ABSTRACT
BACKGROUND: Extranodal lymphomas occurring in the head and neck region account for 12-15% of all malignant tumors of this locality. Classical Hodgkin lymphoma (cHL) is a rare subtype, representing around 1% of all lymphomas in Waldeyer's ring. Cases diagnosed in the Reference Centre for Lymph Node Pathology at the Pathological Institute of the University of Würzburg were further analyzed in this study. MATERIALS AND METHODS: Histological subtype and EBV association of 21 cases were reviewed in conjunction with clinical data. RESULTS: Data of 12 male and 9 female patients with an average age of 51 years (median 45; 35-72) were reviewed. All samples were taken from the lymphatic tissue of the Waldeyer's ring (nasopharynx nâ¯= 15, palatine tonsils nâ¯= 5, lingual tonsils nâ¯= 1). The most common symptoms leading to a consultation with an otorhinolaryngologist were otalgia, swelling, or impaired nasal breathing. Only four patients showed typical Bsymptoms. In 6 cases (29%), an isolated extranodal manifestation was found, 15 patients (71%) showed simultaneous infiltration of cervical lymph nodes during staging, and 6 cases (29%) were EBV positive. CONCLUSION: An exclusively extranodal manifestation of cHL in Waldeyer's ring is rare, whereas infiltration of extranodal tissue in the case of a primary manifestation of lymphoma in cervical nodes can occur more frequently and may often remain undiagnosed. Therefore, a specialized ENT consultation could be a reasonable complementary module in tumor staging to determine the correct tumor extent.
Subject(s)
Head and Neck Neoplasms , Hodgkin Disease , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Hodgkin Disease/diagnosis , Hodgkin Disease/pathology , Humans , Lymph Nodes , Male , Middle Aged , Neck , Neoplasm StagingABSTRACT
BACKGROUND: A collaboration between a hospital in Tanzania and a German institute for pathology was initiated in 2007 with the aim of establishing a working telepathological connection using the internet-based platform iPath to transmit static histological images. OBJECTIVES: This study aimed to describe the diagnostic spectrum evaluated in the course of an aid project in a developing country in Africa. MATERIAL AND METHODS: A total of 5230 diagnoses were analyzed, including cases that could only be definitively concluded after a second analysis of the paraffin-embedded material in Germany. The most frequent diagnoses in the five largest diagnostic groups from 17 different anatomical locations were surveyed. In addition, cases sampled from children/young adults and rare diagnoses were assessed separately. RESULTS: Altogether we diagnosed 2934 (56.1%) benign and 2134 (40.8%) malignant diseases. The number of cases sent to Germany for a second opinion was 734 (14%). The five most common anatomical locations were the uterine cervix (nâ¯= 1211), the prostate (nâ¯= 728), skin (nâ¯= 626), breast (nâ¯= 524), and lymph nodes (nâ¯= 340). Children comprised 504 cases (9.6%). Typical tropical diseases were only rarely seen in the whole collective of cases. CONCLUSIONS: By means of telepathology histopathological diagnoses can be supplied in a short period of time. Difficulties occurred mainly due to the unstable staff situation on site and because the quality of sampled biopsy material was not always sufficient for further investigations. Furthermore, it became clear in the course of this aid project that a predominance of standard diagnostic findings routinely seen in the pathology of tumors and infections can be anticipated rather than exotic diseases.
Subject(s)
Telepathology , Child , Germany , Humans , Male , Prostate , Referral and Consultation , TanzaniaABSTRACT
Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) gamma-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA). While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.
Subject(s)
ADP Ribose Transferases/administration & dosage , Autoantibodies/immunology , Bacterial Toxins/administration & dosage , Exotoxins/administration & dosage , Immunotoxins/administration & dosage , Receptors, Nicotinic/immunology , Recombinant Fusion Proteins/administration & dosage , Rhabdomyosarcoma/drug therapy , Single-Chain Antibodies/immunology , Virulence Factors/administration & dosage , ADP Ribose Transferases/genetics , Animals , Autoantibodies/administration & dosage , Autoantibodies/genetics , Bacterial Toxins/genetics , Cell Growth Processes/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Delivery Systems/methods , Exotoxins/genetics , Female , Flow Cytometry , Humans , Immunotoxins/genetics , Immunotoxins/immunology , Mice , Mice, SCID , Receptors, Nicotinic/administration & dosage , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Rhabdomyosarcoma/immunology , Rhabdomyosarcoma/pathology , Single-Chain Antibodies/administration & dosage , Single-Chain Antibodies/genetics , Virulence Factors/genetics , Xenograft Model Antitumor Assays , Pseudomonas aeruginosa Exotoxin AABSTRACT
Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) inhibits T-cell activation and interleukin-2 (IL-2) production. The PTPN22(gain-of-function)+1858T(+) genotypes predispose to multiple autoimmune diseases, including early-onset (non-thymomatous) myasthenia gravis (MG). The disease association and the requirement of IL-2/IL-2 receptor signaling for intrathymic, negative T-cell selection have suggested that these genotypes may weaken T-cell receptor (TCR) signaling and impair the deletion of autoreactive T cells. Evidence for this hypothesis is missing. Thymoma-associated MG, which depends on intratumorous generation and export of mature autoreactive CD4(+) T cells, is a model of autoimmunity because of central tolerance failure. Here, we analyzed the PTPN22 +1858C/T single nucleotide polymorphism in 426 German Caucasian individuals, including 125 thymoma patients (79 with MG), and investigated intratumorous IL-2 expression levels. Unlike two previous studies on French and Swedish patients, we found strong association of PTPN22 +1858T(+) genotypes not only with early-onset MG (P=0.00034) but also with thymoma-associated MG (P=0.0028). IL-2 expression in thymomas with PTPN22 +1858T(+) genotypes (P=0.028) was lower, implying weaker TCR signaling. We conclude that the PTPN22(gain-of-function) variant biases towards MG in a subgroup of thymoma patients possibly by impeding central tolerance induction.
Subject(s)
Interleukin-2/immunology , Myasthenia Gravis/immunology , Polymorphism, Single Nucleotide , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/immunology , Thymoma/immunology , Thymus Neoplasms/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD/genetics , Antigens, CD/immunology , CTLA-4 Antigen , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Myasthenia Gravis/complications , Myasthenia Gravis/genetics , Thymoma/complications , Thymoma/genetics , Thymus Neoplasms/complications , Thymus Neoplasms/genetics , White People/genetics , Young AdultABSTRACT
BACKGROUND: T-cell lymphomas (T-NHL) generally carry a poor prognosis. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are increasingly used to treat younger patients. DESIGN AND METHODS: We treated patients <61 years with high-risk aggressive lymphoma with four to six courses of dose-escalated CHOP plus etoposide (MegaCHOEP) necessitating repeated ASCT. Outcomes of patients with mature T-NHL (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma) and aggressive B-NHL were compared using multivariate Cox regression analysis. RESULTS: Compared with 84.4% of B-NHL patients, 66.7% of T-NHL patients were able to receive all treatments; the rates of progressive disease were 27.3% in T-NHL and 16.3% in B-NHL patients. At 3 years, event-free survival (EFS) and overall survival were significantly worse for T-NHL [25.9% confidence interval (CI) 10.4% to 41.4% and 44.5% CI 26.5% to 62.5%) than for B-NHL patients (60.1% CI 52.1% to 68.1%; P < 0.001 and 63.4% CI 55.4% to 71.4%; P = 0.016). In multivariate analysis, T-NHL was a strongly significant adverse risk factor for EFS (relative risk 2.2, P = 0.001). CONCLUSIONS: MegaCHOEP for T-NHL patients was no better than other high-dose regimens and was unable to address the major problems of HDT/ASCT: neither early progressions nor early relapses were reduced. This study sheds some doubt on expectations that HDT/ASCT will significantly improve outcomes for patients with T-NHL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, T-Cell/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/therapeutic use , Prognosis , Vincristine/administration & dosage , Vincristine/therapeutic useSubject(s)
Carcinoma, Renal Cell/genetics , Genes, ras/genetics , Kidney Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Antibodies, Monoclonal/therapeutic use , Biopsy, Needle , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Cohort Studies , DNA Mutational Analysis , ErbB Receptors/therapeutic use , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Genes, ras/drug effects , Humans , Immunohistochemistry , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Male , Panitumumab , Polymerase Chain Reaction , Proto-Oncogene Proteins B-raf/drug effects , Risk Assessment , Sensitivity and SpecificityABSTRACT
OBJECTIVES: Adenomas/carcinoid tumors of the middle ear are very rare tumors of young to middle aged patients. The terms adenoma and carcinoid tumor of the middle ear can be used as synonyms, with the WHO favouring the term middle ear adenoma (MEA). These tumors usually present with unspecific clinical symptoms and a long case history. They are classified as benign tumors with only very few reported cases of regional metastasis after years of disease. According to recent literature, the clinical course is usually uncomplicated with complete surgical excision being adequate therapy. METHODS AND PATIENTS: This study describes the clinical course and the diagnostic challenges in four cases of this rare tumor entity. RESULTS: The selected patients (2 males, 2 females, 25-38 years old) showed very similar clinical findings with decreased hearing acuity, tinnitus and sometimes pain. After the primary surgical excision up to 10 further operations were necessary, this being in contrast to the usual clinical course as described in the literature. In two cases a tumor recurrence was documented with one case recurring six times. In this case adjuvant radiotherapy (70 Gy) was performed. The histological differential diagnosis can also be problematic; in one case with a highly atypical morphology it was impossible to arrive at a definite diagnosis during the analysis of a frozen section. CONCLUSION: Adenomas of the middle ear can have a much more complicated clinical course than is suggested by the recent literature. The presented cases in this study and the analysis of previously published cases shows that the typical progression described by the current WHO-classification with unproblematic surgical management of the tumor and an uncomplicated further clinical course does not always correspond to reality. The main reason for this is the difficulty in obtaining a complete surgical excision. Therefore, a well-planned and comprehensive surgical management with a high frequency of follow-up examinations should be chosen. In complicated individual cases adjuvant radiotherapy can be helpful.
Subject(s)
Adenoma/diagnosis , Carcinoid Tumor/diagnosis , Ear Neoplasms/diagnosis , Ear, Middle , Adenoma/pathology , Adenoma/surgery , Adult , Carcinoid Tumor/pathology , Carcinoid Tumor/surgery , Cholesteatoma, Middle Ear/diagnosis , Cholesteatoma, Middle Ear/pathology , Cholesteatoma, Middle Ear/surgery , Diagnosis, Differential , Ear Neoplasms/pathology , Ear Neoplasms/surgery , Ear, Middle/surgery , Female , Humans , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local/surgery , Otoscopy , Reoperation , Tomography, X-Ray ComputedABSTRACT
The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array-comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2-6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array-CGH identified NF-kappaB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2-22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42=19%), salivary gland (2/24=8%), thyroid (1/9=11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (p<0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p=0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p=0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation-negative MALT lymphoma.
Subject(s)
Intracellular Signaling Peptides and Proteins/genetics , Lymphoma, B-Cell, Marginal Zone/genetics , Nuclear Proteins/genetics , Orbital Neoplasms/genetics , Salivary Gland Neoplasms/genetics , Tumor Necrosis Factor-alpha/genetics , Aged , Aged, 80 and over , Chromosome Aberrations , Chromosomes, Human, Pair 6 , Comparative Genomic Hybridization/methods , DNA-Binding Proteins , Female , Gene Expression Profiling/methods , Humans , In Situ Hybridization, Fluorescence , Interphase , Liver Neoplasms/genetics , Lung Neoplasms/genetics , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Sequence Deletion , Skin Neoplasms/genetics , Stomach Neoplasms/genetics , Thyroid Neoplasms/genetics , Translocation, Genetic , Tumor Necrosis Factor alpha-Induced Protein 3ABSTRACT
Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRAS(wt) genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.
ABSTRACT
BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.
Subject(s)
Gene Expression Profiling , Gene Expression , Lymphoma, Large B-Cell, Diffuse/genetics , Stromal Cells/metabolism , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Disease Progression , Doxorubicin , Extracellular Matrix/genetics , Gene Expression Regulation, Neoplastic , Genes, MHC Class II , Germinal Center , Humans , Immunologic Factors/administration & dosage , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Middle Aged , Multivariate Analysis , Neovascularization, Pathologic/genetics , Prednisone , Prognosis , Rituximab , Stromal Cells/pathology , VincristineABSTRACT
For several anatomical localisations of extranodal marginal zone B-cell lymphoma of MALT type (eMZBCL), an association with chronic inflammation caused by microbiological agents (e.g. Helicobacter pylori in the stomach) has been described. In the lung, a link between lymphomagenesis and a defined causative organism is still missing. A comprehensive diversity survey using 16S-rDNA library construction followed by restriction fragment length polymorphism (RFLP) analysis, sequencing, and phylogenetic tree construction was employed for nine cases each of BALT lymphoma and control lung tissues (normal foetal lung, pneumonitis, carcinoid). This highly sensitive method, hereafter termed SHARP screening allowed for identification of the entire bacterial population in the tissue in a cultivation-independent manner. It was noteworthy that in eight of the nine cases of BALT lymphoma, bacteria of the Alcaligenaceae family (Alcaligenes, Achromobacter, AKIW733), were detected, whereas none of the control cases showed the presence of these clades. 16S-rDNA library construction in combination with RFLP screening and phylogenetic analyses, hereafter described as SHARP screening, is a cultivation-independent tool for analysing the microbial environment in chronic inflammation processes giving rise to extranodal marginal zone B-cell lymphomas of MALT-type. Betaproteobacteria of the Alcaligenaceae family may be affiliated with and possibly involved in the lymphomagenesis of BALT lymphomas.
Subject(s)
Alcaligenes/genetics , Bacteria/genetics , Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/microbiology , Lung Neoplasms/microbiology , Lymphoma, B-Cell, Marginal Zone/microbiology , RNA, Ribosomal, 16S/genetics , Adult , Aged , Alcaligenes/classification , Alleles , Bacteria/classification , Bacterial Infections/pathology , Base Sequence , DNA, Ribosomal , Female , Gene Library , Gram-Negative Bacterial Infections/pathology , Humans , Lung/microbiology , Lung/pathology , Lung Neoplasms/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Male , Middle Aged , Phylogeny , Pneumonia/microbiology , Pneumonia/pathology , Polymorphism, Restriction Fragment Length/geneticsABSTRACT
AIMS: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp. METHODS AND RESULTS: Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10-150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases. CONCLUSIONS: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.
Subject(s)
Granuloma, Plasma Cell/pathology , Histiocytoma, Benign Fibrous/pathology , Spleen/pathology , Splenic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Angiomatosis/metabolism , Angiomatosis/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Young AdultABSTRACT
In Europe and the USA, the incidence of primary nasal natural killer (NK)/T-cell lymphoma is rare. The skin is one of the predilection sites for dissemination. Cutaneous dissemination is a poor prognostic sign and is consistently fatal. We describe the case of a 17-year-old white German girl with a primary nasal NK/T-cell lymphoma and cutaneous dissemination. She presented with multiple maculopapular patches involving the trunk and thighs, and a 4-week history of headache, fever and fatigue. Biopsies of the skin and the nasal mucosa were taken. Pathological examination of both specimens revealed a NK/T-cell lymphoma. Epstein-Barr virus RNA was detected in the lymphoma cells by in situ hybridization. Unfortunately, the patient died of disease within 1 week.
Subject(s)
Epstein-Barr Virus Infections/pathology , Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell/pathology , Nose Neoplasms/pathology , Skin Neoplasms/pathology , Adolescent , Diagnosis, Differential , Epstein-Barr Virus Infections/immunology , Fatal Outcome , Female , Humans , Lymphoma, T-Cell/immunology , Lymphoma, T-Cell, Cutaneous/immunology , Nose Neoplasms/immunologyABSTRACT
In Helicobacter pylori gastritis gastric epithelium plays a central role in the innate immunity to H. pylori. However, epithelial receptors interacting with H. pylori have been poorly characterized so far. Recently a new triggering receptor expressed on myeloid cells-1 (TREM-1) has been identified on human neutrophils and monocytes. On these cells TREM-1 triggers innate immunity by stimulating the secretion of interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha and thus amplifies bacterial-induced inflammation. In this study expression and function of TREM-1 in gastric epithelium exposed to H. pylori has been investigated. TREM-1 mRNA and protein were expressed on gastric epithelial cell lines as demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence activated cell sorter analysis. Gastric epithelial TREM-1 expression was up-regulated directly by H. pylori and was independent of epithelial IL-8 induced by H. pylori. Immunohistochemistry and tissue RT-PCR demonstrated significantly stronger TREM-1 expression in H. pylori gastritis compared with the non-inflamed gastric mucosa supporting in vivo that epithelial TREM-1 is up-regulated during H. pylori infection. Stimulation of gastric epithelial TREM-1 receptor resulted in IL-8 up-regulation on mRNA and protein level, as shown by real-time PCR and immunoassay. This is the first study localizing TREM-1 on gastric epithelium. Functional data suggest that TREM-1 expressed on gastric epithelium amplifies inflammation of the underlying gastric mucosa by up-regulation of IL-8.
Subject(s)
Gastric Mucosa/immunology , Helicobacter Infections/immunology , Helicobacter pylori , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , Cell Line , Epithelial Cells/immunology , Gastritis/immunology , Gastritis/microbiology , Gene Expression/immunology , Humans , Immunity, Innate , Interleukin-8/immunology , Lipopolysaccharides/immunology , Membrane Glycoproteins/genetics , RNA, Messenger/genetics , Receptors, Immunologic/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Triggering Receptor Expressed on Myeloid Cells-1 , Up-Regulation/immunologyABSTRACT
Splenic vascular disturbances mainly affect the red pulp and can involve the venous or arterial blood flow. The venous blood flow may be impaired by congestion and morphologically shows dilated splenic sinuses. Disturbances of the arterial blood flow may occur in connection with anomalies of the erythrocyte membrane or in immune haemolysis and usually are characterized by narrow splenic sinuses. Infarction of the spleen is usually caused by arterial embolism.
Subject(s)
Spleen/blood supply , Vascular Diseases/pathology , Arterial Occlusive Diseases/pathology , Arterial Occlusive Diseases/physiopathology , Arteries/pathology , Arteries/physiopathology , Blood Flow Velocity , Embolism/pathology , Erythrocyte Membrane/pathology , Hemolysis , Humans , Infarction/pathology , Veins/pathology , Veins/physiopathology , Venous Insufficiency/pathology , Venous Insufficiency/physiopathologyABSTRACT
The spleen is commonly affected by malignant lymphomas and the macroscopic findings of the spleen correlate with different lymphoma entities. However, most lymphomas are not primarily diagnosed in splenectomy specimens. Exceptions include splenic marginal zone lymphomas and hepatosplenic T-cell lymphomas that are typically diagnosed from histological findings. In addition, hairy-cell leukemia, LGL leukemia and T-cell prolymphocytic leukemia typically show characteristic patterns of infiltration in the spleen which may be diagnostically useful. The different infiltration patterns of these tumors are discussed here.
Subject(s)
Lymphoma/pathology , Splenic Neoplasms/pathology , Antigens, CD/analysis , Diagnosis, Differential , Humans , Leukemia, Hairy Cell/pathology , Leukemia, Prolymphocytic, T-Cell/pathology , Lymphoma/surgery , Lymphoma, T-Cell/pathology , Splenectomy , Splenic Neoplasms/surgeryABSTRACT
Vascular proliferations of the spleen reflect the variability of vascular structures occurring in the normal spleen. Besides haemangiomas, there is a spleen-specific vascular neoplasm, littoral cell angioma, that often occurs as a paraneoplastic lesion and thus may require the differential diagnostic delineation of metastases to the spleen in patients with known neoplasms. The most common malignant vascular tumours of the spleen are angiosarcomas. A recently described vascular lesion of unknown pathogenesis, sclerosing angiomatoid nodular transformation (SANT) of the spleen, usually is an incidental finding detected in the course of imaging studies.