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Myeloid sarcoma (MS) is a localized extra-medullary tumor mass of immature myeloid cells, arising de novo or related to acute myeloid leukemia, of which it can be a forerunner, a coinciding or late event. Less commonly, MS represents an acute blastic transformation of myelodysplastic syndromes or myeloproliferative neoplasms. This rare condition commonly consists of a proliferation of more or less immature cells with a myeloid immunophenotype, very exceptional cases showing a megakaryoblastic or erythroid differentiation. The most common localization of MS is the skin, lymph node, soft tissues and bones, but CNS involvement is exceedingly rare, with no cases reported in the sellar region. We report a 54-year-old man, affected by myeloproliferative neoplasm, JAK2 V617F-positive of 13 years duration, who acutely presented with a third cranial nerve palsy; neuroradiology documented a space-occupying lesion at the level of the sellar, upper clival and right parasellar regions, that was sub-totally removed with a trans-sphenoidal approach. The histological examination documented a proliferation of large, blastic cells, frequently multinucleated; a diagnosis of MS with megakaryoblastic differentiation, arising in a background of chronic idiopathic myelofibrosis, was suggested by immunohistochemistry, owing to CD42b, CD45, CD61 and LAT (linker for activation of T cells) positivity. In addition, homozygous JAK2 V617F mutation was detected from the myeloid sarcoma specimen. A few weeks after surgery, an acute blastic leukemic transformation occurred and, despite chemotherapy, the patient died 2 months after surgery. To the best of our knowledge, this is the first MS case with megakaryoblastic differentiation arising within the CNS.

Objectives Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). Materials and methods We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. Results When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD ( P P P P =0.002), VEGFR2 ( P =0.013), and VEGFR3 ( P =0.041). No differences were observed in terms of PDGFRβ expression. Conclusions According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy.

The purpose of this study was to compare, within a randomized controlled trial, the efficacy of recombinant interferon-alpha in combination with ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic HCV hepatitis.Forty anti-HCV positive chronic hepatitis patients with ALT levels persistently greater than 3 times the upper normal level were randomized to receive either interferon-alpha (6 million units three times/wk for 6 months) plus ursodeoxycholic acid (10 mg/kg/day for 9 months) (n = 20) or interferon-alpha (6 million units three times/wk for 6 months) alone (n = 20). Disease activity was monitored monthly by ALT measurement until 18 months after interferon-alpha cessation. Serum HCV-RNA was measured at baseline and after 6, 9, and 24 months. Liver biopsies (basal and at the 9th month) were evaluated blindly and scored by Knodell's criteria.The probability of full or partial response during interferon-alpha treatment was similar in the two groups. The probability of biochemical relapse (i.e, any persistent return of ALT above normal) after 18-month of posttreatment follow-up was 75% in both the combination and the monotherapy group. Relapse, however, occurred significantly later in the combination than in the monotherapy group (6.6 +/- 5.4 [SD] months and 1.8 +/- 1.6 months after IFN-alpha cessation, respectively, p0.02). Severe biochemical relapse (i.e., a persistent ALT elevation greater than 3 times normal) occurred more frequently and earlier (p = 0.05) in patients treated with interferon-alpha (58.3%) than in those receiving the combination therapy (27.3%). The cumulative duration of normalized ALT periods during and after treatment was significantly greater (p = 0.005, chi 2) in patients treated with IFN-alpha + UDCA than with monotherapy (189/354 months vs 136/323 months. Lobular necrosis improved in both groups (p = 0.056 and p = 0.001, respectively), whereas portal inflammation improved (p = 0.009) only in the combination therapy group. Among the 30 patients who were viremic at entry, plasma HCV-RNA was no longer detectable after 6 months in four from the combination group and in five from the monotherapy group, yet all patients but one returned HCV-RNA positive 3 months after interferon-alpha cessation and were still viremic after 18 months. Cox's multiple regression identified the histological degree of posttreatment portal inflammation as the sole positive indicator of relapse.The combination of interferon-alpha and ursodeoxycholic acid prolongs the efficacy of interferon-alpha alone in chronic hepatitic C by delaying the probability of biochemical relapse and/or by reducing its severity, without affecting HCV viremia.

We report a unique case of primary myxoid chondrosarcoma in the posterior mediastinum. This lesion clinically mimicked a neurogenic tumor due to its location and dumbbell appearance. The histogenesis of this tumor is discussed and a skeletal origin from the thoracic vertebrae is suggested. It is concluded that myxoid chondrosarcoma has to be distinguished for the differential diagnosis among the long list of myxoid tumors arising in the posterior mediastinum.

The case of an 83 year-old male patient undergoing resection of a bulky thymoma situated in the anterior mediastinum is presented. A standard mid-line sternotomy approach was chosen and the left pleural space was widely opened in order to control the left edge of the tumor bulging in the left hemithorax. Macroscopic and histologic examination of the resected specimen evidenced a medullary thymoma without infiltration although tight adhesions between the tumor and the left brachiocephalic vein were present. Postoperative course was uneventful and the patient was discharged in good general condition nine days after surgery.

Although primary mediastinal (thymic) large B-cell lymphoma has been primarily studied, its precise phenotype, molecular characteristics, and histogenesis are still a matter of debate. The International Extranodal Lymphoma Study Group collected 137 such cases for extensive pathological review. Histologically, the lymphomatous growth was predominantly diffuse with fibrosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. On immunohistochemistry, the following phenotype was observed: CD45(+), CD20(+), CD79a(+), PAX5/BSAP(+), BOB.1(+), Oct-2(+), PU.1(+), Bcl-2(+), CD30(+), HLA-DR(+), MAL protein(+/-), Bcl-6(+/-), MUM1/IRF4(+/-), CD10(-/+), CD21(-), CD15(-), CD138(-), CD68(-), and CD3(-). Immunoglobulins were negative both at immunohistochemistry and in situ hybridization. Molecular analysis, performed in 45 cases, showed novel findings. More than half of the cases displayed BCL-6 gene mutations, which usually occurred along with functioning somatic IgV(H) gene mutations and Bcl-6 and/or MUM1/IRF4 expression. The present study supports the concept that a sizable fraction of cases of this lymphoma are from activated germinal center or postgerminal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective immunoglobulin production despite the expression of OCT-2, BOB.1, and PU.1 transcription factors and the lack of IgV(H) gene crippling mutations.

EphB2 and EphA2 control stemness and differentiation in the intestinal mucosa, but the way they cooperate with the complex mechanisms underlying tumor heterogeneity and how they affect the therapeutic outcome in colorectal cancer (CRC) patients, remain unclear. MicroRNA (miRNA) expression profiling along with pathway analysis provide comprehensive information on the dysregulation of multiple crucial pathways in CRC. Through a network-based approach founded on the characterization of progressive miRNAomes centered on EphA2/EphB2 signaling during tumor development in the AOM/DSS murine model, we found a miRNA-dependent orchestration of EphB2-specific stem-like properties in earlier phases of colorectal tumorigenesis and the EphA2-specific control of tumor progression in the latest CRC phases. Furthermore, two transcriptional signatures that are specifically dependent on the EphA2/EphB2 signaling pathways were identified, namely EphA2, miR-423-5p, CREB1, ADAMTS14, and EphB2, miR-31-5p, mir-31-3p, CRK, CXCL12, ARPC5, SRC. EphA2- and EphB2-related signatures were validated for their expression and clinical value in 1663 CRC patients. In multivariate analysis, both signatures were predictive of survival and tumor progression. The early dysregulation of miRs-31, as observed in the murine samples, was also confirmed on 49 human tissue samples including preneoplastic lesions and tumors. In light of these findings, miRs-31 emerged as novel potential drivers of CRC initiation. Our study evidenced a miRNA-dependent orchestration of EphB2 stem-related networks at the onset and EphA2-related cancer-progression networks in advanced stages of CRC evolution, suggesting new predictive biomarkers and potential therapeutic targets. Electronic supplementary material The online version of this article (10.1186/s12943-018-0912-z) contains supplementary material, which is available to authorized users.

Aim of this work is to provide a detailed comparison of clinical-pathologic features between well-differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status. We analyzed RASSF1A methylation by MSP and BRAF mutation by LCRT-PCR with LightMix® kit BRAF V600E in neoplastic thyroid tissues. Immunohistochemical evaluation of RASSF1A expression was also performed by standard automated LSAB-HRP technique. An overall higher degree of RASSF1A over-expression than normal thyroid parenchyma surrounding tumors (P