Background: Malignant pleural effusion (MPE) represents a frequent and clinically challenging manifestation of advanced malignancy, particularly in metastatic non-small cell lung cancer (NSCLC). Its management requires integration of diagnostic imaging, symptom-directed therapeutic strategies, and, increasingly, molecular profiling technologies. Recent advancements in this field based on liquid medium (so-called liquid biopsy) have achieved a significant increase in sensitivity, enhancing our ability to investigate biofluids and suggesting their potential integration into standard diagnostic practices, far beyond the canonical plasma biopsies. Fluid obtained from MPE after cytological sample centrifugation is rich in cell-free DNA and less susceptible to nucleic acid degradation during processing, improving overall diagnostic accuracy. Methods: This narrative review summarizes current evidence on the clinical management of malignant pleural effusions in patients with metastatic NSCLC, integrating imaging, procedural management, and molecular profiling from a multidisciplinary tumor board perspective. The primary objective was to synthesize contemporary knowledge with particular attention to the feasibility, reliability, and reproducibility of pleural fluid-based molecular testing. Results: MPE poses diagnostic and therapeutic challenges for all members of the multidisciplinary tumor board, traditionally associated with an adverse prognosis. However, recent advances in cytopathology, histopathology, and liquid-based techniques demonstrate that MPE could be an important source of prognostic or predictive information. At the same time, optimal patient management requires careful integration of imaging findings and procedural strategies (such as pleurodesis or indwelling pleural catheters) with individualized systemic therapy selection. Cell-free DNA in pleural effusions is a promising field of exploration and study, potentially suitable for future guideline implementation, after validation in adequately powered studies, contributing to improving patient management, particularly useful in fragile subsets. Conclusions: The management of MPE in advanced NSCLC is evolving toward a multidisciplinary, precision-oriented model that integrates clinical evaluation, imaging, procedural interventions, and molecular testing. Liquid biopsy technology has gained enough analytical robustness and clinical feasibility to be a useful tool in routine analysis. Biofluid-based molecular testing may have outstanding potential, contributing to improving patient management, avoiding repetitive procedures, and optimizing the overall efficiency and cost-effectiveness of diagnostic practices. Moreover, collaborative projects among different specialties help in consolidating trust in the tumor board decision-making process.

The presence of a duplicated urinary bladder and prostate has not been described. We report the case of a complete duplication of the urinary bladder and prostate, associated with one urethral meatus and a bifid urethra. A 68-year-old male presented with chronic lower urinary tract symptoms (LUTS), recurrent urinary tract infections, bladder stone removal and epispadias repair. Bladder duplication was incidentally found during imaging. Cystoscopy confirmed one meatus with two bladders and urethras, each with its own prostate. Transurethral resection of both prostates (TURP) was performed. This is the first reported case of complete duplication of both bladder and prostate.

Perineuriomas are soft tissue neoplasms composed almost entirely of cells resembling perineurium and their occurrence in gastrointestinal tract is quite rare, with most of reported cases occurring in the colon. No more than 12 cases of gastric perineurioma have been reported to date, and the diagnosis in a routine endoscopy biopsy service can be challenging given the broad differentials of a bland-looking spindle cell proliferation in gastric mucosa. Here we present a case of a gastric perineurioma in a 39-year-old woman detected in routine endoscopy biopsy where a high degree of suspicion of the pathologist and targeted immunohistochemical investigations for perineurial markers EMA and GLUT1 allowed the correct diagnosis. Reviewing the literature, it appears that gastric perienuriomas most commonly occur in mid-age females and are often detected in routine endoscopies, with appearance of a benign-looking mid-sized sessile polyp. Special attention is needed to discriminate with GIST to avoid inappropriate further investigations and overtreatment. Moreover, we speculate that these lesions are likely underrecognized in busy routine gastrointestinal biopsy service, as most are probably dismissed as benign mesenchymal polyps/submucosal proliferations after exclusion of GIST or are misdiagnosed as inflammatory fibroid polyp in the case of CD34 positivity. However, the case presented demonstrates that, in light of the apparently typical occurrence in mid-aged females with endoscopic impression of benign polyp of the body, general pathologists of routine biopsy services should also have a high degree of suspicion and maybe add a perineural marker to their panel.

Zusammenfassung In bis zu 18% tritt nach kurativer radikaler Zystektomie wegen eines Urothelkarzinoms ein Rezidiv auf. Zumeist manifestieren sich die Rezidive in den regionären Lymphknoten oder im verbliebenen oberen oder unteren Harntrakt. Extrem selten tritt ein Rezidiv in einer Neoblase auf, zumal es sich um ein anderes embryonales Keimblatt handelt. Wir berichten über einen Fall, bei dem 10 Jahre nach der Zystoprostatektomie multiple Urothelkarzinomrezidive nur in der Neoblase auftraten. Daraufhin wurde die Neoblase entfernt und ein Sigma-Conduit angelegt. Trotzdem trat 6 Monate später eine generalisierte Metastasierung auf, woran der Patient wenig später verstarb. Zurzeit gibt es aufgrund der Seltenheit dieses Krankheitsbilds keine Behandlungsrichtlinien. Wir schildern unsere Erfahrungen und geben eine Literaturübersicht.

Background/Objectives: Testicular germ cell tumours (GCT) have high cure rates, especially in early stages. MicroRNA-371a-3p (M371) has recently emerged as a highly sensitive biomarker for malignant GCTs, except teratoma. This study aimed to evaluate the diagnostic performance of M371-test in a real-life clinical setting, compared to conventional markers alpha-fetoprotein (AFP), lactate-dehydrogenase (LDH), and beta-human chorionic gonadotropin (β-HCG) in patients with suspected GCT. Methods: The study, approved by the Ethic-Committee of the Provincial Hospital of Bolzano (N.97-2021), included 91 M371-tests, performed from March 2021 to May 2025. A total of 75 patients had suspected GCT; 19 healthy males served as control. Serum levels of M371, AFP, LDH, and β-HCG were compared with final histopathological diagnosis. M371 was also assessed in controls to evaluate test performance. Secondary analyses investigated correlations between preoperative M371 levels and tumour size in non-metastatic patients, and between M371-levels and clinical stage in the entire GCT cohort. A cut-off of RQ > 5 (relative quantification) was used to calculate sensitivity, specificity, and predictive values. Results: M371 showed a sensitivity of 90.9% and specificity of 89.3%, outperforming in terms of sensitivity AFP (20.4%/96.4%), LDH (40.9%/96.4%), and β-HCG (43.1%/100%). Positive predictive value (PPV) and negative predictive value (NPV) were 93.0% and 86.2%, respectively. Sensitivity was 95% for non-seminomas and 87.5% for seminomas. In non-metastatic patients, M371 levels correlated with tumour size and were significantly higher in advanced stages (median RQ 1128.35 vs. 98.36; p = 0.015). Conclusions: M371 showed excellent diagnostic performance, even for small tumours, supporting its clinical use. Further studies are needed to define its role in treatment planning and follow-up.

In up to 18% of patients, recurrence is observed after curative radical cystectomy. Tumour recurrence occurs in most cases in the locoregional lymph node, as well as in the remaining urinary tract, but very rarely in the orthotopic neobladder. We report a case of multiple recurrence of urothelial carcinoma solely in the orthotopic neobladder of a male patient, 10 years after surgery, without involvement of the urethra or upper urinary tract. Therefore, the patient underwent resection of the neobladder with conversion to a sigmoid conduit. Nevertheless approximately 6 months later the patient developed widespread metastases and died a few months later. Currently, no guidelines are available for the treatment of these rare cases. We present our experience, together with revision of the current literature on this issue.

Multicentric reticulohistiocytosis (MRH) is the most frequent entity in the group of reticulohistiocytoses. It is usually accompanied by symmetrical erosive polyarthritis and is frequently associated with cancer and autoimmune disorders. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is an inflammatory syndrome triggered by adjuvants such as those contained in vaccines or by silicone implants. Here, we report the case of a 71-year-old woman with a history of breast cancer treated with surgery and subsequent prosthesis who developed a systemic hyperinflammatory syndrome including seronegative symmetric polyarthritis, multiple skin lesions, and two large nodular lesions in the oral cavity and larynx. The clinical picture was consistent with a clinical diagnosis of ASIA, with breast implant rupture and/or vaccination against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) as possible triggers. Histopathology of skin, oral nodules, and laryngeal nodules revealed cutaneous/mucous and submucosal infiltration of large epithelioid mononuclear or binucleated cells with fine granular ground glass-like cytoplasm and round to kidney-shaped nuclei with prominent nucleoli, without atypical features or relevant pleomorphism, accompanied by sparse giant cells and lymphocytes. These cells stained positive for CD68 and CD45 and negative for S100, CD1a, and markers of epithelial or neural/melanocytic differentiation, altogether consistent with a diagnosis of reticulohistiocytosis. Clinicopathological correlation allowed the final diagnosis of MRH. To our knowledge, this is the first report of a co-occurrence of MRH with ASIA, and this is relevant to broaden the spectrum of both these rare diseases.

The management of head and neck squamous cell carcinoma (HNSCC) relies heavily on TNM staging and WHO histologic grading; however, in recent years, the analysis of prognostic markers expressed in the tumor stroma has gained attention. The tumor–stroma ratio (TSR) quantifies the proportion of tumor tissue relative to the surrounding stromal tissue; it is assessed with the percentage of stromal tissue within the tumor area, with a cutoff point of 50% being widely used to discriminate high-stroma cancer. In this systematic review and meta-analysis, we investigated the potential prognostic role of the TSR in HNSCC. After a literature screening, 24 studies dealing with the TSR and survival outcomes were included. The TSR showed a significant association with overall survival (OS) in both unadjusted and adjusted measures (RR 2.04, CI 1.57–2.65, p < 0.01; HR 2.36 CI 1.89–2.94, p < 0.00001), with an even stronger prognostic potential in oral cavity/oral tongue cancers (RR 2.44 CI 1.84–3.22, p < 0.00001). The TSR also showed prognostic value when dealing with cancer-specific survival and was associated with a reduction in disease-free survival (DFS). In particular, the TSR also retained its prognostic role in terms of DFS when specifically considering early-stage cancers in both unadjusted and adjusted analyses (RR 1.81 CI 1.57–2.10, p < 0.00001; HR 2.09 CI 1.58–2.76, p < 0.00001). Therefore, we conclude that the TSR is a reliable prognostic marker that is easy to assess in routine histological slides and can be effectively implemented in the routine evaluation of HNSCC.

BACKGROUND/AIM:The aim of the study was to establish the performance of the M371-Test on the Thermocycler Rotor-GeneQ (Qiagen) platform for diagnosis and follow-up of testicular tumors and to evaluate the test under real-life conditions in comparison to the classical markers alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG) and lactate dehydrogenase (LDH).PATIENTS AND METHODS:Forty-four patients, of median age 29 years (range=24-84) were included in this prospective study at our institution between March 2021 and September 2022. Of the 44 patients, 23 had a suspicion of testicular cancer (TC) and 21 were under follow-up for TC. In total, 96 M371-Tests were performed and compared with AFP, β-HCG, LDH using histological diagnosis and/or computer tomography (CT) scan as the gold standard.RESULTS:In the patients with suspicion of TC, the M371-Test showed a sensitivity of 73.7%, AFP of 21%, LDH of 31.6% and β-HCG of 42.1%. In the patients under follow-up for TC, the M371-Test showed a sensitivity of 86.4%, AFP of 50%, LDH of 31.8% and β-HCG of 63.6%. In germ cell tumours (GCT)/non-seminomas, M371-Test had a sensitivity of 83.3%, AFP of 77.8%, LDH of 38.9% and β-HCG of 66.7%. In GCT/seminomas, M371-Test had a sensitivity of 85%, AFP of 5%, LDH of 30% and β-HCG of 50%.CONCLUSION:Under real life conditions performed on the real-time Thermocycler Rotor-GeneQ (Qiagen) platform, the M371-Test shows an outstanding performance and is far beyond the sensitivity of the classical markers for detecting GCTs and in the follow-up of patients after GCT, especially in seminomas.

ZusammenfassungWir berichten über den Fall einer 83-jährigen Patientin, die unter dem Verdacht einer enterovesikalen Fistel hospitalisiert und operiert wurde und schlussendlich die Diagnose eines intestinal metastasierten Mammakarzinoms erhielt.

PURPOSE:Following the current guidelines, diagnosis and staging for upper urinary tract tumours (UTUC) can be performed with Computed Tomography, urography, ureterorenoscopy (URS) and selective cytology. The aim of the study was to evaluate the performance of the Xpert®-BC-Detection and the Bladder-Epicheck®-test in the detection of UTUC and compare it with cytology and the Urovysion®-FISH test using histology and URS as gold standard.METHODS:A total of 97 analyses were collected through selective catheterization of the ureter before URS to test for cytology, Xpert®-BC-Detection, Bladder-Epicheck® and Urovysion®-FISH. Sensitivity, specificity, and predictive values were calculated using histology results/URS as reference.RESULTS:Overall sensitivity was 100% for Xpert®-BC-Detection, 41.9% for cytology, 64.5% for Bladder-Epicheck® and 87.1% for Urovysion®-FISH. The sensitivity of Xpert®-BC-Detection was 100% in both, LG and HG tumours, sensitivity of cytology increased from 30.8% in LG to 100% in HG, for Bladder-Epicheck® from 57.7% in LG to 100% in HG and of Urovysion®-FISH from 84.6% in LG to 100% in HG tumours. Specificity was 4.5% for Xpert®-BC-Detection, 93.9% for cytology, 78.8% for Bladder-Epicheck® and 81.8% for Urovysion®-FISH. PPV was 33% for Xpert®-BC-Detection, 76.5% for cytology, 58.8% for Bladder-Epicheck® and 69.2% for Urovysion®FISH. NPV was 100% for Xpert®-BC-Detection, 77.5% for cytology, 82.5% for Bladder-Epicheck® and 93.1% for Urovysion®FISH.CONCLUSION:Bladder-Epicheck® and Urovysion®FISH along with cytology could be a helpful ancillary method in the diagnosis and follow-up of UTUC while due to its low specificity Xpert®-BC Detection seems to be of limited usefulness.

Objective/Background Telepathology has been widely adopted to allow intraoperative pathology examinations to be performed remotely and for obtaining second opinion teleconsultation. In the Italian northern region of South Tyrol, the widespread geographical distances and consequent cost for the health system of having a travelling pathologist cover intraoperative consultations in peripheral hospitals was a key driver for the implementation of a telepathology system. Methods In 2010, four Menarini D-Sight whole slide scanners to digitize entire pathology slides were placed in the peripheral hospitals of Merano, Bressanone, Brunico, and in the hub hospital of Bolzano. Digital workstations were also installed to allow pathologists to remotely perform intraoperative consultations with digital slides. This study reviews the outcome after 12 years of telepathology for this intended clinical use. Results After an initial validation phase with 100 cases which yielded a sensitivity of 65% (CI 43–84%) and specificity of 100% (CI 95–100%), there were 2058 intraoperative consultations handled by telepathology. The cases evaluated were mainly breast sentinel lymph nodes, followed by urological, gynecological and general surgical pathology frozen section specimens. There were no false-positive cases and 165 (8%) false-negative cases, yielding an overall sensitivity and specificity of 65% (CI 61–69%) and 100% (CI 99–100%), respectively. Conclusion Telepathology is reliable for remote intraoperative diagnosis and, despite technical issues and initial acquaintance issues, proved beneficial for patient care in satellite hospitals, improved standardization, promoted innovation, and resulted in cost savings for the health system.

Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.

AIMS:Xpert® Bladder Cancer Monitor is a urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer (BC). The aim of our study is to update our results regarding the diagnostic accuracy of the Xpert® Bladder Cancer Monitor test in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS:We conducted a prospective study on 1015 samples of 416 patients (mean age 72.2 ± 10.3 years) under follow-up for NMIBC. Patients underwent voided urinary cytology, the Xpert® Bladder Cancer Monitor test and cystoscopy and, if positive, a transurethral resection of the bladder. Xpert® Bladder Cancer Monitor was reported as negative or positive: cut-off total Linear Discriminant Analysis (LDA) = 0.5. RESULTS:We identified 168 recurrent tumours: 126 (75%) were low-grade (LG) and 42 (25%) high-grade (HG). Overall sensitivity was 17.9% for cytology, 52.4% for Xpert® Bladder Cancer Monitor and 54.2% for the two tests combined. The sensitivity of cytology increased from 6.3% in LG to 52.4% in HG tumours whereas Xpert® Bladder Cancer Monitor showed a sensitivity ranging from 42.9% in LG to 80.9% in HG tumours. Combined cytology and Xpert® Bladder Cancer Monitor yielded an overall sensitivity of 45.2% for LG and 80.9% for HG tumours. Overall specificity was 98.5% for cytology and 78.4% for Xpert® Bladder Cancer Monitor and 78.2% for the two tests combined. The area under the curve (AUC) for Xpert® Bladder Cancer Monitor was 0.71; stratifying the patients according to the European Association of Urology risk groups, the AUC was 0.69, 0.67 and 0.85 for low, intermediate and high risk, respectively (p = 0.0003). CONCLUSION:Our data confirm a significantly higher sensitivity of Xpert® Bladder Cancer Monitor than for cytology in a larger patient cohort. The test performed very well in terms of specificity but could not reach the high value of cytology. Along with voided urinary cytology the test could allow to reduce cystoscopies in follow-up patients, reducing discomfort to the patients and costs.

BACKGROUND:The objective of the current study was to compare the diagnostic accuracy of 2 new real-time polymerase chain reaction-based urinary markers with each other and with urinary cytology, cystoscopy, and/or histology in patients being followed for non-muscle-invasive bladder cancer.METHODS:A total of 487 patients were enrolled in the study. Patients were evaluated using voided urine cytology, the Xpert Bladder Cancer Monitor, the Bladder EpiCheck test, and white light cystoscopy.RESULTS:The overall sensitivity was 27.17% for cytology, 64.13% for the Bladder EpiCheck test, and 66.3% for the Xpert Bladder Cancer Monitor. The overall specificity was 98.82% for cytology, 82.06% for the Bladder EpiCheck test, and 76.47% for the Xpert Bladder Cancer Monitor. The negative predictive value was very similar for the 3 tests at 83.56% for cytology, 89.42% for the Bladder EpiCheck test, and 89.35% for the Xpert Bladder Cancer Monitor. When combined, the Bladder EpiCheck test and Xpert Bladder Cancer Monitor detected overall 79.35% of the tumors: 70.37% in low-grade and 92.11% in high-grade tumors.CONCLUSIONS:The Xpert Bladder Cancer Monitor and Bladder EpiCheck test were found to perform very well in terms of sensitivity. Together, the 2 tests detected approximately 92.11% of high-grade tumors. Their specificity was high but could not reach the excellent value of cytology. The negative predictive value was the same for both tests and was higher than that for cytology, especially when the tests were used together (92.24%). These 2 new tests hold promise as urinary biomarkers. They may be used in combination to maximize sensitivity in a less invasive way, thereby reducing invasiveness in the follow-up of patients with non-muscle-invasive bladder cancer and decreasing discomfort for the patients as well as complications and costs.

ZusammenfassungWir berichten über einen 83-jährigen Patienten mit der seltenen Diagnose eines Sarkoms der Harnröhre.