Correlative imaging of cystic lymphangiomas: ultrasound, CT and MRI comparison

Cystic lymphangioma is a rare benign lesion derived from the detachment of the lymph sacs from venous drainage systems; the treatment of choice is a surgical excision and the final diagnosis is of histological type

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

Clear cell myoepithelial carcinoma ex pleomorphic adenoma of parotid gland: Case report and review of literature

Abstract Myoepithelial carcinoma (MC), also known as malignant myoepithelioma, shows an infiltrative and destructive growth [1]. Myoepithelial neoplasms account for about 1.5% of all salivary tumors, and MC is even more rare, representing about 10% of myoepitheliomas [1–3] with a reported incidence of 0.2% of all salivary gland tumors. In this case, the cytological diagnosis (pleomorphic adenoma) and negative lymph nodes, addressed the surgeon for a parotidectomy, following guidelines and literature [27]. The best treatment for huge, relapsing tumors, notwithstanding cytological diagnosis, is not only parotidectomy, as lymphadenectomy should be performed too, given myoepithelial carcinoma's high-grade potential and unpredictable biologic behavior. Careful patient follow-up and staging, is therefore essential for better characterization and understanding of this tumor's behavior in the future. We also considered a more conservative treatment following guidelines, as this case was lacking metastases and lymphatic involvement, considering that application of guidelines, surgical and clinical expertise and appropriate technology can contain potential medicolegal implications [28]

Human Cardiac Progenitor Cell-Derived Extracellular Vesicles Exhibit Promising Potential for Supporting Cardiac Repair in Vitro

Although human Cardiac Progenitor Cells (hCPCs) are not retained by host myocardium they still improve cardiac function when injected into schemic heart. Emerging evidence supports the hypothesis that hCPC beneficial effects are induced by paracrine action on resident cells. Extracellular vesicles (EVs) are an intriguing mechanism of cell communication based on the transport and transfer of peptides, lipids, and nucleic acids that have the potential to modulate signaling pathways, cell growth, migration, mand proliferation of recipient cells. We hypothesize that EVs are involved in the paracrine effects elicited by hCPCs and held accountable for the response of the infarcted myocardium to hCPC-based cell therapy. To test this theory, we collected EVs released by hCPCs isolated from healthy myocardium and evaluated the effects they elicited when administered to resident hCPC and cardiac fibroblasts (CFs) isolated from patients with post-ischemic end-stage heart failure. Evidence emerging from our study indicated that hCPC-derived EVs impacted upon proliferation and survival of hCPCs residing in the ischemic heart and regulated the synthesis and deposition of extracellular-matrix by CFs. These findings suggest that beneficial effects exerted by hCPC injection are, at least to some extent, ascribable to the delivery of signals conveyed by EVs

It is no longer the time to disregard thyroid metastases from breast cancer: A case report and review of the literature

Background: Metastases to the thyroid gland are more frequent than previously thought, although most of them are occult or not clinically relevant. Overall, only 42 cases of metastases to thyroid from breast cancer have been reported thus far. Here we report the case of a patient with breast cancer metastatic to the thyroid. We also review the 42 previously reported cases (published between 1962 and 2012). This is the first review about metastases to thyroid gland from breast cancer. Case presentation: A 64-year-old woman of Caucasian origin was diagnosed with a lobular invasive carcinoma of the breast (luminal A, stage II). She received adjuvant chemotherapy, followed by endocrine therapy. During follow- up, fine-needle cytology of a thyroid nodule revealed malignant cells that were estrogen-positive, which suggested a diagnosis of metastases to the thyroid. Imaging did not reveal any other metastatic site and showed only enlargement of the left thyroid lobe and an inhomogeneous pattern of colloid and cystic degeneration and calcifications. The patient underwent left hemithyroidectomy. Histology of thyroid tissue showed a colloid goitre containing dispersed small atypical neoplastic cells with eccentric nuclei. Immunohistochemistry showed cytokeratin-19 and oestrogen receptor, but not tireoglobulin, e-cadherin or cytokeratin-7, thereby confirming metastases from a lobular breast carcinoma. Hormonal treatment is ongoing. Conclusion: This case report and first review of the literature on metastases to thyroid from breast cancer highlight the importance of a correct early diagnostic work-up in such cases. Indeed, a primary lesion should be distinguished from metastases given the different treatment protocol related to primary cancer and the clinical impact on prognosis

CD10, BCL6, and MUM1 expression in diffuse large B-cell lymphoma on FNA samples

BACKGROUND: Gene expression profiling has divided diffuse large B-cell lymphoma (DLBCL) into 2 main subgroups: germinal center B (GCB) and non-GCB type. This classification is reproducible by immunohistochemistry using specific antibodies such as CD10, B-cell lymphoma 6 (BCL6), and multiple myeloma oncogene 1 (MUM1). Fine-needle aspiration (FNA) plays an important role in the diagnosis of non-Hodgkin lymphoma, and in some cases FNA may be the only available pathological specimen. The objectives of the current study were to evaluate CD10, BCL6, and MUM1 immunostaining on FNA samples by testing the CD10, BCL6, and MUM1 algorithm on both FNA cell blocks (CB) and conventional smears (CS), evaluating differences in CB and CS immunocytochemical (ICC) performance, and comparing results with histological data. METHODS: Thirty-eight consecutive DLBCL cases diagnosed by FNA were studied. Additional passes were used to prepare CB in 22 cases and CS in 16 cases; the corresponding sections and smears were immunostained using CD10, BCL6, and MUM1 in all cases. The data obtained were compared with histological immunostaining in 24 cases. RESULTS: ICC was successful in 33 cases (18 CB and 15 CS) and not evaluable in 5 cases (4 CB and 1 CS). The CD10-BCL6-MUM1 algorithm subclassified DLBCL as GCB (9 cases) and non-GCB (24 cases). ICC data were confirmed on histologic staining in 24 cases. CONCLUSIONS: CD10, BCL6, and MUM1 ICC staining can be performed on FNA samples. The results herein prove it is reliable both on CB and CS, and is equally effective and comparable to immunohistochemistry data

Detailed knowledge of regional anatomy and anatomical variations is fundamental to achieve successful surgical procedure. Although primary objective of neurosurgery is to restore physiological vital functions, remove intracranial mass and prevent further

Detailed knowledge of regional anatomy and anatomical variations is fundamental to achieve successful surgical procedure. Although primary objective of neurosurgery is to restore physiological vital functions, remove intracranial mass and prevent further brain damage, while preserving tissue and organ integrity, the neurosurgeon takes the risk of impairing non-vital functions. Occasionally, as with the hypoglossal nerve, the impairment of anatomical structures found on surgical route is due to their still barely known anatomical relations and variations. In order to provide an anatomically and surgically oriented classification to guide neurosurgical procedures and to ensure the preservation of nerve integrity, the aim of the present study is to detail the course of the 12th cranial nerve (CN) and to establish anatomical landmarks for surgeons. A combination of anatomical dissection of the neck and oral floor and skull base far lateral approach of 6 cadaveric human heads (3 male, 3 female, age 62+4) was performed, on both sides, to explore and follow the entire course of the 12th CN, from its emergence in the preolivary sulcus to the tongue. Skeletal, muscular and vascular relationships were meticulously analyzed and documented during anatomic and surgical dissections. According to our observations, hypoglossal nerve can be divided into five segments. The first two are intracranial, cisternal and intracanalar, and the other three, namely the descending, horizontal and ascending, are extracranial. Intriguingly, we found unreported relations of the nerve that, apart from their anatomical interest, have tremendous significance for surgeons operating on head and neck. Specifically, the intracanalar segment passes through a venous lacuna that, to the best of our knowledge, was never described before as such. This venous structure drains into the jugular bulb and acts as a sheath between the nerve and the osseous wall of the canal. The nerve in the venous sheath bends and it is elastically fixed to the osseous wall of the canal by fibrous bands. Therefore, the venous lacuna guarantees mobility to the nerve, and cushion the nerve from the bone. As for the descending segment, during its course it has very close relationship with the internal jugular vein, the internal carotid artery, the posterior belly of digastric muscle, and the styloid process and muscles inserting on it. The descending segment provides the ansa hypoglossi, branches to muscles inserting on the styloid process and to the sternocleidomastoid muscle. The horizontal segment has relationship with the intermediate digastric tendon, the stylohyoid, hyoglossus and mylohyoid muscles and the submandibular gland. The ascending segment might be very short and sometimes it is absent. The fifth and last segment becomes deeper at the anterior edge of hyoglossus muscle, and terminates into several branches supplying intrinsic and extrinsic musculature of tongue

Triple Blockade of Ido-1, PD-L1 and MEK as a Potential Therapeutic Strategy in NSCLC

BACKGROUND: Despite the recent progress in the treatment and outcome of Non Small Cell Lung Cancer (NSCLC), immunotherapy has still significant limitations reporting a significant proportion of patients not benefiting from therapy, even in patients with high PD-L1 expression. We have previously demonstrated that the combined inhibition of MEK and PD-L1 in NSCLC patients derived three dimensional cultures exerted significant synergistic effect in terms of immune-dependent cancer cell death. However, subsequent experiments analyzing the expression of Indoleamine 2,3-dioxygenase-1 (Ido-1) gene expression demonstrated that Ido-1 resulted unaffected by the MEK inhibition and even increased after the combined inhibition of MEK and PD-L1 thus representing a potential escape mechanism to this combination. METHODS: We analyzed transcriptomic profile of NSCLC lung adenocarcinoma cohort of TCGA (The Cancer Genome Atlas), stratifying tumors based on EMT (Epithelial mesenchymal Transition) score; in parallel, we investigated the activation of Ido-1 pathway and modulation of immune cytokines productions both in NSCLC cells lines, in peripheral blood mononuclear cells (PBMCs) and in ex-vivo NSCLC spheroids induced by triple inhibition with an anti-PD-L1 monoclonal antibody, the MEK inhibitor and the Ido-1 inhibitor. RESULTS: In NSCLC lung adenocarcinoma patient cohort (from TCGA) Ido-1 gene expression was significantly higher in samples classified as mesenchymal according EMT score. Similarly, on a selected panel of NSCLC cell lines higher expression of MEK and Ido-1 related genes was detected in cells with mesenchymal phenotype according EMT score, thus suggesting a potential correlation of co-activation of these two pathways in the context of EMT, with cancer cells sustaining an immune-suppressive microenvironment. While exerting an antitumor activity, the dual blockade of MEK and PD-L1 enhances the secretion of pro-inflammatory cytokines (IFNγ, TNFα, IL-12 and IL-6) and, consequently, the expression of new immune checkpoints such as Ido-1. The triple inhibition with an anti-PD-L1 monoclonal antibody, the MEK inhibitor and the Ido-1 inhibitor demonstrated significant antiproliferative and proapoptotic activity on ex-vivo NSCLC samples; at the same time the triple combination kept increased the levels of pro-inflammatory cytokines produced by both PBMCs and tumor spheroids in order to sustain the immune response and simultaneously decreased the expression of other checkpoint (such as CTLA-4, Ido-1 and TIM-3) thus promoting an immune-reactive and inflamed micro-environment. CONCLUSIONS: We show that Ido-1 activation is a possible escape mechanism to immune-mediated cell death induced by combination of PD-L1 and MEK inhibitors: also, we show that triple combination of anti-PD-L1, anti-MEK and anti-Ido-1 drugs may overcome this negative feedback and restore anti-tumor immune response in NSCLC patients\u27 derived three dimensional cultures

Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis

Chorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a-/- mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, \u3b3-synuclein and phospho-tau proteins in Vps13a-/- basal ganglia secondary to impaired autophagy leading to neuroinflammation. Mice double knockout Vps13a-/- Lyn-/- showed normalization of red cell morphology and improvement of autophagy in basal ganglia. We then in vivo tested pharmacologic inhibitors of Lyn: dasatinib and nilotinib. Dasatinib failed to cross the mouse brain blood barrier (BBB), but the more specific Lyn kinase inhibitor nilotinib, crosses the BBB. Nilotinib ameliorates both Vps13a-/- hematological and neurological phenotypes, improving autophagy and preventing neuroinflammation. Our data support the proposal to repurpose nilotinib as new therapeutic option for ChAc patients