Pulmonary Adenocarcinoma with Enteric Differentiation without TTF-1 Expression Is a Very Rare Subtype with Limited Treatment Options and Poor Prognosis.

Introduction: Pulmonary adenocarcinoma with enteric differentiation (PAED) without thyroid transcription factor-1 (TTF-1) expression is an extremely rare variant of lung cancer. Due to its rarity, few clinicopathological and molecular studies have been performed on PAED, particularly in Caucasian patients. Therefore, it is necessary to obtain clinicopathological data of Caucasian PAED patients without TTF-1 expression, their systemic therapy options, and the efficacy of their systemic treatment.

Solitary Fibrous Tumours of the Orbit - Clinical Pathology, Therapy and Prognosis.

Background: Solitary fibrous tumours are rare. The aim of this study is to describe the clinical features, therapy and outcome of affected patients and to identify factors associated with recurrence.

Methods: Retrospective study of a cohort of 20 patients who underwent surgery for orbital solitary fibrous tumour at the University Department of Oral and Maxillofacial Surgery between 2002 and 2023.

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein.

A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.

Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation.

[Isolated limb perfusion for liposarcoma : Histopathological response and subgroup analysis after TNF melphalan-based ILP].

Background: Tumor necrosis factor alpha (TNF) and melphalan-based isolated limb perfusion (TM-ILP) is one of the most effective treatment modalities for unresectable soft tissue sarcoma (STS) of the extremities. Liposarcomas (LS) are a large and heterogeneous subgroup of STS with different biological behavior and prognoses. The aim of this study was to evaluate LS and the different subentities with respect to their responsiveness towards TM-ILP.

Recurrent mutations in NF-κB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas.

The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is still poorly understood. We analyzed 63 cases of such lymphomas for non-synonymous mutations in 24 candidate genes by amplicon sequencing. We validated frequent mutations in the NF-κB regulators MYD88, TNFAIP3 and TNIP1 in OAML, but also identified recurrent mutations in several additional components of the NF-κB pathway, including BCL10 and NFKBIA.

Intermediate microRNA expression profile in Graves' disease falls between that of normal thyroid tissue and papillary thyroid carcinoma.

Aims: Many studies have previously reported a higher prevalence of papillary thyroid carcinomas (PTC) in patients with Graves' disease (GD). MicroRNAs (miRNAs) are small, non-coding RNAs that are upregulated in PTC compared with benign thyroid tissue. The objective of the study was to examine the miRNA expression of selected miRNAs that are known to be upregulated in PTC in patients with GD.

Targeted massively parallel sequencing of angiosarcomas reveals frequent activation of the mitogen activated protein kinase pathway.

Angiosarcomas are rare malignant mesenchymal tumors of endothelial differentiation. The clinical behavior is usually aggressive and the prognosis for patients with advanced disease is poor with no effective therapies. The genetic bases of these tumors have been partially revealed in recent studies reporting genetic alterations such as amplifications of MYC (primarily in radiation-associated angiosarcomas), inactivating mutations in PTPRB and R707Q hotspot mutations of PLCG1.

TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature.

Background: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation.

Immunocytochemical analysis of glucose transporter protein-1 (GLUT-1) in typical, brain invasive, atypical and anaplastic meningioma.

Glucose transporter-1 (GLUT-1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT-1 in intracranial non-embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT-1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet-like growth, prominent nucleoli, small cell change and "spontaneous" necrosis.

Prognostic stratification of metastatic gastroenteropancreatic neuroendocrine neoplasms by 18F-FDG PET: feasibility of a metabolic grading system.

Unlabelled: The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of (18)F-FDG PET in inoperable multifocal disease.

Drug dosage in isolated limb perfusion: evaluation of a limb volume model for extremity volume calculation.

Background: Exact drug dosing in isolated limb perfusion (ILP) and infusion (ILI) is essential. We developed and evaluated a model for calculating the volume of extremities and compared this model with body weight- and height-dependent parameters.

Methods: The extremity was modeled by a row of coupled truncated cones.

Phase I study of panobinostat and imatinib in patients with treatment-refractory metastatic gastrointestinal stromal tumors.

Background: Panobinostat, a pan-deacetylase inhibitor, overcomes imatinib resistance in preclinical models of gastrointestinal stromal tumours (GIST). Here we determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of panobinostat in combination with imatinib (IM) for treatment of patients with refractory GIST.

Methods: Following a 7-day run-in phase of IM (400 mg per day), escalating doses of panobinostat were added following a '3 plus 3' design.

Vascular and nerval damage after intraoperative radiation therapy of the liver hilum in a large animal model.

It has been demonstrated that intraoperative radiotherapy is a therapeutic option for patients suffering from perihilar cholangiocarcinoma. Aim of our study was to investigate vascular and nerve damages after irradiation of the liver hilum in a pig model. Twenty-four pigs underwent central bile duct resection followed by biliodigestive anastomosis.

Adiponectin attenuates osteolysis in aseptic loosening of total hip replacements.

Joint replacements have a longer durability in patients with high serum levels of adiponectin (APN) than in patients with low levels. We aimed to characterize the unknown pathophysiological effects of APN on wear particle-induced inflammation, apoptosis and osteolysis. Immunohistochemistry was performed to detect APN, its receptors and apoptosis in patients with and without aseptic loosening.

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas.

Background: Hyperthermic isolated limb perfusion with tumor necrosis factor-α and melphalan (TM-HILP) has been successfully used to treat limb soft tissue sarcomas (STSs) with high response rates. The data on the effectiveness of HILP-TM for the treatment of STSs are mainly based on various STS types. The aim of this study was to investigate the responses of synovial sarcomas (SS) to TM-HILP.

TERT promoter mutations in ocular melanoma distinguish between conjunctival and uveal tumours.

Background: Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations.

Methods: The TERT promoter region was analysed by Sanger sequencing in 47 uveal (ciliary body or choroidal) melanomas and 38 conjunctival melanomas.

Trabectedin in metastatic soft tissue sarcomas: Role of pretreatment and age.

Trabectedin has mostly been studied in metastatic leiomyosarcoma and liposarcomas. Only limited data are available in other sarcoma subtypes, heavily pretreated and elderly patients. We retrospectively analyzed 101 consecutive sarcoma patients treated with trabectedin at our center.

Conjunctival melanomas harbor BRAF and NRAS mutations and copy number changes similar to cutaneous and mucosal melanomas.

Purpose: Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment options are limited and the prognosis is poor.

Chemically induced rat Schwann cell neoplasia as a model for early-stage human peripheral nerve sheath tumors: phenotypic characteristics and dysregulated gene expression.

Most malignant human tumors display a high degree of intratumoral heterogeneity at the time of diagnosis that contributes to treatment failure. This also applies to malignant peripheral nerve sheath tumors (MPNSTs) and aggressive soft tissue sarcomas that arise sporadically or in the context of neurofibromatosis type 1. On average, MPNSTs measure 10 cm in diameter at diagnosis.

DOG1 regulates growth and IGFBP5 in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor α(PDGFRA), which can be therapeutically targeted by tyrosine kinase inhibitors (TKI) such as imatinib. Despite long-lasting responses, most patients eventually progress after TKI therapy. The calcium-dependent chloride channel DOG1 (ANO1/TMEM16A), which is strongly and specifically expressed in GIST, is used as a diagnostic marker to differentiate GIST from other sarcomas.

[Schwannoma of the femoral nerve: a rare differential diagnosis of leg pain].

Background: Schwannomas (neurinomas) are among the most frequent peripheral nerve tumors. Nevertheless, these are seldom located in the lower extremities in association with the femoral nerve.

Clinical Presentation: In this case, the occurrence of a schwannoma adjacent to the femoral nerve is described in a patient presenting with nonspecific pain in the thigh accompanied by a palpable mass.