GABAA receptor and anti-titin antibody encephalitis in a patient with thymoma.

Autoimmune encephalitis (AE) associated to antibodies against GABA A R is a rare form of encephalitis. On the other hand, thymoma has been linked to antibodies against both muscular and neuronal epitopes, even if concurrent positivity for more than one antibody is exceptional, and their contribution to the clinical course and treatment decision is unclear. We report a case of a 73-year-old male with AE associated with thymoma secreting both anti-GABAaR and anti-titin antibodies.

Tracing the mobility of a Late Epigravettian (~ 13 ka) male infant from Grotte di Pradis (Northeastern Italian Prealps) at high-temporal resolution.

We present the results of a multi-disciplinary investigation on a deciduous human tooth (Pradis 1), recently recovered from the Epigravettian layers of the Grotte di Pradis archaeological site (Northeastern Italian Prealps). Pradis 1 is an exfoliated deciduous molar (Rdm), lost during life by an 11-12-year-old child. A direct radiocarbon date provided an age of 13,088-12,897 cal BP (95% probability, IntCal20).

Experimental and archaeological data for the identification of projectile impact marks on small-sized mammals.

The role of small game in prehistoric hunter-gatherer economy is a highly debated topic. Despite the general assumption that this practice was uneconomic, several studies have underlined the relevance of the circumstance of capture - in terms of hunting strategies and technology - in the evaluation of the actual role of small mammals in human foraging efficiency. Since very few studies have focused on the recognition of bone hunting lesions, in a previous work we explored the potential of 3D microscopy in distinguishing projectile impact marks from other taphonomic marks, developing a widely-applicable diagnostic framework based on experimental data and focused on Late Epigravettian projectiles.

Mediastinal Rosai-Dorfman Disease With Widespread Lesions: When Surgical Biopsy Is Needed.

Rosai-Dorfman disease (RDD) is a rare benign disorder of the histiocytes, affecting lymph nodes in its classic form. Extranodal RDD is considered the uncommon subtype and potentially impairs all tissues and intrathoracic organs. In our report, a F-fluorodeoxyglucose positron emission tomography scan of a mediastinal mass infiltrating the lungs and of widespread lesions suggested the presence of a metastatic disease.

The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification.

In the last few years different new pulmonary neoplastic lesions have been recognised and some of them, namely NUT carcinoma, PEComatous tumors, pneumocytic adenomyoepithelioma, pulmonary myxoid sarcoma, myoepithelial tumors/carcinomas entered in the last 2015-WHO classification of lung tumors. In addition angiomatoid fibrous histiocytoma and ciliated muconodular papillary tumor have been morphologically and genetically characterized albeit not yet included in the 2015-WHO classification. In the present paper we summarised the clinical, morphological, immunohistochemical and molecular features of these new entities.

The role of macrophages in interstitial lung diseases: Number 3 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

The finding of collections of macrophages/histiocytes in lung biopsy and bronchoalveolar lavage is relatively common in routine practice. This morphological feature in itself is pathological, but the exact clinical significance and underlying disease should be evaluated together with clinical data, functional respiratory and laboratory tests and imaging studies.Morphological characteristics of macrophages and their distribution along the different pulmonary structures should be examined carefully by pathologists.

Overexpression of Hypoxia-Inducible Factor-1α in Primary Graft Dysfunction Developing in an Orthotopic Lung Transplantation Rat Model.

Background: Primary graft dysfunction (PGD) is the major cause of early morbidity and mortality after transplantation. A high rate of PGD is a frequent complication in orthotopic lung transplantation (OLT) models, which are currently used to investigate acute and chronic rejection pathways. Hypoxia-inducible factor (HIF)-1α is a heterodimeric αβ transcription factor that mediates tissue response to hypoxia.

Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift.

We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up.

Idiopathic pulmonary fibrosis: Are any of the morphological-molecular markers useful in clinical management?

Idiopathic pulmonary fibrosis (IPF), the most common form of chronic interstitial lung disease, is a severe progressive fibrotic disorder of unknown aetiology. The disease has a heterogeneous clinical course, with frequent poor prognosis, similar to malignant disease. Correctly diagnosing IPF has become particularly important in view of the availability of more precise therapeutic indications, thus avoiding steroid treatment and allowing new approaches with novel drugs.

Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare.

Higher Risk of Acute Cellular Rejection in Lung Transplant Recipients with Cystic Fibrosis.

BACKGROUND Acute cellular rejection (ACR) affects up to 40% of recipients within the first year after lung transplant (LTx). The aim of this study was to determine the frequency of ACR and associated major risk factors in cystic fibrosis (CF) recipients. Bronchiolitis obliterans syndrome (BOS) and 1-year/long-term survival were also evaluated.

Conflicting or complementary role of computed tomography (CT) and positron emission tomography (PET)/CT in the assessment of thymic cancer and thymoma: our experience and literature review.

Background: To evaluate the role of computed tomography (CT) and positron emission tomography (PET)/CT in patients with thymic cancer and thymoma at initial staging.

Methods: We retrospectively reviewed CT and PET/CT scans of 26 patients with a thymic cancer (n = 9) or thymoma (n = 17). Chest CT findings documented were qualitative and quantitative.

A 72-Year-Old Woman With Previous Pulmonary Metastasis and New Peripheral Nodule.

A 72-year-old female nonsmoker was admitted to our Thoracic Surgery Unit in 2013 because of a lesion detected on chest CT scan during oncologic follow-up. Her medical history was significant for the development of a single pulmonary metastasis discovered 1 year after sigmoidectomy for colic adenocarcinoma. At that time, the patient was treated with six cycles of neoadjuvant chemotherapy followed by left lower lobectomy.

COPD-related adenocarcinoma presents low aggressiveness morphological and molecular features compared to smoker tumours.

Objectives: Adenocarcinoma comprises a group of diseases with heterogeneous clinical and molecular characteristics. COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients. Our aim was to study COPD-associated adenocarcinoma phenotypes mainly focusing on morphological and molecular aspects, in comparison to smoke-related cancer without COPD.

Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma.

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo.

Detecting human presence at the border of the Northeastern Italian Pre-Alps. 14C dating at Rio Secco cave as expression of the first Gravettian and the late mousterian in the Northern Adriatic Region.

In the northern Adriatic regions, which include the Venetian region and the Dalmatian coast, late Neanderthal settlements are recorded in few sites and even more ephemeral are remains of the Mid-Upper Palaeolithic occupations. A contribution to reconstruct the human presence during this time range has been produced from a recently investigated cave, Rio Secco, located in the northern Adriatic region at the foot of the Carnic Pre-Alps. Chronometric data make Rio Secco a key site in the context of recording occupation by late Neanderthals and regarding the diffusion of the Mid-Upper Palaeolithic culture in a particular district at the border of the alpine region.

Necrotizing sarcoid granulomatosis with an uncommon manifestation: clinicopathological features and review of literature.

We report a rare case of an incidental diagnosis of necrotizing sarcoid granulomatosis (NSG) in a 60-y-old non-smoking male. The patient was admitted to the hospital for sudden back pain. Chest x-ray revealed areas of parenchymal consolidation and high-resolution computed tomography demonstrated a pulmonary nodular pattern with no lymph node enlargement.

The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase.

We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions.

Localized pleuropulmonary crystal-storing histiocytosis: 5 cases of a rare histiocytic disorder with variable clinicoradiologic features.

Crystal-storing histiocytosis (CSH) localized to the thoracic region is a rare occurrence, often secondary to lymphoproliferative or plasma cell diseases. About 10 case reports have been previously published, and 3 of these have no relationship with clonal hematologic disorders. We collected here the first series of 5 consecutive cases of CSH involving lungs (4 cases) and pleura (1 case).

Herpes virus infection is associated with vascular remodeling and pulmonary hypertension in idiopathic pulmonary fibrosis.

Background: Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown.

Serpin B4 isoform overexpression is associated with aberrant epithelial proliferation and lung cancer in idiopathic pulmonary fibrosis.

Aims: The aim of the study was to evaluate the role of Serpin B3/B4 in advanced idiopathic pulmonary fibrosis (IPF) patients, mainly focusing on epithelial proliferation.

Methods: Lungs from 48 IPF patients (including cases with cancer or high-grade epithelial dysplasia) were studied and compared with other diffuse parenchymal diseases and normal lungs. Immunohistochemistry for Serpin B3/B4 and Ki-67 was quantified in all cases, distinguishing stained metaplastic cells.

Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

Background: To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT.

Materials And Methods: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features.

Pulmonary eosinophilic infiltrates.

Pulmonary eosinophilic infiltrates include an heterogeneous group of disorders characterized by the presence of eosinophils in the lungs as detected by bronchoalveolar lavage or tissue biopsy, with or without blood eosinophilia. The disease can be idiopathic (simple pulmonary eosinophilia, acute and chronic eosinophilic pneumonia, hypereosinophilic syndrome), secondary (to drugs, parasites, fungal and mycobacterial infection, irradiation, toxic products) or associated with diffuse lung diseases (connective tissue diseases and some neoplasms). Pathologists faced with eosinophils in the lungs (either on cytology or biopsy) should keep in mind several possibilities, although a diagnosis of certainty is rarely based on morphology alone.