Microbial antigens mediate HLA-B27 diseases via TLRs. Authors Pöllänen R1, Sillat T, Pajarinen J, Levón J, Kaivosoja E, Konttinen YT. Author information Journal J Autoimmun. 2009 May-Jun;32(3-4):172-7. doi: 10.1016/j.jaut.2009.02.010. Epub 2009 Mar 18.
Affiliation Abstract
HLA-B27 positive individuals are predisposed to reactive arthritis developing 1-3 weeks after urogenital and gastrointestinal infections. Also ankylosing spondylitis (AS) associates strongly to HLA-B27, but no specific infection, Klebsiella pneumoniae excluded, has been linked to it.
Before the discovery of its HLA-B27 association there were many reports suggesting a link between chronic prostatitis in men or pelvic inflammatory disease in women and AS. They have since been forgotten although HLA-B27 did not help to understand, why this disease has an axial and ascending nature.
It is proposed that the urogenital organs form a source of damage (or danger)-associated molecular patterns (DAMPs), either exogenous pathogen-associated molecular patterns (PAMPs) from microbes or endogenous alarmins, such as uric acid, released from necrotic cells or urate deposits. DAMPs are slowly seeded from low-down upwards via the pelvic and spinal lymphatic pathways.
They reach Toll-like receptors (TLRs) in their target mesenchymal stem cells, which are stimulated to ectopic enchondral bone formation leading to syndesmophytes and bamboo spine. At the same time inflammatory cytokines induce secondary osteoporosis of the spine.
This new paradigm places microbes, HLA-B27 and TLRs in the pathogenic centre stage, but without pinpointing any (one) specific pathogen; instead, shared microbial patterns are indicated. PMID 19299108 [PubMed - indexed for MEDLINE] Elsevier Science: Full text
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110540/
Mesenchymal hamartoma
After hemangiomas, mesenchymal hamartoma of the liver (MHL) is the second commonest benign hepatic tumor in childhood, but these tumors are relatively rare. Most MHLs are large benign multicystic masses that present in the first 2 years of life[28]. Prenatal diagnosis of MHL has been reported, most often in the last trimester of pregnancy and it may be a cause of severe hydrops. An early prenatal diagnosis and a subsequent follow-up could help to establish the best time for delivery. Fetal intervention may be beneficial in selected cases. If the fetus is becoming hydropic, early delivery or fetal treatment (particularly if the tumor is composed of a few large cysts) should be considered. Most affected fetuses have been successfully delivered vaginally[29].
Postnatal presentation is more common with abdominal distension and/or an upper abdominal mass. Liver function tests are usually normal. AFP is occasionally elevated though not to the degree that occurs in hepatoblastoma. About 75% of MHL occur in the right lobe of the liver. In the newborn, the tumor may expand rapidly and cause life-threatening abdominal distension with respiratory distress[30]. Diagnostic imaging studies demonstrate a multiloculated cystic tumor with a variable amount of solid tissue[31]. This may be seen in undifferentiated embryonal sarcoma of the liver (UESL), but rarely in hepatoblastoma. Intratumor calcification, which can be frequently detected in hepatoblastoma or hepatic hemangioma, has been reported very rarely for a MHL.
Ultrasound demonstrates the presence of thin mobile septate and/or round hyperechoic parietal nodules within the cysts, but rarely containing debris. The hepatic architecture is normal beyond the outer rim of compressed liver. On CT-contrast the solid component, septate, and the peripheral rim may enhance. On MRI, MHL has a low signal intensity on T1-weighted magnetic resonance sequences and a variable signal intensity on T2-weighted sequences (Figure (Figure44)[32]. In most patients, the diagnosis of MHL is suggested by imaging and confirmed by histological examination of the resected specimen. If radiological diagnosis is not clear, a percutaneous or open tumor biopsy can be performed[33].
*see preceding link for image
Abdominal computed tomography and magnetic resonance imaging. A: Abdominal computed tomography-contrast shows enhancement of the solid component, septate, and the peripheral rim; B: Abdominal magnetic resonance imaging-contrast shows a high signal intensity ...
Although a laparoscopic or open surgical biopsy is considered by some authors, SIOPEL (International Childhood Liver Tumor Study Group of the International Society of Paediatric Oncology) currently recommends image-guided coaxial plugged needle biopsy for liver tumors (obtaining numerous cores)[34]. Fine needle aspiration cytology is of limited value because hepatoblastoma or a malignant mesenchymal tumor is difficult to exclude. MHL has been considered a focal tumor, but small satellite lesions at the tumor margin have been described, which could explain tumor recurrence after apparent complete resection. Clinical and histological evidence suggest that UESL can develop within a preexisting MHL[28,30]. Both tumors share similar features on gross pathology (cystic and solid components, sometimes pedunculated), histology (mesenchymal elements with benign bile duct epithelial structures), and immunohistochemistry (positive staining for vimentin, desmin, a-1-antitrypsin, actin, cytokeratins). Flow cytometry studies have shown that although most MHLs are diploid, some are aneuploid and cytogenetic studies have demonstrated a balanced translocation involving the same breakpoint on chromosome 19 (band 19q13.4) and chromosome 11. These abnormalities have been found in both, UESL and MHL[28].
The management of MHL remains still controversial. MHL has the potential to involute spontaneously, especially for those tumors with a prominent angiomatous component. Nonoperative management may be appropriate in selected cases (e.g., infants with a biopsy-proven MHL and a prominent vascular component). Percutaneous aspiration or drainage of larger cysts may temporarily control tumor size in life-threatening lesions and it may helpful for the definitive surgical resection. The standard of care is complete resection with the goal of achieving negative margins to avoid the risks of local recurrence and long-term malignant transformation. Enucleation may be adequate in case of very large tumors that replace most of the liver parenchyma. Liver infiltration by MHL is rarely seen and a surgical plain is normally found for resection (Figure (Figure5).5). Pedunculated lesions are amenable to laparoscopic resection. Marsupialization or partial resection are suboptimal because of the risk of tumor recurrence. Liver transplantation can be considered for unresectable tumors[28,30].
* see preceding link for original article & images
Surgical resection of mesenchymal hamartoma of the liver.
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http://www.ncbi.nlm.nih.gov/pubmed/16365828
Mesenchymalhamartoma of the liver in adulthood: immunohistochemical profiles, clinical and histopathological features in two patients.
Mesenchymal hamartoma is an uncommon cystic mass of the liver which occurs primarily in children. There are a few reports of its occurrence in adulthood. Here, we present two cases infemale patients, 54 and 51 years old. Radiological examinations in both patients showed multiple cystic lesions in the liver. Surgically, totalcystectomy was performed in the first patient, while an unroofing procedure was done in the second patient (due to misdiagnosis of the lesion as a simple cyst of the liver). On microscopic examinations of the lesion in each patient, a multilocular cyst was observed, lined by flattenedepithelium and surrounded by a mesenchymal component composed of mature connective tissue, arterial and venous vascular structures, peripheral nerve bundles, and ductal structures. An immunohistochemical panel consisting ofdesmin, smooth-muscle actin, S-100, vimentin, CD34, carcinoembryonic antigen, pancytokeratin, cytokeratin 7, cytokeratin 8, cytokeratin 17, cytokeratin 18, cytokeratin 19, and cytokeratin 20 was applied to paraffin sections. Immunoreactivity for cytokeratin 7 and cytokeratin 19 was observed in cystic epitheliumand ductal structures. Focal and patchy desminimmunoreactivity was observed in connective tissue. S-100 was positive only in peripheral nerve bundles. In conclusion, mesenchymal hamartomaof the liver in adulthood is a localized tumoral abnormality that precedes birth, and which has delayed clinical presentation. These lesions seems to be related to a maturation process. During this period of maturation, immature edematous stroma rich in mucopolysaccharides may convert to mature paucicellular hyalinizedconnective tissue. This maturation process may be also related to loss of premalignant potential of these tumors.
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