First report of Central-line-associated bloodstream infection (CLAB- SI) due to Enterococcus raffinosus (ER) in a cancer patient.

Abstract: Despite the advances made by therapeutic technologies, healthcare-associated infections (HAIs) are currently still a worldwide problem. Central-line-associated bloodstream infections (CLABSIs) are one of the most common causes of HAIs. The cost of CLABSIs is considerable, both for the increase in morbidity and financial resources expenses. Coagulase-negative staphylococci are the common pathogens responsible for CLABSIs, followed by Staphylococcus aureus, Enterococci, and Candida spp. The Enterococcus genus comprises of more than 50 species but E. faecalis and E. faecium are the most common causes of infections in humans. Enterococcus Raffinosus (ER) is a non-faecalis and non-faecium enterococcus even if ER has rarely been proven to be a human pathogen, recent reports of infections caused by enterococci that are relatively resistant to beta-lactam antibiotics by non-p-lactamase mechanisms have included strains of ER. Here we describe a first report of CLABSI due to Enterococcus Raffinosus in a cancer patient.

High-Grade Chondrosarcoma of the Proximal Phalanx: an Unusual Case of a Rare Entity.

Chondrosarcoma of the hand is a rare disease, but is one of the more common malignancies of the hand. Biopsies and imaging are a fundamental step in determining correct diagnosis, grading and selection for best treatment. We describe the case of a 77-year-old male complaining of a painless swelling in the proximal phalanx of the third ray of left hand. A biopsy was performed and the histology revealed a G2 chondrosarcoma. The patient underwent III ray amputation with metacarpal bone disarticulation and sacrifice of the radial digit nerve of the fourth ray. Definitive histology revealed grade 3 CS. Eighteen months after surgery, the patient is apparently disease-free with a good functional and aesthetic outcome although with persistent paresthesia of the fourth ray. Although there is no agreement in the literature for the treatment of low-grade chondrosarcomas, wide resection or amputation can be considered the mainstay treatment for high-grade tumors. Key words: chondrosarcoma, proximal phalanx, ray amputation, surgical treatment, tumor hand.

Undertreatment with Osimertinib in patient with multiple chemical sensitivity. A case report.

Introduction: Multiple chemical sensitivity (MCS), is a syndrome characterised by increased sensitivity to the exposure of environmental chemicals (1). There are considerable difficulties in reaching a good estimate of the prevalence of disease and the main pathogenetic hypotheses take into account both the organic and psychiatric/psychological factors. Treatment with epidermal growth factor tyrosine kinase receptor inhibitors (tkis), like Osimertinib, results in improved progression-free survival (PFS) compared to chemotherapy, in Non-small-cell lung carcinoma (NSCLC) with epidermal growth factor receptor (EGFR) mutation (2). Case report: We describe the case of a 74 year old woman with history of MCS and fibromyalgia in treatment with Osimertinib for EGFR-mutated NSCLC. Patient initially refused any form of active therapy for lung cancer, but thanks to teamwork and the important support of the psychologist, the patient decided to start treatment with Osimertinib at a reduced dose, not 80 mg but 40 mg. Subsequently, after few days , of his own free will and without informing the staff physicians, the patient changed the treatment schedule by taking one quarter of the dose of the medicine every other day, justifying this choice in therapeutic modification because of her fear and intolerance to any type of medicine and/ or chemical substance, being influenced by MCS. Management & outcome: Despite the changes in the treatment plan, a PET scan performed after two months showed a sigificative lung response and the stability of bone metastases. Discussion. Our case describes a significative response with Osimertinib despite the change in dosage and schedule in a patient with MCS. Our experience deserves to be considered in the light of its particularity and uniqueness as it shows an excellent response to treatment with Osimertinib despite the change made to the dosage and schedule, in a patient presenting in her medical history this rare pathological condition: MCS syndrome.

Preoperative Assessment of TERT Promoter Mutation on Thyroid Core Needle Biopsies Supports Diagnosis of Malignancy and Addresses Surgical Strategy.

In the last decade, several molecular markers have been proposed to improve the diagnosis of thyroid nodules. Among these, mutations in the telomerase reverse transcriptase (TERT) promoter have been correlated to malignant tumors, characterized by highest recurrence and decreased patients' survival. This suggests an important role of TERT mutational analysis in the clinical diagnosis and management of thyroid cancer patients. The aim of the study was to demonstrate the adequacy of core needle biopsy (CNB) for the preoperative assessment of TERT mutational status, to reach a more accurate definition of malignancy and a more appropriate surgical planning. Indeed, CNB is gaining momentum for improving diagnosis of thyroid nodules deemed inconclusive by fine needle aspirate (FNA). The study included 50 patients submitted to CNB due to inconclusive FNA report. TERT mutational status was correlated with BRAF mutation, definitive histology, and post-operative TNM staging of the neoplasia. C228T mutation of the TERT promoter was reported in 10% of the papillary carcinomas (PTC) series. When compared with final histology, all cases harboring TERT mutation resulted as locally invasive PTCs. The prevalence of TERT mutated cases was 17.6% among locally advanced PTCs. TERT analysis on CNB allows the assessment of the pathological population on paraffin sections before DNA isolation, minimizing the risk of false negatives due to poor sampling that affects FNA, and gathering aggregate information about morphology and TERT mutational status. Data indicating a worse outcome of the tumor might be used to individualize treatment decision, surgical option, and follow-up design.

Neck schwannoma diagnosed by core needle biopsy: a case report.

Here we present a case of a 58 year old man referred to our hospital to undergo neck and thyroid ultrasonography (US) following palpable neck mass. US revealed a solid hypoechoic nodule in right thyroid lobe, and a solid lesion on the right laterocervical neck region with ultrasound suspicious features of neoplastic lymph node. In order to achieve a diagnosis of the neck mass and to get a proper evaluation of the thyroid nodule, we decided to perform a fine-needle aspiration (FNA) of both lesions. At cytopathologic examination the thyroid nodule appeared as benign, while cytologic sampling of the neck lesion was inadequate for a proper evaluation. Thus, we performed core needle biopsy (CNB) of the neck lesion like recently proposed for thyroid lesions; also, to definitively exclude malignancy of thyroid nodule, this also underwent CNB. Histologic report of CNB confirmed benign thyroid nodule, while the neck lesion revealed a proliferation of neuronal type consistent with schwannoma. The patient has been addressed to clinical and ultrasonographic follow-up. CNB appears as a safe and minimally-invasive approach to diagnose indeterminate neck masses and avoid unnecessary diagnostic surgery.

Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers.

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Phenotypic changes of the thyrocyte membrane in papillary thyroid carcinoma. A three-dimensional study.

Aim of the study was to assess the presence of structural changes in the complex carbohydrate chains of thyroid epithelia undergoing neoplastic transformation. We investigated thyroid cells from neoplastic lesions using a panel of lectins with specific affinity for distinct carbohydrate residues. Sixty samples of thyroid tissue, including normal, hyperplastic and neoplastic lesions were obtained from surgical specimens and blindly evaluated with lectin stains. Confocal microscopy was used to obtain three-dimensional (3-D) images of the samples with a positive reaction. Wheat germ agglutinin (WGA) was consistently positive on the apical membrane of papillary thyroid carcinomas (PTC), was weakly expressed in follicular carcinomas (FC) and resulted negative in normal thyrocytes and in benign conditions. The 3-D microscopy model showed that the WGA staining pattern in light microscopy corresponds to a continuous layer on the luminal surface of both papillary and tubular structures of PTC cells. The other lectins under evaluation did not provide any significant result. In conclusion, in PTC the apical border of thyrocytes showed a strong, specific and consistent staining with WGA. These findings may be related to a modified interaction of thyroglobulin molecule with thyroid cell membrane and with the expression of molecules that are involved in the process of tumorigenesis and tumor progression.

Cytospray fixation of frozen intraoperative sections.

Preservation of cellular morphologic features is well known to be a limit of intraoperative frozen sections. Various techniques have been proposed to improve tissue details, the most common being ethanol immersion of cryostatic slide. We tested fixation with spray formulation for cytology smears on intraoperative frozen section from different organs to obtain a quick alcoholic fixation and a ready-to-use method. Our results of comparative study showed that cytospray fixation of frozen sections provide a significant improvement of cellular details, that it is quick, simple, economic, and that it does not require preorganization.

Utility of HBME-1 immunostaining in serous effusions.

HBME-1 is an anti-mesothelial cell monoclonal antibody derived from human mesothelioma cells. We investigated 227 body cavity effusions to test its utility in differentiating mesothelioma from adenocarcinoma. HBME-1 outlined cell membranes in non-neoplastic mesothelial cells. Thick surface staining was observed on all mesotheliomas. HBME-1 reactivity was also detected in 24% of metastatic carcinomatous effusions. Most ovarian carcinomas (83%) reacted with this antibody, showing surface staining. Cytoplasmic HBME-1 immunoreactivity was observed in a small proportion of non-ovarian adenocarcinomas (14%). Despite its limited specificity, HBME-1 might be added to the battery of other markers of epithelial and/or mesothelial differentiation to be used in cases of suspected mesothelioma. Evaluation of suspicious cells should include careful study of the pattern of immunostaining.

Human malignant thyroid tumors displayed reduced levels of transforming growth factor beta receptor type II messenger RNA and protein.

Transforming growth factor beta (TGF-beta) is a physiological regulator of thyroid epithelial cell growth and differentiation. This factor signals through a heteromeric complex composed of type I (TGF-beta receptor type I) and type II [TGF-beta receptor type II (TbetaRII)] receptors. Loss of TbetaRII expression has been related to resistance to TGF-beta inhibition of cell proliferation. In the present work, we analyzed the TbetaRII expression in a series of human thyroid tumors, from benign lesions (adenomas) to neoplastic lesions of increasing aggressiveness (papillary and follicular carcinomas) up to the extremely aggressive anaplastic tumors. Results obtained indicated a clear reduced expression of TbetaRII mRNA only in the group of thyroid carcinomas when compared with their relative normal tissues. Immunohistochemical analyses with specific anti-TbetaRII antibodies confirm these observations. These data indicate that loss of expression of TbetaRII can contribute to thyroid cancer progression, inducing cancer cells to escape the growth-inhibitory effect of TGF-beta.

The diagnostic value of thrombomodulin immunolocalization in serous effusions.

OBJECTIVE: To test the value of an antithrombomodulin monoclonal antibody as a diagnostic tool in detecting mesothelial cells and in differentiating mesothelioma from other malignant effusions. DESIGN: Thrombomodulin is a thrombin receptor that is distributed on surfaces where an anticoagulant activity is expected, including mesothelium. Antigen expression was studied by immunocytochemistry in 226 peritoneal and pleural exudates. RESULTS: The antigen was found in 33 of 33 mesotheliomas, 35 of 35 reactive effusions, 57 of 145 carcinomatous fluids, and in one case of angiosarcoma among seven metastatic nonepithelial tumors. Three distinct staining patterns were demonstrated: (1) thin cell membranes in benign mesothelial cells; (2) thick cell membranes in mesotheliomas; and (3) cytoplasm in carcinomas. All squamous cell carcinomas had demonstrable thrombomodulin, suggesting that antigen expression likely correlates with squamous differentiation. CONCLUSIONS: Thrombomodulin is of diagnostic utility in distinguishing mesothelioma from adenocarcinoma, provided the characteristic "thick membrane" pattern is present, but it should be used in panels with other markers of mesothelial and/or epithelial differentiation.

Utility of cytokeratin 20 in identifying the origin of metastatic carcinomas in effusions.

Using a commercially available monoclonal antibody (Ks20.1) and the avidin-biotin peroxidase method on cytospins and cell blocks, we analyzed cytokeratin (CK) 20 expression in 169 serous effusions. Cytoplasmic staining was observed in 44/151 malignant fluids. Colon, gastric, and pancreatic adenocarcinomas and mucinous ovarian tumors were most frequently positive. Single cases of transitional-cell and squamous cell carcinomas were reactive as well. Lung and breast cancers were mostly negative. Nonmucinous ovarian tumors were invariably unlabeled as were mesotheliomas and normal mesothelial cells. The study shows that CK 20 is valuable in distinguishing tumor cell origin in effusions. In particular, it identifies a set of carcinomas with the majority arising from the gastrointestinal tract, and represents a highly characteristic marker for colorectal cancer.