Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Diffuse Micro-Nodules on Peritoneal Surfaces at Donor Organ Procurement: Highlights on the Diagnostic Challenge and Transplant Management.

BACKGROUND Guidelines have been designed to stratify the risk of cancer transmission in donors with a history of or ongoing malignancy, although this evaluation is not always straightforward when unexpected and rare lesions are found. CASE REPORT Here, we present a case of a 41-year-old African female donor who died from a cerebral hemorrhage. Her medical history was unavailable. At procurement, multiple diffuse grayish small nodules were noticed along the peritoneal cavity, some of which were sent to the on-call pathologist for urgent frozen section evaluation. Histology showed a multinodular proliferation of uniform bland-appearing spindle cells, with no evidence of necrosis, nor nuclear atypia or mitoses. The overall picture was consistent with the diagnosis of disseminated peritoneal leiomyomatosis, with overlapping morphology with uterine leiomyoma. Given the rarity of the lesion and the potential for recurrence or malignant degeneration, only the liver and heart were allocated to recipients with life-threatening conditions. The decision was taken in a forcedly limited time and took into account the benefit of transplantation and the risk of disease transmission. CONCLUSIONS This case highlights challenges that transplant teams often have to deal with, as lesions that are difficult to diagnose during donor assessment are usually not covered in guidelines. The acceptance and usage of organs in such cases has to be decided in a team-based fashion, with the collaboration of all the transplant professionals involved to optimally assess the transmission risk, carefully balancing the benefits of transplantation for the recipients and the need to guarantee a reasonable degree of safety.

Tracheobronchopathia Osteochondroplastica: A Case Report Illustrating the Importance of Multilevel Workup Clinical, Endoscopic and Histological Assessment in Diagnosis of an Uncommon Disease.

BACKGROUND Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic disease with a stable course, which involves the lumen of the tracheobronchial tree. Clinical manifestations at time of presentation may differ, typically including hoarseness, persistent and/or productive cough, hemoptyses, and dyspnea. There are no well-established guidelines for diagnostic workup and treatment. Our aim here is to present a paradigmatic case of TO together with a concise survey of the most important clinical, radiological, and histological criteria. CASE REPORT We report a case of a 62-year-old non-smoker male with persisting cough and no prior history of respiratory disease. Chest radiography (RX) and computed tomography (CT) were unremarkable. Given the persistence of symptoms, the patient underwent bronchoscopic examination, which revealed protruding sessile nodules into the tracheal lumen, with cobblestone appearance. Histopathological examination of biopsies taken during bronchoscopy showed cartilaginous and osseous submucosal nodules consistent with the diagnosis of TO. CONCLUSIONS TO is not always an easily recognized disease, and a multidisciplinary team work is often required for diagnosis, with particular importance of endoscopic-pathological correlation.

Low-grade neuroepithelial tumor: Unusual presentation in an adult without history of seizures.

Low-grade neuroepithelial tumors (LGNT) show a broad histopathological spectrum and may be difficult to classify using current World Health Organization (WHO) criteria. A 57-year-old man came to medical attention because of headaches. The patient medical history was otherwise unremarkable. Magnetic resonance imaging (MRI) revealed a 2.5 cm lesion, partially cystic, with an increased signal on T2-weighted imaging, located in the right frontal lobe. The patient underwent right frontal craniotomy and the surgical specimen was entirely evaluated. Microscopic examination showed a tumor arranged predominantly in sheets and nests, with an infiltrative growth pattern and oligodendroglioma-like appearance. Tumor cells were round to oval with cytoplasmic clearing, hyperchromatic nuclei and inconspicuous nucleoli. Only one mitosis was identified. Necrosis was absent. Differential diagnostic considerations included oligodendroglioma, clear cell ependymoma, polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and long-term epilepsy-associated tumor with clear cell morphology. Neoplastic cells showed positivity for glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor 2 (OLIG2), α-thalasemia X-linked mental retardation syndrome (ATRX) (retained nuclear expression) and CD34. Epithelial membrane antigen (EMA), neuronal nuclear antigen, microtubule-associated protein-2e, cyclo-oxygenase-2, chromogranin A and isocitrate dehydrogenase 1 (IDH1) (R132H) were negative. Ki-67 labeling index was 2-3%. Molecular analysis identified neither IDH1/IDH2 mutations nor 1p19q codeletion. Rapidly accelerated fibrosarcoma homolog B1 (BRAF) V600E mutation was also absent by both molecular and immunohistochemical testing. Polymerase chain reaction analysis revealed the presence of fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil (TACC) fusion. Taken together, the morphological, immunohistochemical and molecular findings supported the final diagnosis of PLNTY.

Urinary metabolic profiling by 1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy.

To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary proton nuclear magnetic resonance (1H-NMR) spectra were acquired and NMR data from 52 patients with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were compared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stage liver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE (OHE, n = 21), covert HE (cHE, n = 7) or no HE (n = 17). Urinary proton nuclear magnetic resonance (1H-NMR) spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The results showed good discrimination between patients with cirrhosis (n = 52) and healthy controls (n = 17) (R2X = 0.66, R2Y = 0.47, Q2Y = 0.31, sensitivity-60 %, specificity-100 %) as the cirrhosis group had higher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinic acid levels. While patients with OHE could be discriminated from those with no HE, with higher histidine, citrate and creatinine levels, the best models lack robust validity (R2X = 0.65, R2Y = 0.48, Q2Y = 0.12, sensitivity-100 %, specificity-64 %) with the sample size used. Urinary 1H-NMR metabolic profiling did not discriminate patients with cHE from those without HE, nor discriminate subjects on the basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed different urinary 1H-NMR metabolic profiles compared to healthy controls and those with OHE may be distinguished from those with no HE although larger studies are required. However, urinary 1H-NMR metabolic profiling did not discriminate patients with differing grades of HE or according to severity of underlying liver disease.