Mucosa-associated Lymphoid Tissue Type Research Articles

Real-World Data of Outcome of Patients with Newly Diagnosed Bronchial-Associated Lymphoid Tissue Lymphoma: A Multi-Center Retrospective Analysis with Long-Term Survivors

Introduction Extranodal marginal-zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) is an indolent type of non-Hodgkin's lymphoma. Although the lung is the second most common site, it accounts for less than 1% of all lymphomas. Extranodal MZL of MALT type of the lungs originates from bronchial-associated lymphoid tissue (BALT) and is clinically referred to as “BALT lymphoma” or “BALToma”. The indolent nature of BALTomas results in none or mild symptoms and their slow growth pattern allows for various treatment approaches. Depending on the case, active surveillance may be considered, while others may benefit from surgery, radiotherapy or chemotherapy. Despite some existing reviews on this lymphoma, comprehensive characterization of optimal management and prognostic factors remains inadequately defined. Limited case reports and small-scale retrospective data analyses have been conducted, but the number of patients included in these studies was highly restricted. In this study, we conducted a retrospective analysis of clinical data from 67 BALToma patients in South Korea. Methods 67 patients were included in our analysis, all of whom were diagnosed with BALToma between September 1996 and January 2023 at three institutions in South Korea. The criteria for case inclusion was histologically confirmed diagnosis of extranodal MZL of pulmonary origin in accordance with WHO classifications, and availability of clinical data. Extranodal MZL was diagnosed based on WHO classifications, along with the findings from immunohistochemical staining for CD20 and CD3. If needed, CD5, CD10, CD23, cyclin D1, BCL6, and Ki-67 was also stained. Gene rearrangement studies targeting the IgH gene were conducted using PCR analysis. Patients were treated according to the stage and location of the disease. The patients were analyzed into two groups; observation or localized treatment and systemic chemotherapy. Localized treatment included surgery or radiotherapy. Systemic chemotherapy regimens used were mainly (R)-CVP and (R)-CHOP. Baseline characteristics was analyzed with Fisher's exact test. Overall survival (OS) and Progression Free Survival (PFS) were estimated using the Kaplan-Meier method. PFS was calculated from the date of diagnosis to the date on which progression was noted, the date of the last follow-up, or the date of death. OS was measured from the date of diagnosis to the date of death or the last follow-up visit. Survival rates were compared for statistical differences via Generalized Wilcoxon analyses. Prognostic factor analysis and hazard ratio was calculated using univariate and multivariate Cox Regression method. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. All data was analyzed using SPSS Statistics for Windows, Version 27.0. Results The clinical characteristics of patients according to treatment modality was analyzed (Table 1). Gender, age, performance status was not significantly different between each group. Notably, involvement of single or multiple lobe (p=0.045), involvement of bilateral lung (p<0.001), nodal involvement (p=0.033), and involvement of extrapulmonary organ (p=0.010) was significantly different between each group. The PFS and OS according to treatment method are provided in Figure 1 and 2. 10-year PFS for observation or localized treatment was 78.7% whereas chemotherapy was 56.9% (p=0.044). 10-year OS for observation or localized treatment was 100%, whereas chemotherapy was 71.7% (p=0.016). The prognostic factors for progression of disease were significant only for the involvement of extrapulmonary organ in both univariate and multivariate (hazard ratio 3.615, p=0.023) analysis (Table 2). Prognostic factor analysis for overall survival did not yield any significant result. Conclusion This study concludes that the most important prognostic factor for the progression of disease is the involvement of extrapulmonary organ. This study implies that the feasibility of simply monitoring patients whose disease is confined exclusively to the lung is a viable strategy. However, in the case of extrapulmonary involvement, the implementation of systemic chemotherapy ought to be deliberated. Given the heightened potential for disease progression, this underscores the necessity for meticulous consideration during the development of therapeutic plans.

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome.

To assess the usefulness of [18F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate systemic disease activity in pSS. ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. Receiver operating characteristic curve analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma. Of the 70 included patients, 26 were diagnosed with a pSS-associated lymphoma, mostly of the mucosa-associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax > 3.1 and submandibular SUVmax > 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs. FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.

PSAT289 Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) Type of the Thyroid: A Rare Tumor That Requires a Second Look

Abstract Background Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type of the thyroid, or MALT lymphoma of the thyroid, is a rare, indolent tumor that accounts for only 1-2% of extranodal lymphomas. It is often associated with lymphocytic thyroiditis - a benign condition that might not be given additional investigation. Clinical case A 79-year-old male consulted due to a 3-year history of a gradually enlarging, painless anterior neck mass accompanied by hoarseness. He denied fever, weight loss, dysphagia, dyspnea, palpitations, heat or cold intolerance, or changes in bowel movement. On physical exam, a 4×3×1 cm firm, fixed, non-tender right anterior neck mass and a 2×2 cm right supraclavicular mass were palpated. Thyroid function tests showed: TSH 3.301 uIU/mL (0.55 - 4.78 uIU/ml), FT3 2.560 pg/mL (2.30 - 4.20 pg/mL) and FT4 0.720 ng/dL (0.89 - 1.76 ng/dL). Neck ultrasound revealed multiple cervical lymph nodes measuring 1-2 cm in the right anterior, posterior, submandibular, and left submandibular areas. A lobulated heterogeneous mass measuring 9.7×2.9×4.3 cm occupied almost the entire right thyroid lobe, with intralesional and peripheral vascularity. The left thyroid lobe had an irregular, solid, isoechoic nodule measuring 0.9×0.5×0.9 cm. Fine needle aspiration biopsy of the right thyroid mass showed lymphocytic thyroiditis (Bethesda category II). The patient underwent total thyroidectomy with frozen section and selective neck dissection on the right (levels II, III, IV, and V). Final histopathology and immunohistochemical stains revealed extranodal marginal zone lymphoma of the thyroid gland, with high grade transformation to diffuse large B-cell lymphoma in 10% of the tumor. Level II, III and V lymph nodes were positive for marginal zone lymphoma. Histopathology also showed an adenomatous goiter with lymphocytic thyroiditis. The patient was started on levothyroxine 75 mcg once daily. He completed 1 cycle of chemotherapy (R-CHOP). Two weeks after chemotherapy, he developed febrile neutropenia and expired due to sepsis. Conclusion In thyroid nodules and masses where lymphocytic thyroiditis is identified on fine needle aspiration biopsy, particularly in large masses accompanied by cervical lymphadenopathy, the possibility of an existing MALT lymphoma of the thyroid should be considered, and further investigation may be warranted. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

EXTRANODAL LYMPHOMA SIMILAR TO A BENIGN TUMOR IN THE ORAL CAVITY: A CASE REPORT

A 68-year-old woman arrived at our clinic with a slow-growing nodule in the buccal region, next to tooth 45. The patient had a 9-year history of a diagnosis of mucosa-associated lymphoid tissue-type lymphoma in the gastrointestinal region. She reported pain on palpation. In the intraoral examination, a submucosal nodule, sessile, of firm consistency and with the color of the mucosa was observed. The lesion did not appear on imaging exams. An excisional biopsy was performed under local anesthesia, because of the benign aspect, with a clinical diagnosis of pleomorphic adenoma. The histologic analysis showed atypical lymphocyte cells. Furthermore, the specimen showed positivity for CD20, Ki-67, and BCL-2. The diagnosis was of a lesion suggestive of MALT lymphoma. The patient was referred to and oncologist, where she underwent a computed tomography scan, but no other injured sites were found. The patient is under medical supervision. A 68-year-old woman arrived at our clinic with a slow-growing nodule in the buccal region, next to tooth 45. The patient had a 9-year history of a diagnosis of mucosa-associated lymphoid tissue-type lymphoma in the gastrointestinal region. She reported pain on palpation. In the intraoral examination, a submucosal nodule, sessile, of firm consistency and with the color of the mucosa was observed. The lesion did not appear on imaging exams. An excisional biopsy was performed under local anesthesia, because of the benign aspect, with a clinical diagnosis of pleomorphic adenoma. The histologic analysis showed atypical lymphocyte cells. Furthermore, the specimen showed positivity for CD20, Ki-67, and BCL-2. The diagnosis was of a lesion suggestive of MALT lymphoma. The patient was referred to and oncologist, where she underwent a computed tomography scan, but no other injured sites were found. The patient is under medical supervision.

Gastric marginal zone B-cell lymphoma of MALT type – An updated histo- and molecular pathological summary

Gastric marginal zone lymphoma (gMZBL) is the most frequent type of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The histology of gMZBL shows typical small cell morphology, however, there also exists a large cell variant.

Clinicopathologic Characteristics Associated with Prognosis in Ocular Extranodal Marginal Zone B Cell Lymphoma.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7–109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273–41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Gallbladder Burkitt’s lymphoma mimicking gallbladder cancer: A case report

BACKGROUNDMalignant lymphoma is a rare form of gallbladder malignancy. Most of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas; however, Burkitt’s lymphoma of the gallbladder is extremely rare, and only two previous reports are available in the literature. Herein, we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder adenocarcinoma.CASE SUMMARYAn 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography (CT) performed for hypertension screening. His laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 receptor. Imaging examinations revealed two irregular and contrast-enhanced masses extending into the gallbladder lumen, but these did not infiltrate the serosa. Moreover, a periportal lymph node had enlarged to 30 mm. Based on these findings, we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis, which was treated using bile duct resection with gallbladder bed resection and periportal lymph node dissection. However, the patient was finally diagnosed as having Burkitt’s lymphoma. Although the surgical margin was pathologically negative, recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after discharge. Thus, he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone.CONCLUSIONBurkitt’s lymphoma can occur in the gallbladder. Biopsy can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

Safety of COVID-19 vaccination in patients with clonal mast cell disorders

Safety of COVID-19 vaccination in patients with clonal mast cell disorders

Extra Nodal Non Hodgkin’s Lymphomas using Immunohistochemistry from a Tertiary Care Centre, Andhra Pradesh, India- A Retrospective Study

Introduction: Primary Extranodal Lymphomas (pENL) are a group of lymphomas arising from tissues other than lymph nodes and even sites which normally contain no lymphoid tissue. Over the past 25 years pENLs have shown a rapid increase in incidence. pENLs can originate from almost any anatomical site such as the gastrointestinal tract (most common), head and neck (waldeyer’s ring, nose/paranasal sinuses/nasopharynx, salivary glands, etc.,), skin, Central Nervous System (CNS) etc. The definition of Extranodal Lymphoma (ENL), particularly in the presence of both nodal and extranodal disease remains a controversial issue. To categorise these entities, different criteria were proposed by different authors. Aim: To study the occurrence of extranodal non hodgkin’s lymphomas in different sites/organs using Immunohistochemistry (IHC). Materials and Methods: This was a retrospective study carried out in the Department of Pathology, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, Andhra Pradesh, India, over a period of 7 years 6 months starting from January 2010 to July 2017. Data was retrieved from the medical records and paraffin blocks were retrieved from the stores. All cases of extranodal primary lymphomas were included in the study. All cases were classified based upon morphologic and immunophenotypic criteria according to World Health Organisation (WHO) 2008 classification. The distribution of primary extranodal lymphomas among different age groups with mean age of occurrence was noted. Distribution of pENLs among male and female population with male to female ratio was calculated. The percentage of different sub-types of ENL and the Immunohistochemistry (IHC) markers in each subtype of ENL were calculated. Results: In this retrospective study, a total of 317 newly diagnosed lymphoma cases were included. Among them, 79 cases were pENL. A total of 77 (24.29%) cases of primary extranodal non Hodgkin’s lymphomas were included in the study. The age of the patients ranged from 4-81 years with mean age of 48.42 years, with male predominance (M:F-1.85:1). Gastrointestinal Tract (GIT) (35/77-45.45%) was the most common site, followed by head and neck (16/77-20.77%), mediastinum (4/77-5.19%), kidney (4/77-5.19%) were the common sites of occurrence of primary extranodal NHLs. In the GIT, stomach was the most commonly involved site (24/35) followed by the small intestine (5/35), colon and anal canal (3/35) and ileo-caecal region (3/35). The Diffuse Large B-cell Lymphoma (DLBCL) was the most common histological type observed in 51/77 (66.23%), followed by Peripheral T-cell Lymphoma- Not Otherwise Specified (PTLNOS) were observed in 14/77 (18.18%) cases, and extranodal marginal zone lymphoma of Mucosa-associated Lymphoid Tissue (MALT) type seen in 9/77 (11.68%) cases. Conclusion: pENLs are a diverse group of haemato-lymphoid malignancies, the incidence of which is low in India compared to rest of the world, the prognosis of which depends on the extranodal site. The diagnosis is challenging due to the morphological mimics and varied clinical presentation and that is

Integrative Analysis of MALT1 as a Potential Therapeutic Target for Prostate Cancer and its Immunological Role in Pan-Cancer.

Background: Mucosa-associated lymphoma antigen 1 (MALT1) is an oncogene in subsets of diffuse large B cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue type (MALT) lymphoma. However, the role of MALT1 across cancers, especially in prostate cancer is still poorly understood. Methods: Here, we used several public datasets to evaluate MALT1 expression. Then, PCa cell lines and nude mice were used to investigate the cellular functions in vitro and in vivo. Microarray data were downloaded from The Cancer Genome Atlas and MALT1 was subjected to gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis to identify the biological functions and relevant pathways. Additionally, the correlations between MALT1 expression and mismatch repair (MMR) gene mutation, immune checkpoint gene expression, tumor mutational burden (TMB), and microsatellite instability (MSI) were investigated by Pearson correlation analysis. Moreover, the correlation between MALT1 expression and tumor immune infiltration was analyzed by the Tumor Immune Evaluation Resource (TIMER) database. Results: MALT1 overexpression was significantly correlated with MMR gene mutation levels and crucially promoted proliferation and colony genesis while reducing PCa cell apoptosis levels in vivo and in vitro. MALT1 expression showed strong correlations with immune checkpoint genes, TMB, and MSI in most cancers. The GO analysis indicated that MALT1-coexpressed genes were involved in heterotypic cell-cell adhesion, actin filament-based movement regulation, and action potential regulation. GSEA revealed that MALT1 expression was associated with several signaling pathways, including the NF-κB signaling, Wnt/β-catenin and TGF-β signaling pathways, in PCa. Additionally, MALT1 expression was significantly correlated with the infiltration of immune cells, including B cells, CD8+ T cells, dendritic cells and macrophages, and negatively correlated with CD4+ cell infiltration in PCa. Conclusion: MALT1 expression is higher in pancancer samples than in normal tissues. MALT1 promoted proliferation and colony genesis while reducing PCa cell apoptosis levels, and MALT1 suppression could inhibit xenograft tumor establishment in nude mice. Furthermore, MALT1 expression is closely related to the occurrence and development of multiple tumors in multiple ways. Therefore, MALT1 may be an emerging therapeutic target for a variety of cancers especially PCa.

Low Mutational Burden of Extra Nodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in Patients with Primary Sjogren's Syndrome

Background: Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of the exocrine glands. Patients with pSS are at increased risk of developing extra nodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type, predominantly in the salivary glands. The presence of cryoglobulinemia, low C4 levels and salivary gland enlargement, are important risk factors for lymphoma development in pSS. Although lymphoma associated mutations have been described in circulating B-cells of patients with pSS associated cryoglobulinemia, it is unknown which somatic aberrations underlie the development of pSS-associated MALT lymphomas. The aim of the current study was to define the genomic landscape of pSS salivary gland MALT lymphomas. Identification of specific recurrent mutations or copy number aberrations and defining the affected pathways would help to understand the mechanisms by which intra-epithelial B-cells undergo malignant transformation.Methods: Whole exome sequencing was performed on 14 fresh frozen and 3 paraffin embedded MALT tissue samples of pSS patients at the University Medical Center Groningen (UMCG). Matched peripheral white blood cell samples were available for 12 patients and were used as germline controls. Fluorescence in situ hybridization was performed for the detection of MALT1 translocations.Results: Presence of a clonal B-cell population, indicative of a MALT lymphoma was confirmed by IgH PCR (BIOMED-2) for all patients. Whole exome sequencing resulted in a median target coverage of 130x, ranging from 84-163. More than 90% of the target regions had a coverage of >50x. In total we identified 232 somatic mutations in 184 genes. Three cases had a relatively high mutational load (>25 / case), while the median number of mutations in the remaining 14 cases was 7. Across the 17 cases there were 18 recurrently mutated genes. PRKD1, associated with malignant epithelial tumor of the salivary glands, was the most frequently mutated gene (six cases). Besides PRKD1, five additional recurrently mutated genes are also involved in epithelial surface and/or extracellular matrix (MAMDC4, COL14A1, CAMSAP3, TMEM2 and MUC4). Five genes, all with mutations in two cases, were shown to be associated with lymphomagenesis (ID3, TBL1XR1, PAX5, IGLL5, APC). A total of 18 copy number alterations (CNAs) were detected in 8 of the 14 evaluable cases, with gains of part of chromosomes 2 and 19, and loss of chromosome 6 each being detected in two cases. With respect to outcome, only 2 cases with high mutational load relapsed outside of the salivary glands, suggesting a more advanced stage of lymphoma.Conclusion: The low mutational load and lack of a clear lymphoma related gene signature suggests that localized pSS MALT lymphomas are genetically stable and most likely depend on the inflammatory state of the micro-environment. Only those cases characterized by higher mutational load showed a relapse-remitting disease, as is typical for indolent lymphoma. These observations could be translated to the clinical setting and potentially have value as biomarker for identification of patients with a more aggressive disease. Confirmation in larger cohorts are required to confirm this potential association. This study also paves way for treatment strategies targeting the micro-environment. DisclosuresNo relevant conflicts of interest to declare.

O29 Keeping a watchful eye: IgG4-positive lymphoma masquerading as IgG4-related ocular disease

Case report - IntroductionIgG4-related disease (IgG4-RD) is increasingly recognised in rheumatology practice. We describe a case of orbital swelling initially diagnosed as IgG4-RD. It was exquisitely steroid responsive and she was treated with 6 years of immunosuppression but her symptoms later deteriorated. She developed worsening left eye swelling that required debulking surgery; histopathology demonstrated IgG4-positive lymphoma. She had an excellent response to localised radiotherapy and remains in remission. Although her initial presentation was typical of IgG4-RD, her subsequent lack of response to steroids prompted reconsideration of the initial diagnosis and re-examination of her previous biopsy specimen, confirming IgG4-positive Iymphoma at both timepoints.Case report - Case descriptionA 25-year-old lady presented in 2008 with a swollen left eye. She had a history of childhood eczema, asthma and sinusitis. Diagnostic excision was undertaken; histology was considered to show chronic inflammation, scattered eosinophils, dense fibrosis and no granulomas. She was diagnosed with a ‘granulomatosis with polyangiitis-like’ orbital pseudotumour. It was exquisitely steroid responsive; mycophenolate mofetil was added from an early stage of treatment.The patient was referred to rheumatology 3 years after diagnosis as she was unable to reduce her prednisolone below 5mg daily. Her immunology screen was negative. Although her plasma IgG4 levels were normal at 0.14g/L, the original histology was reviewed and immunostained for IgG4. This demonstrated more than 80% of plasma cells to be IgG4 positive, with the previously noted dense fibrosis and chronic inflammatory infiltrate. Her diagnosis was revised to orbital IgG4-RD. She commenced azathioprine as she was planning a pregnancy.Following an uncomplicated pregnancy in 2014, her symptoms significantly deteriorated, with worsening pain, discharge and swelling in her left eye. A repeat MRI scan showed a new cuff of abnormal tissue within the lateral aspect of the left orbit. She was referred to ophthalmology and underwent left anterior orbitotomy with debulking. Histopathology at this time was consistent with extranodal marginal zone lymphoma (EMZL) of MALT (mucosa-associated lymphoid tissue) type, IgG4 positive. An extraordinary feature was an abundance of crystal-storing histiocytes, presumed to contain ingested IgG4.To investigate whether she had an IgG4-secreting lymphoma from the beginning or whether there had been malignant transformation of her orbital IgG4-RD, the histology from 2009 was reviewed. This was considered to indicate a MALT-type EMZL.The patient was referred to haematology and she was treated with localised radiotherapy with an excellent response. She remains in remission following this and she has subsequently been discharged from haematology follow-up.Case report - DiscussionIgG4-RD is a condition involving fibroinflammatory lesions that can affect any organ in the body. As a newly recognised condition, the role of IgG4 in IgG4-RD is still not fully understood. Questions that remain unanswered include whether or not IgG4 is directly pathogenic and whether there is an increased risk of malignancy in patients with IgG4-RD.Our patient’s case demonstrates how IgG4-positive lymphoma can mimic IgG4-RD. It is important to keep a broad differential diagnosis in complex cases, and to support the eventual diagnosis with blood results, imaging studies and histology. It is essential to involve colleagues in radiology and histopathology so that a multidisciplinary decision can be made with regards to management. IgG4-RD is a steroid-responsive condition. When there is poor response to conventional treatment, this should raise doubts regarding the diagnosis, and it would be prudent to consider a repeat biopsy as well as obtaining previous pathology specimens so that they can be re-reviewed.Ocular adnexal lymphomas form 1—2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Over recent decades the incidence has increased, partly reflecting better diagnostic techniques. The most common subtype of ocular adnexal lymphomas are EMZL of MALT type, as in our patient.There are several case reports of lymphoma arising in patients with established IgG4-RD, raising the question of potential lymphomagenesis in IgG4-RD. The earliest reports come from Asia and most have been reported in patients with ocular IgG4-RD. However, the link between malignancy and IgG4-RD is still being investigated. It is important to consider a potential malignancy when managing patients with IgG4-RD, especially if there is a lack of response to steroids.Case report - Key learning pointsThere is no single diagnostic test for IgG4-RD. Diagnosis should be based on the overall clinical picture, supported by blood results, imaging and histopathology.IgG4-RD is a steroid-responsive disease. If there is a poor response to treatment, the diagnosis should be re-considered.Re-examination of previous biopsy specimens can be invaluable, especially in patients refractory to standard treatment.The link between IgG4-RD and malignancy has not been established and it is important to remain vigilant. As ocular adnexal lymphomas are not uncommon, it is important to keep this differential diagnosis in mind when reviewing patients with eye swelling thought to be secondary to IgG4-related ocular disease.

Ten-year epidemiological study of ocular and orbital tumors in Chiba University Hospital

BackgroundThe purpose of this study is to determine the epidemiology of tumors of the ocular adnexa and orbit in Japan.MethodsWe conducted a retrospective study on the histopathological reports in the medical records of the Chiba University Hospital from April 2009 to March 2019. Three hundred and seventy two records were examined. In addition, we examined the annual changes in the major types of tumors including malignant lymphomas and IgG4-related diseases (IgG4-RDs).ResultsThere were 270 conjunctival or eyelid tumors with 166 benign and 104 malignant. There were 102 orbital tumors with 55 benign, 47 malignant tumors, and 21 cases of IgG4-RDs. Ten cases of adenoma (2.7%), another benign tumor, was also diagnosed. The major malignant tumors were malignant lymphoma in 74 cases, sebaceous gland carcinoma (SGC) in 28 cases, basal cell carcinoma in 15 cases, and squamous cell carcinoma in 8 cases. The SGCs were the most common malignant eyelid tumor at 54%. Among the malignant lymphomas, extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type, MALT lymphomas, was the most common at 51 cases and the second most common was the diffuse large B-cell lymphoma at 11 cases. The ratio of MALT lymphomas to that of all malignant lymphomas increased significantly with years. The serum IgG4 values were measured more often in the last 5 years (70%) than in the former 5 years (33%).ConclusionsWe conclude that malignant lymphoma is a major malignant tumor in Japan and pathological biopsies should be done proactively to prevent missing IgG4-positive MALT lymphomas.

Is it Worthwhile to Undergo the Extended Stage Assessment in Orbital and Ocular Adnexal MALT Lymphoma with Symptoms Limited to the Ocular Adnexa?

Compared to ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) patients with symptoms related invasion beyond the ocular adnexa, the different approaches to staging assessment may be required in OAML patients with symptoms limited to the ocular adnexa. Seventy-six patients to be diagnosed with OAML and performed bone marrow biopsy and imaging study at Yeungnam University Hospital in 1995-2014 were enrolled. Patients with symptoms limited to the ocular adnexa were included. Computed tomography, magnetic resonance imaging, positron emission tomography (PET), and bone marrow biopsies were performed for diagnosis, NM staging and follow up evaluation. Most patients were treated with external beam irradiation (median dose, 30Gray (Gy)).The relapse-free survival (RFS) was analyzed according to the tumor laterality and TNM stage. The median follow-up period was 72months. The 5-year RFS and overall survival rates were 82.1% and 95.6%respectively.Of all76patients, lymph node and bone marrow involvement was identified in 1 patient, respectively. Among the 3 patients withT4 stage as tumor invasion beyond ocular adnexa, bone marrow involvement was confirmed in a patient with left cheek invasion. Only 11 of the 43 patients who underwent PET showed positive uptakes in orbital lesion. The patients with advanced stage were alive without recurrences. Bone marrow examination is useful in OAML patients with T4 for extended stage assessment. The AJCC TNM staging system was not significantly predictive factor for relapse, but may contribute to clarifying the patient group that needs bone marrow study.

Long-Term Clinical Outcome and Predictive Factors for Relapse after Radiation Therapy in 145 Patients with Stage I Gastric B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type.

Simple SummaryHelicobacter pylori-associated gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) constitutes >80% of gastric MALT lymphoma. Eradication therapy has been accepted as a standard approach for initial treatment. However, in patients who present without evidence of infection or who fail to respond to eradication therapy, a solid consensus for treatment is not available. Furthermore, few studies have evaluated the predictive factors for response or relapse after radiation therapy (RT) as heterogeneous, relatively small study populations have been treated with RT, and only a small number of events have been reported after treatment. In this study, we report the long-term clinical outcome of stage I gastric MALT lymphoma treated with RT. We also identified that the tumor’s dominant location in the stomach is a predictive factor for relapse after RT.This study aimed to evaluate the clinical outcomes of radiation therapy (RT) for stage I gastric mucosa-associated lymphoid tissue (MALT) lymphoma and find predictive factors for relapse after RT. This retrospective study included 145 patients without a prior history of treatment, except Helicobacter pylori eradication therapy, who were irradiated for stage I gastric MALT lymphoma. The gastric body was the most commonly involved location of the dominant lesion (66.9%), and H. pylori infection at first diagnosis was detected in 61 (42.1%) patients. The median RT dose was 30 Gy (range, 24–40). Seven patients had an autoimmune disease. All patients except one achieved a complete remission at post-treatment endoscopic biopsy after a median of 2 months (range, 1–36). During the median follow-up at 51 months (range, 2–146), 11 patients experienced relapses: in the stomach (n = 5), in a distant site (n = 4), and in both (n = 2). The five-year overall, local relapse-free, distant relapse-free, and relapse-free survival (RFS) rates were 98.6%, 94.0%, 97.1%, and 92.3%, respectively. In multivariate analysis for RFS, the location of MALT lymphoma other than in the gastric body was significantly associated with an increased risk of relapse (hazard ratio 5.85 (95% CI 1.49–22.9), p = 0.011). RT results in favorable clinical outcomes in patients with stage I gastric MALT lymphoma. Tumor location could be a predictive factor for relapse after RT.

S1798 Composite Lymphomas in the Colon: Two Separate Entities, Treated as One

INTRODUCTION: Composite lymphoma (CL) is defined as two histologically distinct variants of malignant lymphoma occurring in the same organ or mass. Our case describes an asymptomatic patient with two extranodal B-Cell lymphomas discovered after routine colonoscopy. Further, we discuss pathogenesis and treatment philosophy of follicular lymphoma and marginal cell lymphoma. CASE DESCRIPTION/METHODS: A 62 year old Japanese female with multiple medical morbidities including cirrhosis and hypothyroidism presented for surveillance colonoscopy. On presentation, patient denied any fever, chills, night sweats, unintentional weight loss, hematochezia, or melena. Colonoscopy revealed multiple sessile polyps, 2−5 mm in size. H&E and immunohistochemical staining of specimens demonstrated grade 3A follicular lymphoma with 100% follicular pattern and positron emission tomography/computed tomography (PET/CT) demonstrating a prominent, isolated pericaval lymph node. Per NCCN guidelines for follicular lymphoma grade 3A, stage II (non-contiguous), observation with follow up PET/CT and colonoscopy was recommended. Repeat colonoscopy after 6 months revealed multiple polyps with demonstrating extranodal marginal zone b-cell lymphoma of Mucosa-Associated Lymphoid Tissue (MALT). The diagnosis of MALT type lymphoma was rendered based on histologic patterns of infiltration, the cellularity of the infiltrate, their locations, presence of clear cells, and immunostaining. Of note, repeat PET/CT was negative for lymphadenopathy. 6 months later, another colonoscopy was performed, and 6 more polyps were biopsied. Histological examination was consistent with tubular adenomas and follicular lymphoid proliferation. Given that she was clinically stable with minimal disease, plan was to continue monitoring with colonoscopy and PET/CT annually. DISCUSSION: CLs are defined as 2 or more morphologically and/or immunophenotypically different components in the same anatomic site. They can arise synchronously or metachronously. CLs are rare, with a frequency ranging from 1 to 4.7% of lymphoma cases. More rarely, CL has seldom been witnessed in the gastrointestinal tract. To our knowledge, this is the first case reporting composite follicular lymphoma and extranodal marginal zone b-cell lymphoma of MALT in the colon. Current literature suggests the components of CLs progress as separate entities and treatment should be focused on the component with the least favorable prognosis.

Epstein-Barr virus-associated large B-cell lymphoma transformation in marginal zone B-cell lymphoma: a series of four cases.

To present four examples of clonally related Epstein-Barr virus (EBV)-associated large-cell transformation of marginal zone lymphoma (MZL) (of nodal, extranodal and splenic types), occurring 120, 11 and 5months after the initial diagnosis in three instances, and concurrently in one case; and to discuss several interesting features of EBV infection. Somatic mutations were detected by use of a customised panel for next-generation sequencing and polymerase chain reaction studies of IgH in both low-grade and high-grade components of each case. In case 1, the initial biopsy of nodal MZL showed scattered EBV-positive cells, which might constitute an indication of EBV-induced progression. Case 2 showed heterogeneous EBV expression, a phenomenon attributable to loss of the EBV episomes during cell division, or to a secondary superinfection or reactivation of the virus. In case 3, p53 overexpression related to gene mutation and EBV-encoded small RNAs were identified in the same neoplastic component. In case 4, the mucosa-associated lymphoid tissue-type MZL and the high-grade component were identified concurrently in a patient previously treated with methotrexate for an autoimmune disorder. These data suggest that the presence of EBV should be added to the list of potential markers to be analysed for MZL prognosis.

Shear wave elastography as a new method to identify parotid lymphoma in primary Sjögren Syndrome patients: an observational study.

Parotid non-Hodgkin lymphoma (NHL) in primary Sjögren syndrome (pSS) has no specific biomarker for diagnosis. Salivary glands ultrasound (US) is largely used, but its contribution in detecting parotid NHL has not been established. The aim of our study was to determine the added value of bidimensional shear wave elastography (2D-SWE) in pSS diagnosis and to determine its accuracy in identifying parotid NHL. Grey-scale US (GSUS) and 2D-SWE of salivary glands were performed in 35 patients with pSS and 35 healthy controls. The GSUS scores were calculated and the mean of three SWE consecutive measurements was used to appreciate the gland stiffness. SWE increase the diagnostic rate at a cut-off of 6.45kPa (from 88.6 to 94.2%, p < 0.001) only if applied in patients with insufficient GSUS criteria for pSS diagnosis. The parotid glands with NHL (8 patients, all mucosa-associated lymphoid tissue type) had hyperechoic bands in more than half of the glandular parenchyma (in 68.75% of the glands), large hypoechoic area > 20mm (all glands), traced gland area over 5cm2 (all glands), parotid US score greater than 13 (in 68.75% of the glands), and high stiffness (elasticity modulus 13.9 ± 4.08 vs 6.32 ± 2.24) (all p < 0.001). These findings give high sensitivity (92.3%), specificity (100%), and positive (100%) and negative predictive values (98.3%) for NHL identification. The rest of GSUS findings did not correlate with the classic risk factors for lymphoma development (all p > 0.05). 2D-SWE had added value for pSS diagnosis in cases where GSUS aspect is normal or nonspecific. The higher stiffness of parotid NHL can be used for early diagnosis, biopsy guidance, and, possible, for treatment monitoring.

Use of Rituximab in NHL Malt Type Pregnant in I° Trimester for Two Times.

Administration of rituximab, one of the basic drugs for the therapy of B-cell lymphoproliferative diseases, during pregnancy has been suspected to cause developmental fetal events, particularly if given during the first trimester of pregnancy. Therefore, use in pregnancy is not permitted. Howe ver, several cases of pregnant women being treated with rituximab are reported herein; an exception is often made in cases with grave illness.We describe an exceptional case of a woman with non-Hodgkin lymphoma of the mucosa-associated lymphoid tissue type where rituximab was given as a single agent without interruption during two consecutive pregnancies. This case can certainly supply important indications on the safety of rituximab.

Primary Mediastinal Nodal and Extranodal Non-Hodgkin Lymphomas: Current Concepts, Historical Evolution, and Useful Diagnostic Approach: Part 2.

Primary mediastinal non-Hodgkin lymphomas (PM-NHLs) represent ∼5% of all non-Hodgkin lymphomas (NHLs) and comprise lymphomas of B-cell and T-cell origin. PM-NHLs are defined as involvement of mediastinal lymph nodes, thymus, and/or mediastinal organs (heart, lung, pleura, pericardium) by NHL without evidence of systemic disease at presentation. The clinical scenario is variable and depends on the lymphoma subtype. The radiologic presentation is also variable ranging from a mediastinal mass with or without superior vena cava syndrome, a pleural or a cardiac mass associated with effusion, or as an effusion only. The diagnosis of PM-NHLs can only be established by microscopic evaluation, and therefore, general pathologists should be aware of these tumors and familiar with their diagnostic approach. The most common anterior mediastinal NHLs (90% to 95%) are primary mediastinal (PM) large B-cell lymphoma and T-lymphoblastic lymphoma. Thymic marginal zone lymphoma and mediastinal gray zone lymphoma are very rare. The remainder PM-NHLs involving middle or posterior mediastinum include diffuse large B-cell lymphoma (DLBCL) and rare cases of T-cell lymphoma, including anaplastic large cell lymphoma and breast implant-associated anaplastic large cell lymphoma extending to the anterior mediastinum. Primary pleural and cardiac NHLs are mostly DLBCLs. Other rare subtypes of PM-NHLs include DLBCL associated with chronic inflammation/pyothorax-associated lymphoma, fibrin-associated DLBCL (both Epstein-Barr virus positive), and pleural and/or pericardial primary effusion lymphoma (human herpesvirus-8 positive/Epstein-Barr virus positive). We review the historical aspects, epidemiology, clinicoradiologic features, histopathology, immunohistochemistry, differential diagnosis, and relevant cytogenetic and molecular features of the remaining mediastinal B-cell lymphomas, including primary thymic marginal zone lymphoma of the mucosa-associated lymphoid tissue type, other PM small B-cell lymphomas, PM plasmacytoma, and the most relevant PM T-cell lymphomas.