time of diagnosis and their correlation with the occurrence of CRPC in patients with advanced PCa within 2 years of ADT. METHOD: A retrospective case-control study was conducted to evaluate the incidence of CRPC within 2 years. The inclusion criteria were patients with PCa who had received treatment with ADT and a first-generation anti-androgen (AA) for 2 years. We classified patients based on whether they developed CRPC within 2 years (CRPC) of the therapy or did not experience CRPC within 2 years (non-CRPC) of the therapy. We performed immunohistochemical (IHC) staining for CD44 and CD133 on the prostate biopsy tissue samples. RESULTS: Data were collected from records spanning 2011-2019. We analyzed a total of 65 samples, including 22 patients with CRPC and 43 patients with non-CRPC who had received treatment with LHRH agonists and AA for up to 2 years. Our findings showed a significant H-score difference in CD44 protein expression between CRPC prostate adenocarcinoma samples 869 (200-1329) and non-CRPC 524 (154-1166) (p = 0.033). There was no significant difference in CD133 protein expression between the two groups (p = 0.554). However, there was a significant difference in the nonoccurrence of CRPC between the high expressions of both CD44 and CD133 groups with other expressions of CD44/CD133 groups (25% vs. 75%; p = 0.011; odds ratio = 4.29; 95% confidence interval [1.34, 13.76]). CONCLUSION: This study found a low expression of at least one CD44/CD133 protein in the patients without early occurrence of CRPC. This result might suggest that CD44/CD133 may function as a potential prognostic marker for PCa, especially in a low expression, to identify patients who have a better prognosis regarding the occurrence of early CRPC.

Unilateral tongue atrophy as the initial clinical manifestation in a patient with prostate cancer.

Key Clinical Message: Unilateral tongue atrophy can be a rare and crucial early indicator of metastatic prostate cancer, highlighting the need for vigilant monitoring in clinical assessments. This case underscores the importance of considering cranial nerve involvement, especially the twelfth, for timely intervention and comprehensive patient care. Abstract: Prostate cancer, ranking among the most prevalent cancers, often manifests with skeletal metastases. Cranial nerve involvement, particularly the twelfth cranial nerve (XII), as an initial presentation is exceptionally rare. This case report outlines a unique instance of unilateral tongue atrophy as the primary clinical manifestation in a patient diagnosed with metastatic prostate cancer. A 54-year-old man presented with dysarthria and progressive weakness, later revealing signs of hypoglossal nerve paralysis, unilateral tongue atrophy, and skeletal metastases involving the base of the skull. Imaging studies, including CT and MRI, confirmed diffuse lytic lesions and cranial nerve entrapment. Further investigations identified elevated PSA levels, confirming acinar prostate adenocarcinoma. The patient underwent hormone therapy due to the poor prognosis. Prostate cancer's skeletal metastases are well-documented, but cranial nerve involvement remains rare, particularly with isolated XII nerve manifestation. The discussion emphasizes the diagnostic challenges, imaging techniques' roles, and the impact on prognosis and quality of life. This case underscores the rarity of unilateral XII nerve involvement as the initial presentation of metastatic prostate cancer. Clinicians should consider this manifestation, especially in men over 40, warranting a thorough diagnostic approach, including PSA measurement and referral for appropriate oncological and urological interventions.

A case report of two synchronous primary urologic malignancies in one patient.

It is quite unusual to have numerous primary malignant tumors at the same time in the same patient. These cancers are classified as metachronous or synchronous. The occurrence of synchronous urologic tumors poses diagnostic and treatment challenges and has always been a subject of controversy in the clinical decision-making process. Unfortunately, no clear standardized management protocols for these patients exist. Therefore, diagnosis and treatment may be difficult, especially with few resources. We present a 75-year-old man with simultaneous prostate and kidney cancers successfully treated at our center. This is one of the rare cases in the English literature with two primary urologic cancers.

Synchronous Pelvic Schwannoma With Metastatic Prostate Cancer: A Rare Case and Pathology Review.

Schwannomas are benign tumors arising from well-differentiated Schwann cells of peripheral nerves. They are usually found on the limbs, head, and neck. It is uncommon for schwannoma to occur in the pelvis and when it does, it is often diagnosed late. Pelvic schwannoma when diagnosed are often bigger in size (>5 cm) and may present with local symptoms such as constipation and bladder outlet obstruction. We hereby present a patient with concurrent metastatic prostate carcinoma and pelvic schwannoma. The patient is a 57-year-old man initially diagnosed with prostate cancer and was lost to follow-up. One year later, he presented with metastatic prostate disease and bladder outlet obstruction. Further evaluation revealed a concurrent pelvic mass that was increasing in size. The biopsy of this mass was suggestive of schwannoma. It was decided at the multidisciplinary tumor board conference to offer treatment for his metastatic prostate disease and observe the schwannoma. His obstructive symptoms worsened in the face of clinical evidence of regression of his prostatic disease, and it was decided to resect the pelvic mass. The surgery revealed a huge soft tissue mass within the pelvis that was adherent to the bladder, prostate, and rectum. Morphology and immunohistochemistry studies of the pelvic mass confirmed the diagnosis of ancient schwannoma. We hereby highlight the clinical importance of this presentation and the diagnostic and therapeutic dilemma involved in the management of this patient who presented with two pathologic conditions causing similar symptoms but of different prognostic and therapeutic significance.

Long-Term Survival After Definitive Concurrent Chemoradiation Therapy for Synchronous Small Cell Neuroendocrine Carcinoma of the Urinary Bladder and Adenocarcinoma of the Prostate: A Case Report.

Available reports of synchronous prostate and bladder cancer have exclusively described radical cystoprostatectomy with or without perioperative chemotherapy as the treatment of choice. There are no reports of curative intent or definitive chemoradiation therapy for synchronous primary bladder and primary prostate cancers. Small cell carcinoma of the bladder is a rare and aggressive tumor. We present the first case of synchronous mixed small cell carcinoma and urothelial carcinoma of the urinary bladder and adenocarcinoma of the prostate in a 70-year-old male who attained long-term survival after curative intent and definitive concurrent chemoradiotherapy with minimal acute and late toxicities. The patient remained alive and disease-free at 41 months post-treatment and achieved excellent functional outcomes with organ preservation. Definitive chemoradiation therapy offers a safe and effective, curative-intent organ preservation treatment for localized synchronous prostate and bladder cancers.

Dural metastasis of prostate carcinoma mimicking intracranial hematoma: a case report and literature review.

Dural metastases of prostate adenocarcinoma are an extremely rare complication and may mimic intracranial hematoma. Preoperatively diagnosis may be difficult due to similarities in symptoms and radiological appearance. We present a 65-year-old man admitted to the ED with a history of headache, nausea, vomiting, vertigo, diplopia, as well as numbness of his left lower extremity. Past medical history confirmed metastatic prostate cancer disease. After computed tomography and contrast computed tomography, the consulting radiologist diagnosed a chronic subdural hematoma. After burr hole trephination and dural opening, tumorous mass was detected. Histopathologic samples were taken. Histopathological examination was consistent with metastatic adenocarcinoma of the prostate. Although rare, dural metastases need to be included in oncological patients presenting in the ED with symptoms and radiological imaging suggesting hematoma. Both neurooncological and neurosurgical consultations are essential in order to apply the best treatment strategy.

Aggressive prostatic adenocarcinoma with urothelial-like morphology, with frequent CK7/CK20/HMWK expression and occasional diffuse neuroendocrine features: A clinicopathologic study of 12 cases.

INTRODUCTION: Prostatic adenocarcinoma can occasionally display urothelial carcinoma morphology, which prompts immunohistochemistry (IHC) studies to determine its lineage. Typically, prostate cancer is characterized by the lack of cytokeratin (CK) 7, CK20 and high molecular weight keratin (HMWK) expression, as opposed to bladder cancer. METHODS: We report a series of 12 prostatic adenocarcinoma cases with unusual urothelial-like morphology, diagnosed at two academic institutions in Toronto between 2018 and 2023, and analyzed by immunohistochemistry for prostatic, urothelial, and neuroendocrine marker expression. We collected patient age, androgen deprivation therapy (ADT) status, tumour site, histomorphology, Grade group (GG) and results of genetic testing. RESULTS: The median age of the 12 patients included in this case series was 75.5 years (range 41-85). A history of prostatic cancer was noted in 7/12 (58%) patients. Five of nine (56%) patients had elevated serum PSA level at diagnosis. Six of eleven (55%) patients had prior ADT. Tumour sites were prostate (n = 6), bladder (n = 3), liver metastases (n = 2), and lung metastasis (n = 1). GGs of the primary tumours were GG3 (n = 1) and GG5 (n = 8). The observed urothelial-like morphology was diffuse in ten cases, and focal in two cases. CK7 was strong/diffuse in 8/11 tested cases, and focal weak in one case. CK20, HMWK, p63 and GATA3 were patchy/focal/weak/moderate in 3/6, 4/7, 4/8 and 2/9 cases, respectively. Ten (83%) cases were positive for at least one prostatic marker; eight (67%) cases had loss/weak staining of at least one prostatic marker. AR loss was seen in 2/7 (29%) cases. Seven of ten (70%) cases had diffuse/strong expression of at least one neuroendocrine marker. No trend was evident between prior ADT/AR status and any IHC result. Molecular analyses for DNA damage repair (DDR) genes (n = 6) demonstrated one ATM deletion (bladder). In addition, one TMPRSS2:ERG fusion (lung metastasis) was identified. CONCLUSION: This series comprises high-grade and/or metastatic prostatic adenocarcinoma cases with distinctive urothelial-like morphology and frequent aberrant CK7/CK20/HMWK expression. Their histomorphology, highly suggestive of an urothelial origin, represents a diagnostic pitfall that can lead to considerable management repercussions. The fact that a high proportion of the reported cases had loss/weak expression of at least one of the tested prostatic-specific markers, and occasionally a diffuse positivity for neuroendocrine markers highlights the importance of (1) clinical history and (2) utilization of broad IHC panels to correctly diagnose such unusual prostate cancer cases.

PRADclass: Hybrid Gleason Grade-Informed Computational Strategy Identifies Consensus Biomarker Features Predictive of Aggressive Prostate Adenocarcinoma.

BACKGROUND: Prostate adenocarcinoma (PRAD) is a common cancer diagnosis among men globally, yet large gaps in our knowledge persist with respect to the molecular bases of its progression and aggression. It is mostly indolent and slow-growing, but aggressive prostate cancers need to be recognized early for optimising treatment, with a view to reducing mortality. METHODS: Based on TCGA transcriptomic data pertaining to PRAD and the associated clinical metadata, we determined the sample Gleason grade, and used it to execute: (i) Gleason-grade wise linear modeling, followed by five contrasts against controls and ten contrasts between grades; and (ii) Gleason-grade wise network modeling via weighted gene correlation network analysis (WGCNA). Candidate biomarkers were obtained from the above analysis and the consensus found. The consensus biomarkers were used as the feature space to train ML models for classifying a sample as benign, indolent or aggressive. RESULTS: The statistical modeling yielded 77 Gleason grade-salient genes while the WGCNA algorithm yielded 1003 trait-specific key genes in grade-wise significant modules. Consensus analysis of the two approaches identified two genes in Grade-1 (SLC43A1 and PHGR1), 26 genes in Grade-4 (including LOC100128675, PPP1R3C, NECAB1, UBXN10, SERPINA5, CLU, RASL12, DGKG, FHL1, NCAM1, and CEND1), and seven genes in Grade-5 (CBX2, DPYS, FAM72B, SHCBP1, TMEM132A, TPX2, UBE2C). A RandomForest model trained and optimized on these 35 biomarkers for the ternary classification problem yielded a balanced accuracy ∼ 86% on external validation. CONCLUSIONS: The consensus of multiple parallel computational strategies has unmasked candidate Gleason grade-specific biomarkers. PRADclass, a validated AI model featurizing these biomarkers achieved good performance, and could be trialed to predict the differentiation of prostate cancers. PRADclass is available for academic use at: https://apalania.shinyapps.io/pradclass (online) and https://github.com/apalania/pradclass (command-line interface).