The clinical presentation of MZL depends on the type of lymphoma and differs between extranodal MZL, splenic MZL, and nodal MZL [1]:

• Extranodal MZL is the most common type of MZL. Its presentation varies depending on the site of tumor growth. Most frequently, it develops in the stomach. Gastric MZL, or other involvement of the digestive tract, usually provokes abdominal pain, nausea, vomiting, hematemesis, melena, or hematochezia. Tumors developing in the salivary glands, lung, or skin interfere with the function of the respective organs and may cause additional symptoms by compressing neighboring tissues. This also applies to any other site that may be affected. Constitutive symptoms are rare and don't usually develop until advanced stages of the disease, when the bone marrow and other organs have become involved.
• MZL of the spleen is characterized by involvement of the spleen, bone marrow, and peripheral blood without other sites of disease. Splenomegaly without lymphadenopathy is the clinical hallmark of splenic MZL. The infiltration of the bone marrow with numerous small lymphoid cells interferes with hematopoiesis and frequently results in anemia and thrombocytopenia. On the other hand, hemolytic anemia and immune thrombocytopenia may accompany splenic MZL, raising doubts as to the causes of cytopenias.
• About 10% of MZL cases correspond to nodal MZL. In adults, this variant of the disease is usually diagnosed in advanced stages, with multiple lymph nodes being affected. By contrast, localized nodal MZL following an indolent course is more commonly observed in pediatric patients [2]. The vast majority of nodal MZL is reported in adults. Here, bone marrow involvement may be noted, but cytopenias are uncommon. Contrary to the aforedescribed types of the disease, nodal MZL is frequently associated with constitutive symptoms like fever, night sweats, and weight loss. Serum levels of lactate dehydrogenase are elevated; concentrations of β2 microglobulin may be increased, too.

• Infectious Mononucleosis

  mononucleosis, autoimmune disorders and other reactive disorders Stains Plasmacytoid cells may be negative for B cell markers but are strongly immunoreactive for kappa or lambda, and carry a serum paraprotein (M-component) in peripheral blood Back to [pathologyoutlines.com]

  SHORT-TERM (ACUTE) INFECTIOUS DISEASE Acute bronchitis or pneumonia Acute viral syndrome Infectious mononucleosis (EBV) Influenza Lyme disease LONG-TERM (CHRONIC) INFECTIOUS DISEASE AIDS Chronic active hepatitis Disease caused by parasites Tuberculosis [pennstatehershey.adam.com]

  Most cases of this type are linked to infection with the Epstein-Barr virus (EBV, which can also cause infectious mononucleosis or “mono”). This type of Burkitt lymphoma is rare in the United States. [cancer.org]

  mononucleosis-like PTLD Polymorphic PTLD Monomorphic PTLD (B- and T/NK-cell types)† Classical Hodgkin lymphoma type PTLD† Other iatrogenic immunodeficiency-associated lymphoproliferative disorders ◎ Histiocytic and dendritic cell neoplasms Histiocytic [koreahealthlog.com]

  Bone marrow analysis can also be performed in patients with idiopathic thrombocytopenia purpura (ITP), incidental elevated serum paraprotein levels, iron deficiency anemia, polycythemia vera, essential thrombocytosis, or infectious mononucleosis; but [emedicine.medscape.com]

• Sepsis

  Oral Antibiotics for Neutropenic Sepsis Giving Early Hospital Discharge [ORANGE] Unknown status NCT00445497 Phase 3 amoxicillin-clavulanate potassium;ciprofloxacin 11 Multicenter, Double-Blind, Randomized Study to Compare the Safety and Efficacy of Levofloxacin [malacards.org]

  Title: A Study of Current Trend of Sepsis Causative Organisms (Fungal and Bacterial) in Neonatal Blood Culture and their Drug Susceptibility Patterns at a Tertiary Care Hospital, Visakhapatnam, South India Authors: Dr Rakesh Penta, Dr Rajasri Jalla, Dr [jmscr.igmpublication.org]

  One of the cases was diagnosed with a recurrence and died from pneumonia and sepsis secondary to adjuvant therapy (38), while the other two cases succumbed after 2 and 6 months of treatment, respectively. [frontiersin.org]

• Mediastinal Lymphadenopathy

  Because of its rarity, extranodal marginal zone lymphoma of MALT should be considered in the differential diagnosis when we encounter mediastinal lymphadenopathy in patients with lung adenocarcinoma. [ncbi.nlm.nih.gov]

• Cough

  The patient was a 66-year-old male presented with 1 month history of recurrent cough and hemoptysis. Chest CT showed solitary ground-glass opacity (GGO) in the upper lobe of the right lung and mediastinal lymph node enlargement in station 3p. [ncbi.nlm.nih.gov]

  Common symptoms include gastro-esophageal reflux epigastric pain eye redness (in involvement of ocular adnexa) unilateral salivary gland enlargement diarrhea colicky abdominal pain (in involvement of intestines) cough (in pulmonary involvement) 2 The [radiopaedia.org]

  The patient was asymptomatic and denied fevers, sweats, weight loss, shortness of breath or dyspnea on exertion, or cough. Her history was notable for exposure to parrots over several months before presentation. [ascopubs.org]

  If you have this chest infection, you might have fever, chills, cough, and chest pain. Mononucleosis ("mono"). If mono is the cause of your malaise, you could have a sore throat, headache, and swollen tonsils and lymph nodes. Flu. [webmd.com]

• Respiratory Distress

  Symptoms of severe malaria include: fever and chills impaired consciousness prostration, or adopting a prone position multiple convulsions deep breathing and respiratory distress abnormal bleeding and signs of anemia clinical jaundice and evidence of [medicalnewstoday.com]

  distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment Abnormalities in blood coagulation Low blood pressure caused by cardiovascular [cdc.gov]

  Children with severe malaria frequently develop one or more of the following symptoms: severe anaemia, respiratory distress in relation to metabolic acidosis, or cerebral malaria. In adults, multi-organ failure is also frequent. [who.int]

  Title: A Randomised Controlled Trial of 12 Hours vs 24 Hours Betamethasone Dosing Interval in Preterm Premature Rupture of Membranes for Prevention of Respiratory Distress Syndrome (RDS) in Neonates Authors: Dr Pratibha Gupta, Dr Sandeep Sharma, Dr Vinay [jmscr.igmpublication.org]

• Abdominal Pain

  An 85-year-old woman underwent emergent splenectomy due to left abdominal pain and active bleeding in a massively enlarged spleen. The histological diagnosis was splenic marginal zone lymphoma (SMZL). [ncbi.nlm.nih.gov]

  Common symptoms include gastro-esophageal reflux epigastric pain eye redness (in involvement of ocular adnexa) unilateral salivary gland enlargement diarrhea colicky abdominal pain (in involvement of intestines) cough (in pulmonary involvement) 2 The [radiopaedia.org]

  Symptoms include jaundice, fever, enlarged liver, abdominal pain and dark urine. Hepatitis can be caused by a variety of toxins or viruses, including the 5 different types of hepatitis virus (A, B, C, D and E). [cancer.ca]

  Symptoms associated with all forms of the disease include: fever without an infection night sweats unexplained weight loss skin rash chest or abdominal pain tiredness You may also have symptoms specific to the type of lymphoma. [healthline.com]

• Epigastric Pain

  Common symptoms include gastro-esophageal reflux epigastric pain eye redness (in involvement of ocular adnexa) unilateral salivary gland enlargement diarrhea colicky abdominal pain (in involvement of intestines) cough (in pulmonary involvement) 2 The [radiopaedia.org]

• Jaundice

  Malaria symptoms include chills, flu-like symptoms, fever, vomiting, diarrhea, and jaundice. A blood test can diagnose it. It can be life-threatening. However, you can treat malaria with drugs. [medlineplus.gov]

  Symptoms include jaundice, fever, enlarged liver, abdominal pain and dark urine. Hepatitis can be caused by a variety of toxins or viruses, including the 5 different types of hepatitis virus (A, B, C, D and E). [cancer.ca]

  Symptoms of severe malaria include: fever and chills impaired consciousness prostration, or adopting a prone position multiple convulsions deep breathing and respiratory distress abnormal bleeding and signs of anemia clinical jaundice and evidence of [medicalnewstoday.com]

  Along with high fever, shaking chills and sweating, symptoms can include: Throwing up or feeling like you're going to Headache Diarrhea Being very tired (fatigue) Body aches Yellow skin (jaundice) from losing red blood cells Kidney failure Seizure Confusion [webmd.com]

  Malaria may be associated with anaemia and jaundice, and P. falciparum infections can cause seizures, mental confusion, kidney failure, coma, and death, particularly in young children. 3. [ecdc.europa.eu]

• Hepatomegaly

  It presents primarily as splenomegaly; hepatomegaly can also be present, but lymphadenopathy is rare. [cancernetwork.com]

  Diagnosis Examination in patients with low-grade lymphomas may demonstrate peripheral adenopathy, splenomegaly, and hepatomegaly. [emedicine.medscape.com]

• Fracture

  The major presenting symptoms are soft tissue swelling, bone pain and pathological fracture. Treatment options are chemotherapy, radiotherapy, surgery, or a combination of these modalities. [ncbi.nlm.nih.gov]

  Intersection, New Delhi Author : Hariom Maheshwari Abstract | Full Text Flexural Behavior of Multi-Layer PUF Cored Sandwich Beams Author : Mohamed Aqhil Ahmed M.A, Mir Safiulla, Irfan Pasha Abstract | Full Text Study of Operative Results of Complex Fractures [olddrji.lbp.world]

  Title: Pauwels’Type-3 Femoral Neck Fractures in Young Population: A Comparative Study of Three Internal Fixation Methods Authors: Dr Imtiyaz Ahmad BEIGH, Dr Tanveer Ahmed Bhat, Dr Karanbir Singh, Dr Tanveer Ali, Dr Zubair Ahmad Lone DOI: https://dx.doi.org [jmscr.igmpublication.org]

  NIRMITHA DEV .M 3)NAVEEN BALARAJU 4)HS NIKHIL 5)UME HANI (57) Abstract : An apparatus and a method for reduction of forearm bone fracture on a patient, a radiolucent base plate having a first end and a second end, including a plurality of members which [slideshare.net]

• Erythema

  On examination, there was erythema and swelling of the left knee and both wrists. [ncbi.nlm.nih.gov]

• Kidney Failure

  The P. falciparum parasite can lead to life-threatening conditions such as brain damage (cerebral malaria), severe anemia, and kidney failure. Survivors are often left with permanent neurological damage. [nationalgeographic.com]

  Along with high fever, shaking chills and sweating, symptoms can include: Throwing up or feeling like you're going to Headache Diarrhea Being very tired (fatigue) Body aches Yellow skin (jaundice) from losing red blood cells Kidney failure Seizure Confusion [webmd.com]

  Malaria may be associated with anaemia and jaundice, and P. falciparum infections can cause seizures, mental confusion, kidney failure, coma, and death, particularly in young children. 3. [ecdc.europa.eu]

  According to the CDC, some complications of severe malaria, which is more common with P. falciparum infections, may include: Liver and kidney failure Mental confusion, convulsions and coma Severe anemia from destruction of red blood cells Jaundice (yellowing [livescience.com]

  Severe anemia (due to destruction of red blood cells) Kidney failure Cerebral malaria -- seizures, unconsciousness, abnormal behavior, or confusion Cardiovascular collapse Low blood sugar (in pregnant women after treatment with quinine) Latest Travel [medicinenet.com]

MZL are indolent lymphomas and may be detected incidentally, e.g., by endoscopy or other techniques of diagnostic imaging [1]. Nevertheless, neither type of image allows for a reliable diagnosis of MZL. The latter requires histopathological, immunophenotypic, and, ideally, genetic studies. Tissue samples have to be obtained from the affected tissue. MZL growth patterns are variable, and thus, diffuse, perifollicular, or nodal infiltration may be observed. Residual germinal centers may be recognized and are possibly surrounded by a mantle cuff. Tumor cells are clonal in origin and may show morphological features of monocytes, centrocytes, or plasma cells [3] [4]. They may or may not contain Dutcher bodies [3]. Immunophenotyping usually reveals the expression of CD19, CD20, CD22, CD79a, and PAX5, whereas most MZL test negative for CD5, CD10, and CD23 [1] [3]. With regards to genetic features, they may guide treatment decisions and be used as prognostic factors. Translocation t(11;18)(q21;q21), for instance, is predictive of a poor response to chemotherapy [1].

Once the diagnosis of MZL is confirmed, lymphoma staging needs to be carried out. It involves whole-body imaging as well as the examination of a bone marrow biopsy specimen [2]. Peripheral blood samples should also be analyzed. In case of splenic MZL, there may be circulating lymphocytes displaying short villous projections with a polar orientation [1].

• Mediastinal Mass

  Computed tomography of the chest showed a posterior mediastinal mass in the right thoracic paravertebral region with right pleural effusion. [ncbi.nlm.nih.gov]

  Radiation may also be required for palliation of symptomatic masses, such as a mediastinal mass with compression. Note that radiation is never the sole treatment modality. [emedicine.medscape.com]

• Lymphocytosis

  Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved. [ncbi.nlm.nih.gov]

  Peripheral blood shows lymphocytosis with or without villous cells. The villous lymphocytes show cytoplasmic projections at one pole of the cell. Autoimmune manifestations such as autoimmune hemolytic anemia are sometimes present. [webpathology.com]

  (SMZL) The purpose of this protocol is to collect blood, tissue (bone marrow and lymph node biopsies) and/or imaging studies (PET and CT scans) from patients with monoclonal B cell lymphocytosis (MBL) chronic lymphocytic leukemia/small lymphoma (CLL/SLL [centerwatch.com]

  In some patients, SMZL is occasionaly diagnosed after the detection of peripheral lymphocytosis; in advanced-stage SMZL, symptomatic splenomegaly and cytopenia can be the presenting features. [bloodjournal.org]

  There is no extranodal involvement, except for the bone marrow and liver.3,4 About 25% of the patients are asymptomatic and the presence of B symptoms or high lactate dehydrogenase levels (LDH) at diagnosis is not usual.5,6 Lymphocytosis is commonly present [scielo.br]

• Hyperuricemia

  The sudden osmotic load overwhelms the patient’s kidneys; renal failure typically occurs, with a rising creatinine level, hyperkalemia, and hyperuricemia, and may progress to oliguria and hypotension. [emedicine.medscape.com]

There is no standard treatment of MZL [5]. Watchful waiting is a valid approach to the management of MZL in patients without cytopenias, constitutive symptoms, and autoimmune complications. Accordingly, this conservative strategy is often followed in those diagnosed with extranodal or splenic MZL [1]. Beyond that, the following recommendations can be given:

• Treatment of extranodal MZL is usually tailored to the needs of the individual patient. If lymphomagenesis is related to chronic infection, eradication of the pathogen may induce tumor regression [6]. Otherwise, cytostatics and immunomodulators such as chlorambucil, cyclophosphamide, and rituximab may be administered. Rituximab may be combined with either of the aforementioned drugs but may also be given with bendamustine, or with fludarabine and mitoxantrone [7]. Patients diagnosed with localized tumor disease frequently benefit from radiotherapy [1].
• While surgery isn't usually considered in MZL of mucosa-associated lymphoid tissue, splenectomy has long since been the treatment of choice of splenic MZL. In case of hepatitis C-associated MZL, antiviral treatment should be provided before opting for the removal of the spleen. Poor candidates for surgery are more likely to improve under rituximab or combined chemotherapy [1].
• In the rare cases where nodal MZL is diagnosed during early stages of the disease, radiotherapy should be offered. Disseminated nodal MZL is generally treated with rituximab and chemotherapy. Distinct regimens have been proposed to this end, but no consensus has been reached as to the treatment schedule to achieve optimum results. Affected individuals have been treated with rituximab plus cyclophosphamide, vincristine, and prednisone; with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; and with rituximab plus fludarabine [1].

What's more, Bruton's tyrosine kinase inhibitor ibrutinib has recently been tested in a clinical trial in distinct types of MZL [5]. Ibrutinib has been developed as an antagonist of B-cell receptor signaling, which sustains tumor cell proliferation in MZL, but the drug has also been shown to interfere with Toll-like receptor signaling, B-cell adhesion and migration [8]. All these effects may contribute to the drug's antitumor activity, and in fact, ibrutinib has been shown to induce durable responses with a favorable benefit-risk profile in patients suffering from relapsed or refractory MZL [5]. It has been approved for that use in 2017.

MZL is considered an indolent type of lymphoma. The five-year overall survival rate is >60%, relative survival after that same period of time is >75%. Patients with extranodal MZL tend to have a better outcome than those diagnosed with nodal neoplasms [9]. With regard to extranodal MZL, dissemination at the time of diagnosis doesn't seem to affect the outcome, and this fact further highlights the non-aggressive behavior of this type of lymphoma [1].

The patient's prognosis worsens if MZL transforms into diffuse large B-cell lymphoma [4]. This is a rare event that may occur in any type of MZL [10].

The triggers of MZL remain unknown, but the disease has repeatedly been related to sustained immune stimulation due to autoimmune disorders or chronic infection. The incidence of MZL increases with age, which is usually attributed to an increased prevalence of immune disorders among the elderly and physiological immune senescence [11]. In this context, patients suffering from Sjogren’s syndrome have a 40-fold increased risk of developing salivary gland MZL [11] [12]. The persistent infection with Chlamydia psittaci, Helicobacter pylori, Campylobacter jejuni, Borrelia burgdorferi, or hepatitis C virus predisposes to MZL of the ocular adnexa, stomach, small intestine, skin, and spleen, respectively [13].

Furthermore, both genetic and environmental factors have been discussed as possible causes of MZL development. Patients with a family history of Non-Hodgkin lymphoma have been shown to be at higher risks of MZL, and this is possibly due to genetic variations in the major histocompatibility complex [14] [15]. Similarly, occupation as a metalworker and the frequent use of hair dye may predispose to MZL [14]. In sum, the individual roles of genetic, environmental, and immune factors in lymphomagenesis remain poorly defined, and further research is necessary to establish a sound risk assessment framework.

According to some studies, MZL account for only 3% of lymphoid neoplasms [11], but estimates as high as 10% of Non-Hodgkin lymphomas have been given elsewhere [16]. In the United Kingdom, the annual incidence of MZL has been estimated to be 2.6 per 100,000 inhabitants [9]. In the United States, incidence rates of 5.7 and 12.3 per million person-years have been reported for nodal and extranodal MZL, respectively. In the same study, an incidence of 1.6 per million person-years has been indicated for splenic MZL, rendering it the second most common form of extranodal MZL, preceded only by gastric MZL [11]. The overall incidence of MZL has been rising during the last decades, but it is currently not known whether this trend reflects improvements in MZL diagnosis or a true increase of its incidence rate [11] [12].

MZL is usually diagnosed in the elderly; its incidence peaks in the seventh decade of life [11]. Pediatric MZL rarely occurs but should be taken into account when diagnosing lymphoid neoplasms in children [17]. In general, men are affected more often than women, and Caucasians are more frequently diagnosed with MZL than black people [11].

MZL are thought to arise from memory B cells to be found in the marginal zone of the secondary follicles in mucosa-associated lymphoid tissue, spleen, or lymph nodes [12]. In the context of sustained antigenic stimulation, i.e., under conditions promoting the proliferation of lymphocytes or limiting their apoptosis, these cells' genetic instability may become a factor favoring lymphomagenesis [13]. These conditions are met in patients suffering from inherited or acquired immune disorders, autoimmune disease, or infection. Presumably, (auto-)antigens mediate the permanent activation of B-cell receptors and stimulate the proliferation of lymphocytes. This is pathogenetically different from constitutive B-cell receptor signaling in other types of lymphoma, which is usually triggered by somatic mutations in downstream elements of the signaling cascade. In MZL patients, B-cell receptor signaling and tumor cell proliferation may thus be inhibited by antigen removal or pharmacological antagonism of the receptor [1] [8].

Considerable knowledge gaps remain with regards to additional factors involved in the development of MZL, which is assumed to be a multistep process implicating the consecutive loss of regulatory checkpoints. Both genetic and environmental factors are likely to contribute to the accumulation of genetic and molecular abnormalities culminates in the uncontrolled proliferation and neoplastic transformation of B cells [12].

Recommendations to prevent MZL can only be given insofar as the avoidance of risk factors as discussed above may possibly reduce the likelihood of developing this type of cancer. Sustained antigenic stimulation may be prevented by means of infection prophylaxis, antimicrobial therapies, or adequate treatment of autoimmune disorders, if available. Evidence on the role of genetic and environmental factors in MZL pathogenesis is scarce and doesn't yet allow for the definition of preventive measures.

According to the current classification of the World Health Organization, there are three main types of lymphoma, namely B-cell lymphoma, T-cell lymphoma, and Hodgkin lymphoma. MZL is a type of mature B-cell neoplasm. It may develop in distinct tissues, so nodal MZL is distinguished from splenic MZL and extranodal MZL of mucosa-associated lymphoid tissue [18]. According to current knowledge, all types of MZL share common pathogenetic mechanisms, so they may respond to similar treatment regimens. The development of causal therapies is still in its early stages, though, and most patients are currently treated with cytostatics and immunomodulators, or radiotherapy. Due to the mostly indolent course of MZL, they generally have a favorable prognosis.

Lymphocytes are key players in the immune system. The uncontrolled proliferation of lymphocytes leads to lymphoma, which is a type of cancer. Marginal zone lymphoma (MZL), in turn, is a subtype of lymphoma. It originates from memory B cells in lymph nodes, in the spleen, or lymphoid tissue to be found in other organs. Memory B cells are required for the production of antibodies. Chronic infections, autoimmune disease, and other immune disorders favor the proliferation of these cells and have been shown to augment the risk of developing MZL. Otherwise, little is known about the causes of the disease.

Fortunately, MZL usually follows an indolent course. The majority of patients remains asymptomatic for prolonged periods of time, and the coincidental detection of MZL is not uncommon. Once the diagnosis of MZL is confirmed, a treatment schedule is established according to the general condition of the patient, the site of tumor growth and dissemination of the disease. Affected individuals may be treated with cytostatics and immunomodulators, or radiotherapy. Most patients have a favorable prognosis.

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