The FcεRI 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.

Gastric marginal zone lymphoma of mucosa-associated tissue and Epstein-Barr Virus associated lymphoepithelioma gastric carcinoma: Two primaries with an unusual metachronous presentation

Introduction/Objective Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and Epstein-Barr virus (EBV) lymphoepithelioma gastric carcinoma, are two distinct gastric malignancies, with well-known clinicopathological characteristics. Synchronous or metachronous presentation of both entities in the same patient is extremely rare. Methods/Case Report We report a case of a 78-year-old woman, who presented with a 3 cm gastric body mass. Histologically, the biopsy showed H. pylori gastritis, with diffuse monotonous atypical lymphocytic cells and prominent lymphoepithelial lesions. CD20 immunostain was diffusely positive in these cells, supporting the diagnosis of MALT lymphoma. The patient was treated for H. pylorieradication, followed by Rituxan for resistant MALT lymphoma found in a surveillance biopsy. After being free of disease for one year, the patient developed a 2.0 cm, ulcerated lesion adjacent to the previous site. Biopsy of this lesion showed gastric mucosa with diffuse lymphoepithelial lesions, and atypical epithelial cells highlighted by pan-cytokeratin. The associated dense inflammatory infiltrate was comprised predominantly of CD3 T-lymphocytes. EBV was detected by in-situ hybridization (ISH) for EBV encoded RNA, and was positive in the epithelial cells, but negative in lymphocytes. These findings are consistent with EBV associated lymphoepithelioma carcinoma. Results (if a Case Study enter NA) NA Conclusion This case is presented due to its rarity, with only two cases reported previously, which invokes further research into the interaction between both infectious agents. Secondly, lymphoepithelial lesions are a common finding in both diseases, and in small biopsies, these entities can mask or mimic each other. EBV ISH and background B and T lymphocytes may be a clue and help in the diagnosis.

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.

Ocular Extranodal Marginal Zone Lymphoma - A Study of Twenty-Two Cases Presented at Bangalore, Karnataka

BACKGROUND Ocular adnexa lympho-proliferative disorders are a divergent diverse category of ocular malignancies, comprising roughly about 1 % to 2 % of Non-Hodgkin’s lymphomas (NHLs) and 8 % of extranodal lympho-proliferative disorders. The most frequent type, approximating for up to 80 % of cases that constitutes the primary is marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) type. Marginal zone lymphomas which usually have an extranodal presentation are routinely diagnosed by histomorphology by the diffuse infiltration of atypical lymphoid cells with plasmacytoid appearance and presence of pathognomonic lymphoepithelial lesions. Lymphoepithelial lesions are the existence of lymphocytes in the cytoplasm of epithelial cells. Immunohistochemistry shows a consistent absence of CD5 and CD23 staining, hence considered as diagnosis of exclusion on histo-immunomorphology. METHODS This is a case-series study. Twenty-two cases of ocular extranodal marginal zone lymphoma were obtained from the archives of pathology from 2013 to 2015. The histopathology and immunohistochemistry slides were reviewed by three expert histopathologists for confirmation of diagnosis. Immunohistochemical markers mainly used were CD45, CD3, CD5, CD20, cyclin D1, CD10, Ki - 67, BCL - 2, PAX 5 and CD23. The immunohistochemical markers such as CD10, BCL - 2 and cyclin D1 IHC expression were studied in cases of ocular extranodal marginal zone lymphoma (OENMZL). Relevant clinical details were collected from the patients such age, sex and history of autoimmune condition if any. RESULTS Eighteen cases (81 %) of OENMZL belonged to the age group of more than 40 years. There was a definite male preponderance (77 %) and it was associated with autoimmune conditions such as Hashimoto’s thyroiditis (18 %) and Sjogren’s syndrome (22 %). 22 cases of OENMZL were analysed and all showed consistent immunoexpression for CD20, CD45 while were immunonegative for CD5, CD23 and cyclin D1. 6 cases (27 %) showed CD10 positivity while 20 cases showed Bcl2 positivity (90 %). CONCLUSIONS OENMZL shows positivity for CD20 and CD45 while immunonegative for CD5, CD23 and cyclin D1, and a fraction of cases can show IHC positivity for CD10 and Bcl-2. KEYWORDS OENMZL: Ocular Extranodal Marginal Zone Lymphoma, MZL: Marginal Zone Lymphoma, CD: Cluster Differentiation. NHL: Non-Hodgkin Lymphoma. OL: Ocular Lymphoma. PCR: Polymerase Chain Reaction, FISH: Fluorescent In Situ Hybridization

The Role of the Complement System Classical and Alternative Pathways in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

Objective: The complement system plays an important role in chronic inflammation and autoimmune diseases. On the basis of previous studies, this paper further analyzed the role of the complement system classical pathway and alternative pathway in the pathogenesis of lacrimal gland benign lymphoepithelial lesions (LGBLEL).Methods: Six cases of LGBLEL and six cases of orbital cavernous hemangioma (CH), diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013 were randomly selected for proteomic analysis. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the signaling pathways of differentially expressed genes and proteins. Four LGBLEL and three orbital CH cases, diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between October 2018 and August 2019, were randomly selected as the experimental group and the control group, respectively. RT-PCR, immunohistochemical staining and western blotting were used to verify the genes and proteins related to the complement system signaling pathway.Results: The expression of complement system signaling pathway in LGBLEL tissue was significantly different (P<0.0001) compared with orbital CH, and C3, C5 and C9 were differentially expressed genes. RT-PCR results showed that mRNA expression levels of C1qA, C3, C5 and C9 related to the complement signaling pathway were higher in LGBLEL tissues than in orbital CH (P<0.0001). Immunohistochemical staining results showed that C1qA, C3, C5 and C9 protein expression was significantly higher in LGBLEL tissues than in orbital CH. Western blotting showed that the levels of C1qA, C3, C5 and C9 proteins were significantly higher in LGBLEL tissues than in orbital CH (P=0.0008; P=0.0375; P=0.0306; P=0.0073, respectively).Conclusion: Both the classical and alternative pathways of complement system are involved in the pathogenesis of LGBLEL.

Graves’ Disease, a Late Complication of Chronic Graft vs Host Disease

Introduction: Graft-versus-host disease (GVHD), a complication of bone marrow transplant (BMT), occurs when the donor white blood cells attack the recipient’s host cells and can occur acutely or chronically several years post-transplant. It is very rare for chronic GVHD to cause hyperthyroidism due to Grave’s disease and thyrotoxicosis years after BMT. Hyperthyroidism after BMT is thought to occur by GVHD or by donor’s auto-reactive lymphocytes transferred to recipient, with majority of cases occurring with donors that have an underlying autoimmune thyroid condition. Case Report: We report a 62 year old male who presented with palpitations, tremors, sweating, weight loss, and anxiety for 3 weeks. Past medical history was significant for allogenic BMT due to AML 14 years ago, which was further complicated by GVHD of eye, liver and skin. Physical exam was negative for thyromegaly or thyroid tenderness. Initial work up showed TSH 0.03 (normal 0.4-5.0 MUI/l), free T4 3.32 (normal 0.6-1.2 ng/dl), TSI 194 % (normal &lt;140 %). Ultrasound revealed a diffuse hypervascular thyroid gland with numerous avascular cystic areas in both lobes and increased homogenous, symmetrical uptake consistent with Graves’ disease was noted on radioactive iodine uptake scan. With clinical suspicion of GVHD leading to Graves’ disease with subsequent thyrotoxicosis, he was started on methimazole. However, due to persistent increase in transaminases, concern for agranulocytosis with methimazole, and risk of developing worsening GVHD of the skin or eye with radioactive iodine therapy, he underwent total thyroidectomy. His pathology showed bilateral lymphoepithelial lesions with florid follicular hyperplasia, marked monocytoid hyperplasia, and Germinal B cells positive for CD10 and negative for BCL2. Lymphoepithelial lesions can be seen in chronic lymphocytic thyroiditis due to persistent inflammation. Conclusion: This case raises the question on the etiology of thyroid nodules and Graves’ disease occurring after BMT. We believe that his pathology findings may be due to chronic GVHD. Hyperthyroidism after BMT is extremely rare, with only a few case reports documenting this phenomenon. We believe that our patient developed hyperthyroidism 14 years after BMT most likely as a sequela of chronic GVHD with underlying immune dysregulation leading to formation of TSI and thyroiditis due to cellular invasion. This suggest a multifactorial etiology of hyperthyroidism in patients with GVHD. However, more prospective studies are required to the explain etiology of hyperthyroidism in GVHD. Moreover, such patients should be closely monitored for development of thyroid dysfunction or thyroid nodules.