Different serum levels of IgG and complements and recurrence rates in IgG4-positive and negative lacrimal gland benign lymphoepithelial lesion

·AIM:To analyze the differences in immune indicators and prognosis between Ig G4-positive and negative lacrimal gland benign lymphoepithelial lesion(LGBLEL).·METHODS:This was a single-center retrospective clinical study including 105 cases of Ig G4-positive LGBLEL and 41 cases of Ig G4-negative LGBLEL.Basic information,related indicators of peripheral venous blood samples using immunoscattering turbidimetry,treatment(partial surgical excision and glucocorticoid therapy)and prognosis(recurrence and death)were collected.Survival curves for recurrence were created using the Kaplan-Meier analysis.Univariate analysis and multivariate regression analysis were used to analyze prognostic factors.·RESULTS:The mean age was 50.10±14.23y and 44.76±11.43y(P=0.033)in Ig G4-positive and negative group respectively.The serum C3 and C4 was lower in Ig G4-positive group(P=0.005,P=0.002),while the serum Ig G and Ig G2 was higher in Ig G4-positive group(P=0.000 and P=0.008).Twenty-one cases had recurrence in Ig G4-positive group and 3 cases recurrence in Ig G4-negative group.The 5-year recurrence-free cumulative percentages of Ig G4-positive group was 81.85%,and 83.46%in the Ig G-negative group(P=0.216).The history of preoperative glucocorticoid therapy,serum C4,Ig G1 and Ig G2 were the factors affecting recurrence in Ig G4-positive group,while serum C4,and Ig G1 were the factors affecting recurrence of LGBLEL.·CONCLUSION:Serum C4 and Ig G1 are the factors affecting recurrence of LGBLEL,while the Ig G4 does not affect recurrence of LGBLEL.

Association analysis of BclI with benign lymphoepithelial lesions of the lacrimal gland and glucocorticoids resistance

AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism(SNP)genotypes.The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin(HE)and Masson staining analysis.The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed.The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids(GCs)sensitivity.RESULTS:There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity(P>0.05);BclI GC genotype was closely related to GCs resistance(P=0.03)as is the minor allele C(P=0.0017).The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis(P<0.05),especially for GCs-dependent patients(P<0.0001).Meta-analysis showed that BclI was not significantly associated with GCs responsiveness.CONCLUSION:The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression.The results may guide the clinical treatment strategy for the LGBLEL patients.

Benign lymphoepithelial cyst of parotid gland without human immunodeficiency virus infection:A case report

BACKGROUND Benign lymphoepithelial cyst(BLEC)of the parotid gland is a rare benign embryonic-dysplastic cystic tumor in the anterolateral neck that occurs most commonly in human immunodeficiency virus(HIV)-positive adults and rarely in non-acquired immune deficiency syndrome patients.The main presentation is a slow-growing,painless mass,and secondary infection may cause acute inflammatory symptoms.CASE SUMMARY A 44-year-old Chinese male patient presented with a 1-year history of a mass in the left side of the neck.On physical examination,a mass similar in size and shape to a quail egg was found in the left parotid gland.The mass was tough,without tenderness,and easily moveable.The results of HIV tests,including antibody and nucleic acid tests and CD4+T cell examination,were negative.Imaging examination revealed a left parotid gland mass.The patient underwent surgical treatment,and BLEC was diagnosed based on postoperative pathology.After 2years of follow-up,the patient survived well without related discomfort.CONCLUSION The detailed characteristics of a BLEC in a patient without HIV infection contribute to an improved understanding of this rare disease.

Clinical and radiological feature of lymphoepithelial cyst of the pancreas

A lymphoepithelial cyst(LEC)of the pancreas is a rare benign lesion.Because patients with LEC of the pancreas have a good prognosis,it is important that these lesions are accurately differentiated from other more aggressive pancreatic neoplasms for an appropriate treatment strategy.Previous studies have reported that a definitive diagnosis of LEC often cannot be obtained based solely on the findings of preoperative imaging(e.g.,Computed tomography or Magnetic resonance imaging).In this study,we reviewed four cases of pancreatic LECs to investigate the feature of LECs.We reviewed these cases with regard to symptoms,imaging findings,surgical procedures,and other clinical factors.We found that LEC was associated with unique characteristics on imaging findings.A preoperative diagnosisof LEC may be possible by comprehensively evaluating its clinical and imaging findings.

Association of TCR-signaling pathway with the development of lacrimal gland benign lymphoepithelial lesions

·AIM: To identify the association of the T cell receptor(TCR) signaling with the development of benign lymphoepithelial lesions(BLEL) of the lacrimal gland.· METHODS: We collected affected lacrimal gland tissues from 9 patients who underwent dacryoadenectomy in the Capital Medical University Beijing Tongren Hospital Eye Center between August2010 and March 2013 and were confirmed to have lacrimal gland BLEL by histopathological analysis. Tumor tissues from 9 patients with orbital cavernous hemangioma were also collected and used as control.Whole genome gene expression microarray was used to compare gene expression profiles of affected lacrimal gland tissues from patients with lacrimal gland BLEL to those from of orbital cavernous hemangiomas.Differential expression of TCR pathway genes between these tissues was confirmed by polymerase chain reaction(PCR) and immunohistochemistry.·RESULTS: Microarray analysis showed that in lacrimal glands with BLEL, 32 signaling pathways were enriched in the upregulated genes, while 25 signaling pathways were enriched in the downregulated genes. In-depth analysis of the microarray data showed that the expression of 27 genes of the TCR signaling pathway increased significantly. To verify the differential expression of three of these genes, CD3, CD4, and interleukin(IL)-10, reverse transcription-PCR(RT-PCR)and immunohistochemistry assays were performed. RT-PCR analysis showed that CD3 and CD4 were expressed in the lacrimal glands with BLEL, but IL-10 was not expressed. Immunohistochemistry confirmed that CD3 and CD4 proteins were also present, but IL-10 protein was not. CD3, CD4, or IL-10 expression was not found in the orbital cavernous hemangiomas with either RT-PCR or immunohistochemistry.· CONCLUSION: TCR signaling pathway might be involved in the pathogenesis of lacrimal gland BLEL.

Lymphoepithelial cysts and cystic lymphangiomas: Underrecognized benign cystic lesions of the pancreas

AIM: To identify their diagnostic and prognostic clinical characteristics in a large series.METHODS: Retrospective review of clinicopathologic and imaging characteristics of patients diagnosed with lymphoepithelial cysts and cystic lymphangiomas of the pancreas at Massachusetts General Hospital.RESULTS: Twelve patients were identified between 1/1/1997 and 8/1/2007. Their median age was 55.5 years(range 19-78 years), and 6 were females. The le-sion was incidentally discovered in half of the patients.Contrast enhanced computed tomography demonstrat-ed that the cysts had thin walls, without calcifications, pancreatic duct dilation or pancreatic parenchyma inva-sion. Endoscopic ultrasound with fine needle aspiration(EUS/FNA) confirmed the diagnosis of a lymphoepithe-lial cyst in 3 patients, one of whom was spared an op-eration and continues to do well after 6 years. Eleven patients had a resection: 3 pancreaticoduodenecto-mies, 7 distal pancreatectomies, and 1 enucleation. The median size of the cysts was 3 cm(range 2-20 cm). At a median follow-up of 57 mo no recurrences or other pancreas-related conditions occurred.CONCLUSION: Lymphoepithelial cysts and cystic lymphangiomas of the pancreas can be diagnosed with a combination of contrast-enhanced computed tomog-raphy scans and EUS/FNA. If the lesion is asymptom-atic, an operation might be avoided.

Association of the macrophage migration inhibitory factor promoter polymorphisms with benign lymphoepithelial lesion of lacrimal gland

AIM： To identify the association of the macrophage migration inhibitory factor （MIF） gene polymorphism with the susceptibility of benign lymphoepithelial lesions （BLEL） of the lacrimal gland. METHODS： A total of 40 BLEL of lacrimal gland cases were matched with 40 healthy subjects （HS）. Extraction the plasma and whole blood DNA of patients of lacrimal gland BLEL and HS. Elisa and polymerase chain reaction was used to determine in plasma contents of MIF and MIF gene SNP-173G〉C and STR -794 CATT（8） polymorphism, respectively. RESULTS： The MIF levels in plasma were significantly higher in patients with lacrimal gland BI.EL versus HS （P〈0.001）. The -173 G〉C MIF polymorphism was significantly associated with lacrimal gland BLEL, with a significantly higher frequency of the C allele in lacrimal gland BLEL patients compared with HS （OR=2.38, 95% C1=1.07-5.31, P=0.032）, and the -173 C/x is more frequent in patients than in HS, P=0.037. Besides, we found that the carriage rate of the MIF -173C/x is associated with higher plasma levels of MIF in the BLEI. of lacrimal gland. CONCLUSION： MIF -173G/C variants play an insidious role in susceptibility of BLEL of lacrimal gland. Otherwise,there is no statistically significant correlation exists between MIF-794 CATT （） and BLEL of lacrimal gland.

Lymphoepithelial cysts of the pancreas:a management dilemma

Pancreatic lymphoepithelial cysts（LECs） are rare,benign lesions that are typically unexpected post-operative pathological findings. We aimed to review clinical, radiological and pathological features of LECs that may allow their preoperative diagnosis. Histopathology databases of two large pancreatic units were searched to identify LECs and notes reviewed to determine patient demographic details, mode of presentation, investigations, treatment and outcome. Five male and one female patients were identified. Their median age was 60 years. Lesions were identified on computed tomography performed for abdominal pain in two patients, and were incidentally observed in four patients. Five LECs were located in the tail and one in the body of the pancreas, with a median cyst size of 5 cm. Obtaining cyst fluid was difficult and a largely acellular aspirate was yielded. The pre-operative diagnosis was mucinous cystic neoplasm in all patients. This series of patients were treated distal pancreatectomy and splenectomy. A retrospective review of radiological examinations suggested that LECs have a relatively low signal on T2 imaging and a high signal intensity on T1 weighted images. LECs appear more common in elderly males, and are typically incidental, large, unilocular cysts. Close attention to signal intensity on MRI may allow preoperative diagnosis of these lesions.

30-bp DELETION IN LATENT MEMBRANE PROTEIN 1 (LMP-1) ONCOGENE IN LYMPHOEPITHELIAL CARCINOMA OF SALIVARY GLANDS

Objective: To investigate the 30 bp deletion in LMP-1 in lymphoepithelial carcinoma of salivary glands, and to clarify the deletion rate. Methods: 46 cases of LEC were subjected to PCR examination for the 3?terminal region of LMP-1 gene, in order to observe the 30 bp deletion. To reduce the influence of unsuccessful DNA extraction from paraffin-embedded tissue sections, a bactin PCR was performed at the same time. Additionally, DNA sequencing was performed on 1 case without deletion and 1 case with deletion. Results: 4 of 46 specimens were proved to contain no suitable DNA sample by bactin gene amplification. In the remaining 42 cases, LMP-1 DNA was detected in 35/42 (83.3%) LEC cases. Two kinds of PCR products were found in these 35 cases after further DNA sequencing. 31 cases (88.6%) carried 316 bp product and 4 cases (11.4%) carried 286 bp product. Conclusion: Some LECs of salivary glands carry del-LMP-1. In our study, the deletion rate was 11.4% (4/35).

Clinical Research on Benign Lymphoepithelial Lesions of Lacrimal Gland in 20 Chinese Patients

Background：Benign lymphoepithelial lesion （BLEL） is characterized by symmetric bilateral swelling of the lacrimal and salivary glands and considered a subtype of immunoglobulin G4 （IgG4）-related sclerosing disease,the etiology and pathogenesis of which has not been determined.The purpose of the present study was to analyze the clinical features of BLEL in the lacrimal gland and the relationship between the serum level of IgG4 and BLEL.Methods：Twenty consecutive patients with BLEL diagnosed in Department of Ophthalmology at Beijing Tongren Hospital,Capital Medical University between January 2012 and December 2013 were observed.The clinical features,imaging findings,laboratory tests,treatments and follow-up status of these 20 consecutive patients were analyzed.Results：In all 20 patients,the ratio of male to female was 1：4,the ages ranged from 28 to 57 years,the ratio of unilateral to bilateral eyes involvement was 1：4,and painless uncongested symmetrical swelling of the upper eyelid was the main clinical manifestation.Orbital magnetic resonance imaging （MRI） showed that all patients involved lacrimal gland,which were obviously enlarged with equal signals in T1W images and T2W images and obvious enhancement on contrast MRI.Extraocular muscles were involved in 5 patients,salivary gland in 8 patients,and frontal nerve in 3 patients.Serum IgG4 concentration was elevated in 18 patients.The treatment strategy mainly included surgery and steroid administration.Three patients were lost to follow-up,17 patients reached complete response,and no recurrence was observed.Conclusions：Eyelid swelling is the typical symptom of BLEL.Most of the patients involved bilateral lacrimal glands.High serum IgG4 level and abundant IgG4-positive plasma cell infiltration are the important features,which can be found in most of BLEL patients.Surgery combined with glucocorticoids is an efficient treatment strategy.

Primary mucosa-associated lymphoid tissue lymphoma of the liver: A report of two cases and review of the literature

Mucosa-associated lymphoid tissue(MALT) lymphoma of the liver is a very rare condition and thus the diag-nosis may be challeng-ing-. The clinical presentation is usually variable, rang-ing- from minimal clinical symptoms to severe end stag-e liver disease. In this paper, we describe the clinicopatholog-ic finding-s in two cases of primary hepatic MALT lymphoma. One case is an 80-year-old female with no underlying- chronic liver disease and the second case is a 30-year-old female with autoimmune hepatitis complicated by MALT lymphoma. In both specimens, there was diffuse infiltration of atypical B-lymphocytes that were positive for CD20 and CD79 a, but neg-ative for CD5, CD43 and CD10. There were occasional lymphoepithelial lesions involving- the hepatocytes or bile ducts. Polymerase chain reaction analysis showed monoclonal immunog-lobulin heavy chain g-ene rearrang-ement in both cases. The first case was treated with surg-ery but developed pulmonary recurrence a year after complete resection but went into remission following- treatment with rituximab. A second recurrence occurred in the rig-ht parotid g-land 7 years later, which was treated with idelalisib. The second case was effectively treated with rituximab. To our knowledg-e, the second case is the first reported case linked to autoimmune hepatitis.

T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes

Background： Atopic dermatitis （AD） is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 （Th 1/Th2） cytokine expression.Filaggrin （FLG） is the key protein to maintaining skin barrier function.Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes.However, the role ofThl/Th2 cytokines on FLG processing is not substantially documented.Our aim was to investigate the impact ofThl/Th2 cytokines on FLG processing.Methods： HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin （IL）-4, 13 or interferon-γ（IFN-γ）.FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor （LEKTI） were measured by both real-time quantitative polymerase chain reaction and Western blotting.Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.Results： IL-4/13 significantly reduced, while IFN-γsignificantly up-regulated FLG expression.IL-4/13 significantly increased, whereas IFN-γsignificantly decreased the expression ofkallikreins 5 and 7, matriptase and channel-activating serine protease 1.On the contrary, IL-4/13 significantly decreased, while IFN-γincreased the expression of LEKTI and caspase-14.Similar trends were observed in AD lesions.Conclusions： Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes.The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.