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Can You Cure Marginal Zone Lymphoma

author
Daniel Brown
• Wednesday, 09 December, 2020
• 9 min read

Lymphoma is a cancer that starts in the lymphatic system. The lymphatic system is a network of tissues and organs that remove waste and toxins from the body.

lymphomas indolent lymphoma marginal zone nodal extra mucosa
(Source: www.slideshare.net)

Contents

Nodal MEL can cause a painless lump in the groin, armpit, or neck area. Splenic MEL can cause an abnormal blood count, fatigue, and discomfort due to an enlarged spleen.

In the case of MALT, inflammation due to an infection may be responsible. This bacterium can enter your body and attack your stomach lining.

Because MALT is linked to an infection, your doctor may recommend antibiotic therapy over a two-week period. The Lymphoma Research Foundation states that around 70 to 90 percent of people with MALT respond well to this treatment.

If lymphoma returns, you’ll also receive traditional cancer therapy in the affected areas. Your doctor may also prescribe a corticosteroid in combination with cancer treatment.

This drug suppresses your immune system and controls inflammation. As a result, you avoid grueling side effects of cancer treatment, like anemia, hair loss, fatigue, and nausea.

lymphoma marginal zone splenic spleen non microscopic pathology dovemed hodgkins
(Source: www.dovemed.com)

Once symptoms develop, treatment options include chemotherapy, radiation, or surgery. Your doctor may suggest surgery to remove an enlarged spleen.

It involves evaluating the location and size of the tumors and determining whether cancer has spread to other parts of the body. Age, stage of the disease at diagnosis, and location affect the outlook for remission and long-term survival.

Talk to your doctor if you suspect you might have MEL, and toucan work to treat it together. With early diagnosis and treatment, remission is possible and the outlook is positive.

Since gastric MALT lymphoma is often the result of an infection with H. pylori, the initial treatment is antibiotic therapy, usually combined with proton pump inhibitors (PPI's), which is typically given for two weeks. PPI's reduce the production of stomach acid to help prevent or heal ulcers.

Most gastric MALT lymphomas are low-grade lesions that grow slowly and do not tend to spread to other places in the body. Physicians may defer treatment until symptoms appear, an approach called “watch and wait” or “watchful waiting.” With this strategy, patients’ overall health and disease are monitored through regular checkup visits and various evaluating procedures, such as laboratory and imaging tests.

marginal lymphoma zone nodal cell bcl2 lymph node pathpedia histopathology stain bcl cells pathology negative
(Source: www.pathpedia.com)

Active treatment is started if the patient begins to develop lymphoma -related symptoms or there are signs that the disease is progressing based on testing during followup visits. When necessary, treatment typically includes surgery for certain sites (lung, breast) or radiation therapy.

Antibiotic therapy such as doxycycline has been shown to be effective in MEL that affects the area around the eye (ocular adnexal lymphoma), which has been associated with infection. Since nodal MEL is most often a slow-growing disease, physicians may adopt an approach often referred to as active surveillance (i.e. watch and wait) until symptoms appear.

Patients with MALT lymphoma have a varied presentation depending on the primary site of disease. Common sites include the stomach, small intestines, lacrimal glands/orbit, thyroid, lungs, skin, and salivary glands.

Despite proliferation of lymphoid tissues, patients are often asymptomatic and the disease may present as an incidental finding. Patients with splenic marginalzonelymphoma (SML) commonly present with splenomegaly and bone marrow involvement, both of which may produce cyclopedias.

Patients with DL BCL typically experience rapid progression of disease and are often symptomatic at the time of diagnosis. Physicians should consider searching for loci of transformation in patients with marginalzonelymphoma who experience rapid disease progression, or increase in clinical symptoms.

lymphoma pathology marginal zone outlines frequent mitoses atypia marked
(Source: www.pathologyoutlines.com)

However, MCL is typically CD5+ and is characterized by the over expression of cycling D1 and/or the presence of t(11;14) by cytogenetics or fluorescent in situ hybridization (FISH). MCL is typically more aggressive than marginalzonelymphoma, although up to one third of cases may follow an indolent course for several months or years.

A para protein, usually immunoglobulin M (IGM), is common but is not diagnostic of LPL and can also occur in cases of marginalzonelymphoma with plasmacytoid differentiation, although usually to a lesser degree. Morphologically, marginalzonelymphoma is characterized by small to medium-sized lymphocytes surrounding a reactive follicle.

SML typically produces infiltrates of small lymphocytes in both the white and red pulp of the spleen. The exception is primary cutaneous marginalzonelymphoma, which appear to undergo class switching and more commonly express Egg, IGA, and IGE (immunoglobulins G, A and E).

Extra nodal marginal zone lymphomas are commonly associated with chromosomal abnormalities, including t(11;18)(q21;q21), t(14;18)(q32;q21), t(1;14)(p22;q32), t(3;14)(p12;q32), and trisomy 3 or 18. The nuclear factor kappa B (NFL) pathway is frequently involved in the pathogenesis of marginal zone lymphomas.

Mutations leading to constitutive activation of NFL have been detected in splenic and extra nodal marginal zone lymphomas including BIRC3 and TRAF3. The tumor suppressor genes responsible for histone modification, KMT2D and MLL2, are often mutated in nodal marginalzonelymphoma.

lymphoma marginal zone malt stomach pathology mzl
(Source: librepathology.org)

Similarly, testing for Chlamydia pitta in ocular adnexal lymphoma or B. burgdorferi in cutaneous marginalzonelymphoma is reasonable. Standard Ann Arbor lymphoma staging and response assessment is performed using computed tomography (CT) imaging of the neck, chest, abdomen, and pelvis.

The utility of PET (positron emission tomography) imaging remains unclear, with a high false negative rate. Nonetheless, PET imaging can occasionally be useful to help identify sites of extra nodal disease in patients that were previously felt to have nodal lymphoma.

Similarly, dissemination of MALT lymphoma to regional nodes can occasionally be detected by PET scan in patients with normal CT imaging. Nonetheless, PET imaging is not considered standard of care and generally has limited clinical utility.

MRI imaging is often helpful in assessing the extent of disease in patients with ocular adnexal MALT lymphoma. Due to the slow nature of progression, most patients present before developing significant complications.

In the rare cases of life or organ-threatening marginalzonelymphoma, high dose corticosteroids (for example, dexamethasone 40 mg daily) can be used to temporize matters before starting more definitive (immune) chemotherapy or radiotherapy. Treatment of indolent lymphoma should be individualized according to the disease subtype, presentation, comorbid conditions, and patient preferences.

lymphoma marginal zone immunophenotype
(Source: www.slideshare.net)

Most patients with nodal marginalzonelymphoma present with advanced stage disease and are not likely to achieve cure, even with aggressive chemotherapy regimens. Asymptomatic patients with slowly progressive, non-bulky disease may be safely observed, often for many months, before developing indications for therapy.

Similarly, there are reports of resolution of ocular adnexal MALT lymphoma following antibiotic therapy of Chlamydia pitta. Patients with early stage MALT lymphoma with no underlying infectious etiology, or those for whom antibiotic therapy has failed, can be effectively managed with external beam radiotherapy.

Surgery is rarely the primary mode of therapy for localized disease, but may be the only treatment necessary in cases where the entire tumor was removed during a diagnostic biopsy. Patients with symptomatic advanced stage disease, or those with symptomatic early stage disease not amenable to radiation therapy, may be managed with rituximab +/- chemotherapy, depending on comorbid conditions and urgency for treatment response.

Observation with deferred initial therapy should be considered in most patients with SML without cyclopedias or symptoms. Traditionally, splenectomy has been considered the best first-line therapy for patients with SML and symptomatic splenomegaly or severe cyclopedias.

However, treatment with rituximab +/- chemotherapy may be equally likely to yield clinical benefit and will also result in a reduction in tumor bulk outside the spleen (that is, the bone marrow). These patients require aggressive therapy and may benefit from autologous stem cell transplantation.

lymphoma cutaneous cell skin lesions nejm nose had
(Source: www.nejm.org)

Gastric MALT lymphoma is the sole subtype for which strong evidence of response to antibiotic therapy exists. However, among patients with early stage gastric MALT lymphoma, the response to H. pylori eradication can vary significantly.

Second, tumors that demonstrate the t(11;18) abnormality are unlikely to respond to H. pylori eradication and should probably be managed with alternative therapies (for example, radiation). Patients that respond but subsequently relapse may benefit from another course of H. pylori eradication in cases where reinfection occurs.

Patients with other subtypes of nodal and extra nodal marginalzonelymphoma are at high risk for relapse following initial therapy (advanced stage disease is rarely, if ever, curable). Nonetheless, there is typically a lag between relapse of disease and the point at which patients develop clinically relevant symptoms sufficient to warrant therapy.

The Burton’s tyrosine inhibitor ibrutinib is indicated for treatment of relapsed/refractory marginal lymphoma based on the results of a phase 2 clinical trial in which it was dosed continuously at 560 mg daily. As has been observed in other lymphomas, ibrutinib was associated with side effects including fatigue, anemia, and infections and should therefore be reserved for patients with symptomatic relapsed or refractory disease.

Patients with limited stage extra nodal MALT lymphoma should be treated with curative intent with antibiotics or locally directed therapy when possible. In circumstances where such therapy is not feasible, when patients present with advanced stage lymphoma, or when patients relapse at sites distal to their original presentation, cure is unlikely with anything short of allergenic stem cell transplantation (something that is usually not indicated).

cell approach lymphomas pathology figure aggressive 1076 jcp bmj
(Source: jcp.bmj.com)

Nonetheless, patients typically live for many years, requiring intermittent therapy when the disease becomes symptomatic. Despite similar International Prognostic Index (IPI) scores at presentation and rates of aggressive transformation, patients with nodal marginalzonelymphoma fare somewhat worse than patients with MALT lymphomas, with a reported 5-year OS closer to 60%.

In a large retrospective series from Italy, hemoglobin less than 12g/L, lactate dehydrogenase (LDH) greater than the upper limit of normal, and albumin less than 3.5g/DL were associated with a 5-year OS of 88%, 73%, and 55% for one, two, or three factors. Patients experiencing transformation will typically manifest new constitutional symptoms, rapid tumor growth, or resistance to less aggressive forms of therapy.

Radioimmunotherapy may be appropriate for those patients that are not candidates for tetracycline based regimens, if hematologic and bone marrow parameters allow. Such patients should be considered for aggressive second-line regimens, followed by autologous stem cell transplantation.

Although the tumor microenvironment clearly plays a role in the biology of many cancers, rarely is the relationship as strong as that which exists in marginalzonelymphoma. The association of MALT lymphomas with infectious/autoimmune conditions, the restricted variable gene repertoire, and ongoing somatic hypermutation, all strongly suggest a role for chronic antigenic stimulation.

Moreover, expression of chemokine receptor CXCR3 on tumor cells (except maybe primary cutaneous marginalzonelymphoma) is consistent with the suggestion that they are dependent on inflammatory cytokines. It is likely that there is a stepwise progression from reactive B-cell, to localized antigen-dependent tumor, to antigen independence, and more aggressive phenotypes.

cd3 cd20 lymphoma pathology malt outlines extranodal lymphoid marginal zone
(Source: www.pathologyoutlines.com)

For example, it has been hypothesized that the t(11;18) may be an early event that results in antigen independence, but is also associated with low incidence of transformation to DL BCL. These data support the hypothesis that aberrant NFL activation plays an important role in the pathogenesis of marginal zone lymphomas.

Additional studies will be required to determine whether the components of this signaling pathway could be targeted with novel therapeutic agents. No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC.

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