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Introduction: To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomog-raphy (PET/CT) vs. multiparametric magnetic resonance imag-ing (mpMRI) targeted biopsy (TPBx) in the diagnosis of clinical-ly significant prostate cancer (csPCa: Grade Group ≥ 2). Materials and methods: From January 2021 to June 2022, 100 patients (median age: 66 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnor-mal PSA values (median 7.5 ng/ml). Before prostate biopsy, all patients underwent mpMRI and 68Ga-PET/CT examinations and mpMRI (PI-RADS version 2 ≥ 3) or 68Ga-PET/CT index lesions suspicious for cancer (SUVmax > 5 g/ml) underwent cognitive targeted cores (mpMRI-TPBx and PSMA-TPBx: four cores) com-bined with extended systematic prostate biopsy (eSPBx: median 18 cores). The procedure was performed transperineally using a tru-cut 18-gauge needle under sedation and antibiotic prophy-laxis. Results: PCa was found in 58/100 (58.0%) men; in detail, 44/58 (75.9%) were csPCa; mpMRI and 68Ga-PSMA showed 66/100 (66%) and 62/100 (60%) lesions suspicious for PCa, respective-ly. 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. eSPBx diagnosed 42 (95.4%) vs. 36 (81.8%) vs. 30 (68.2%) csPCa, respectively; mpMRI-TPBx vs. 68Ga-PSMA-TPBx showed a diagnostic accuracy of 76.9% vs. 84.9% in diagnosing csPCa. Conclusions: 68GaPSMA PET/CT TPBx demonstrated good accuracy in the diagnosis of csPCa, which was not inferior to mpMRI TPBx (84.9% vs. 76.9%) improving the detection rate for cancer of systematic biopsy.

Introduction: The detection rate for clinically significant prostate cancer (csPCa) in men with mpMRI PI-RADS score 3 diagnosed by affiliated radiology centers vs radiological reference center was evaluated. Materials and methods: From January 2017 to December 2020, 950 men (median age 64 years) underwent mpMRI for abnormal PSA values (median 6.3 ng/ml). Among the 950 patients who underwent mpMRI 500 were evaluated by a reference center and 450 by outpatient radiological affiliated centers. All the mpMRI index lesions characterized by a PI-RADS 3 underwent targeted cores combined with extended prostate biopsy. Two radiologists of the radiological reference center revised all the mpMRI lesions 3. Results: Overall, 361/950 (38%) patients had a mpMRI lesion PI-RADS score 3: 120/500 cases (24%) vs 241/450 cases (53.5%) were diagnosed by reference vs affiliated radiological centers. The detection rate for cT1c csPCa was equal to 26.7% (35/120 cases) vs 16.6% (40/241 cases) in men with PI-RADS 3 lesions diagnosed in the reference vs the affiliated radiological centers (p < 0.05). Among the 241 PI-RADS score 3 lesions diagnosed by affiliated radiological centers 86/241 (35.7%) and 36/241 (15%) were downgraded (PI-RADS scores < 3) and upgraded (PI-RADS score 4) by the dedicated radiologists of the reference center. Conclusions: In our series, about 35% and 15% of PI-RADS score 3 lesions diagnosed by affiliated radiological centers were downgraded and upgraded when revised by experencied radiologists, therefore a second opinion is mandatory especially in men enrolled in active surveillance protocols in whom mpMRI is recommended to reduce the number of scheduled repeated prostate biopsies.

BACKGROUND/AIM: To evaluate the diagnosis and treatment of prostate cancer (PCa) during 1 year of the COVID-19 pandemic. PATIENTS AND METHODS: The management of men with PCa during COVID-19 pandemic (March 2020-2021) was compared with the clinical activity of the 12 months before the COVID-19 pandemic (March 2019-2020). RESULTS: The number of clinical visits, prostate biopsy, and men enrolled in active surveillance was significantly lower during the COVID-19 pandemic (p

Introduction: The reclassification rate for clinically significant prostate cancer (csPCa) in men enrolled in Active Surveillance (AS) as been prospective-ly evaluated. Patients and methods: One hundred patients with very low risk PCa underwent after 8 years a scheduled transperineal prostate biopsy (SPBx = 20 cores) combined with additionalmpMRI/TRUS fusion biopsies (4 cores) of lesions PI-RADS scores ≥ 3. All the patients, after initial diagnosis, previously had mpMRI evaluation combined with transperineal saturation prostate biopsy (confirmatory and 3-year scheduled biopsy). Risk reclassification at repeat biopsy triggering the recommen-dation for active treatment was defined as over 3 or more than 10% of positive cores, Gleason score > 6/ISUP Grade Group ≥ 2, greatest percentage of cancer (GPC) > 50%.Results: Multiparametric MRI was suspicious (PI-RADS ≥ 3) in 30 of 100 cases (30.0%); 70 (70.0%) vs. 20 (20.0%) vs. 10(10.0%) patients had a PI-RADS score ≤ 2 vs. 3 vs. 4, respec-tively. Two (2.0%) patients with PI-RADS score 3 and 4 were upgraded (ISUP Grade Group 2); SPBx and MRI/TRUS fusion biopsy diagnosed 100% and 0% of csPCa, respectively. Conclusions: Transperineal SPBx combined with mpMRI at ini-tial confirmatory biopsy allow to select an high number of men at very low risk of reclassification during the AS follow up (2.0%of the cases at 8 years from diagnosis); these data could be use-ful to reduce the number of scheduled repeated prostate biopsy during the AS follow up.

To evaluate the diagnostic accuracy ofFrom January 2021 to January 2022, 45 patients (median age: 67 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnormal PSA values (median 7.3 ng/ml). Before prostate biopsy, all patients underwent mpMRI andPCa was found in 29/45 (64.4%) men; in detail, 22/45 (48.9%) were csPCa.

Pre-eclampsia is a pregnancy complication characterized by defective vascular remodeling in maternal decidua responsible for reduced blood flow leading to functional and structural alterations in the placenta. We have investigated the contribution of the complement system to decidual vascular changes and showed that trophoblasts surrounding unremodeled vessels prevalent in preeclamptic decidua fail to express C1q that are clearly detected in cells around remodeled vessels predominant in control placenta. The critical role of C1q is supported by the finding that decidual trophoblasts of femaleC1qa-/-pregnant mice mated toC1qa+/+male mice surrounding remodeled vessels express C1q of paternal origin. UnlikeC1qa-/-pregnant mice, heterozygousC1qa+/-and wild type pregnant mice share a high percentage of remodeled vessels. C1q was also found in decidual vessels and stroma of normal placentae and the staining was stronger in preeclamptic placentae. Failure to detect placental deposition of C1r and C1s associated with C1q rules out complement activation through the classical pathway. Conversely, the intense staining of decidual endothelial cells and villous trophoblast for ficolin-3, MASP-1 and MASP-2 supports the activation of the lectin pathway that proceeds with the cleavage of C4 and C3 and the assembly of the terminal complex. These data extend to humans our previous findings of complement activation through the lectin pathway in an animal model of pre-eclampsia and provide evidence for an important contribution of C1q in decidual vascular remodeling.

Background/Aim: The aim of the study was to determine the rate of clinically significant prostate cancer (csPCa) cases in men submitted to early second round mpMRI/TRUS (multiparametric magnetic resonance imaging/transrectal ultrasound) fusion biopsy (TPBx). Materials and Methods: From January 2016 to December 2018, 256 men with a PI-RADS (Prostate Imaging-Reporting and Data System) score 3 (80 cases) or 4 (176 cases) and negative repeat transperineal saturation biopsy plus TPBx, underwent a new TPBx (four cores) for the persistent clinical suspicion of cancer. The accuracy of mpMRI ADC (apparent diffusion coefficient) values in the diagnosis of csPCa were evaluated. Results: Overall detection rate of csPCa was equal to 10.1% (26/256 cases): 2.5% (2/80) versus 13.6% (24/176) had a PI-RADS score equal to 3 versus 4, respectively. The presence of csPCa was significantly correlated with an ADC value of 0.747×10(–3) mm(2)/sec. Conclusion: A negative TBPx missed a csPCa in 13.6% of PI-RADS score 4 that was diagnosed by an early second round TBPx; the evaluation of ADC maps could select mpMRI lesions deserving a repeat TPBx.

Juan Rosai, the “Maradona” of surgical pathology, played a role not only as a diagnostician but also as a researcher, a consultant and a teacher, distinguishing himself as a real icon at all levels of modern pathology. He was an innovative promoter of emerging technologies including digital pathology. These few lines commemorate the digital side of the “Maestro” Juan Rosai from a junior’s perspective highlighting how Rosai supported digital pathology and remembering that, according to his own words, digital pathology “will revolutionize the field of pathology, if it is not doing that already”. (read more)

Background Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with the presence of Lewy bodies and genetic factors are involved in its pathogenesis. Several studies have indicated that the expression of target genes in patients with PD is inversely related to cancer development; this phenomenon has been named "inverse comorbidity". The present study was undertaken to evaluate whether a genetic dysregulation occurs in opposite directions in patients with PD or PCa. Methods and results In the present study, next-generation sequencing transcriptome analysis was used to assess whether a genetic dysregulation in opposite directions occurs in patients with PD or PCa. The genes SLC30A1, ADO, SRGAP2C, and TBC1D12 resulted up-regulated in patients with PD compared to healthy donors as controls and down-regulated in patients with PCa compared with the same control group. Conclusions These results support the hypothesis of the presence of inverse comorbidity between PD and PCa.

BACKGROUND Bronchoalveolar lavage (BAL) in patients with severe coronavirus disease 2019 (COVID‐19) may provide additional and complementary findings for the management of these patients admitted to intensive care units (ICUs). This study addresses the cytological features of the infection and highlights the more influential inflammatory components. The correlation between pathological variables and clinical data is also analyzed. METHODS The authors performed a retrospective analysis of the cytopathological features of BAL in 20 COVID‐19 patients and 20 members of a matched cohort from a critical ICU who had acute respiratory distress syndrome caused by other pulmonary conditions. RESULTS A comparison of the controls (n = 20) and the COVID‐19 patients (n = 20) revealed that the latter had a higher neutrophil count (median, 63.8% of the cell count) with lower percentages of macrophages and lymphocytes. An increase in the expression of CD68‐positive, monocytic multinucleated giant cells (MGCs) was reported; megakaryocytes were not detected on CD61 staining. Perls staining showed isolated elements. In situ RNA analysis demonstrated scattered chromogenic signals in type II pneumocytes. An ultrastructural analysis confirmed the presence of intracytoplasmic vacuoles containing rounded structures measuring 140 nm in diameter (putative viral particles). In COVID‐19 patients, the clinicopathological correlation revealed a positive correlation between lactate dehydrogenase values and MGCs (r = 0.54). CONCLUSIONS The analysis of BAL samples might be implemented as a routine practice for the evaluation of COVID‐19 patients in ICUs in the appropriate clinical scenario. Additional studies using a larger sample size of patients who developed COVID‐19 during the second wave of the epidemic in the autumn of 2020 are needed to further support our findings., An analysis of the cytological features of bronchoalveolar lavage samples can provide useful information for the management of coronavirus disease 2019 patients in the intensive care unit.

A Caucasian man 84 years old was admitted to our Department for acute renal failure secondary to severe bilateral hydronephrosis; moreover, the patient referred chronic fatigue and was anuric from two days. Serum creatinine and PSA values were equal to 9.6 mg/dl and 4.8 ng/ml and digital rectal examination was highly suspicious for prostate cancer. In emergency, the patient underwent bilateral application of percutaneous renal nephrostomies to restore kidney function and, after three days, was submitted to ultrasound-guided extended transperineal biopsy; the histology showed the presence of a prostatic small cell carcinoma (SCC) fulfilling the World Health Organization criteria. The patient underwent clinical staging including chest and abdominal computed tomography evaluation and total body scan that did not demonstrated distant metastases and/or others primitive tumors; in addition, cystoscopy and urinary cytology were negative. The patient underwent multidisciplinary evaluation, but he died 20 days from the diagnosis for progressive clinical worsening (physical and cognitive impairments) before beginning oncological treatment. In conclusion, primitive SCC represents a very rare cancer provided of poor prognosis; only the execution of prostate biopsy combined with an accurate specimen analysis allow to make the correct diagnosis and therapeutic treatment.

Introduction The reclassification rate for clinically significant prostate cancer (csPCa) has been evaluated in men enrolled in active surveillance (AS) protocol who previously underwent confirmatory biopsy. Materials and Methods From May 2013 to September 2017, 110 patients (median age 63 years) with very low risk PCa underwent 3-years scheduled prostate biopsy performing repeated transperineal saturation biopsy (SPBx); in addition, the mpMRI lesions characterized by Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores ≥ 3 were submitted to additional mpMRI/TRUS fusion biopsies (4 cores). The reclassification rate for csPCa (over 3 or more than 10% of positive cores, ISUP Grade Group/GG ≥ 2, greatest percentage of cancer > 50%) has been evaluated. Results Six (5.4%) patients with PI-RADS score 3 (4 men) vs. 4 (2 men) were reclassified based on upgraded (GG2); SPBx and MRI/TRUS fusion biopsy diagnosed 100% and 0% of csPCa, respectively. Of the remaining 104 (94.5%) patients, 75 (72.2%) were found to have very low-risk PCa and in 29 (27.8%) cancer was absent (normal parenchyma). Conclusion SPBx combined with mpMRI at confirmatory and repeated evaluation allow to reduce the reclassification rate during AS follow up (5.4% of the cases at 3 years from diagnosis).

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that act as key regulators in various physiological and pathological processes as prostate cancer (PCa). In this study we describe molecular evaluation of 132 and 212 miRNAs expression, by Real-time reverse-transcription PCR (qRT-PCR), in a Caucasian man 64-year-old with locally advanced PCa (PSA 160 ng/ml, Gleason score 4+3/ISUP Grade Group 3, clinical stage T3NXM0) who underwent radical retropubic prostatectomy plus extended pelvic lymphadenectomy (LAD) as first step of a multimodal therapeutic treatment. A normal prostate of a 67-year-old man removed by post mortem autopsy was used as a control in the study. The mRNA for this study was conducted on paraffined prostatic sections of: a) index case of PCa; b) metastatic lymph node of index case; c) normal prostate. MiRNA-132, miRNA- 212 and Glyceraldehyde 3-phosphate dehydrogenase (as reference gene) assays were obtained. Definitive specimen showed a pT3bN1R1 stage: acinar cells adenocarcinoma with involvement of the seminal vesicles, multifocal positive surgical margins, Gleason score 8 (4+4/ISUP Grade Group 4), metastases in 5/25 iliac lymph nodes. An increased expression of miRNA-132 and miRNA-212 in index case of prostatic adenocarcinoma compared to normal prostate tissue was found; moreover, a lower expression of miR-132 and miR-212 in metastatic lymph node compared to primitive PCa and normal prostate tissue was demonstrated. Although a greater number of patients should be evaluated, these data suggest that the biology of the primary PCa, in our clinical case, was different from metastatic lymph node.

We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging to diagnose clinically significant prostate cancer and compared it with the diagnostic accuracy of transperineal saturation prostate biopsy.From January 2011 to February 2018 repeat saturation prostate biopsy (the reference test) was done due to suspicion of cancer in 1,032 men with a median age of 63 years in whom median prostate specific antigen was 8.6 ng/ml. All patients underwent 3.0 Tesla pelvic multiparametric magnetic resonance imaging before saturation prostate biopsy. Additional targeted fusion prostate biopsy was done of lesions with a PI-RADS™ (Prostate Imaging Reporting and Data System) score of 3 or greater.T1c prostate cancer was found in 372 of the 1,032 patients (36%). Of these cases 272 (73.1%) were classified as clinically significant prostate cancer. Saturation prostate biopsy vs targeted fusion prostate biopsy and a PI-RADS score of 3 or greater vs targeted fusion prostate biopsy and a PI-RADS score of 4 or greater diagnosed 95.6% vs 83.8% vs 60.3% of clinically significant prostate cancers (p0.0001). Saturation prostate biopsy missed 12 of 272 clinically significant prostate cancers (4.5%) vs 44 (16.2%) and 108 of 272 (39.7%) missed by targeted fusion prostate biopsy and a PI-RADS score of 3 or greater and a score of 4 or greater, respectively (p0.0001). As a triage test multiparametric magnetic resonance imaging would have spared 49.3% vs 73.6% of patients using a PI-RADS cutoff of 3 or greater vs 4 or greater.Multiparametric magnetic resonance imaging could significantly reduce the number of unnecessary repeat prostate biopsies in about 50% of cases in which a PI-RADS score of 3 or greater is used. At the same time patients should be informed of the 16.2% and 39.7% false-negative rates of clinically significant prostate cancer for targeted fusion prostate biopsy of PI-RADS 3 or greater and 4 or greater lesions, respectively.

Background Inguinal hernia is one of the most common benign pathologies that primarily affects men. Primary gastrointestinal non-Hodgkin’s lymphoma (PGI NHL) is the most common type of extranodal lymphoma. This study reports a rare case in which these two conditions co-exist. Case presentation An 85-year-old male complained of bowel movement pattern change, abdominal distension and loss of weight, without vomiting but with nausea. A computed tomographic scan of the abdomen showed a small bowel obstruction caused by a migration of a small bowel loop in the right inguinal canal, with a clinically non-reducible inguinal hernia. The patient underwent surgery. The histopathological report showed small bowel large B cell non-Hodgkin’s lymphoma. Conclusion When the diagnosis of the contents of an inguinal hernia is not well-established, surgery should be performed as soon as possible to ensure the cure of the disease and the correct diagnosis of the contents.

Objective To evaluate the number of needle cores combined with multiparametric magnetic resonance imaging (mpMRI) findings needed to diagnose all clinically significant cases of prostate cancer (csPCa) in men subject to transperineal saturation biopsy (SPBx; 30 cores). Methods From January 2016 to June 2019, 875 men (median age 63 years) underwent repeat SPBx (median 30 cores) for the suspicion of cancer. All of the patients underwent for the first time 3.0 Tesla pelvic mpMRI before SPBx, and the lesions with Prostate Imaging-Reporting and Data System category ≥3 underwent additional transperineal-targeted fusion prostate biopsies (TPBx). Results StageT1c PCa was found in 306/875 (34.5%), and 222/306 (72.5%) of them were classified as csPCa. SPBx missed 2/222 (1%) csPCa with International Society of Urologic Pathology Grade Group (GG) 3. TBPx missed 33/222 (14.9%) csPCa (21 vs 12 cases were GG1 vs GG3). The initial 20 needle SPBx cores obtained from the peripheric (16 cores) and anterior gland (4 cores) diagnosed all of the 222 (100%) csPCa only missing 84/129 (65.1%) indolent PCa thus presenting diagnostic accuracy, sensitivity, and specificity equal to 83.1%, 100%, and 65.1%, respectively. Conclusion In men subject to mpMRI and/or TPBx, a maximum of 20 systematic transperineal needle cores detected all cases of csPCa and minimized the diagnosis of indolent cancers.

Aims: Malignant tumours from the upper aerodigestive tract are grouped collectively in the class of head and neck squamous cell carcinoma (HNSCC). The head and neck tumours were responsible for more than 500 000 cancer cases in 2012, accounting for the sixth highest incidence rate and mortality worldwide among all tumour types. Laryngeal squamous cell carcinoma (LSCC) possesses the second highest incidence rate among all HNSCC. Despite significant advances in surgery and radiotherapy during the last few decades, no treatment has been shown to achieve a satisfactory therapeutic outcome and the mortality rate of LSCC is still high, with a 5-year survival rate of 64%. Therefore, further investigations are required to identify the pathogenesis of LSCC. Methods and results: In order to search for new LSCC biomarkers, we have analysed the expression of the HMGA family members, HMGA1 and HMGA2, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. HMGA proteins are usually absent in the healthy adult tissues. In contrast, their constitutive expression is a feature of several neoplasias, being associated with a highly malignant phenotype and reduced survival. Here, we report HMGA2 overexpression in larynx carcinomas. Conversely, HMGA1 does not show any differences in its expression between normal and carcinoma tissues. Interestingly, HMGA2 overexpression appears associated with that of two HMGA1-pseudogenes, HMGA1P6 and HMGA1P7, acting as a sponge for HMGA1- and HMGA2-targeting microRNAs and involved in several human cancers. Conclusions: Therefore, HMGA2 overexpression appears to be a strong feature of larynx carcinoma, supporting its detection as a valid tool for the diagnosis of these malignancies.

AIM: To evaluate the accuracy of multiparametric magnetic resonance imaging apparent diffusion coefficient (mpMRI ADC) in the diagnosis of clinically significant prostate cancer (PCa). PATIENTS AND METHODS: From January 2016 to December 2016, 44 patients who underwent radical prostatectomy for PCa and mpMRI lesions suggestive of cancer were retrospectively evaluated at definitive specimen. The accuracy of suspicious mpMRI prostate imaging reporting and data system (PI-RADS >=3) vs. ADC values in the diagnosis of Gleason score >=7 was evaluated. RESULTS: Receiver operating characteristics (ROC) curve analysis gave back an ADC threshold of 0.747×10-3 mm2/s to separate between Gleason Score 6 and >=7. The diagnostic accuracy of ADC value (cut-off 0.747×10-3 mm2/s) vs. PI-RADS score >=3 in diagnosing PCa with Gleason score >=7 was equal to 84% vs. 63.6% with an area under the curve (AUC) ROC of 0.81 vs. 0.71, respectively. CONCLUSION: ADC evaluation could support clinicians in decision making of patients with PI-RADS score

Objective: To assess the predictive and prognostic value of progressive metabolic disease (PMD) by the use of early 18Fluorodeoxyglucose positron emission tomography (18FDG-PET) in patients with clinical stage IV non-small cell lung cancer (NSCLC) treated with first-line chemotherapy. Methods: An 18FDG-PET performed following the first cycle of chemotherapy (PET-1) was compared with a pretreatment 18FDG-PET (PET-0) and a computed tomography (CT) scan after the third cycle (CT-3). The primary endpoint was the positive predictive value (PPV) of PMD. Secondary endpoints included the prognostic value of PMD. Results: Eleven of 38 patients (29%) had a PMD by PET-1, and 15 (39%), including all patients with a PMD, experienced a progressive disease by CT-3. The PPV of PMD was 100% according to both the European Organization for Research and Treatment of Cancer (EORTC) criteria and the PET Response Criteria In Solid Tumors (PERCIST) (p value for both, Conclusions: Early 18FDG-PET assessment deserves further investigation for the identification of NSCLC patients who do not benefit from first-line chemotherapy.

Objective: To evaluate the detection rate of anterior zone (AZ) prostate cancer (PCa) in patients submitted to initial and repeat transperineal prostate biopsy. Methods: From January 2013 to August 2013, 226 patients (median age 64 years) with negative digital rectal examination underwent initial (144 cases) and repeat (82 cases) transperineal prostate biopsy for PSA >10 ng/ml, PSA 4.1-10.0 or 2.6-4.0 ng/ml with free/total PSA ≤25% and ≤20%, respectively. A median of 22 versus 32 cores were performed, including 4 cores of the AZ versus 6 cores (4 anterior plus 2 cores of the transition zone, TZ) at initial versus repeat biopsy, respectively. The detection rate of PCa of the peripheral zone (PZ), AZ and TZ was prospectively evaluated. Results: The median PSA was 7.6 ng/ml; overall, a stage cT1c PCa was found in 104/226 (46%) patients, in 70 (48.6%) and 34 (41.5%) of the men who underwent initial and repeat biopsy, respectively. An AZ PCa was found in 11.5 vs. 8.8% (p = 0.32) of the patients submitted to initial versus repeat biopsy, respectively. AZ cancers demonstrated a number of positive cores (p = 0.03), greatest percentage of cancer (p = 0.001) and total percentage of cancer (p = 0.001) significantly lower in comparison with PZ PCa; moreover, 56.2 vs. 36.5% of AZ versus PZ PCa were characterized by a microfocus of cancer (p = 0.001), respectively. Conclusions: AZ biopsies increase the detection rate of PCa (about 10% of cases) at initial and repeat biopsy, allowing reduction of the biopsy false-negative rate.

Prostate cancer (PCa) is the most frequent cancer among men in many developing countries, and the second leading cause of cancer-related death in men. A genetic component has been implicated in PCa onset and development. The cerebellar degeneration-related autoantigen 1 ( CDR1) gene, mapping in Xq26-q27.2, is expressed in cerebrum, cerebellum, heart, lung, liver, and kidney. In addition, CDR1 expression has been detected in neuroblastoma, renal carcinoma cell lines, and other cancer cell lines. In this study, we investigated the expression of the CDR1 gene in the LNCaP and PC-3 PCa cell lines, and in the PNT1A normal prostate cell line. CDR1 mRNA expression was evaluated by qRT-PCR. We found that the CDR1 gene was overexpressed in the LNCaP and PC-3 PCa cell lines as compared with the PNT1A normal prostate cell line. These data suggest that CDR1 could be a new biomarker for PCa identification.

Objectives: To evaluate the incidence of indolent prostate cancer (PCa; Methods: From January 2005 to December 2008, 413 patients (median age 61.5 years) underwent SPBx (median 30 cores). A single neoplastic microfocus (5% or less of cancer in a single core) was found in 55 men and all patients underwent retropubic prostatectomy. Median PSA was equal to 8.2 ng/ml, digital rectal examination was negative and GS was 6 in 40 cases and not evaluable in 15 cases. Results: Prostatectomy specimens showed a significant cancer in 48/55 (87.3%) patients with a median GS of 6.2 (range 5–8), presence of extraprostatic extension and positive surgical margins in 15 (27.3%) and 8 (14.5%) cases, respectively. Six patients had an indolent PCa, and in 1 case no tumor was found. Conclusions: Patients with a single microfocal PCa diagnosed on SPBx corresponded to an insignificant cancer in surgical specimens only in 12.7% of cases, but they should be informed that they may harbor more aggressive disease with a risk of non-organ-confined cancer that in our series was 27.3%.

Objectives: To evaluate retrospectively the detection rate of prostate cancer (PCa) located only in the transition zone (TZ) by directed cores at repeated saturation prostate biopsy (SPB). Methods: From July 2001 to December 2009, 380 and 43 patients (median age: 63 years) underwent second and third SPB because they were persistently suspicious for PCa. Indications for biopsy were: prostate-specific antigen (PSA) of >10 ng/ml, and PSA between 4.1 and 10 ng/ml or 2.6 and 4 ng/ml with free/total PSA of ≤25 and ≤20%, respectively. A median of 23 cores were taken in the posterior zone, including 3 (median) cores in the TZ. The median PSA was 12.8 and 19.5 ng/ml and the digital rectal examination was positive in 36 (9.5%) and in no cases at second and third SPB, respectively. In patients with persistent and/or increasing PSA or abnormal free/total PSA values after negative second and third SPB, a transurethral prostate resection (TURP) was suggested to avoid the risk of missing a cancer localized in the TZ. Results: PCa was detected in the TZ only in 2/82 cases (2.5%), and in details in 1/79 (1.2%) and 1/3 (33.3%) of the men diagnosed at second and third SPB, respectively. After TURP, a PCa was found in 18/95 men (18.9%; 14 stage T1a and 4 stage T1b) and in 3/15 men (20%; 2 stage T1a and 1 stage T1b) previously having had negative second and third SPB. Conclusions: Sampling from the prostatic TZ by directed needle biopsies at repeated SPB was associated with a very low incidence of PCa (2.5%), especially if compared to TURP (19% detection rate), and could be omitted.

To evaluate prostate cancer (PCa) detection after repeated negative saturation biopsy, 75 patients, aged 53-78 years, underwent transurethral resection of prostate (TURP) because of persistent suspicion of cancer; median PSA was 11.8 ng ml(-1) and 58 men complained lower urinary tract symptoms (LUTS). In 12 (16%) and 3 (4%) men a T1a and T1b PCa was found with median PSA and Gleason score equal to 14.2 vs 23.6 ng ml(-1) and 5.6 vs 7 ng ml(-1). In case of persistent suspicion of PCa after repeated negative saturation biopsy, TURP may be proposed, aside from the coexistence of LUTS, to rule out a PCa, in younger patients with high PSA values (or =20 ng ml(-1)).

Purpose: Detection rate for anterior prostate cancer (PCa) in men who underwent initial and repeat biopsy has been prospectively evaluated. Materials and Methods: From January 2013 to March 2014, 400 patients all of Caucasian origin (median age 63.5 years) underwent initial (285 cases) and repeat (115 cases) prostate biopsy; all the men had negative digital rectal examination and the indications to biopsy were: PSA values > 10 ng/mL, PSA between 4.1-10 or 2.6-4 ng/mL with free/total PSA≤25% and ≤20%, respectively. A median of 22 (initial biopsy) and 31 cores (repeat biopsy) were transperineally performed including 4 cores of the anterior zone (AZ) and 4 cores of the AZ plus 2 cores of the transition zone (TZ), respectively. Results: Median PSA was 7.9 ng/mL; overall, a PCa was found in 180 (45%) patients: in 135 (47.4%) and 45 (36%) of the men who underwent initial and repeat biopsy, respectively. An exclusive PCa of the anterior zone was found in the 8.9 (initial biopsy) vs 13.3% (repeat biopsy) of the men: a single microfocus of cancer was found in the 61.2% of the cases; moreover, in 7 out 18 AZ PCa the biopsy histology was predictive of significant cancer in 2 (28.5%) and 5 (71.5%) men who underwent initial and repeat biopsy, respectively. Conclusions: However AZ biopsies increased detection rate for PCa (10% of the cases), the majority of AZ PCa with histological findings predictive of clinically significant cancer were found at repeat biopsy (about 70% of the cases).

Plasmablastic lymphoma is a rare, highly aggressive lymphoma characterized by large lymphoid cells with immunoblastic or plasmablastic features, absent expression of CD45 and CD20, positivity for CD138, and monoclonal rearrangement of the immunoglobulin heavy chain gene. It was originally reported in oral cavity in the setting of underlying human immunodeficiency viral infection but may occur also in lymph nodes or extranodal sites after transplantation and, more rarely, immunocompetent patients. Herein, we report a case of PBL presenting as an ulcerated lesion of the tongue in an HIV-negative patient, 6 years after renal transplantation. To date, only rare cases of plasmablastic lymphoma presenting after solid organ transplantation have been reported. Although a reduction of immunosuppression and an aggressive chemotherapy were performed, the patient died after a few months because of septic and cardiovascular complications.

The commercial multi-pathogen probe-based real-time PCR SeptiFast (SF) was evaluated as a rapid and complementing tool for the microbiological diagnosis of bloodstream infections (BSIs) in a series of 138 matched blood samples from 65 patients with bacteraemia, hospitalized in an intensive care unit, when antibiotics had already been administered. SF was positive in 32.6 % of the samples, whereas blood culture (BC) was positive in 21.7 % (P

Introduction. Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated. Materials and Methods. From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA >10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA < 25% and < 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. Results. A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p < 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively. Conclusion. Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers.

MicroRNAs (miRNAs) are small noncoding RNAs that act as posttranscriptional regulators of gene expression, and are frequently altered in human neoplasias. Here, we have analyzed the miRNA expression profile of human gonadotroph adenomas versus normal pituitary tissue using a miRNACHIP microarray. We demonstrate that miRNA-410 is downregulated in gonadotroph adenomas when compared with normal pituitary gland. We validate CCNB1 as target of miRNA-410 since its overexpression reduces CCNB1 at protein and mRNA levels, decreasing cell proliferation. In conclusion, our study suggess that the downregulation of miRNA-410 plays a role in the behavior of gonadotroph tumors.

Immunoreactivity for fascin, an actin-bundling protein related to cell motility, has been reported in breast, ovary, pancreas, skin, and non-small cell carcinomas, and associated with more advanced disease stage and poorer prognosis. Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated the expression of fascin by immunohistochemistry--using two different monoclonal antibodies--in surgical specimens of pulmonary NE tumors of all the diverse histological types from 128 consecutive patients recruited between 1987 and 2001, and investigated its relationship with the presence of lymph node metastases. Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P0.001), Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No statistically significant differences in fascin immunoreactivity were found between the two antibodies. In TC and AC but not high-grade NE tumors, fascin immunoreactivity closely correlated with the occurrence of lymph node metastases, the pN class and the number of involved lymph nodes (P0.001). It was also significantly associated with an increased proliferative activity (Ki-67 labeling index5%) (P=0.020), and with either down-regulation or altered subcellular compartmentalization of E-cadherin (P0.001) and CD99 (P=0.030), two cell adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin emerged as an independent predictor of lymph node metastases in this tumor group (HR 30.28; 95% confidence intervals: 1.59-574.49; P=0.023). This study indicates that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients with different metastatic potential to regional lymph nodes. Targeting the fascin pathway could be a novel therapeutic strategy of pulmonary carcinoids.

We investigated 31 cases of pleomorphic carcinomas of the lung, with a double component of neoplastic epithelial cells and of spindle and/or giant cells. To correlate the morphologic diversity of these two cell components with their immunophenotype, we evaluated the expression of several gene products involved in cell differentiation (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, vimentin, S-100 protein, smooth muscle actin, desmin), cell cycle control and apoptosis (p53, p21Waf1, p27Kip1, FHIT), tumor growth (proliferative fraction, assessed by Ki-67 antigen, and microvascular density, assessed by CD34 immunostaining), and tumor cell motility (fascin). We found the epithelial component to be significantly more immunoreactive for cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, cell cycle inhibitors p21Waf1, p27Kip1 and tumor suppressor gene FHIT, whereas the sarcomatoid component, independent of tumor stage and size, was more immunoreactive for vimentin, fascin, and microvascular density. Accordingly, we suggest a model of tumorigenesis whereby the mesenchymal phenotype of pleomorphic cells is likely induced by the selective activation and segregation of several molecules involved in cell differentiation, cell cycle control, and tumor cell growth and motility. Whether pleomorphic carcinomas of the lung are tumors with a dismal prognosis still remains an unsettled issue. In our series, however, stage I pleomorphic carcinomas have the same clinical behavior as ordinary non-small cell lung cancer, and only a high proliferative index (Ki-67 labeling index >35%) is associated with a worse prognosis in these tumors.

The p63 protein, a member of the p53 family of nuclear transcription factors, is characterized by different capabilities of transactivating reporter genes, inducing apoptosis, and functioning as dominant-negative agent. This study evaluated the prevalence and prognostic implications of p63 immunoreactivity in 221 patients with stage I non-small cell lung carcinoma (NSCLC) and in 57 patients with stage I-IV neuroendocrine tumours (NET). The results were correlated with the tumour proliferative fraction, the accumulation of p53 protein, and with patient survival. p63 immunoreactivity was seen in 109/118 squamous cell carcinomas, 15/95 adenocarcinomas, 2/2 adenosquamous carcinomas, 4/6 large cell carcinomas, 9/20 poorly differentiated NET, and 1/37 typical and atypical carcinoids (p < 0.001). Furthermore, the prevalence of p63-immunoreactive cells increased progressively from pre-neoplastic and pre-invasive lesions to invasive squamous cell carcinomas. In these latter tumours, but not in adenocarcinomas, p63 immunoreactivity correlated directly with the tumour proliferative fraction (p = 0.028), and inversely with the tumour grade (p = 0.004). No relationship was found with p53 protein immunoreactivity or the other clinico-pathological variables examined. Although p63 is likely to be involved in the development of pulmonary squamous cell carcinoma, it does not carry any prognostic implication for NSCLC patients.

The prostate-specific antigen (PSA) nadir and long-term outcome in patients with pT3b prostate cancer were evaluated.From July 2000 to December 2012, in 100 patients (median age=62 years) with pT3b prostate cancer following radical retropubic prostatectomy (RRP) preoperative and pathological findings predictive of PSA nadir (≤0.2 vs.0.2 ng/ml) were retrospectively evaluated; moreover, biochemical recurrence-free survival (bRFS), cancer specific survival (CSS) and overall survival (OS) in patients who underwent watchful waiting (16 cases), adjuvant (84 cases) and salvage (10 cases) therapy were recorded.A PSA nadir0.2 ng/ml was correlated with node involvement, Gleason score ≥9, cT2, PSA20 ng/ml, positive surgical margins and total cancer percentage20%. At a median follow-up of 90 months (range=10-155 months) bRFS, OS and CSS were 92%, 96% and 80%, respectively.Radical retropubic prostatectomy combined with adjuvant and salvage treatments demonstrated a satisfactory outcome for pT3b prostate cancer.

Preoperative findings, pathological stage PSA recurrence in patients with prostate cancer incidentally detected (iPCa) at radical cystectomy (RCP) were prospectively evaluated.From July 2000 to July 2013, 242 men 71 years old (median) underwent RCP; preoperatively, all patients underwent digital rectal examination (DRE), total and free/total PSA. The bladder was totally examined; moreover, the prostate gland was step-sectioned at 4-mm intervals. The incidence of iPCa that fulfilled criteria for clinically significant iPCa was recorded: tumor volume ≥0.5 mL, Gleason grade ≥4, extracapsular extension, seminal vesicle invasion, lymph node metastasis or positive surgical margins. In the presence of iPCa, the patients underwent PSA evaluation during the follow-up and recurrence was defined as two subsequent rises0.2 ng/mL.Among the 50 (20.6%) out of 242 patients submitted to RCP, an iPCa was found and 18 (36%) of them met criteria for insignificant iPCa; moreover, 30% of the patients had apex involvement. Median total PSA and PSA F/T values were not significantly different in the presence versus the absence of iPCa (2.6 vs 2.7 ng/mL and 26 vs 27%; p0.05) and between significant versus insignificant iPCa (p0.05). None of the patients during the follow-up (median 58 months; range 6-102 months) had PSA recurrence.PSA and PSA F/T values are provided for poor accuracy in distinguishing preoperatively significant from insignificant iPCa; however, the life expectancy of the patients is dramatically influenced by bladder cancer pTN (in our series, none developed PSA failure). In younger men in whom a prostate-sparing cystectomy could be proposed, an accurate preoperative evaluation should be mandatory to rule out significant iPCa at the risk of apex involvement (in our series equal to 30% of the cases).

Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined. A case of epithelial-myoepithelial tumor of the lung arising from bronchial mucosa-submucosa and occurring as a polypoid lesion of the upper left bronchus in a 47-year-old man is reported. The tumor did not infiltrate the cartilaginous wall of the bronchus and showed a biphasic histological appearance with a double layering of epithelial and myoepithelial cells. Myoepithelial spindle cells with eosinophilic cytoplasm were also observed. Mitotic figures were very rare and necrosis absent. Immunohistochemical study for epithelial and muscular markers confirmed the presence of a double-cell component in the tumor, namely epithelial and myoepithelial. The patient is alive and well, with no evidence of recurrent or metastatic disease 6 months after surgery. On the basis of the present case and the six previously reported cases, we suggest using the noncommittal term pulmonary epithelial-myoepithelial tumor of unproven malignant potential (PEMTUMP) for this type of neoplasm. In addition, we first introduce p63 as a novel marker for highlighting the myoepithelial cells of the respiratory tract and speculate on the role of these cells in the development of this unusual tumor.

Magnetic resonance imaging (MRI) accuracy in prostate cancer (PCa) diagnosis in men submitted to saturation prostate biopsy (SPBx) was evaluated.From June 2011 to December 2012, 78 patients (median 63 years) underwent repeat SPBx (median 28 cores). Multiparametric MRI using a 3 Tesla pelvic phased-array coil was performed before SPBx and lesions suspicious for PCa were submitted to additional targeted biopsies.A T1c PCa was found in 32 (41%) cases. SPBx vs. MRI-suspicious targeted biopsy diagnosed 28 (87.5%) vs. 26 (81.2%) PCa missing four (12.5%) and six (18.8%) cancers localized in the anterior zone and in the lateral margin of the prostate, respectively; moreover, MRI diameter lesions correlated with PCa diagnosis and Gleason score (p0.05).Multiparametric MRI improved SPBx accuracy in diagnosing PCa of the anterior zone; moreover, suspicious areas10 mm resulted as highly predictive of cancer (about 70% of the cases).

Clinical recurrence in the absence of biochemical PSA failure is uncommon and accounts for less than 1%; we report a rare case of solitary lung metastasis in a patient with undetectable PSA level (0.1 ng/mL) after radical prostatectomy (RP) for prostate cancer (PCa). An asymptomatic 75-year-old man nine years after RP showed a solitary lung mass (about 2 cm) at chest radiography; the 18-FDG-PET/CT confirmed the presence of an isolated mass suspicious for primitive pulmonary cancer. The initial histological specimen after RP showed a mixed acinar and ductal PCa (Gleason score 7, pT3aNO stage, negative surgical margins). A segmental pulmonary resection was performed and definitive specimen demonstrated a single ductal PCa metastasis; after six months from surgery the patient was free from recurrence. In conclusion, in patients with atypical PCa variants imaging studies may be considered in the follow up even in presence of undetectable PSA because they could benefit from early salvage therapy.

The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18-75 years, ECOG PS 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m(2) on day 1, and i.v. gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3-G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2-72), median PFS was 10.5 months (95 % CI 9.9-11.4) and median OS was 21.1 months (95 % CI 19.7-22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2-19.7) and a median OS of 25.5 months (95 % CI 23.0-28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.

PURPOSE: To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIALS AND METHODS: From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20%, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS: All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1%): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50%, 90.6 vs 71.9%, 27.9 vs 41.8%, 31.9 vs 31.5% and 88.9 vs 80%, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS: Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1% of biopsies while missing 9.4% and 28% diagnosis of PCa.

A case of sarcomatoid carcinoma of the bladder (SCB) presenting as a giant intravesical mass in a 75-year-old man complaining of lower urinary tract swmptoms (LUTS), abdominal pain and fever is reported. SCB is a rare (0.1% of all primary bladder tumors), aggressive cancer with a complex histology (a biphasic tumor with malignant epithelial and mesenchymal elements) and poor prognosis.

Objective: To evaluate prostate cancer gene 3 (PCA3) score accuracy in preoperative staging of cases of single microfocus of prostate cancer (PCa; less than 5% with Gleason score ≤6) diagnosed after repeat saturation biopsy (median 30 cores). Methods: From January 2009 to March 2012, 38 patients (median 64 years) with a microfocus of PCa, median PSA of 9.1 ng/ml and T1c clinical stage underwent radical retropubic prostatectomy. PCA3 score (cut-off of 20 vs. 35) was evaluated in predicting insignificant PCa (pIPCa: cancer volume Results: Median PCA3 score results were equal to 10 versus 53 (p < 0.05) versus 108 (p < 0.05) in the presence of pIPCa (13.2%), versus OC (65.8%) versus non-OC PCa (21%), respectively. PCA3 scores were significantly correlated with tumor volume. Conclusions: A PCA3 score cut-off >20 in the presence of a microfocus of PCa is highly predictive of significant PCa (diagnostic accuracy equal to 86.8%) at definitive specimen.

To evaluate the concordance between the PSAD (PSA density) values calculated using the actual prostate weight and the PSAD values calculated by using the dimensions of the gland given by the pathologist when freshly excised (volume 1) or using TRUS measures (volume 2). Diagnostic accuracy of PSAD in diagnosing PCa (prostate cancer) was evaluated and compared with accuracy obtained using PSA free/total (FIT).102 consecutive patients with PSA included between 2 and 10 ng/mL underwent radical prostatectomy. Indications to perform prostate biopsy were: abnormal digital rectal examination, PSAor = 2.5 ng/mL, PSA between 2.6 and 4 ng/mL and between 4.1 and 10 ng/mL with PSA F/T (free/total)or = 15%,or = 20% andor = 25%, respectively We compared the PSAD values obtained using the actual prostate weight (PSAD1) vs those calculated using volume 1 (PSAD2) and volume 2 (PASD3).The mean weight of prostate specimen was 55.61 grams, while the estimated mean volumes were 50.02 mL (volume 1) and 48.49 mL (volume 2). A statistically significant difference among actual weight vs volume 1 vs. volume 2 (p0.0001) was found. In the patients with PSA ranging from 4.1 to 10 ng/mL a cumulative accuracy of 82.6% was found using a cut-off0.10 whereas, with a cut-off0.15, a diagnostic accuracy of 36.9% (PSAD1), 58.6% (PSAD2) and 60.8% (PSAD3) was reported.No concordance between the actual prostate weight and the estimated volume was found; moreover PSAD accuracy was of poor value in diagnosing PCa in comparison with PSA F/T.

Congenital lymphangiectasia-lymphedema is a rare disorder that presents with edema of the lower half of the body, the face, hands, and scrotum, or with protein-losing enteropathy owing to structural anomalies in the endothelium of the lymphatic system. We describe a biopsy-proven case of severe lymphangiectasia-lymphedema in a 16-year-old boy who was born to consanguineous parents and who, in addition, had mild (20 to 40 dB), early onset, sensorineural deafness and skin abnormalities, consisting of angiokeratomas of the face, hands, and feet, and also a large, localized angiokeratoma of the scrotum and the penis (Fordyce type). Both of the proband's parents had profound (>80 dB), congenital, mixed conductive/sensorineural, nonsyndromic deafness to low-mid frequencies. To the best of our knowledge, this constellation of lymphatic, skin, hearing, and systemic abnormalities seen in the proband has not been previously reported.

To evaluate the role of quantitative histologic findings in predicting nonorgan-confined (non-OC) prostate cancer (PCa) in patients undergoing saturation prostate biopsy (SPBx).A total of 69 patients who had undergone SPBx underwent radical retropubic prostatectomy. Their prostate-specific antigen level was10 ng/mL, and 49 and 20 patients had T1c and T2 PCa, respectively. The following biopsy variables from the quantitative histologic examination were evaluated as predictive of OC vs non-OC PCa: Gleason score (or=6 vs6), total percentage of PCa (or=20% vs20%), greatest percentage of PCa (or=50% vs50%), number of PCa-positive cores (or=2 vs2), presence of PCa-positive cores in both lateral margins (yes vs no), and PCa localization (unilateral vs bilateral). The results obtained from patients who had undergone SPBx were compared with those of 183 patients who had undergone 12-core prostate biopsy before radical retropubic prostatectomy.Overall, 32 patients had non-OC PCa. Among the men with Stage T1c PCa, the quantitative histologic findings were predictive of non-OC PCa in 12 of 17 cases. The area under the receiver operating characteristic curve was 0.935 +/- 0.29, supporting the high accuracy of quantitative histologic examination in predicting for non-OC PCa. The sensitivity in patients who underwent SPBx vs the 12-core biopsy was 78.1% and 89.4%, respectively. Also, although the specificity of each histologic parameter was significantly lower in the SPBx group, it was equivalent using quantitative histologic examination (85.6% vs 86.5%).In the preoperative staging of patients with clinical Stage T1c-T2 PCa and a prostate-specific antigen level10 ng/mL who had undergone SPBx, quantitative histologic examination demonstrated good accuracy in predicting for non-OC PCa only when all pathological variables were considered.

To find a predictor of extraprostatic extension in clinically localized prostate cancer (PCa), pre-operative ultrasound-guided prostate needle biopsies and clinico-pathological data were reviewed.One hundred and eighty-three consecutive patients who underwent radical retropubic prostatectomy for clinical T1-T2 PCa and serum PSA10 ng/ml were reviewed. Pre-operative biopsy was performed according to an extended protocol and whole-mount prostatectomy specimens were processed. The following biopsy variables were categorized to this analysis: Gleason score (or =6,6), TPC (or =20%;20%), GPC (or =50%;50%), cancer-positive cores (or =2;2), cancer-positive cores in both lateral portions (yes; no), PCa (monolateral; bilateral).Only 60/183 specimens showed an organ-confined PCa; the remaining ones showed pT3a in 57 cases, pT3b in 11 and pT3 with positive surgical margins in 55. A locally advanced PCa was found in 60.2 and 76.8% of T1c and T2 clinical stage, respectively. The positive predictive value and negative predictive value of biopsy findings to predict a locally advanced PCa was 89.9 and 75%, respectively. All biopsy variables associations were statistically significant; however, among these variables (non-categorized), in multivariate logistic regression analysis, only GPC was significantly associated with pathologic stage (odds ratio estimate was 1.075, 95% CI: 1.053-1.098).Quantitative histology, especially GPC, seems to be helpful for pre-operative staging of PCa in patients with T1c-T2 clinical stage and PSA10 ng/ml.

A 67-year-old man is presented who was admitted to our hospital for the onset of hematuria and acute urinary retention and who was found to have a 10-cm solid mass in the right obturator fossa compressing the bladder wall. Histology revealed the presence of a distant metastases from thyroid cancer. To the best of our knowledge, this is the first case of a thyroid cancer presenting with hematuria and acute urinary retention caused by distant metastases to intrapelvic soft tissue.

CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or >/=5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27(Kip1) and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.

We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.

Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the transcriptional activity of lung-specific genes in the normal and neoplastic bronchioloalveolar cells. It has been implicated in the normal growth and development of the lung, and the disruption of the TTF-1 locus leads to neonatal death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and clinical significance of TTF-1 immunoreactivity in 222 patients with stage I non-small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and we investigated its relationship with other markers of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using the commercially available monoclonal antibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF-1 immunoreactivity correlated significantly with microvessel density (p = 0.04) and inversely with the tumor proliferation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-immunoreactive adenocarcinomas showed a trend for a size less than 3 cm (p = 0.08). TTF-1 expression was not related to specific growth patterns, tumor grade, or tumor cell typing. TTF-1 immunoreactivity did not significantly affect patient survival, although patients with more than 75% immunoreactive neoplastic cells showed a trend for longer overall and disease-free survival. Our findings suggest that TTF-1 could be involved in the development of small pulmonary adenocarcinomas, but it has not prognostic implications in patients with stage I NSCLC.