Parotid Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Deep characterization of tumor microenvironments using single cell multi-omics analysis

Abstract Understanding the complexity of cell interactions in the tumor microenvironment (TME) requires the ability to distinguish each cell type, and is a prerequisite of personalized cancer treatments. Here, we use a fully integrated system for single cell RNA sequencing, to simultaneously profile the transcriptome, cell surface proteins and immune repertoire of cells from primary colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Each tumor varied in type and proportion of its cellular components, and in particular in the proportion of immune cells. The CRC tumor consisted of T (3% CD4+, 3% CD8+), B lymphocytes (5% CD79A+) and plasma B cells (11% IGH high). Repertoire sequencing identified a clonal expansion (>4% of B cell clonotypes) suggesting a strong B cell response in this tumor. The NSCLC tumor displayed a marked immune cell infiltration containing predominantly B cells (30% CD79A+ and 8% IGH high plasma B) with a very limited clonal expansion. The MALT lymphoma consisted of only T and B lymphocytes (31% CD4+, 8% CD8+, 57% CD79A+). In addition to the activated CD4+ and CD8+ T cells, Tfh and Treg cells were clearly identified as well as two distinct large B cell populations showing plasmacytic differentiation. Analysis of the B cell repertoire revealed a large expanded clone bearing an IGHV segment associated with parotid MALT lymphoma. These findings emphasize the importance of combining repertoire and gene expression sequencing data to determine the nature and clonality of an immune response. This method enables full characterization of tumor heterogeneity and the adaptive immune response to the TME and will be key in the development of successful immunotherapies.

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.

Simultaneous MALT lymphoma of the thymus and parotid gland: independent lymphomas or metastatic spread?

Background: Mucosa associated lymphoid tissue (MALT) lymphoma of the thymus is rare and generally associated with autoimmune disorders. It is generally suspected in middle-aged asian women with Sjogren’s syndrome or other autoimmune diseases presenting a multicystic mediastinal mass. Contrary to other MALT lymphomas, the etiology of these tumors is still uncertain especially those affecting patients with no autoimmune diseases. Thymic MALT lymphoma with simultaneous salivary gland involvement is extremely rare, with only few cases described in literature. Case presentation: We present a case of a 33 years-old male, with a recent history of MALT lymphoma of right parotid gland, affected by thymic mass. The patient underwent a right video-assisted thoracoscopy with radical thymectomy. The histological examination revealed a MALT lymphoma of the thymus. The molecular analysis on both thymic and parotid MALT lymphoma for clonal rearrangement of the immunoglobulin heavy chain gene suggests the origin from the same lymphomatous clone. Conclusions: It is still unclear if multiple localizations of MALT lymphomas are attributable to the development of different primary lymphomas or can be caused by lymphatic metastatic spread. Our analysis reveal that the hypothesis of metastatic spread cannot be excluded in patients with simultaneous MALT lymphoma of the thymus and parotid gland, especially in non-autoimmune related MALT lymphomas.

Treatment of Parotid Non-Hodgkin Lymphoma: A Meta-Analysis.

PurposeThis meta-analysis aimed to review the published outcomes of parotid non-Hodgkin lymphoma (NHL) pertaining to different treatment modalities.Materials and MethodsA total of 48 journal articles published between 1993 and 2015, comprising 742 cases of parotid NHL, were initially evaluated. In total, 108 patients from 12 studies who had sufficient data for analysis, including age, tumor histopathology, treatment modality, and outcome at final follow-up, were included. Patients were randomly assigned to different categories on the basis of histopathology and treatment modality. Groups were compared using Kaplan-Meier survival curve analysis and the Mann-Whitney U test.ResultsLog-rank tests demonstrated that for early-stage (I and II) parotid NHL of all histopathology variants, radiation therapy significantly improved the survival rate versus chemotherapy (P = .043), as well as combined treatment with chemotherapy and radiation therapy (P = .023). For early-stage diffuse large B-cell lymphoma, combined treatment significantly improved survival versus single treatment (P = .028). No treatment was received by seven patients with early-stage mucosa-associated lymphoid tissue lymphoma after undergoing parotidectomy. When the clinical outcomes of these patients were compared with those of other patients with the same histology who underwent further treatment, no significant differences were noted in survival outcomes.ConclusionRadiation therapy seems to be a valid treatment of early-stage parotid NHL. However, for diffuse large B-cell lymphoma, survival was higher with combined treatment versus single treatment. For early-stage parotid mucosa-associated lymphoid tissue lymphoma, complete excision of the tumor through superficial parotidectomy may have similar survival outcome.

Germinal centres in diagnostic labial gland biopsies of patients with primary Sjögren’s syndrome are not predictive for parotid MALT lymphoma development

ObjectivePatients with primary Sjögren’s syndrome (pSS) have an increased risk of developing non-Hodgkin’s lymphoma (NHL), particularly parotid gland mucosa-associated lymphoid tissue (MALT) lymphomas. Presence of germinal centres (GCs) in labial...

FcRL4+ B-cells in salivary glands of primary Sjögren's syndrome patients

Fc receptor-like protein 4 (FcRL4) is normally expressed on a small subset of mucosa-associated B-cells, as well as on mucosa-associated lymphoid tissue (MALT) lymphoma B-cells. Primary Sjögren's syndrome (pSS) patients have an increased risk of developing MALT lymphomas, preferentially in the parotid glands. For this reason we studied here by immunohistochemistry and mRNA analysis whether FcRL4 expressing B-cells are present in salivary gland tissue (labial and parotid) of pSS patients (n = 54) and non-pSS sicca patients (n = 16) and whether parotid gland MALT lymphomas in pSS patients (n = 49) also express this receptor. We also studied the effect of treatment (rituximab and abatacept) on the presence of FcRL4+ B-cells, and whether numbers in labial gland biopsies at time of diagnosis of pSS can predict whether patients are at risk for MALT lymphoma development.We demonstrate that FcRL4+ cells are present in salivary gland tissue of pSS patients where they are closely associated with ductal epithelial cells forming lymphoepithelial lesions. The glandular FcRL4+ cells are highly proliferative, genuine PAX5+ B-cells. These FcRL4+ B-cells are far more frequent in parotid gland than in labial gland tissue (p = 0.003). We further show that expression of FcRL4 is present in pSS-related parotid MALT lymphomas. The FcRL4 mRNA expression level in parotid MALT lymphoma is increased compared to parotid gland tissue of pSS patients without lymphoma (p = 0.017). However, numbers of FcRL4+ B-cells in labial gland biopsies taken at the time of pSS diagnosis, are not predictive for later development of MALT lymphoma. Reduction of parotid gland FcRL4+ B-cells by rituximab, but not abatacept is accompanied by restoration of the glandular epithelium, illustrating the crosstalk between these B-cells with the ductal cells.In conclusion, intraepithelial FcRL4+ B-cells are present in the salivary glands of pSS patients. These cells are likely involved in the epithelial changes seen in pSS. Their enrichment in parotid glands may explain why MALT lymphomas in pSS patients preferentially develop at this specific location.

Non-Hodgkin lymphoma involving the parotid gland: CT and MR imaging findings

As an uncommon neoplasm, parotid non-Hodgkin lymphoma (NHL) comprises mucosa-associated lymphoid tissue (MALT) and non-MALT lymphomas. Both types of lymphoma vary in prognosis and treatment. The aim of this study was to explore CT and MRI characteristics of these two types of lymphoma. 61 cases of parotid NHL, 34 MALT and 27 non-MALT lymphomas with histopathological confirmation were examined with routine CT and MR scans prior to treatment, and retrospectively reviewed. On CT and MRI, 34 MALT lymphomas presented with 11 solid and 23 solid-cystic forms, whereas 27 non-MALT lymphomas presented with 25 solid and 2 solid-cystic forms (p < 0.01). Parotid MALT lymphoma is characterized mainly by the solid-cystic form, whereas non-MALT lymphoma is characterized mainly by the solid form. The differences on CT and MRI can offer helpful information for differentiation of both types of parotid NHL.

Nodular Pulmonary Amyloidosis Is Characterized by Localized Immunoglobulin Deposition and Is Frequently Associated With an Indolent B-cell Lymphoproliferative Disorder

Nodular pulmonary amyloidosis, a rare localized form of amyloidosis, has been associated with immunoglobulin light chains (AL type) and variably with low-grade lymphoma. The clinicopathologic features of 18 cases were investigated; 5 of 14 had autoimmune disease. In 14 cases monotypic plasma cells could be demonstrated by immunohistochemistry. By mass spectrometry analysis of the amyloid deposits, all 18 cases showed a peptide profile with an abundance of immunoglobulin light chains (12 κ, 4 λ, and 2 mixed κ and λ), with 13 also showing significant codeposition of heavy chains (10 γ, 2 α, 1 δ). Of 14 patients with follow-up, 3 developed recurrent pulmonary amyloidoma, 2 had pulmonary recurrence plus cutaneous extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type with and without amyloid, and 1 had a history of parotid gland MALT lymphoma. This study highlights the unique features of this localized form of amyloidosis. AL κ type is more frequent than AL λ type, with a ratio of 3:1, in contrast to the AL λ predominance that characterizes systemic AL amyloidosis. In addition, the majority of nodular pulmonary amyloid is of mixed AL/AH type, a rare finding in systemic amyloidosis. The association of nodular pulmonary amyloidoma with autoimmune disease and lymphoma indicate the majority of these lesions relate to an underlying lymphoplasmacytic neoplasm in the spectrum of MALT lymphoma.

Primary Parotid MALT Lymphoma: Clinical Characteristics and Treatment – a Single Institution Experience

Abstract 1580 Background:Extranodal Marginal Zone Lymphomas of Mucosa Associated Lymphoid Tissue (MALT) account for approximately 5% of all non-Hodgkin Lymphoma cases. Specific MALT lymphomas are characterized by distinct clinical features, treatment strategies, and outcome, depending on site of the disease. While previous reports have described clinical course and treatment of gastric and pulmonary MALT lymphomas, a paucity of data exist describing primary parotid MALT lymphoma. This is a single institution experience. Methods:Patients with primary parotid MALT lymphoma were identified from the Mayo Clinic Lymphoma Database since 1986. This database includes all consenting patients with lymphoma seen at Mayo Clinic Rochester. Clinical characteristics, treatment, and outcomes were collected. Pathology was reviewed by a lymphoma pathologist; WHO criteria were used for diagnosis. PFS and OS were assessed using the Kaplan-Meier method and Cox proportional hazard model was used to asses the impact of variables on PFS and OS. Results:Seventy-six consecutive patients with primary parotid MALT lymphoma were evaluated and treated at Mayo Clinic from 1986 to 2010. The median age at diagnosis was 60 years (18–90). 58 (76%) were female. 42 (55.3%) patients had a history of Sjögren’s Disease and 51 (67.1%) had a history of autoimmune disorders. 52 (68.4%), 4 (5.3%), and18 (23.7%) had stage I, II, and IV disease, respectively. 2 cases did not have complete staging information. 6 (7.8%) and 2 (2.6 %) had bone marrow and lung involvement, respectively. No patients had GI tract, liver, or CNS involvement. Median estimated OS (overall survival) was 18.3 years and median PFS (progression free survival) was 7.9 years. ALC<0.96 (p=0.0162) were associated with shorter survival. Age, ECOG performance score, stage, LDH, and history of Sjögren’s disease were not prognostic for overall survival. The treatment approach and PFS are outlined in the table. For stage I disease, outcomes were excellent with local therapy. The median estimated PFS was 7.9 years with 72% of patients undergoing surgery surviving at 8 years. Patients receiving radiotherapy had an estimated median PFS of 15.7 years and median OS of 18.3 years. In contrast, patients being observed had a median PFS of 5.5 years. The use of systemic therapy with chemotherapy, immunotherapy or in combination was associated with a median PFS of 7.4 years. Summary:Primary parotid MALT lymphoma is strongly associated with Sjögren’s disease. This lymphoma is usually limited to the parotid and associated with a favorable prognosis. For limited disease, local treatment with radiation or surgery appears to be an effective treatment options. For extensive disease, both immunotherapy and chemotherapy are efficacious treatments. Further prospective studies and long-term follow up are needed to determine the optimal treatment approaches and efficacy of chemotherapy/immunotherapy regimens. [Display omitted] Table 1Treatmentn (%)Response Rate CR/PR n (%)Median PFSSurgery29 (38%)26 (90%)/07.9 yearsRadiation14 (18%)14 (100%)/015.7 yearsObservation13 (17%)NA5.5 yearsChemotherapy/Immunotherapy7 (9%)7 (100%)/07.4 yearsIncomplete Data13 (17%)NANA Disclosures:No relevant conflicts of interest to declare.

Clinicopathological aspects of mucosa‐associated lymphoid tissue (MALT) lymphoma of the parotid gland: A retrospective single‐center analysis of 28 cases

In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland has not been studied extensively. We analyzed the clinicopathological features and the clinical course of all patients with parotid gland MALT lymphoma diagnosed and treated at our institution. Patient characteristics including an underlying autoimmune disease, disease stage, genetic aberrations, treatment, and clinical course were assessed and evaluated. Twenty-eight patients (19 women, 9 men) were identified; median age at diagnosis was 49 years (interquartile range [IQR], 40-56), and 18 patients (64%) had an underlying autoimmune disease. Eleven had stage IE, 7 patients had stage IIE, and 10 had advanced disease (stage IV). Genetic aberrations were detected in 9 of 20 patients; 5 patients had trisomy 3, 2 patients had a t(11;18)(q21;21) translocation, 1 had trisomy 3 and 18, and 1 patient had a t(14;18)(q32;q21) translocation plus trisomy 18. After a median follow-up time of 62 months (IQR, 32-98 months), 24 patients (86%) are alive. Fifteen patients are free from lymphoma, whereas 13 patients (46%) have had a relapse. Our data suggest that MALT lymphoma of the parotid gland is often associated with autoimmune diseases and that trisomy 3 is the most common genetic feature of this disease. The high rate of relapse warrants further study on optimal therapy of such patients.

Cytogenetic abnormalities in MALT lymphomas and their precursor lesions from different organs. A fluorescence in situ hybridization (FISH) study

To analyse the possible activation of distinct molecular pathways in mucosa-associated lymphoid tissue (MALT) lymphoma, we determined the prevalence of trisomies 3, 12, 18 in MALT lymphomas from different organs, as well as the prevalence of translocations of the MALT1 gene in a subset of primary breast MALT lymphomas. We compared the numerical cytogenetic alterations in lymphomas, precursor lesions and in normal non-haematolymphoid tissue from the same organs. Forty-two samples of paraffin-embedded tissue (29 MALT lymphomas from stomach, breast, parotid and thyroid; two Sjögren's syndrome; two Hashimoto's thyroiditis and nine reactive samples) were studied by fluorescence in situ hybridization (FISH). Analysed together, the cases of gastric, parotid and thyroid MALT lymphomas presented trisomy 3 in 46%, trisomy 12 in 28% and trisomy 18 in 21% of the cases. In contrast to other locations, trisomy 3 was not present in the majority of the cases of primary breast MALT lymphomas. None of the nine breast cases presented MALT1 gene rearrangements. Half of the cases of preneoplastic lesions exhibited trisomy 3 and trisomy 12; none exhibited trisomy 18. Trisomy 3 is the most frequent numerical abnormality in gastric, parotid and thyroid but not in primary breast MALT lymphomas. MALT1 gene rearrangements are also rare in this location, suggesting that distinct molecular pathways may be activated in breast cases.

Mucosa-associated lymphoid tissue lymphoma presented as diffuse swelling of the parotid gland

Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct subtype of lymphoma. Parotid MALT lymphoma is a rare tumor that is hard to diagnose by fine-needle aspiration cytology. Therefore, partial parotidectomy is often required for a pathological diagnosis. We report a case of MALT lymphoma presented as unilateral diffuse swelling of the parotid gland, who was diagnosed by partial parotidectomy and underwent radiotherapy.

MALT-type lymphoma and Warthin's tumour presenting in the same parotid gland

Non-disseminated malignant lymphomas of salivary glands occurring in association with Warthin's tumour have rarely been reported. We describe the first case of association of an extranodal mucosa-associated lymphoid tissue (MALT)-type non-Hodgkin's lymphoma with Warthin's tumour of the parotid gland. Total parotidectomy with preservation of the facial nerve was performed. Surgical and pathological evidence confirmed that the parotid MALT lymphoma did not arise in the lymphoid stroma of the Warthin's tumour. Immunostaining of the MALT lymphoma cells proved negative for Epstein–Barr virus and Helicobacter pylori antibodies and polymerase chain reaction assays did not identify human herpesvirus 8. The patient has been followed up for 11 months, without evidence of recurrent disease. It cannot be ruled out that long-term immunological stimulation by the Warthin's tumour may have caused lymphoid accumulation, chronic stimulation of B cells and extranodal parotid MALT lymphomagenesis.