Extranodal Mucosa-associated Lymphoid Tissue Research Articles

Primary lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) in the urinary bladder mimicking recurrent urinary tract infection: a case report and literature review

We report the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder. The patient, with urinary frequency, urgency and suprapubic pain had several emergency room visits due to recurrent urinary tract infection. Both sonogram and cystoscopy identified bladder tumors near the bladder neck. An abdominal contrast-enhanced computed tomography scan revealed a polypoid lesion on the anterior bladder wall without enlarged lymph nodes. Transurethral resection of the bladder tumor was conducted. The pathology report confirmed extranodal marginal zone MALT lymphoma. The clinical stage was IEA. Follow-up imaging reported residual bladder tumors, prompting adjuvant radiotherapy. The patient was treated successfully and was disease-free at the 9-month follow-up visit. Primary lymphoma is an uncommon pathological subtype. Its clinical and radiological differentiation from urothelial carcinoma (UC) can be challenging, but treatment strategies differ significantly. A definitive diagnosis relies on histopathology and immunohistochemistry. Typically, bladder lymphoma has a favorable prognosis, but further research is required to identify the optimal treatment.

Linfoma não Hodgkin da Zona Marginal Extranodal Tipo MALT com Acometimento da Coluna Torácica: revisão Sistemática da Literatura e Relato de Caso em um Hospital Universitário no Brasil

Background: Primary bone lymphomas are rare, accounting for less than 1% of non-Hodgkin's lymphomas (NHL). Extranodal marginal zone non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the vertebral spine is extremely rare, with only seven cases reported. Methodology: A systematic literature review was conducted on cases from 2012 to 2022 of extranodal marginal zone MALT lymphoma involving the vertebral spine and associated with spinal cord compression. Additionally, a case report from a university hospital in Rio de Janeiro is described. The study was approved by the Research Ethics Committee (approval number: 5.818.416). Searches were performed in SciELO, PubMed, and LILACS databases, using the Health Sciences Descriptors: ("Vertebral Body" OR Spine) AND ("Lymphoma B-Cell Marginal Zone" OR "MALT Lymphoma" OR "Lymphoma of Mucosa Associated Lymphoid Tissue" OR "Mucosa Associated Lymphoid Tissue Lymphoma"). Articles with full texts available in English or Portuguese were selected. Case Description: A 56-year-old female presented with right-sided back pain, progressing to right flank irradiation, lower limb weakness (LLLL), and constitutional symptoms. MRI revealed a solid extradural mass occupying two-thirds of the vertebral canal's diameter, displacing and compressing the dorsal cord to the left. A bone marrow biopsy confirmed infiltration. Laminectomy was performed, and histopathology identified stage IVB extranodal marginal zone MALT lymphoma. Adjuvant chemotherapy led to complete remission. Results and Discussion: The literature review uncovered two relevant case reports. The thoracic spine was the most commonly affected region, and LLLL weakness was the most frequent symptom, with normal laboratory results. Treatment typically involved surgical tumor removal combined with radiotherapy or chemotherapy. Recurrence occurred in both cases, but follow-up showed no evidence of disease. The clinical presentation and exam findings of the current patient were similar to those in the literature, though with bone marrow infiltration. Treatment was consistent with cases in the review, with no recurrence to date. Conclusion: This case represents an uncommon manifestation of primary extranodal marginal zone MALT lymphoma with spinal cord compression, distinguished by bone marrow infiltration—a feature not previously reported in the two cases found in the literature. The case may be considered within the same group of cases reviewed.

Extranodal Marginal Zone Lymphoma of Mucosa Associated Lymphoid Tissue (MALT LYMPHOMA) With Extensive Plasma Cell Differentiation and Localized Amyloid Deposition.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature and clinically indolent B cell lymphoma composed of heterogeneous cell population. Plasma cell differentiation is commonly seen in MALT lymphomas. However, plasmacytic differentiation along with localized amyloid deposition in the lungs is an extremely rare. We encountered a unique case of Extranodal MALT lymphoma with extensive plasmacytic differentiation and amyloid deposition. A 78-year-old female with past history of Gastric MALT lymphoma, status post chemotherapy presented in outpatient clinic. PET scan revealed an incidental 9 mm nodule in left lung, and subsequently underwent biopsy. Histology showed sheets of heterogeneous neoplastic cells including small lymphocytes, monocytoid cells, and abundant number of plasma cells (Fig A) in the background of hyalinization (Fig B). Immunohistochemical (IHC) reveals lymphoma cells are positive for CD20 (Fig C) and CD43, and plasma cells showed lambda restriction (Fig D). Furthermore, Congo Red stain of eosinophilic background showed positive birefringence upon polarization, consistent with Amyloid. Great caution is required in differentiating these cases from lymphoplasmacytic lymphoma as the histologic and IHC features can significantly overlap, and studies have also suggested that plasmacytic differentiation in these cases represent precursor neoplasm of plasma cells. Amyloid depositions in MALT lymphomas are rare and organ confined but can lead to local complications and cause considerable morbidity. Therefore, it is necessary to be aware of the association between MALT lymphoma with extensive plasma cell differentiation and amyloid deposition, as close clinical follow up is recommended.

The clinical significance of increased large cells in marginal zone lymphoma

Marginal zone lymphoma (MZL) is a primary, indolent small B-cell lymphoma. Subtypes include nodal, splenic, and those of extranodal mucosa-associated lymphoid tissue (MALT). These are slow growing and generally exhibit low rates of transformation to diffuse large B-cell lymphoma (DLBCL). At initial diagnosis, there can be an increase in large cells (LCs) that does not meet criteria for DLBCL. Prior studies have noted this finding, but the clinical significance of these LCs has not been well established. A total of 161 cases of MZL from 1994 to 2021 were evaluated, including all subtypes. There were 33 cases with increased LCs (>10 LCs per high-power field [hpf]), with the majority containing >15 LCs/hpf (28/33) and 128 cases without increased LCs. Cases with increased LCswere significantly more likely to have a Ki-67 proliferation index of ≥30% (P<.0001). Overall survival was not significantly different between the groups but progression-free survival was significantly worse in the LC group (P<.0001). MZL with increased LCs was also associated with a higher stage at diagnosis (P=.0035), was more likely to transform to DLBCL (P=.0016), and had a greater frequency of relapse (P<.0001). Subgroup analysis showed that both nodal and MALT LC groups had a worse progression-free survival and a higher rate of relapse than their standard nodal and MALT lymphoma counterparts, but only within the MALT subgroup did the LC cases present at a higher stage and have a higher rate of transformation to DLBCL than the standard cases. Although larger studies are needed for validation, these results suggest that the presence of LCs in MZL may serve as a useful prognostic indicator and potentially help guide clinical decision-making.

A rare cause of hematochezia: colonic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma): A case report and literature review.

Colonic extranodal mucosa-associated lymphoid tissue lymphoma as a cause of hematochezia is rare. Here, we report a case of colonic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) with presentation of freshy bloody stool and successfully treated by endoscopic mucosal resection. This case was a 69-year-old woman with history of hypertension, reflux esophagitis, and peptic ulcer. She had several episodes of hematochezia and thus sought medical attention at the outpatient clinic. Colonoscopy revealed a 12-mm semipedunculated lesion in the ascending colon. Histopathological examination and immunochemistry were compatible with colonic extranodal mucosa-associated lymphoid tissue lymphoma. Endoscopic mucosal resection was done for tumor removal and hemoclipping was done to achieve hemostasis. The patient remained well without recurrence during 3 years of outpatient follow-up. Colonic MALToma is a rare disease, and could present as hematochezia. En bloc endoscopic resection could achieve long-term remission. The prognosis of colonic MALToma is excellent with its indolent characteristics.

A Rare Case of Hepatic MALT Lymphoma with Coexistence of Hepatitis B Virus and Echinococcus Infection

Primary hepatic extranodal mucosa-associated lymphoid tissue (MALT) lymphoma is seen extremely rare compromising 0,016% among non-Hodgkin lymphomas. Association of chronic inflammatory conditions or infectious processes mostly hepatitis B virus (HBV) infection has been reported by scarce number of case presentations. Whereas MALT lymphoma accompanied by echinococcus granulosus infection was described only in one primary pulmonary lymphoma case. We herein present a primary hepatic MALT lymphoma case with both HBV carrier state and liver hydatid cyst history. A 86 years old male patient referred to our clinic with a sole liver mass and was diagnosed with primary hepatic MALT lymphoma by core biopsy. Positron emission tomography detected increased uptake in the liver lesion without any other uptake site. He was successfully treated with rituximab-chemotherapy, tenofovir and albendazole. By adding one more case to the literature we aimed to emphasize the probable etiologic causative role of echinococcus infection in MALT lymphoma.

Is There a Role for [18F]FDG PET-CT in Staging MALT Lymphoma?

Simple SummaryMALT lymphoma represents a relatively rare lymphoma subtype that arises in different extranodal anatomic locations. In the current paper we summarize our experience in assessing disease extent and metabolic characteristics of MALT lymphomas with [18F]FDG PET-CT at staging, and aim to highlight the strengths and challenges this imaging modality poses. In our data, all extranodal lesions located in subcutaneous-tissue, lung and liver were detected on PET, while some of those located in other tissues (such as along the digestive tract) were not detected on PET. We also evaluated the predictive role of PET in these patients, and found that increased [18F]FDG-uptake in extranodal lesions was associated with worse disease progression.The role of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography—computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [18F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the “hottest” extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [18F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [18F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01–1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [18F]FDG-uptake is excellent on [18F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS.

P27 Lymphoma-mimicker of IgG4-related dacryoadenitis and sialadenitis

Case report - IntroductionMajor salivary gland (sialadenitis) and lacrimal gland (dacryoadenitis) involvement can be a common feature of IgG4-related disease. There can be involvement of lacrimal and parotid gland which was previously called as Mikulicz disease and/or submandibular gland enlargement which was previously called Küttner tumour. These were previously mistakenly considered to be subcategories of Sjogren’s syndrome, but are now classified as IgG4-related disease. Here we discuss a case report of a patient who presented with bilateral dacryoadenitis and unilateral submandibular gland enlargement which initially was thought to be IgG4-related disease but turned out to be low-grade lymphoma.Case report - Case descriptionA 15-year-old boy presented with 6-month history of bilateral eyelid swelling. The swelling was more on the lateral side of the eyelids and was painless. It had come on suddenly over a couple of days. No history of weight loss, dry eyes, dry mouth, joint issues or skin rashes or any other symptoms. Physical examination revealed bilateral ptosis, no visual impairment and systemic examination revealed an enlarged right submandibular gland. He had initially been to a local hospital where he had investigations which included autoimmune screen including ANA, ENA, ANCA, dsDNA, serum ace and complement levels which were all negative. C1 esterase inhibitor was normal. Routine bloods including complete blood count, urea and electrolytes, thyroid stimulating hormone and erythrocyte sedimentation rate were within normal limits. Urine albumin to creatinine ratio was not raised. Hepatitis serology including Hepatitis B & C and HIV was negative. Ultrasound abdomen was unremarkable. CT scan of orbits showed bilateral enlarged lacrimal glands with patchy post contrast enhancement and the glands extending up to insertion of lateral rectus muscle. CT chest some enlarged axillary lymph nodes and nodes in lung query infective etiology. CT abdomen and pelvis was unremarkable. Ultrasound neck showed right submandibular node enlargement with colour doppler showing increased vascularity. Fine needle aspirate of the submandibular gland showed reactive lymphoid hyperplasia. He was given two short courses of steroids and each time the swelling rapidly responded to the steroids but recurred on cessation of the steroids. IgG subset analyses revealed elevated IgG4 levels of 1152mg/dl. The differential here was IgG4-related disease but as there was no clear tissue diagnosis a core biopsy of the right submandibular gland was done. This revealed tissue suspicious of low grade (extranodal marginal zone and mucosa-associated lymphoid tissue [MALT]) lymphoma and excision biopsy was performed for definitive diagnosis.Case report - DiscussionIgG4-related disease is an immune mediated fibroinflammatory condition which can affect a variety of organs and can present as tumour-like enlargement and/or organ dysfunction. The pathological findings in IgG4-related disease are lymphoplasmocytic infiltrates of IgG4-positive cells along with increased levels of serum IgG4 levels. Salivary and lacrimal glands can be commonly affected and present as enlargement, which is usually painless and bilateral. The combination of lacrimal gland enlargement with both parotid and submandibular gland enlargement is called IgG4-related Mikulicz disease.Apart from salivary glands, another commonly affected organ is the pancreas which can present as a pancreatic mass and painless jaundice, sclerosing cholangitis, retroperitoneal fibrosis, aortitis and periaortitis. Less commonly it can affect thyroid, kidney and lungs.Early recognition, diagnoses and treatment is important due to the fibroinflammatory nature of the disease. Malignancy is always in the differential and should be excluded. Steroids are the mainstay of treatment. If patients experience flare, rituximab can be added.Diagnosis should be confirmed with biopsy but histopathological findings are never alone diagnostic of IgG4-related disease and should be interpreted with clinical, serological and radiological findings.Case report - Key learning pointsAlthough this patient had typical presentation of IgG4-related disease with painless enlargement of salivary and lacrimal glands and elevated IgG4 serum levels, biopsy was imperative to get to the diagnoses of low-grade lymphoma and fine needle aspirate was not adequate. As mentioned above, biopsy in IgG4-related disease will confirm the diagnosis provided there are other supporting features (radiological and serological). However, it is imperative for excluding other important diseases like lymphoproliferative disorders.

A Case Report of Non-Hodgkin Low-grade B-cell Mucosa-associated Lymphoid Tissue Lymphoma Presenting as a Suspected Endodontic Lesion

Extranodal mucosa-associated lymphoid tissue lymphoma is a rare oral disease. This case report describes a 71-year-old woman who presented for endodontic evaluation and treatment for swelling on the right posterior palatal. The case details the evaluation and diagnostic processes and treatment course. The case report draws attention to the importance of performing a biopsy, having proper sampling, and the additional steps sometimes required to arrive at a definitive diagnosis. This case report is the first to document a definitive low-grade B-cell mucosa-associated lymphoid tissue lymphoma mimicking endodontic pathology. The case shows the importance of proper examination, clinical imaging, and pathologic testing to arrive at a definitive diagnosis. It highlights that collaboration with other medical and dental specialties is essential for appropriate diagnosis and treatment and describes the “buttonhole” diagnostic strategy.

PNEUMONIA OR LYMPHOMA? DO NOT BE FOOLED!

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Mucosa-associated lymphoid tissue (MALT) Lymphoma, also known as Extranodal Marginal Zone B cell lymphoma (EMZL), is a rare type of non-Hodgkin’s lymphoma with an incidence rate of 18.3 cases per 1 million in the United States. The objective of this case is to describe a challenging case of EMZL presenting as persistent localized lung consolidation that was mistaken for pneumonia. CASE PRESENTATION: 77-year-old male, former smoker who presented with complains of nonproductive cough for several weeks, chest-x-ray (CXR) showed a 4.3 cm rounded hazy right parahilar mass. A follow up computed tomography (CT) of the chest revealed 4.7 x2.8 cm consolidative opacity along the interlobar fissure in the right upper lobe (RUL). Reviewing back a year ago, CT scan done for nonspecific chest pain, showed the mass size was unchanged but appeared to be less solid compared to the current scan. Patient underwent a Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan which showed elevated FDG activity SUV 3.0 associated with a consolidative pulmonary opacity in the posterior portion of the right upper lobe silhouetting the major fissure. The patient subsequently underwent a CT guided percutaneous biopsy of the right upper lobe airspace consolidation. Histologic sections showed interstitial expansion and bronchial epithelium involvement by small monocytoid- appearing lymphocytes and significant amount of plasma cells (Figure 1). Immunohistochemistry was positive for CD20 and BCL-2 and negative for BCL-6 and CD10. CD138 which highlights plasma cell component was positive. Immunostaining for kappa and lambda showed findings most suggestive of monotypic lambda expression. Fluorescence in situ hybridization (FISH) studies for MALT1 (18q21) rearrangement identified a MALT1 gene rearrangement and B cell clonality studies done by PCR were positive for a clonal rearrangement. Therefore, the final diagnosis was small B-cell non-hodgkin lymphoma consistent with extranodal MALT. In retrospect the lymphoma was likely present a year ago however mistaken as a pneumonia. Given the lack of symptoms and minimal progression of over one year, was consistent with the indolent clinical behavior of the tumor. Decision was made not to treat at this point by the physician and patient. Till date patient remain asymptomatic. DISCUSSION: EMZL has been associated with persistent inflammatory state, either infectious or autoimmune in nature. EMZL can present in various ways from an incidental finding on imaging to ambiguous symptoms such as dyspnea, chest pain, cough, and rarely hemoptysis. Prognosis in MALT-type lymphomas is generally good with mean survival of more than 10 years. CONCLUSIONS: In conclusion, EMZL of the lung is uncommon and unique therefore a collaborative effort addressing early diagnosis and less invasive diagnostic testing for these high-risk EMZL patients are needed. Reference #1: Khalil MO, Morton LM, Devesa SS, et al. Incidence of marginal zone lymphoma in the United States, 2001 to 2009 with a focus on primary anatomic stie. Br J Haematol 2014; 165:67 Reference #2: Santos IG, Marchiori E, Zanetti G, Mano CM, SarcielliLuz B, Vianna FG. Primary pulmonary mucosaasociated lymphoid tissue lymphoma computed tomography findings: A case report. Cases J. 2009;2:6329. [PMCID:PMC2740136] [PubMed: 19829788] DISCLOSURES: No relevant relationships by Hussein Hussein, source=Web Response No relevant relationships by Ahmad JABRI, source=Web Response No relevant relationships by Sonya Joshi, source=Web Response No relevant relationships by Sujith Modugula, source=Web Response No relevant relationships by Elizabeth Verghese, source=Web Response

PTEN Loss and Cyclin A2 Upregulation Define a PI3K/AKT Pathway Activation in Helicobacter pylori-induced MALT and DLBCL Gastric Lymphoma With Features of MALT.

Helicobacter pylori infection is strongly associated with primary gastric diseases, such as extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma (DLBCL) with histologic evidence of MALT origin, and gastric carcinoma. The cytotoxin-associated gene A (CagA) protein behaves as a bacterial oncoprotein, promoting tumorigenesis via dysregulation of the phosphatidylinositol 3-kinase/AKT pathway (PI3K/AKT). We investigated the molecular mechanisms of PI3K/AKT pathway dysregulation in H. pylori-induced MALT and DLBCL gastric lymphoma. Immunohistochemical assays for CagA, phospho(p)-S473-AKT, PTEN, SHIP, and cyclin A2 proteins were performed on samples from 23 patients with H. pylori-positive MALT lymphoma and 16 patients with H. pylori-positive gastric DLBCL. We showed that CagA localization is correlated with the activation of the AKT pathway in both MALT and DLBCL lymphoma cells. Interestingly, we found a close association between the loss of PTEN, the overexpression of cyclin A2, and the phosphorylation of AKT in gastric MALT and DLBCL tumor cells.

MRI and PET/MRI in hematologic malignancies

The role of MRI differs considerably between the three main groups of hematological malignancies: lymphoma, leukemia, and myeloma. In myeloma, whole‐body MRI (WB‐MRI) is recognized as a highly sensitive test for the assessment of myeloma, and is also endorsed by clinical guidelines, especially for detection and staging. In lymphoma, WB‐MRI is presently not recommended, and merely serves as an alternative technique to the current standard imaging test, [18F]FDG‐PET/CT, especially in pediatric patients. Even for lymphomas with variable FDG avidity, such as extranodal mucosa‐associated lymphoid tissue lymphoma (MALT), contrast‐enhanced computed tomography (CT), but not WB‐MRI, is presently recommended, despite the high sensitivity of diffusion‐weighted MRI and its ability to capture treatment response that has been reported in the literature. In leukemia, neither MRI nor any other cross‐sectional imaging test (including positron emission tomography [PET]) is currently recommended outside of clinical trials. This review article discusses current clinical applications as well as the main research topics for MRI, as well as PET/MRI, in the field of hematological malignancies, with a focus on functional MRI techniques such as diffusion‐weighted imaging and dynamic contrast‐enhanced MRI, on the one hand, and novel, non‐FDG PET imaging probes such as the CXCR4 radiotracer [68Ga]Ga‐Pentixafor and the amino acid radiotracer [11C]methionine, on the other hand. Level of Evidence: 5 Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1325–1335.

CHRONIC PARENCHYMAL INFILTRATION FROM MALT LYMPHOMA: DIAGNOSIS BY ENDOBRONCHIAL ULTRASOUND

SESSION TITLE: Lung Pathology 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare cause of pulmonary infiltrate. The lung accounts for only 4% of all extra-nodal marginal zone MALT lymphomas [1] and presents mostly as an incidental finding or with non-specific symptoms. CASE PRESENTATION: A previously healthy 59-year-old man presented with chest pain in 2013. A chest radiograph noted bilateral infrahiliar masses. Computed tomography (CT) of the chest showed bilateral lung consolidations (Figure 1). He was treated with antibiotics and lost to follow up. Five years later the patient presented with transient stroke-like symptoms and a chest x-ray showed a persistent infiltrate. CT chest noted large bibasilar consolidations with air bronchograms and dilated bronchi (Figure 2). These infiltrates were hypermetabolic on positron emission tomography (PET) with a maximum standardized uptake value (SUV) of 6.4. The patient underwent bronchoscopy with endobronchial ultrasound guided transbronchial 19 gauge needle aspiration (EBUS-TBNA) of the consolidative lesions. Immunohistochemistry and flow cytometry confirmed a diagnosis of MALT lymphoma. He was referred to oncology and initiated on rituximab and bendamustine. DISCUSSION: MALT lymphoma of the lung is a relatively rare disease that has been associated with chronic antigen stimulation in the context of infection, autoimmune disease and toxic exposure. The clinical presentation and radiographic findings are varied and can be mistaken for more common entities. Lesions are usually bilateral and often have associated air bronchograms and bronchiectasis [2]. The disease usually has an indolent course with a favorable prognosis. In most reported cases, diagnosis was achieved with open lung or CT-guided biopsy. The role of EBUS-TBNA for pulmonary MALT lymphoma has been previously described in mediastinal lymphadenopathy and was found to be useful [3]. To our knowledge, this is the first case of EBUS-TBNA of lung infiltrates to diagnose this condition. CONCLUSIONS: MALT lymphoma is a rare lung malignancy that should be considered in the differential diagnosis of non-resolving pulmonary lesions. Minimally invasive approaches such as bronchoscopy and EBUS-TBNA can retrieve sufficient tissue for diagnosis. Reference #1: Schreuder MI, Van den Brand M, Hebeda K, et al. Novel developments in the pathogenesis and diagnosis of extranodal marginal zone lymphoma. J Hemathopatol. 2017; 10: 91-107. Reference #2: Wislez M, Cadranel J, Antoine M, et al. Lymphoma of pulmonary mucosa-associated lymphoid tissue: CT scan findings and pathological correlations. Eur Respir J. 1999; 14: 423-429. Reference #3: Nunez AL, Jhala NC, Carroll AJ, et al. Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases. Cytojournal. 2012;9:14. DISCLOSURES: Consultant relationship with Boston Scientific Please note: $1-$1000 Added 03/02/2018 by Alex Chee, source=Web Response, value=Consulting fee No relevant relationships by Isabel Londono Marulanda, source=Web Response Consultant relationship with Boston Scientific Please note: $5001 - $20000 Added 03/04/2018 by Adnan Majid, source=Web Response, value=Consulting fee Consultant relationship with Olympus Please note: $5001 - $20000 Added 03/04/2018 by Adnan Majid, source=Web Response, value=Consulting fee No relevant relationships by Mihir Parikh, source=Web Response No relevant relationships by Andrew Schissler, source=Web Response

A Case of Mucosa-Associated Lymphoid Tissue Lymphoma in Nasopharynx and Thyroid Gland

Mucosa associated lymphoid tissue (MALT) lymphoma refers to a type of marginal zone lymphomas, which represent a group of non-Hodgkin lymphomas originated from B lymphocytes of marginal zone. They are classified as extranodal MALT type (MALT lymphoma), splenic marginal zone B-cell lymphoma and nodal marginal zone B-cell lymphoma according to clinical and therapeutic implications of the tumor. MALT lymphoma is the most common type of marginal zone lymphoma, and about 5-8% of all B-cell lymphomas are diagnosed as MALT lymphoma. MALT lymphomas are usually found in the gastrointestinal tract, mostly in the stomach associated with H pylori infection; the non-gastric MALT lymphoma can also be found in the salivary gland, lung, head and neck, ocular adnexa, skin, thyroid, or breast. However, the involvement of nasal cavity and nasopharynx is rare. Based on our recent experience and a review of related literature, we report a case of MALT lymphoma that occurred in the nasopharynx and thyroid gland, which were treated with localized radiotherapy. Key words: Mucosa-associated lymphoid tissue lymphoma ㆍ Nasopharynx ㆍ Thyroid gland

Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand.

Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56years (range, 16-99years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8months, P=.0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

Chlamydia and ocular adnexal lymphomas: An Indian experience

Chlamydia and ocular adnexal lymphomas: an Indian experienceOcular adnexal lymphomas (OALs) are a heterogeneous group of malignancies, majority being extranodal mucosa-associated lymphoid tissue (MALT) type. Different geographical regions have reported association of Chlamydia with OALs (MALT type). In India, role of Chlamydia in OALs remains unexplored. The aim of this study was to detect Chlamydia and to correlate with clinicopathological features of OALs in India. The clinicopathological features of 41 OAL cases were studied prospectively. Chlamydia DNA was detected by genus specific PCR amplifying major outer membrane protein (MOMP) gene followed by DNA sequencing. Chlamydia immunoexpression was evaluated by immunofluorescence and immunohistochemistry. The results were correlated with clinicopathological features including follow-up and survival. Chlamydia genome was detected in 3/41 (7.3%) OAL cases by PCR. Direct sequencing revealed C. trachomatis in 3 positive cases. Immunofluorescence and immunohistochemistry showed Chlamydia antigen in 5/41 and 1/41 cases respectively. Immunofluorescence demonstrated higher sensitivity than immunohistochemistry. A significant association was observed between Chlamydia positivity and orbital location (P=0.05). Follow-up revealed relapse in 2 Chlamydia positive cases (P=0.056). Our results demonstrate for the first time presence of C. trachomatis genome in 7.3% OAL cases in India. As no other reports are documented, more detailed studies from different regions within India are needed to explore status of Chlamydia in OALs.

Underutilization of radiation therapy in early-stage marginal zone lymphoma negatively impacts overall survival

PurposeMultiple population-based studies have suggested increasing omission of radiation therapy in favor of alternative treatment strategies in lymphomas, with an associated negative impact on survival. Radiation therapy has long been considered the standard management for many mucosa-associated lymphoid tissue lymphomas. Thus, we aimed to evaluate patterns of treatment utilization and survival. Methods and materialsA retrospective analysis based on the National Cancer Database was performed on 22,378 patients with splenic, nodal, or extranodal stage I-II marginal zone lymphoma diagnosed between 1998 and 2012. A logistic regression model was used to assess the association between sociodemographic, tumor, and treatment characteristics and the utilization of radiation therapy. Multivariate propensity score-adjusted Cox proportional hazards models were performed to identify factors independently associated with overall survival (OS). ResultsOf 22,378 patients, 82% had stage I disease, 77% had extranodal mucosa-associated lymphoid tissue lymphoma, 5% had splenic marginal zone lymphoma, and 64% were older than 60 years. Radiation therapy utilization decreased from a peak of 39% in 2007 to 33% in 2011 (P < .001), with a corresponding significant increase in systemic therapy utilization. Radiation therapy was associated with a 5- and 10-year OS of 86.7% and 68.8% compared with 78.3% and 54.3% for no radiation therapy (P < .001). On multivariate propensity score-adjusted survival analysis, radiation therapy remained independently associated with improved OS (hazard of death, 0.75; 95% confidence interval, 0.65-0.85; P < .001). ConclusionsAlthough clinical guidelines endorse radiation therapy as the preferred initial therapy for early-stage nongastric and Helicobacter pylori–negative gastric mucosa-associated lymphoid tissue lymphoma, radiation therapy is underused. Radiation therapy with or without systemic therapy was associated with a significant improvement in OS and should remain standard of care.

MYD88 (L265P) somatic mutation in marginal zone B-cell lymphoma.

MYD88 L265P is a somatic mutation that has been identified in about 90% of Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (LPLs). It has also been detected in a subset of marginal zone lymphoma (MZL) cases, but the frequency and clinical and histologic features of these mutated MZL cases has only been partially characterized. We have developed a customized TaqMan allele-specific polymerase chain reaction for sensitive detection of this mutation in paraffin-embedded tissue. We analyzed samples from 19 patients with LPL, 88 patients with splenic marginal zone lymphoma (SMZL), 8 patients with nodal marginal zone lymphoma (NMZL), 21 patients with extranodal mucosa-associated lymphoid tissue (MALT), and 2 patients with B-cell lymphoma not otherwise specified. By integrating mutational, histologic, and clinical data, 5 cases were reclassified as LPL. After reclassification, MYD88 L265P was detected in 13/86 (15%) SMZL and in 19/24 LPL (79%) cases. The mutation was absent from NMZL and MALT cases. A strong correlation was found between the presence of an IgM monoclonal paraproteinemia and the MYD88 L265P mutation (P<0.0001). SMZL cases positive for MYD88 L265P were also associated with monoclonal IgM paraproteinemia (4/13 cases; P<0.0283), although with less serum paraproteinemia. They also had a higher frequency of plasmacytic differentiation (9/13) but with no correlation between the presence of mutation and of light chain-restricted plasma cells in tissue. Demonstration of the MYD88 L265 mutation is a valuable tool for the diagnosis of LPL, although some SMZL cases carrying the mutation do not fulfill the diagnostic criteria for LPL.

Inflammatory pseudotumor of eyelid: a probable IgG4-related sclerosing disease clinically mimicking eyelid pilomatrixoma

BackgroundOcular adnexal IgG4-related sclerosing disease (IgG4-SD) has been categorized as a novel disease entity. It is characterized by stromal sclerosis and an infiltration of mass-forming lymphoplasmic cells containing many IgG4-positive plasma cells. Although ocular adnexal tissue involvement has been increasingly reported, a focal nodular sub-brow mass is not typical in an IgG4-SD presentation. We report a rare case of probable ocular adnexal IgG4-SD that clinically mimicked eyelid pilomatrixoma.Case presentationA 42-year-old woman presented with a nodular mass in her left sub-brow area. The initial clinical impression of her lesion was eyelid pilomatrixoma. However, the final pathologic diagnosis was IgG4–SD, but extranodal marginal zone B-cell lymphoma could not be excluded. The patient underwent testing to determine tumor malignancy and systemic IgG4-SD involvement. Laboratory testing showed normal IgG and IgG4 serum levels and imaging revealed no remarkable findings. Oral prednisolone was administered and slowly tapered to manage the possible remnant lesion and to prevent disease recurrence. Two years after initiating therapy, there was no evidence of relapse. The patient is under close surveillance for signs of recurrence, systemic involvement, and potential malignant transformation.ConclusionsWe found an unusual case of probable ocular adnexal IgG4-SD, which presented as a unilateral restricted mass involving the sub-brow area. Although the mass was surgically removed, systemic steroid treatment and long-term surveillance were initiated due to the possibility of recurrence, the potential association with systemic disease, and the potential development of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma.

The origin and targeting of mucosa-associated lymphoid tissue lymphomas.

Extranodal mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct clinical-pathological entity that can be distinguished from other lymphomas by a number of unique features, including their location in various extranodal sites, being preceded by chronic inflammatory or infection processes; a characteristic histopathological picture; and the presence of exclusive chromosomal translocations which increase MALT1 proteolytic activity to promote constitutive NF-κB signaling and eventually drive lymphomagenesis. This review explores the major molecular and cellular events that participate in MALT lymphoma pathogenesis, focusing on gastric MALT lymphoma as a model of chronic inflammation-induced tumor development. In addition, the pivotal roles of activated MALT1 protease, its substrate TNFAIP3/A20, and the MyD88 adaptor protein in abnormally triggering downstream NF-κB pathway are overviewed. These new insights provide a mechanistic basis for using novel therapies targeting MALT1 protease or IRAK4 kinase activities. Finally, the putative cellular origin of MALT lymphomas is also discussed. Over the last decade, unraveling the biological complexity of MALT lymphomas has shed light on the fundamental cellular and molecular aspects of the disease that are to be translated into clinical diagnostics and therapy.