Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary haemangiomatosis (PCH) are rare disorders, with the estimated prevalence of less than 1 case per million inhabitants. The vascular ...pathology in PVOD/PCH involves pre-septal and septal veins, alveolar capillaries and small pulmonary arteries. According to the ERS/ESC classification of pulmonary hypertension (PH) from 2015, PVOD/PCH have been included in the subgroup 1' of pulmonary arterial hypertension (PAH). Recent data indicate, however, the possibility of PVOD/PCH pathology in the patients diagnosed in the group 1. The problem may concern PAH associated with scleroderma, drug- induced PAH, PAH due to HIV infection and up to 10% of patients with idiopathic PAH (IPAH). Recently, bi-allelic EIF2AK4 mutations were found in the cases with heritable form of PVOD/PCH and in about 9% of sporadic cases. Moreover, an association between occupational exposure to organic solvents and PVOD/PCH was proved. The present review is an attempt to summarise the current data on pathogenesis, risk factors, clinical features and diagnostic algorithm for PVOD/PCH.
Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic ...variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.
Primary mediastinal large B-cell lymphoma (PMBL) cells depend on the constitutive activity of NF-κB and STAT transcription factors, which drive expression of multiple molecules essential for their ...survival. In a molecularly related B-cell malignant tumor (classic Hodgkin lymphoma), tumor Reed-Sternberg cells overexpress oncogenic (proviral integration site for Moloney murine leukemia virus (PIM) 1, 2, and 3 kinases in a NF-κB– and STAT-dependent manner and PIMs enhance survival and expression of immunomodulatory molecules. Given the multiple overlapping characteristics of Reed-Sternberg and PMBL cells, we hypothesized that PIM kinases may be overexpressed in PMBL and involved in PMBL pathogenesis. The expression of PIM kinases in PMBL diagnostic biopsy specimens was assessed and their role in survival and immune escape of the tumor cells was determined. PIMs were abundantly expressed in primary tumors and PMBL cell lines. Inhibition of PIM kinases was toxic to PMBL cells, attenuated protein translation, and down-regulated NF-κB– and STAT-dependent transcription of prosurvival factors BCL2A1, BCL2L1, and FCER2. Furthermore, PIM inhibition decreased expression of molecules engaged in shaping the immunosuppressive microenvironment, including programmed death ligand 1/2 and chemokine (C-C motif) ligand 17. Taken together, our data indicate that PIMs support PMBL cell survival and immune escape and identify PIMs as promising therapeutic targets for PMBL.
We have analyzed mtDNA variation in various cancer samples, comparing them with normal tissue controls, and identified mutations and polymorphisms, both known and novel, in mitochondrial tRNA, rRNA ...and protein genes. Most remarkably, in a colon cancer sample we have found the A3243G mutation in the homoplasmic state. This mutation is known to cause severe mitochondrial dysfunction and, until now, has not been found in cancer cells, nor in the homoplasmic state in living subjects. The mutation was absent from normal tissue, suggesting that mtDNA mutation and resulting respiratory deficiency played a role in carcinogenesis.
Kaposiform Lymphangiomatosis with Human Papillomavirus Infection Radzikowska, Elżbieta; Błasińska-Przerwa, Katarzyna; Szołkowska, Małgorzata ...
American journal of respiratory and critical care medicine,
2017-Jun-15, 2017-06-15, 20170615, Letnik:
195, Številka:
12
Journal Article
Recenzirano
Histological examination of lung and mediastinal samples obtained by thoracoscopy showed irregular, thin-walled vascular spaces covered by spindle-shaped lymphatic endothelial cells, focally in ...clusters (Figure 2A). KLA is characterized by progressive hemorrhagic effusions in the body cavities, hemoptysis, anemia, thrombocytopenia, elevated D-dimer levels, specific magnetic resonance imaging findings, and the histological presence of dilated lymphatic vessels with clusters of spindle cells. Author Contributions: E.R., study design, data collection, manuscript preparation, and final approval; M.S., histological...
Common and rare carcinomas of the thymus Roden, Anja C.; Szolkowska, Malgorzata
Virchows Archiv : an international journal of pathology,
2021/1, Letnik:
478, Številka:
1
Journal Article
Recenzirano
Thymic carcinoma encompasses a diverse group of rare tumors that occur almost exclusively in the prevascular (anterior) mediastinum. Thymic carcinomas have a worse outcome than thymomas with a median ...time to death of under 3 years. These tumors lack the typical lobulation of thymomas, exhibit commonly more cytologic atypia, are associated with a desmoplastic stromal reaction, and lack thymocytes, features that distinguish them from thymomas. The most common thymic carcinoma is squamous cell carcinoma; other subtypes include mucoepidermoid carcinoma, NUT carcinoma, and adenocarcinoma, among others. Largely due to multi-institutional and global efforts and meta-analysis of case reports and series, some of the thymic carcinoma subtypes have been studied in more detail and molecular studies have also been performed. Morphology and immunophenotype for the vast majority of thymic carcinoma subtypes are similar to their counterparts in other organs. Therefore, the distinction between thymic carcinoma and metastatic disease, which is relatively common in the prevascular mediastinum, can be challenging and in general requires clinical and radiologic correlation. Although surgical resection is the treatment of choice, only 46 to 68% of patients with thymic carcinoma can undergo resection as many other tumors present at high stage with infiltration into vital neighboring organs. These patients are usually treated with chemotherapy and/or radiation. The search for better biomarkers for prognosis and treatment of thymic carcinomas is important for improved management of these patients and possible targeted therapy.
Background
Thymic epithelial tumors constitute a morphologically and clinically diverse group of rare neoplasm of the anterior mediastinum.
Methods
Here, we present an analysis of 188 patients ...diagnosed with primary thymic tumors between 1995 and 2015. The prognostic value of selected clinical and morphological factors was assessed in relation to overall survival and recurrence‐free survival.
Results
The risk of recurrence increased significantly in thymic carcinoma diagnosis (P = 0.0036), co‐occurrence of other diseases, and weight loss (P = 0.0012 and 0.0348, respectively). Multivariate analysis showed that the most important independent risk factor for disease recurrence was clinical stage IV (P = 0.0036). A total of 63 patients (33.5%) died. In the univariate analysis, the following factors were considered as independent prognostic factors for overall survival: clinical stage (P < 0.0001), histological type (P < 0.0001), lymph node involvement (P < 0.001), WHO performance status 2 (P < 0.0001), anemia (Hb <9.5 g/dL; P = 0.0002), leucocytosis (>12.5 G/L; P = 0.0011), LDH level (>185 U/L; P < 0.0001), concomitant diseases (P = 0.0012) and weight loss (P < 0.0001).The strongest independent risk factor for death was stage IV disease (P < 0.001).
Conclusions
The results confirmed a fairly good prognosis for patients with thymic epithelial tumors. Clinical stage was the most important prognostic factor, but, some additional clinical factors may also have prognostic value.
We present an analysis of 188 patients diagnosed with primary thymic tumours. The prognostic value of selected clinical and morphological factors was assessed in relation to survival. Multivariate analysis showed that the most important independent risk factor was CS IV. The risk of recurrence increased significantly in thymic carcinoma, comorbidities occurrence and weight loss. Some additional clinical factors including LDH elevation, leucocytosis, anemia may have prognostic value.
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