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BACKGROUND: Secondary rectal linitis plastica (RLP) from prostatic adenocarcinoma is a rare and poorly understood form of metastatic spread, characterized by a desmoplastic response and concentric rectal wall infiltration with mucosal preservation. This complicates endoscopic diagnosis and can mimic gastrointestinal malignancies. This case series underscores the critical role of magnetic resonance imaging (MRI) in identifying the distinct imaging features of RLP and highlights the importance of considering this condition in the differential diagnosis of patients with a history of prostate cancer. CASE SUMMARY: Three patients with secondary RLP due to prostatic adenocarcinoma presented with varied clinical features. The first patient, a 76-year-old man with advanced prostate cancer, had rectal pain and incontinence. MRI showed diffuse prostatic invasion and significant rectal wall thickening with a characteristic "target sign" pattern. The second, a 57-year-old asymptomatic man with elevated prostate-specific antigen levels and a history of prostate cancer exhibited rectoprostatic angle involvement and rectal wall thickening on MRI, with positron emission tomography/computed tomography PSMA confirming the prostatic origin of the metastatic spread. The third patient, an 80-year-old post-radical prostatectomy, presented with refractory constipation. MRI revealed a neoplastic mass infiltrating the rectal wall. In all cases, MRI consistently showed stratified thickening, concentric signal changes, restricted diffusion, and contrast enhancement, which were essential for diagnosing secondary RLP. Biopsies confirmed the prostatic origin of the neoplastic involvement in the rectum. CONCLUSION: Recognizing MRI findings of secondary RLP is essential for accurate diagnosis and management in prostate cancer patients.
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Prostatic adenocarcinoma is characterized by elevated phosphatidylcholine metabolism. 18F-choline positron emission tomography/computed tomography (PET/CT) is widely used for patients with biochemical recurrence and a prostate-specific antigen threshold above 2 ng/mL. We report a case of a patient with high-risk prostatic adenocarcinoma undergoing 18F-choline PET/CT for biochemical recurrence. In addition to hypermetabolic abdominal lymph nodes, an unexpected right testicular hypermetabolism was observed. Such findings on 18F-choline PET/CT may suggest a primary tumor or testicular metastasis of prostate cancer. Bilateral orchiectomy revealed a vitelline tumor associated with known primary prostatic cancer. The incidental discovery of a testicular vitelline tumor during prostate cancer imaging is rare, highlighting the importance of thorough diagnostics. This case underscores the need for comprehensive care in managing complex and atypical cancer cases, emphasizing the potential for unrelated tumor discoveries during diagnostic workup. Further research is essential for a better understanding of these rare co-occurring cancers and their treatment implications.
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INTRODUCTION: Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma. METHODS: Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses. RESULTS: In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05). CONCLUSION: Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.
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Synchronous prostatic adenocarcinoma found in patients with muscle-invasive bladder cancer (MIBC) that undergo radical cistoprostatectomy is not uncommon. Nonetheless, the occurrence of collision metastasis, where both prostate cancer and bladder cancer involve the same lymph node, is exceptionally uncommon, with few cases being reported in the literature. We present a case of a 65-year-old patient diagnosed with MIBC who underwent laparoscopic radical cistoprostatectomy with extended lymph node dissection and intracorporeal ileal conduit. The final pathology revealed urothelial carcinoma pT3bN1 as well as prostatic adenocarcinoma pT3bN1. One lymph node presented metastasis from both bladder cancer and prostate cancer.
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Metástase Linfática , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Masculino , Idoso , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Prostatectomia/métodos , Linfonodos/patologia , Excisão de Linfonodo/métodosRESUMO
Large cell neuroendocrine carcinoma (LCNEC) is one of the rarest types of bladder cancer, with an aggressive course and a poor prognosis. We report a case of LCNEC of the bladder associated with a prostatic adenocarcinoma. A very rare association, to our knowledge, is described for the first time in the literature. The patient was a 76-year-old non-smoker male, who presented with intermittent hematuria and dysuria. Cystoscopy revealed a lesion on the right lateral bladder wall. Biopsy was in favor of a LCNEC with muscle invasion. The CT scan showed the presence of a second lesion in the prostate, confirmed by histological examination. The patient was treated by neoadjuvant chemotherapy of the cisplatin-etoposide type for large-cell bladder neuroendocrine carcinoma, and hormone therapy with luteinizing hormone-releasing hormone (LH-RH) analogs for prostatic adenocarcinoma, followed by radical surgery. Given the rarity of this tumor, LCNEC treatment lacks precision. Many cases are published with different therapeutic strategies. A literature review would be interesting to codify the therapeutic strategy for this rare tumor.
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Introduction: Multiple primary malignant neoplasms (MPMNs) are cancers presenting distinct pathological types that originate from different tissues or organs. They are categorized as either synchronous or metachronous. Nowadays, the incidence of MPMN is increasing. Patients and methods: We present a case of a 71-year-old male patient with a medical history of hepatitis B and a family history of breast and endometrial cancers. The patient reported a nasal tip skin lesion with recurrent bleeding, and the history disclosed lower urinary tract symptoms. Further investigations revealed the coexistence of four primary cancers: basosquamous carcinoma of the nasal lesion, prostatic adenocarcinoma, hepatocellular carcinoma, and clear cell renal cell carcinoma. Results: A multidisciplinary team cooperated to decide the proper diagnostic and therapeutic modules. Conclusion: To the best of our knowledge, the synchronization of these four primary cancers has never been reported in the literature. Even so, multiple primary malignant neoplasms, in general, are no longer a rare entity and need proper explanations, a precise representation of definition and incidence, further work-up approaches, and treatment guidelines as well.
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Background & Objective: Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical biomarkers becomes mandatory. This study aims to investigate P4HB and SOX4 expression in prostatic carcinoma, their possible roles, and clinical significance. Methods: This retrospective study included fifty-six cases of PAC and an equal number of nodular prostatic hyperplasia (NPH) that were immunohistochemically stained by P4HB and SOX4. The results of expression were compared between PAC and NPH cases, followed by correlations with available clinicopathological parameters. Results: There was a highly significant difference between PAC and NPH regarding P4HB and SOX4 expressions in favor of PAC (both P<0.001). ROC curve analysis of the diagnostic power of P4HB showed 79% sensitivity, 76% specificity, and an area under the ROC curve of 0.845, while SOX4 showed (89%, 100%, and 0.946, respectively). P4HB and SOX4 expression showed a direct correlation (P<0.001). Moreover, the H-score of SOX4 expression showed a significant inverse relation with ERG expression (P=0.047). There was a significant correlation between P4HB and SOX4 and Gleason score (P<0.001). Moreover, P4HB expression was significantly associated with lymphovascular invasion (P=0.013), while SOX4 expression showed a significant association with perineural invasion (P=0.05). Conclusion: SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected.
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The presence of villous adenoma in the urinary tract is an exceedingly rare finding. On a histological and cytological level, this tissue is essentially identical to that typically found in the colon. These lesions do have malignancy potential and, when present with coexistent adenocarcinoma, have a risk of recurrence and metastasis even after surgical resection. Although villous adenomas of the urinary tract have been almost exclusively treated with surgical intervention in the literature, we present a case of villous adenoma with underlying adenocarcinoma of the prostatic urethra that was successfully treated with combined chemoradiation therapy. While surgical excision has been shown to be curative in diseases with isolated villous adenoma, more aggressive treatment with radiation and/or chemotherapy can be considered in patients with concurrent adenocarcinoma. However, more research into this subject is required to properly determine the best choice of therapy for this niche patient population.
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INTRODUCTION: The impact of pelvic irradiation on kidney transplant surgery is still unclear. The main objective of our study is to evaluate the feasibility and the safety of renal transplantation following pelvic radiotherapy. METHODS: We collected characteristics and kidney transplant data from patients with a history of pelvic cancer treated with pelvic irradiation between 2005 and 2021. These data were collected via the prospective information system "Computerized Data Validated in Transplantation" (DIVAT) and medical records. We carried out a comparative study with a non-irradiated matched control group to compare the data of intraoperative surgeries, complications reported postoperatively as well as survival of the graft and the patient. Patients were matched on age, sex, side of graft implantation, and graft rank. RESULTS: Twenty-four patients were collected with an average age of 65, 18 patients were treated for prostatic adenocarcinoma, 4 for gynecological cancer and 2 testicular cancers. Twenty-one patients were treated by radiotherapy, 3 by brachytherapy. Eight patients had a target dose on the iliac lymph nodes. The comparative study showed a significant difference in operative difficulty (n=15 versus n=1, P<0.01), operative duration (190min versus 149min, P=0.005), occurrence of lymphocele (P=0.041). Urinary anastomosis surgical techniques were different, 83.3% of control patients had an uretero-vesical anastomosis against 58.3% of patients with a history of irradiation (P=0.057) and about 29% of irradiated patients had an uretero-ureteral anastomosis. There was no other significant difference in per and postoperative criteria or survival. DISCUSSION: A history of pelvic irradiation significantly increases the technical complexity of kidney transplantation without impacting safety and kidney graft survival. A history of pelvic irradiation should not be a contraindication to kidney transplant.
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Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Neoplasias Pélvicas/radioterapia , Neoplasias Pélvicas/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos de Viabilidade , Sobrevivência de Enxerto/efeitos da radiação , Estudos Retrospectivos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Estudos de Casos e ControlesRESUMO
A 72-year-old male with a history of systemic hypertension, asthma, chronic obstructive pulmonary disease (COPD), and hyperlipidemia presents with diffuse patches of cutaneous depigmentation. A shave biopsy of different regions of depigmented skin indicated vitiligo. The patient was prescribed Opzelura (ruxolitinib) 1.5% topical cream as well as tacrolimus 0.1% topical ointment for vitiligo. He also had a history of prostate cancer. A prostate biopsy revealed three sites of prostatic adenocarcinoma with a Gleason score of 6 and a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2. The patient remained in active surveillance for prostate cancer without treatment, due to its low severity. A subsequent biopsy five years later revealed a decrease in prostate cancer prevalence, with cancer present in only one core and at a lower severity. The purpose of this case presentation is to discuss possible links between vitiligo and prostate cancer, as well as their shared mechanisms and pathways.
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Canine prostatic carcinoma (PC) has incompletely defined CT features. The purpose of this multicenter retrospective case series was to assess prostatic, regional, and distant findings of PC. Thirty dogs were enrolled. Consistent prostatic features included postcontrast heterogeneity with hypoattenuating, nonenhancing areas (30/30), capsular distortion (29/30), prostatic urethral effacement, displacement, or invasion (28/30), precontrast heterogeneity (27/30), and mineralization (24/30) which was always within or at the margin of the hypoattenuating areas. Consistent extraprostatic features included medial iliac lymph node enlargement (20/30), internal iliac lymph node enlargement (15/30), and periprostatic fat streaking or fluid (15/29). In a minority of dogs, there was lymph node mineralization, bladder trigone invasion, ureteral dilation, ductus deferens invasion, and bony changes consistent with hypertrophic osteopathy. Strongly suspected and potential bony metastases were noted infrequently (8/26), all in vertebrae regional to the prostate. In conclusion, these findings provide guidance on the expected CT features of canine PC.
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Doenças do Cão , Neoplasias da Próstata , Tomografia Computadorizada por Raios X , Cães , Animais , Masculino , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia , Neoplasias da Próstata/veterinária , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/veterinária , Próstata/diagnóstico por imagem , Próstata/patologia , Carcinoma/veterinária , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Carcinoma/secundárioRESUMO
Primary well-differentiated neuroendocrine tumor (WDNT)/carcinoid of the genitourinary tract is rare. Many WDNT reported in the prostate gland have been seen in close association with conventional prostatic adenocarcinoma and/or label for prostate-specific immunohistochemical markers and are best considered prostatic adenocarcinomas with "carcinoid-like" features. We present a case of primary WDNT/carcinoid incidentally detected in a 67-year-old man who underwent radical prostatectomy for Grade group 2 prostatic adenocarcinoma. Morphologically, the neuroendocrine (NE) lesion appeared distinct from the prostatic adenocarcinoma, labeled for NE markers, was negative for prostatic markers (NKX3.1, PSA, and ERG), and showed an overall low Ki-67 proliferation index (<1%). Follow-up was uneventful with no evidence of residual disease or metastasis.
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Adenocarcinoma , Biomarcadores Tumorais , Tumor Carcinoide , Tumores Neuroendócrinos , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico , Idoso , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/diagnóstico , Tumor Carcinoide/patologia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirurgia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Próstata/patologia , Próstata/cirurgia , Achados IncidentaisRESUMO
Clinicopathologic data in dogs with prostate cancer (PCa) may aid in the differentiation between tumor types and subsequent treatment decisions; however, these data are often unreported. Demographic, clinicopathologic, cytologic, histologic and survival data from dogs with primary prostatic adenocarcinoma (PRAD) (n = 56) and primary prostatic transitional cell carcinoma (P-TCC) (n = 74) were acquired from a tertiary veterinary teaching hospital from 1992 to 2022. Red blood cell distribution width (RDW) to albumin ratio (RAR) was evaluated for diagnostic utility in differentiating between PRAD and P-TCC. Sections from PRAD tumors (n = 50) were stained for androgen receptor (AR) expression, and laboratory data were compared between AR positive (AR+) and AR negative (AR-) groups. RDW was increased in PRAD, while albumin was decreased (p < 0.05). P-TCC was associated with Melamed-Wolinska bodies (MWB) and necrosis on cytology (p < 0.05). RAR had acceptable diagnostic utility in the differentiation of PCa tumors (AUC = 0.7; p < 0.05). Survival rates and metastases were equivocal. AR+ and AR- PRAD tumors did not differ in clinicopathologic data or survival (p > 0.05). In conclusion, hypoalbuminemia was significantly associated with PRAD and decreased survival, while MWB and necrosis were significantly associated with P-TCC on cytology. These clinicopathologic data may help clinicians differentiate between these tumors ante mortem to guide appropriate treatment and intervention.
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OPINION STATEMENT: Localized high-risk (HR) prostate cancer (PCa) is a heterogenous disease state with a wide range of presentations and outcomes. Historically, non-surgical management with radiotherapy and androgen deprivation therapy was the treatment option of choice. However, surgical resection with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is increasingly utilized as a primary treatment modality for patients with HRPCa. Recent studies have demonstrated that surgery is an equivalent treatment option in select patients with the potential to avoid the side effects from androgen deprivation therapy and radiotherapy combined. Advances in imaging techniques and biomarkers have also improved staging and patient selection for surgical resection. Advances in robotic surgical technology grant surgeons various techniques to perform RP, even in patients with HR disease, which can reduce the morbidity of the procedure without sacrificing oncologic outcomes. Clinical trials are not only being performed to assess the safety and oncologic outcomes of these surgical techniques, but to also evaluate the role of surgical resection as a part of a multimodal treatment plan. Further research is needed to determine the ideal role of surgery to potentially provide a more personalized and tailored treatment plan for patients with localized HR PCa.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Androgênios , Excisão de Linfonodo/métodos , Terapia Combinada , Prostatectomia/métodosRESUMO
AIMS: The distinction of high-grade prostate cancer (PCa) from poorly differentiated urothelial carcinoma (UC) can be somewhat challenging on clinical and morphological grounds alone, yet it is of great importance for prognostication and choice of treatment. GATA3 is a useful immunohistochemical marker to confirm urothelial origin. However, recent works report strong GATA3 immunoexpression in primary high-grade PCa. The aim of this study was to explore GATA3 expression specifically in metastatic PCa. METHODS AND RESULTS: The pathology databases of four tertiary institutions were queried for cases of metastatic PCa. Available slides and clinical records were reviewed by experienced genitourinary pathologists. Prostatic markers (PSA, PSAP, NKX3.1) and GATA3 immunohistochemistry were performed. A total of 163 metastatic PCa cases were included. At least one prostate marker was positive in each case of non-regional distant metastasis, confirming prostatic origin. GATA3 strong staining was found in four (2.5%) cases: two liver, one bone and one non-regional lymph-node metastases. All four patients had Grade Group 5 PCa at the initial diagnosis. The metastatic prostatic adenocarcinomas were solid, either with no gland formation (n = 3) or with only focal cribriforming (n = 1). CONCLUSIONS: To our knowledge, this is the first study exploring GATA3 expression specifically in metastatic PCa. Despite being infrequent, GATA3 positivity in high-grade PCa may lead to misdiagnosis, with clinical implications. We recommend a panel of immunohistochemical markers, both prostatic and urothelial, for ruling out UC, either in primary tumour samples or in the event of metastases of unknown primary, when a genitourinary origin is suspected.
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Adenocarcinoma , Carcinoma de Células de Transição , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Masculino , Humanos , Carcinoma de Células de Transição/metabolismo , Próstata/patologia , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais , Adenocarcinoma/patologia , Neoplasias da Próstata/patologia , Fator de Transcrição GATA3/metabolismoRESUMO
Background & Objective: Prostatic adenocarcinoma (PAC) is one of the most common tumors worldwide. Immunohistochemical expression of cytokeratins has been evaluated in the diagnosis and prognosis of tumors. The aim of the present study is the evaluation of Cytokeratin-7 (Ck-7) and Cytokeratin-19 (Ck-19) expression and its relationship with Gleason score in patients with PAC. Methods: In this cross-sectional study, 78 samples from 78 patients with PAC referred to Mostafa Khomeini Hospital were gathered. Samples were immunohistochemically stained by Ck-7 and Ck-19 markers. The percentage of each marker in tumor cells was determined, and its relationship with Gleason scores and Gleason grade groups was analysed by SPSS version 24. Results: The expression of Ck-7 and Ck-19 were seen in 37.2% and 82.1% of samples, respectively. The mean of Ck-7 expression in tumor cells was 4.98%±7.19 (ranged 0 to 26%), while the mean of Ck-19 expression was 41.02%±23.36 (ranged 0 to 78%). There was no relationship between Ck-7 expression with Gleason scores and Gleason grade groups. However, Ck-19 expression was increased in higher Gleason scores and Gleason grade groups (P<0.001). No relationship was found between age and Ck-7 (P=0.309) and Ck-19 (P=0.375). Conclusion: The Ck-7 expression in PAC samples is weak and focal and had no relationship with the Gleason scores and Gleason grade groups. However, Ck-19 expression in PAC was high and was associated with tumor dedifferentiation of samples. There was no relationship between the expression of both markers with the patient's age.
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Paraneoplastic pemphigus (PNP) is a rare, autoimmune, blistering condition defined by severe stomatitis, polymorphous cutaneous eruptions, and underlying neoplasms. PNP associated with solid cancer is extremely rare. An association with prostate adenocarcinoma remains exceptional. We describe a 69-year-old patient with recalcitrant PNP associated with prostate adenocarcinoma showing spectacular response immediately after associating hormonotherapy with conventional immunosuppressive drugs.
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Hypercalcemia of malignancy is commonly associated with several malignancies, but its existence in prostate cancer is an uncommon finding. The concurrent existence of a parathyroid adenoma and a history of hypercalcemia over several decades further adds to the enigma. Our case is of an 82-year-old man with a history of prostate cancer who presented to the endocrinology clinic with hypercalcemia. His PET-CT showed osteolytic metastasis to the T10 vertebrae which were presumed to be the cause of his high serum calcium. Further investigations revealed increased parathyroid hormone-related peptide (PTHrP). Denosumab therapy was started but his calcium remained elevated and hence, he underwent palliative radiation therapy. A follow-up PET-CT revealed significant disease regression and his serum calcium decreased from 11mg/dL to 10mg/dL. However, one month post radiation his serum calcium started showing an upward trend. Further investigations revealed an elevated parathyroid hormone (PTH) and an ultrasound of the thyroid revealed parathyroid adenoma. The patient subsequently underwent a parathyroidectomy with resolution of hypercalcemia.
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High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations. Tissue samples from 86 patients with prostate cancer were assessed by routine haematoxylin and eosin staining and immunohistochemistry (IHC) with a biomarker panel (Appl1/Sortilin/Syndecan-1) and a PIN4 cocktail (34ßE12+P63/P504S). Appl1 strongly labelled atypical secretory cells, effectively visualising intraductal lesions. Sortilin labelling was moderate-to-strong in > 70% of cases, while Syndecan-1 was moderate-to-strong in micropapillary HGPIN/AIP lesions (83% cases) versus flat/tufting HGPIN (≤ 20% cases). Distinct biomarker labelling patterns for atypical intraductal lesions of the prostate were observed, including early atypical changes (flat/tufting HGPIN) and more advanced atypical changes (micropapillary HGPIN/AIP). Furthermore, the biomarker panel may be used as a tool to overcome the diagnostic uncertainty surrounding AIP by supporting a definitive diagnosis of IDCP for such lesions displaying the same biomarker pattern as cribriform IDCP.
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Endophytic fungi allied to plants have sparked substantial promise in discovering new bioactive compounds. In this study, propagation of the endophytic fungus Alternaria alternata HE11 obtained from Colocasia esculanta leaves led to the isolation of Ergosterol (1), ß-Sitosterol (2), Ergosterol peroxide (3), in addition to three dimeric naphtho-γ-pyrones, namely Fonsecinone A (4), Asperpyrone C (5), and Asperpyrone B (6), which were isolated from genus Alternaria for the first time. Structures of the isolated compounds were established on the basis of extensive 1D and 2D NMR and, MS measurements. The ethyl acetate extract, as well as compounds 1, 3, 4 and 6 were evaluated for their antimicrobial activity using agar well-diffusion and broth microdilution assays. Molecular docking study was carried out to explore the pharmacophoric moieties that governed the binding orientation of antibacterial active compounds to multidrug efflux transporter AcrB and the ATP binding site to E. coli DNA gyrase using MOE software. Results revealed that the most active antibacterial compounds 4 and 6 bind with high affinity in the phenylalanine-rich cage and are surrounded with other hydrophobic residues. The antiproliferative activity of all isolated compounds was in vitro evaluated using the human prostatic adenocarcinoma cell lines DU-145, PC-3, PC-3 M, 22Rv1 and CWR-R1ca adopting MTT assay. Compound 4 was the most active against almost all tested cell lines, with IC50 values 28.6, 21.6, 17.1 and 13.3 against PC-3, PC-3 M, 22Rv1 and CWR-R1ca cell lines, respectively.