Benign Lymphoepithelial Lesion Research Articles

Loss of CCL28 and CXCL17 Expression and Increase in CCR1 Expression May Be Related to Malignant Transformation of LGBLEL into Lymphoma.

To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and orbital cavernous hemangioma (CH). Three cases of LGBLEL and three cases of lymphoma were randomly selected as control and experimental groups, respectively. A real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate genes associated with the chemokine signaling pathway. Immunohistochemical (IHC) staining and quantitative Western blotting (WB) were performed for precise protein quantification. Transcriptome analysis revealed differential expression of the chemokine signaling pathway between the LGBLEL and lymphoma groups, identifying ten differentially expressed genes: CCL17, VAV2, CXCR5, NRAS, HCK, RASGRP2, PREX1, GNB5, ADRBK2, and CCL22. RT-qPCR showed that, compared to the lymphoma group, the LGBLEL group had significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.001, <0.001, <0.001, <0.001, =0.020, <0.001, respectively) and lower expression of CCR1 (p = 0.002). IHC staining and quantitative analysis confirmed significant differences in protein expression between the groups for CCL28, CCR1, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.003, 0.011, 0.001, 0.024, 0.005, 0.019, and 0.031, respectively). While IHC provided localization, WB offered greater precision. WB revealed that, compared to the lymphoma group, the LGBLEL group exhibited significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.012, 0.005, 0.009, 0.011, 0.008, and 0.003, respectively) and lower expression of CCR1 (p = 0.014). The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma.

Diffuse Lymphocytic Infiltration Syndrome (DILS) as a Mode of Revelation of HIV: On a Case

Diffuse Lymphocyte Infiltration Syndrome (DILS) is a rare condition observed in HIV patients, characterized by infiltration of CD8+ T lymphocytes in several organs. In this article, a case of revelation of HIV infection is presented, diagnosed following bilateral parotidomegaly associated with DILS. The patient, aged 60, presented a progressive deterioration in general condition, significant asthenia, weight loss, and local symptoms including bilateral parotid swelling, cervical lymphadenopathy, and intermittent fever. Investigations revealed HIV-1 seropositivity, lymphocytosis with high T-CD8+ levels, salivary gland enlargement on imaging, and benign lymphoepithelial lesions on parotid biopsy. The diagnostic criteria for DILS were met, highlighting the importance of salivary gland involvement in this syndrome. Treatment with HAART resulted in significant regression of symptoms. In summary, DILS represents a multisystem complication of HIV, requiring appropriate management including antiretroviral treatment to improve patient prognosis.

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

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). 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. 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. 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.

Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL.

Lacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4-related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset. Seventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development. The serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERβ and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ERα was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis. Therefore, the tissue-heterogeneous expression pattern of ERβ is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.

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

To analyze the differences in immune indicators and prognosis between IgG4-positive and negative lacrimal gland benign lymphoepithelial lesion (LGBLEL). This was a single-center retrospective clinical study including 105 cases of IgG4-positive LGBLEL and 41 cases of IgG4-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. The mean age was 50.10±14.23y and 44.76±11.43y (P=0.033) in IgG4-positive and negative group respectively. The serum C3 and C4 was lower in IgG4-positive group (P=0.005, P=0.002), while the serum IgG and IgG2 was higher in IgG4-positive group (P=0.000 and P=0.008). Twenty-one cases had recurrence in IgG4-positive group and 3 cases recurrence in IgG4-negative group. The 5-year recurrence-free cumulative percentages of IgG4-positive group was 81.85%, and 83.46% in the IgG-negative group (P=0.216). The history of preoperative glucocorticoid therapy, serum C4, IgG1 and IgG2 were the factors affecting recurrence in IgG4-positive group, while serum C4, and IgG1 were the factors affecting recurrence of LGBLEL. Serum C4 and IgG1 are the factors affecting recurrence of LGBLEL, while the IgG4 does not affect recurrence of LGBLEL.

Evaluation of the Efficacy of Immune and Inflammatory Markers in the Diagnosis of Lacrimal-Gland Benign Lymphoepithelial Lesion.

This study retrospectively analyzes the immune and inflammatory indices of patients with lacrimal-gland benign lymphoepithelial lesion (LGBLEL) in order to screen out reference indices with higher diagnostic efficacy. The medical histories of patients whose diagnoses of LGBLEL and primary lacrimal prolapse were confirmed by pathology between August 2010 and August 2019 were collected. In the LGBLEL group, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), and immunoglobulins G, G1, G2, and G4 (IgG, IgG1, IgG2, IgG4) were higher (p < 0.05) and the expression level of C3 was lower (p < 0.05) compared to the lacrimal-gland prolapse group. Multivariate logistic regression analysis showed that IgG4, IgG, and C3 were independent risk factors for predicting LGBLEL occurrence (p < 0.05). The area under the receiver operating characteristic (ROC) curve of the prediction model (IgG4+IgG+C3) was 0.926, which was significantly better than that of any single factor. Therefore, serum levels of IgG4, IgG, and C3 were independent risk factors for predicting the occurrence of LGBLEL, and the combined diagnostic efficacy of IgG4+IgG+C3 was the highest.

Clinicopathological analysis of primary thyroid non-Hodgkin lymphoma: a single-center study.

Primary thyroid lymphoma (PTL) is very rare. The aim of this study was to describe the clinical characteristics, pathological features, and survival outcomes of primary thyroid non-Hodgkin lymphoma, including the diagnostic value of clonal immunoglobulin (Ig) gene rearrangements in diagnosing mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland with co-existing Hashimoto thyroiditis (HT). Paraffin-embedded tissues of patients diagnosed in our institute with PTL between 2007 and 2021 were collected. Clinicopathological features and follow-up data were retrospectively analyzed. Analysis of clonal Ig gene rearrangements were performed in patients with suspected PTL. Of the 22 patients included in our study, 17 were female. The median age at diagnosis was 65.5 years (range, 44-80 years). We detected 11 cases of diffuse large B-cell lymphoma (DLBCL), 10 cases of MALT lymphoma, and 1 case of T-cell lymphoma. A total of 18 patients (81.8%) had early stage (I/II) disease. B-cell lymphoma showed diffuse positivity for CD20 but negative markers for thyroid-origin cells. Double-hit and triple-hit lymphomas were not found in the 8 DLBCL cases, and 2 cases of HT with lymphoid tissue dysplasia were diagnosed with MALT lymphoma with gene rearrangement testing. The median follow-up time was 47 months (range, 4-160 months), and the overall survival was 80% for MALT lymphoma (8 of 10), 72.7% for DLBCL lymphoma (8 of 11), and 100% for T-cell lymphoma (1 of 1). There was no significant difference between the groups. PTL mostly affects middle-aged and older adult females with HT, and its main histological type is non-Hodgkin B-cell lymphoma. For patients with HT along with a histologically benign lymphoepithelial lesion, the identification of clonal Ig gene rearrangements is important for differential diagnosis. The prognosis between DLBCL and MALT is not statistically significant.

Study on the role of classical complement pathway in the development of benign lymphoepithelial lesions of lacrimal gland

Study on the role of classical complement pathway in the development of benign lymphoepithelial lesions of lacrimal gland

The Fc\u03b5RI signaling pathway is involved in the pathogenesis of lacrimal gland benign lymphoepithelial lesions as shown by transcriptomic analysis

This study aimed to analyze the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland (LGBLEL). Transcriptomic analysis was performed on LGBLEL and orbital cavernous hemangioma (CH) patients diagnosed via histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Four LGBLEL and three orbital CH patients, diagnosed between October 2018 and August 2019, were randomly selected as experimental and control groups, respectively. RT-PCR, immunohistochemical staining, and western blotting were used to verify genes and proteins related to the FcεRI signaling pathway. Transcriptomic analysis showed that the FcεRI signaling pathway was upregulated in the LGBLEL compared with the CH group. The mRNA expression levels of important genes including SYK, p38, JNK, PI3K, and ERK were significantly increased in the LGBLEL group (P = 0.0066, P = 0.0002, P = 0.0003, P < 0.0001, P < 0.0001, respectively). Immunohistochemical staining results showed that SYK, p38, and ERK were positively expressed in LGBLEL, while JNK and PI3K were not. The protein contents of P-SYK, P-p38, P-JNK, P-PI3K, and P-ERK were significantly higher in the LGBLEL than in the CH group (P = 0.0169, P = 0.0074, P = 0.0046, P = 0.0157, P = 0.0156, respectively). The FcεRI signaling pathway participates in the pathogenesis of LGBLEL.

Mélange of Lymphoepithelial Lesions of Salivary Glands from a Tertiary Care Center of North East India: Diagnostic Conundrums

Background Lymphocytic infiltrates of the major salivary glands are involved in a spectrum of diseases that range from reactive to benign and malignant neoplasms. Occasionally, these pathologic entities present difficulties in the clinical and pathological diagnosis. Aim and Objective The aim of this study was to highlight the importance of meticulous cytopathological and histopathological examination (HPE) in solving the diagnostic challenges encountered in the analysis of these salivary gland lesions. Materials and Methods A retrospective analysis of salivary gland lesions was undertaken over a period of 5 years from 2013 to 2018 in the Department of Pathology at our institute. Salivary gland pathologies diagnosed either as chronic sialadenitis or reactive/benign/malignant lymphoepithelial lesions on fine-needle aspiration cytology (FNAC) and as lymphoepithelial carcinoma (LEC) were included in this study. Results A total of 86 cases of salivary gland lesions diagnosed as mentioned above were found during this period. Out of the 86 cases, 16 were subjected to HPE. Biopsy was not warranted in most of the cases diagnosed as chronic sialadenitis. HPE was concordant with the FNAC diagnoses in 13 out of the 16 cases (81.3%), with a single case misinterpreted as LEC on FNAC. Conclusion Benign and malignant lymphoepithelial lesions of salivary glands may sometimes be difficult to differentiate not only from one another on FNAC but also from other malignant lesions. FNAC is an effective tool for the diagnosis of nonneoplastic lesions, but in cases of benign lymphoepithelial lesions in the absence of salivary acini, biopsy is advisable.

Non-Hodgkin’s Lymphoma in the Parotid Gland Similar to Benign Lymphoepithelial Lesion: A Case Indonesian Male

Background: Primary parotid non-Hodgkin’s lymphoma (NHL) is a very rare case. Case presentation: A66-year-old Indonesian male with a complaint of a lump in front of the right ear about 1 year with a history ofpostoperative primary parotid NHL 3 years ago. Patients underwent Fine Needle Aspiration Biopsy (FNAB)examination, showing a distribution of lymphoid cells with a diverse population (benign lymphoepitheliallesion / BLL) different from the results of FNAB 3 years ago. The patient underwent a right superficialparotidectomy, and the results of the histopathological examination revealed mature lymphocyte cells mixedwith histiocytes, forming foci of the follicle in part with an active germinal center. Conclusion: NHL reportsare necessary to minimize misdiagnosis between primary parotid NHL and BLL.

A CT-based radiomics nomogram for differentiation of lympho-associated benign and malignant lesions of the parotid gland.

Preoperative differentiation between benign lymphoepithelial lesion (BLEL) and mucosa-associated lymphoid tissue lymphoma (MALToma) in the parotid gland is important for treatment decisions. The purpose of this study was to develop and validate a CT-based radiomics nomogram combining radiomics signature and clinical factors for the preoperative differentiation of BLEL from MALToma in the parotid gland. A total of 101 patients with BLEL (n = 46) or MALToma (n = 55) were divided into a training set (n = 70) and validation set (n = 31). Radiomics features were extracted from non-contrast CT images, a radiomics signature was constructed, and a radiomics score (Rad-score) was calculated. Demographics and CT findings were assessed to build a clinical factor model. A radiomics nomogram combining the Rad-score and independent clinical factors was constructed using multivariate logistic regression analysis. The performance levels of the nomogram, radiomics signature, and clinical model were evaluated and validated on the training and validation datasets, and then compared among the three models. Seven features were used to build the radiomics signature. The radiomics nomogram incorporating the clinical factors and radiomics signature showed favorable predictive value for differentiating parotid BLEL from MALToma, with AUCs of 0.983 and 0.950 for the training set and validation set, respectively. Decision curve analysis showed that the nomogram outperformed the clinical factor model in terms of clinical usefulness. The CT-based radiomics nomogram incorporating the Rad-score and clinical factors showed favorable predictive efficacy for differentiating BLEL from MALToma in the parotid gland, and may help in the clinical decision-making process. • Differential diagnosis between BLEL and MALToma in parotid gland is rather difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, demographics, and CT findings facilitates differentiation of BLEL from MALToma with improved diagnostic efficacy.

The Swollen Parotid Gland

Several systemic diseases and local inflammatory processes can cause diffuse enlargement of the parotid gland. Clinical information regarding the patient's age, localization (including laterality), duration, clinical course of the disease, and presence of associated symptoms can aid in determining the diagnosis. CT and MRI features that help narrow the differential diagnosis include the appearance of the gland (homogeneous, single, or multiple masses); inflammatory changes in, or adjacent to, the parotid gland; pattern of disease spread to adjacent spaces; and the presence of lymphadenopathy. In some cases, imaging is used to monitor treatment response, progression of disease, and identify complications. Some of the diseases/conditions that produce diffuse enlargement of a parotid gland include Sjögren syndrome, sarcoidosis, IgG4 disease, benign lymphoepithelial lesions of HIV, sialolithiasis, sialosis, and Rosai-Dorfman syndrome.

Multimodality fMRI with perfusion, diffusion-weighted MRI and 1 H-MRS in the diagnosis of lympho-associated benign and malignant lesions of the parotid gland.

Differential diagnosis of the mucosa-associated lymphoid tissue lymphoma (MALToma) and tumor-like benign lymphoepithelial lesion (BLEL) in the parotid gland is difficult. To distinguish MALToma and BLEL with multimodality MRI including hydrogenproton magnetic resonance spectroscopy (1 H-MRS), diffusion-weighted imaging (DWI-MR), and dynamic contrast-enhanced (DCE-MR), and evaluate each sequence. Retrospective. Twenty-five patients with parotid tumor-like BLEL and 20 with parotid MALToma. 1.5-T/T1 WI, T2 WI, single-voxel 1 H-MRS, DWI-MR, and DCE-MR. All MR images were interpreted and agreed upon by two radiologists who were blinded to clinical information and histopathologic results. The imaging diagnoses were then compared to the histopathologic results. Youden index was used to determine the optimized threshold value. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of different functional (f)MRI methods. Fisher's exact test indicated a significant difference between the 1 H-MRS images of the two lesions (P < 0.001). The sensitivity, specificity, and accuracy of positive choline (Cho) peak in 1 H-MRS of parotid MALToma were 80%, 76%, and 77.7%, respectively. The mean apparent diffusion coefficient (ADC) was 0.992 × 10-3 mm2 /s in patients with parotid tumor-like BLEL and 0.634 × 10-3 mm2 /s in patients with parotid MALToma, and the difference was statistically significant (t-test, P < 0.001). Choosing the Youden index as 0.669 × 10-3 mm2 /s, the sensitivity, specificity, and accuracy of the assay were 78.9%, 95.8%, and 88.4%, respectively. Assuming that time-intensity curve (TIC) type I indicated parotid MALToma (positive), and type II and type III indicated parotid tumor-like BLEL (negative), the sensitivity, specificity, and accuracy of time-to-peak (TTP) and initial slope of increase (ISI) in diagnosing MALToma were 94.1%, 95.2%, and 94.7%, respectively. Combining methods of TTP, ADC, and Cho peak reached the highest AUC (1.000). Combined use 1 H-MRS, DWI-MR, and DCE-MR increased the accuracy of the differential diagnosis between these lesions to 100%. Cho peak in 1 H-MRS, ADC less than 0.669 × 10-3 mm2 /s, TIC type I together indicated parotid MALToma. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:423-432.

Macrophage migration inhibitory factor contributes to the pathogenesis of benign lymphoepithelial lesion of the lacrimal gland

BackgroundBenign Lymphoepithelial Lesion (BLEL) is a rare disease observed in the adult population. Despite the growing numbers of people suffering from BLEL, the etiology and mechanisms underlying its pathogenesis remain unknown.MethodsIn the present study, we used gene and cytokines expression profiling, western blot and immunohistochemistry to get further insight into the cellular and molecular mechanisms involved in the pathogenesis of BLEL of the lacrimal gland.ResultsThe results showed that Macrophage Migration Inhibitory Factor (MIF) was the most highly expressed cytokine in BLEL, and its expression positively correlated with the expression of Th2 and Th17 cells cytokines. MIF was found to regulate biological functions and pathways involved in BLEL pathogenesis, such as proliferation, resistance to apoptosis, MAPK and PI3K/Akt pathways. We also found that MIF promotes fibrosis in BLEL by inducing BLEL fibroblast differentiation into myofibroblasts as well as the synthesis and the deposit of extracellular matrix in BLEL tissues.ConclusionsOur findings demonstrate the contribution of MIF to the pathogenesis of BLEL of the lacrimal gland and suggested MIF as a promising therapeutic target for its treatment.

Imaging of Benign Neoplastic and Nonneoplastic Salivary Gland Tumors.

This article reviews the multimodality diagnostic imaging features of benign neoplastic and nonneoplastic tumors associated with the major salivary glands. Examples of neoplastic conditions that are depicted and discussed include pleomorphic adenoma, Warthin tumor, oncocytoma, peripheral nerve sheath tumors, lipoma, and hemangiomas or hemangioendotheliomas. Examples of nonneoplastic conditions that are depicted and discussed include ranulas, benign lymphoepithelial lesions, Kimura disease, and vascular malformations. Specific imaging and clinical features of these conditions are emphasized in this article.

Toll-like Receptors Regulate MIF Expression in Benign Lymphoepithelial Lesion of the Lacrimal Gland

Despite a perpetual increase in the prevalence of benign lymphoepithelial lesion, data on the mechanisms governing its pathogenesis are still missing. Thus, we aimed in the present study to evaluate whether TLRs could regulate the expression of the pleiotropic pro-inflammatory and tumor-related cytokine MIF in BLEL. Using gene expression profiling and protein expression analysis methods, we found that TLRs were overexpressed and that their signaling pathways were activated in BLEL. We have also confirmed in tissues biopsies, the overexpression of MIF reported previously in plasma of BLEL specimen. The analysis of the TLR7/8 impact on the expression of MIF in BLEL primary cells showed that when activated, TLR7/8 stimulate mainly BLEL lymphocytes to release MIF but not the fibroblast-like cells. No significant change was observed when MIF expression was investigated at the transcriptional level 24h post TLR7/8 activation. Taken together, these data suggest that TLR7 and TLR8 are activated in BLEL and may induce a cell type-dependent regulation of MIF secretion and expression.

Evaluation of the diagnostic value of immunoglobulin clonal gene rearrangements in patients with parotid gland MALT lymphoma using BIOMED-2 protocol

The aim of this study was to evaluate the diagnostic value of immunoglobulin (Ig) clonal gene rearrangements for mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland. We collected and retrospectively analyzed clinical data of 21 patients referred to our institution between 2009 and 2017. Eight patients had been primarily diagnosed MALT lymphoma of the parotid gland and the remaining patients with lymphoepithelial lesion. Paraffin-embedded tissues were chosen for extracting genomic DNA and multiplex primer polymerase chain reaction amplification by using BIOMED-2 primers. Polymerase chain reaction amplification products were analyzed by heteroduplex analysis. Generally, 17 patients were identified to have parotid gland MALT lymphoma; 47.06% of them had Sjögren syndrome. The sensitivity of IGH VH-JH FR1, FR2, FR3, IGK Vκ-Jκ, and IGK (Vκ-Kde and intron-Kde) as targets was 76.47%, 82.35%, 88.24%, 29.41%, and 35.29%, respectively. The sensitivity of combined application of the above-mentioned 3 IGH primers as targets was 100%. The sensitivity of combined application of the above two IGK primers as targets was 58.82%. Ig clonal gene rearrangements assays using BIOMED-2 protocol can be a highly reliable diagnostic method for parotid gland MALT lymphoma. For patients with Sjögren syndrome along with histologically benign lymphoepithelial lesion, identification of Ig clonal gene rearrangements is important for routine differential diagnosis.

Genes and pathways associated with the occurrence of malignancy in benign lymphoepithelial lesions.

There is increasing evidence concerning the occurrence of malignant lymphoma among people suffering from Mikulicz disease, also termed benign lymphoepithelial lesion (BLEL) and immunoglobulin G4-associated disease. However, the underlying molecular mechanism of the malignant transformation remains unclear. The present study aimed to investigate the gene expression profile between BLEL and malignant lymphoepithelial lesion (MLEL) conditions using tissue microarray analysis, to identify genes and pathways which may be associated with the risk of malignant transformation. Comparing gene expression profiles between BLEL tissues (n=13) and MLEL (n=14), a total of 1,002 differentially expressed genes (DEGs) were identified including 364 downregulated and 638 upregulated DEGs in BLEL. The downregulated DEGs in BLEL were frequently associated with immune-based functions, immune cell differentiation, proliferation and survival, and metabolic functions, whereas the upregulated DEGs were primarily associated with organ, gland and tissue developmental processes. The B cell receptor signaling pathway, the transcription factor p65 signaling pathway, low affinity immunoglobulin γ Fc region receptor II-mediated phagocytosis, the high affinity immunoglobulin ε receptor subunit γ signaling pathway and Epstein-Barr virus infection, and pathways in cancer, were the pathways associated with the downregulated DEGs. The upregulated DEGs were associated with three pathways, including glutathione metabolism, salivary secretion and mineral absorption pathways. These results suggested that the identified signaling pathways and their associated genes may be crucial for understanding the molecular mechanisms underlying malignant transformation from BLEL, and they may be considered to be markers for predicting malignancy among the BLEL group.

Benign lymphoepithelial cyst in an adolescent female mimicking lymphoma: A diagnostic dilemma in a retrovirus negative patient

Cystic lesions of the parotid gland are uncommon and may masqueradeneoplasms clinically. Benign lympho-epithelial cysts (BLEC) comprise the most common causes of the parotid gland swelling in human immunodeficiency virus (HIV)-positive patients. It is, however, less common amongst those not infected with HIV. We present a case of a12 years old female who presented with a swelling over left parotid region since one year.Local examination revealed a soft, cystic and non-tender swelling in the left parotid region measuring 5x4x3 cm. Serological investigations for viral markers were non-reactive.A differential diagnosis of granulomatous parotitis versus benign lymphoepithelial lesion was rendered on radiological investigations and superficial parotidectomy was planned. On histopathological examination, a cyst lined by cuboidal to low columnar lining was seen, underlying which, was dense lympho-plasmacytic infiltrate present in diffuse sheets. On immunohistochemistry, this lymphoid population was found to be reactive in nature (positive for kappa and lambda), thus excluding lymphoma. This case is being presented due to its rarity in HIV negative individuals and the histopathological diagnostic dilemma it presented with, mimicking a lymphoma. DOI: 10.21276/APALM.1163