Management of Cytological Material, Pre-Analytical Procedures and Bio-Banking in Lymph Node Cytopathology

The range of pathologies that Lymph Node (LN) Fine-Needle Cytology (FNC) may deal with is extremely wide and ancillary techniques, in addition to traditional smears, are generally required to reach reliable cytological diagnoses. For this purpose, in the pre-analytical phase of LN-FNC, using the most effective vials, fixatives and supports is essential, since they may perform differently with different ancillary techniques, and even in different pathologies. Moreover, storing part of the cytological material may be useful or necessary for molecular testing. The main difficulties concern the generally small size of the sample and the different ways of acquisition of LN-FNC. Therefore, the pre-analytical phase is extremely important for LN-FNC. This study investigates the management of LN-FNC material, vials, technical supports and main ancillary techniques in order to assess their optimal application, taking into account the different diagnostic needs and cell storage. This article is protected by copyright. All rights reserved

Targeting αvβ3 and αvβ5 integrins inhibits pulmonary metastasis in an intratibial xenograft osteosarcoma mouse model

Osteosarcoma is an aggressive bone cancer that has a high propensity for metastasis to the lungs. Patients with metastatic disease face a very poor prognosis. Therefore, novel therapeutics, efficiently suppressing the metastatic process, are urgently needed. Integrins play a pivotal role in tumor cell adhesion, motility and metastasis. Here, we evaluated αvβ3 and αvβ5 integrin inhibition with cilengitide as a novel metastasis-suppressive therapeutic approach in osteosarcoma. Immunohistochemical analysis of αvβ3 and αvβ5 integrins expression in a tissue microarray of tumor specimens collected from osteosarcoma patients revealed that αvβ5 integrin is mainly found on tumor cells, whereas αvβ3 is predominantly expressed by stromal cells. In vitro functional assays demonstrated that cilengitide dose-dependently inhibited de novo adhesion, provoked detachment and inhibited migration of osteosarcoma cell lines. Cilengitide induced a decline in cell viability, blocked the cell cycle in the G1 phase and caused anoikis by activation of the Hippo pathway. In a xenograft orthotopic mouse model cilengitide minimally affected intratibial primary tumor growth but, importantly, suppressed pulmonary metastasis. The data demonstrate that targeting αvβ3 and αvβ5 integrins in osteosarcoma should be considered as a novel therapeutic option for patients with metastatic disease

Worse prognosis of osteosarcoma patients expressing IGF-1 on a tissue microarray

BACKGROUND It is hardly possible to define osteosarcoma (OS) patients at greatest risk for non-response to chemotherapy, metastasis and short survival times. Our goal was the investigation of local expression of insulin-like growth factor (IGF-1) with regard to survival time of OS patients using a tissue microarray (TMA). MATERIALS AND METHODS Tumor tissue specimens from surgical primary tumor resections were collected from patients with OS. A TMA was composed, sections were stained with rabbit anti-IGF-1 and grading was performed. Statistics involved Kaplan-Meier curves and the log-rank test. RESULTS We analyzed immunohistochemical expression of local IGF-1 on a TMA based on surgical primary tumor resections of 67 OS patients. The mean clinical follow-up time was 98 months. Twenty-two (33%) OS patients stained negatively and 44 (66%) OS patients stained positively for IGF-1. Significantly shorter survival was detected with expression of IGF-1 (p=0.007). The 5-year survival rate for patients expressing IGF-1 was 63% compared to 92% in patients without expression of IGF-1. Non-responders to chemotherapy and patients with metastasis, who also stained positively for IGF-1 manifested a significantly (p=0.002 and p<0.0001, respectively) shorter survival. CONCLUSION Expression of local IGF-1 in primary tumor tissue appears to significantly affect the aggressiveness of OS, may predict survival time and, above all, may discriminate patients with non-response to chemotherapy and metastasis. This represents the basis for successful patient selection with regard to the decision process for or against chemotherapy and the choice of the most effective therapeutic drug. It may be a more important marker of tumor progression and indicator of prognosis than serum IGF-1. Novel tumor markers and therapeutic agents targeting the local IGF-1 pathway may increase the likelihood of therapeutic success

Unlocking the Power of Benchmarking: Real-World-Time Data Analysis for Enhanced Sarcoma Patient Outcomes

Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector$^{®}$, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector$^{®}$, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector$^{®}$ can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs

Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis

Background. Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity. Methods. We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies. Results. Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin). Conclusions. EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EP

Flow cytometry and effusions in lymphoproliferative processes and other hematologic neoplasias

Cytopathologists are regularly confronted with lymphocyte-rich effusions, and the definite decision of whether the lymphocytosis is of a purely reactive nature or a presentation of an indolent lymphoma may be an extremely difficult one based on microscopy alone. Flow cytometry (FC) offers many advantages in terms of its application in body cavity fluids, and it has proven to be very useful both in the setting of a known disease and for new lymphoma diagnoses. In this paper, the studies published in recent years dealing with the applications of FC in body cavity effusions in the context of hematologic neoplasia are reviewed, stressing the integrative diagnostic approach. The incorporation of microscopical, immunophenotypical, and molecular findings from examinations of the cellular content of effusions and the interpretation of results in relation to the current WHO classification of hematolymphoid malignancies give cytopathologists new perspectives on advanced and clinically highly relevant diagnostics

Moderne histopathologische Klassifikation und Klinik der Weichteiltumoren

Weichteiltumoren bilden eine sowohl klinisch wie auch histopathologisch heterogene Gruppe von mesenchymalen Neoplasien. Einige der gutartigen Weichteiltumoren wie Lipome sind verbreitet, während die klinisch aggressiven Sarkome sehr selten sind. Die prä-operative bildgebende und bioptische Abklärung von Weichteilschwellungen verhindert falsche Behandlung und sollte bei allen grossen und tief liegenden Läsionen obligatorisch stattfinden. Die früher ausschliesslich mikroskopisch basierte Klassifikation der mesenchymalen Neoplasien wurde in den letzten Dekaden durch neue Erkenntnisse der Genetik dieser Tumoren ergänzt und modifiziert. Die präzise histopathologische Diagnostik setzt heutzutage die multimodale Anwendung moderner diagnostischen histopathologischen Methoden, inklusive Molekulargenetik (FISH, RT-PCR), voraus und ist in vielen Fällen nur in spezialisierten Zentren durch auf mesenchymale Neoplasien spezialisierten Pathologen mit auf grossen Fallzahlen basierenden Erfahrung möglich. Enge multidisziplinäre Zusammenarbeit diverser Fachrichtungen (Radiologie, Pathologie, orthopädische-, viszerale- plastische- / rekonstruktive-, Thorax-Chirurgie, Radioonkologie, Onkologie), im Rahmen der Sarkomboarde bietet den Patienten beste Chancen für eine optimale Gestaltung der Diagnostik, der Therapie und der Nachsorge wie auch die Möglichkeit der Teilnahme an Studienprotokollen

News in der aktuell gültigen WHO-Klassifikation der HPV-assoziierten Zervix-Läsionen

Die neusten Erkenntnisse zu der Pathogenese des Zervixkarzinoms führten zu Anpassungen in der zytologischen und histologischen Nomenklatur seiner Vorstufen. Die aktuelle, 2014 eingeführte histologische WHO-Terminologie unterscheidet, analog zum zytologischen Bethesda-System, zwischen zwei histologischen Stufen der HPV-bedingten Veränderungen: LSIL und HSIL, die mit unterschiedlichen Risiken der Progredienz zum invasiven Karzinom einhergehen und klinisch entsprechend unterschiedlich gehandhabt werden sollen. Die immunhistochemische Detektion des p16-Proteins als Surrogat der neoplastischen Transformation der HPV-infizierten Zellen hilft, die rein mikroskopische Diagnose zu objektivieren und zu sichern, und ist ein wichtiges Hilfsmittel in der Histopathologie. Die Verfügbarkeit der HPV-Impfung und die HPV-Detektion werden in den kommenden Jahren die Abläufe in der Frühentdeckung und die Epidemiologie der Zervixkarzinom-Vorstufen beeinflussen

Giant cell angioblastoma in an adult: a unique presentation

Giant cell angioblastoma is a very rare, locally destructive vascular tumor of intermediate malignancy without metastatic potential. There are only a few cases reported in the literature exclusively in the soft tissue of children. For the first time, we report on an adult patient with a giant cell angioblastoma in the popliteal fossa. The therapy included tumor resection with favorable clinical, oncological and functional outcome. Due to its locally destructive nature, surgery remains the mainstay of treatment. Histologically, giant cell angioblastoma is comprised of nodular aggregates of histiocytoid cells arranged around bland angiomatous spaces. Because of insufficient available data in regard to the definition of the entity, diagnostic criteria and its biological potential, it is not included in the new World Health Organization classification of tumors of soft tissue and bone. The differential diagnosis includes plexiform fibrohistiocytic tumor, myofibroma and giant cell fibroblastoma