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Lo spazio tiro-crico-aritenoideo (TCAS): implicazioni cliniche e prognostiche nel carcinoma laringeo.La recente letteratura riguardante la chirurgia oncologica laringea si sta sempre più focalizzando sul significato prognostico negativo del coinvolgimento da parte della neoplasia della porzione posteriore dello spazio paraglottico inferiore, che può essere definito spazio “tiro-crico-aritenoideo” (TCAS). Abbiamo valutato retrospettivamente il significato prognostico del coinvolgimento di tale sito anatomico in una coorte di 84 pazienti trattati con laringectomia parziale orizzontale open. È stato inoltre valutato mediante analisi univariata il significato prognostico dei parametri clinici e patologici. I casi con coinvolgimento del TCAS hanno avuto un maggior tasso di recidiva ed una minore sopravvivenza libera da malattia, rispetto ai casi senza coinvolgimento dello stesso. In conclusione, le neoplasie coinvolgenti questo sito laringeo dovrebbero essere considerate e trattate come tumori extra-laringei. I carcinomi glottici posteriori con invasione del TCAS hanno una prognosi peggiore quando gestiti mediante chirurgia conservativa. Nei casi di carcinoma glottico localmente avanzato con coinvolgimento del TCAS la laringectomia totale dovrebbe essere considerata il trattamento di scelta.The recent literature on laryngeal surgical oncology has increasingly focused on the negative prognostic impact of neoplastic involvement of the posterior portion of the inferior paraglottic space, which we refer to as the “thyro-cricoarytenoid space” (TCAS). We retrospectively considered the prognostic significance of TCAS involvement in a cohort of 84 patients treated with open partial horizontal laryngectomy for glottic squamous cell carcinoma. Univariate analysis was conducted on the prognostic value of several clinical and pathological parameters. Cases with TCAS involvement experienced a higher recurrence rate and shorter disease-free survival. Neoplasms involving the TCAS should be considered and treated as extralaryngeal malignancies. Posterior glottic tumours with TCAS invasion have worse prognosis when managed with conservative surgery. Total laryngectomy should be considered in cases of locally-advanced glottic carcinoma with TCAS involvement.

Purpose The present paper describes our experience in surgical treatment of laryngeal ACC, and discuss the effectiveness of conservative surgery. Methods We retrospectively reviewed the clinical charts of 17 patients with laryngeal ACC treated surgically at the Otolaryngology Unit of Vittorio Veneto Hospital (Italy) from November 1989 to April 2020. Results Fourteen patients underwent partial laryngectomy, and three had a total laryngectomy. Five patients (29%) experienced a laryngeal ACC relapse after a disease-free survival of 66.6 ± 50.1 months. The distant metastasis rate was 17%. At latest follow-up, two patients had died of distant metastatic disease after 156 and 243 months. Conclusions Radical surgery for laryngeal ACC does not warrant free margins and even cases with positive deep margins rarely experience any relapsing disease. We recommend that surgical treatment for laryngeal ACC be as conservative as possible.

Colorectal cancer incidence in patients undergoing screening protocols is decreasing because of the higher rate of discovered preneoplastic colonic lesions; however, adenomatous polyps may not always be removable endoscopically and surgery may still be necessary. The aim of this study was to assess the vascular endothelial growth factor expression in the different steps of colorectal carcinogenesis to explore its potential role as a marker of malignancy in polypoid lesions. A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Real-time reverse transcription polymerase chain reaction for VEGF-A messenger RNA expression and immunohistochemistry for VEGF-A were performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Non-parametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. VEGF-A messenger RNA expression was higher in patients with high-grade dysplasia or colorectal cancer than in those with low-grade dysplasia adenomas (p = 0.01). At immunohistochemistry, VEGF-A expression was significantly higher in colorectal cancer patients compared to dysplastic adenomas (p

Myxoid liposarcoma exhibits a peculiar clinical behavior, with a tendency to spread to serosal membranes, distant soft tissues, and bones, even in the absence of lung metastases. Therapy-related hematological neoplasms are well-known side effects of cytotoxic chemotherapy. We describe an exceptional case of metastatic myxoid liposarcoma of the spine associated with therapy-related refractory anemia with excess of blasts in a 37-year-old woman who underwent multi-agent chemotherapy for a myxoid liposarcoma of the left thigh. Microscopic examination of the bone marrow biopsy revealed dysplastic features, with abnormal localization of immature precursors and micromegakaryocytes, and islands of undifferentiated oval small/medium-size cells, suggestive of acute myeloid leukemia arising in the setting of a myelodysplastic syndrome. Immunohistochemistry was not discriminant. Cytogenetic analyses of bone marrow aspirate disclosed the presence of 2 different rearrangements, subsequently confirmed by fluorescent in situ hybridization and was crucial in making the correct diagnosis.

// Marco Scarpa 1,* , Cesare Ruffolo 2,* , Fabio Canal 3 , Melania Scarpa 1 , Silvia Basato 4 , Francesca Erroi 4 , Alain Fiorot 2 , Lucia Dall’Agnese 4 , Anna Pozza 4 , Andrea Porzionato 5 , Ignazio Castagliuolo 5 , Angelo P. Dei Tos 3 , Nicolo Bassi 2 and Carlo Castoro 1 1 Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy 2 General Surgery Unit (IV), “Ca’ Foncello” Hospital, Treviso, Italy 3 Pathology Unit, “Ca’ Foncello” Hospital, Treviso, Italy 4 Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy 5 Department of Molecular Medicine, University of Padova, Padova, Italy * These authors have contributed equally to this work Correspondence to: Marco Scarpa, email: // Keywords : mismatch repair, colorectal cancer, immune surveillance, CD80 Received : June 03, 2015 Accepted : October 07, 2015 Published : October 19, 2015 Abstract Background: There is evidence that colorectal cancers (CRC) with DNA mismatch repair deficiency (MMR-D) are associated with a better prognosis than the generality of large bowel malignancies. Since an active immune surveillance process has been demonstrated to influence CRC outcome, we investigated whether MMR-D can enhance the immune response in CRC. Patients and Methods: A group of 113 consecutive patients operated for CRC (42 stage I or II and 71 with stage III or IV) was retrospectively analyzed. The expression of MMR genes (MSH2, MLH1, MSH6 and PSM2) and co-stimulatory molecule CD80 was assessed by tissue microarray immunohistochemistry. In addition, tumor infiltrating mononuclear cells (TIMC) and T cell subpopulations (CD4, CD8, T-bet and FoxP-3) were quantified. The effect of specific siRNA (siMSH2, siMLH1, siMSH6 and siPSM2) transfection in HT29 on CD80 expression was quantified by flow cytometry. Non parametric statistics and survival analysis were used. Results: Patients with MMR-D showed a higher T-bet/CD4 ratio ( p = 0.02), a higher rate of CD80 expression and CD8 lymphocyte infiltration compared to those with no MMR-D. Moreover, in the MMR-D group, the Treg marker FoxP-3 was not expressed ( p = 0.05). MMR-D patients with stage I or II and T-bet expression had a significant better survival ( p = 0.009). Silencing of MSH2, MLH1 and MSH6, but not PSM2, significantly increased the rate of CD80+ HT29 cells ( p = 0.007, p = 0.023 and p = 0.015, respectively). Conclusions: CRC with MMR-D showed a higher CD80 expression, and CD8+ and Th1 T-cell infiltration. In vitro silencing of MSH2, MLH1 and MSH6 significantly increased CD80+ cell rate. These results suggest an enhanced immune surveillance mechanism in presence of MMR-D.

Objective. We studied circulating precursor cells (CPC) in type 2 diabetes mellitus (T2DM) with neuropathic foot lesions with or without critical limb ischemia and relationships between endothelial precursor cells (EPC) and peripheral neuropathy.Methods and Subjects. We measured peripheral blood CD34, CD133, and CD45 markers for CPC and KDR, CD31 markers for EPC by citofluorimetry and systemic neural nociceptor CGRP (calcitonin gene related protein) by ELISA in 8 healthy controls (C) and 62 T2DM patients: 14 with neuropathy (N), 20 with neuropathic foot lesions (N1), and 28 with neuroischemic recent revascularized (N2) foot lesions. Timing of lesions was: acute (until 6 weeks), healed, and not healed.Results. CD34+ and CD133+ were reduced in N, N1, and N2 versus C, and CD34+ were lower in N2 versus N1 (P=0.03). In N2 CD34+KDR+ remain elevated in healed versus chronic lesions and, in N1 CD133+31+ were elevated in acute lesions. CGRP was reduced in N2 and N1 versus C (P<0.04versus C26±2 pg/mL). CD34+KDR+ correlated in N2 with oximetry and negatively in N1 with CGRP.Conclusions. CD34+ CPC are reduced in diabetes with advanced complications and diabetic foot. CD34+KDR+ and CD31+133+ EPC differentiation could have a prognostic and therapeutic significance in the healing process of neuropathic and neuroischemic lesions.

Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterised by a very aggressive clinical course. Despite conventional treatment, usually intensive adriamycin-containing...

The O (6)-methylguanine-DNA-methyltransferase (MGMT) gene encodes for a DNA repairing enzyme of which silencing by promoter methylation is involved in brain tumorigenesis. MGMT promoter methylation represents a favorable prognostic factor and has been associated with a better response to alkylating agents in glioma and systemic lymphoma. Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal malignant lymphoma. The current standard of care, based on high-dose methotrexate chemotherapy, has improved prognosis but outcome remains poor for a majority of patients. Therapeutic progress in this field is conditioned by limited biological and molecular knowledge about the disease. Temozolomide has recently emerged as an alternative option for PCNSL treatment. We aimed to analyze the MGMT gene methylation status in a series of 24 PCNSLs, to investigate the relationship between methylation status of the gene and immunohistochemical expression of MGMT protein and to evaluate the possible prognostic significance of these biomarkers. Our results confirm that methylation of the MGMT gene and loss of MGMT protein are frequent events in these lymphomas (54 % of our cases) and suggest that they are gender and age related. MGMT methylation showed high correlation with loss of protein expression (concordance correlation coefficient = -0.49; Fisher exact test: p 0.01), different from what has been observed in other brain tumors. In the subgroup of ten patients who received high dose chemotherapy, the presence of methylated MGMT promoter (n = 4), seems to be associated with a prolonged overall survival (60 months in three of four patients). The prognostic significance of these molecular markers in PCNSL needs to be further studied in groups of patients treated in a homogeneous way.

Thymoma is the most common primary neoplasm of the anterior mediastinum. We describe the case of a 40-year-old man with asymptomatic thymoma involving the right atrium, and the diagnostic pathway.

Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumor of the skin that demonstrates a remarkable tendency to metastasize. However, only a few cases of MCC brain metastases have been reported in the literature. We here present a unique case of a pituitary metastasis of MCC in a 65-year-old patient with a history of pituitary adenoma. This case is particularly novel due to the fact that the primary site of the MCC is unknown.

The concept of bilineal acute leukemia is defined in the WHO classification, where, along with the undifferentiated acute leukemia and the biphenotypic acute leukemia, it is included in the group o...

Summary The family of small round-cell tumours (SRCTs) represents a heterogeneous group of malignancies featuring a primitive, undifferentiated round-cell morphology. SRCTs mostly occur in children, adolescents and young adults, and tend to involve the skeletal system or soft tissue. They constitute approximately 20% of solid tumours in children and, because of their significant morphological overlap, have become a paradigm for an integrated approach to diagnosis. The combination of both immunophenotypic and genetic analysis with classic morphology has proved useful not only on diagnostic grounds, but also in the context of prognostication. This review will focus on SRCTs primarily involving soft tissues and includes the Ewing's family of tumours, also known as Ewing's sarcoma/primitive neuroectodermal tumour, alveolar rhabdomyosarcoma, desmoplastic SRCT, poorly differentiated round-cell synovial sarcoma and mesenchymal chondrosarcoma.

The simultaneous appearance of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) has been rarely reported, with AML occurring more frequently as a secondary event in patients receiving cytotoxic drugs for a primary lymphoproliferative disorder. We describe a case of simultaneous CLL and AML documented by morphological and cytometric analysis in a previously untreated patient. In particular, on the basis of morphological and immunological features, the patient was diagnosed as being affected by CD34 + /CD13 + /CD33 + /HLA-DR + /CD7 + FAB-M2 AML, along with a B-CLL characterized by neoplastic cells expressing a VH3-53/D3-22/JH4 Ig, bearing, on average, 3.9% IgVH mutations without evidence of antigen-driven selection. To establish whether the two neoplastic cell populations shared some common molecular signature, we performed IgH gene rearrangement studies on CD34 + /CD19- and CD34-/CD19 + immunomagnetically sorted cell populations: only genomic DNA from the CD19 + /CD34- cell fraction revealed the presence of the IgH gene rearrangement. These results provide evidence that the rare concomitant association of CLL and AML likely arises from simultaneous expansion of two independent clones.

Over-expression of P53-related protein detected by immunohistochemistry (IHC) and absence of p21waf1— expression, the main downstream target following P53 activation, are useful surrogate markers in identifying diffuse large B-cell lymphoma (DLBCL) patients with mutated P53-gene. Following recent studies on gene expression, tissue micro-array technology has been shown to represent a reliable technique in discriminating DLBCL with germinal center B-cell like (GC), or post- germinal center (non-GC) origin. We analyzed 80 consecutive patients with de-novo DLBCL, homogeneously treated with cure-intent (CHOP-like regimens +/− Rituximab) in a single Institution, for expression of p53/p21waf1—, with regard to the expression of GC (CD10+, bcl-6+/mum-1−/CD138−), and post-germinal center (CD10−, mum-1+, CD138+) IHC markers. Cases with 50% or more p53-positive neoplastic cells were defined as p53+++. All patients were provided with complete clinical information. Median age of our patients was 50 years, AAS was III or IV in half of patients, IPI was high or int/high in 36%. Median follow-up for survivors was 77 months. A p53+++/p21waf1— phenotype (corresponding to loss of function of the P53-gene) was detected in 19 of 80 patients (23%), while a GC phenotype characterized 42 patients (52%). Patients with P53+++/p21waf1— phenotype were more frequently resistant to induction therapies (p Our results strongly point to the usefulness of a combined molecular and clinical approach for prognostic considerations in DLBCL, and should be validated in larger series.

BACKGROUND Genomic defects in DNA mismatch repair (MMR) genes (MSH2, MLH1, PSM2 or MSH6) characterize the hereditary non polyposis colon cancer (HNPCC). However most colorectal cancers (CRC) with high-frequency microsatellite instability are sporadic, wherein the MMR defect develops because of inactivation of the MLH1 gene by DNA methylation. Multiple retrospective studies, including a population-based study and a metaanalysis, have demonstrated that patients with MMR-deficient colon cancers have a more favourable stage-adjusted prognosis compared with patients whose tumors have intact MMR. Since the immune environment of CRC has been demonstrated to influence its prognosis, we aimed to investigate the interplay between MMR genes and the immune environment in CRC PATIENTS AND METHODS A group of 98 consecutive patients operated on for colorectal cancer was retrospectively analysed. Familial and medical history were retrieved to assess the presence of Bethesda criteria for HNPCC diagnosis. Immunohistochemistry for CD80, TLR4, MyD88, MSH2, MLH1, MSH6 and PSM2 was performed on tissue sections. Moreover, lamina propria mononuclear cells (LPMC), polymorphonuclear cells and eosoinophil tumour infiltration was quantified. Patients were stratified in three groups: no MMR genes defect, MMR gene defects alone and MMR genes defects and at least one positive Bethesda criteria. Non parametric statistics was used. RESULTS In the three groups no difference was observed in term of polymorphonuclear cells and eosinophil infiltration and in term of TLR4 and MyD88 expression. On the contrary, LPMC infiltration was significantly higher in patients who had a MMR gene defect alone compared to patients who had no MMR genes defect and to those with MMR gene defect and positive Bethesda criteria (p= 0.014). Similarly, a significantly higher frequency of patients with high CD80 expression was observed in patients who had a MMR genes defect alone compared to patients who had no MMR gene defect and to those with MMR genes defect and positive Bethesda criteria (p=0.048). CONCLUSION In patients with MMR defects and no Bethesda criteria for HNPCC antigen presenting cells function seems enhanced as shown by higher frequency of hiCD80+ patients and higher LPMC infiltration. This immune activation may play a role in the prognosis of these patients.