Considerations for Diagnosing MZL

Ariela Noy, MD:There are 3 types of marginal zone lymphoma. These include the nodal subtype, the splenic subtype, and the extranodal subtype. The extranodal subtype is also called mucosa-associated lymphoid tissue, or MALT, and can present in various organs such as the conjunctiva or stomach.

Each of these subtypes has its own pathophysiology and, sometimes, etiology, and it’s important to make a distinction between those. In addition, the responses to treatment may actually be different.

One of the important things to know is that splenic marginal zone lymphoma is highly associated regionally, in different parts of the world, with hepatitis C. Many years ago, it was elegantly demonstrated that treating and eradicating hepatitis C permanently eliminates both hepatitis C and lymphoma. So, it’s always important to test patients for hepatitis C.

Gastric marginal zone lymphoma, an associated lymphoid type known as gastric MALT, can be associated with another infectious organism calledHelicobacter pylori(H. pylori). Patients have to be tested forHelicobacter pyloriwhen they have gastric MALT. If they have gastric MALT that hasH. pyloriin it, a 2-week course of antibiotics typically eliminates both the infection and the lymphoma. So, these are 2 of the most common examples of infection-related lymphoma and are pretty unique to marginal zone lymphoma.

Marginal zone lymphoma does appear, at times, like other indolent lymphomas. Because there are 3 different subtypes, it can be different. For example, the gastric marginal zone lymphoma is pretty unique compared to follicular lymphoma. Also, the conjunctival subtype presenting as stage I disease, that is easily treatable with local therapies, is very different.

One of the most important things that distinguishes follicular lymphoma from marginal zone lymphoma is that follicular lymphoma is almost always disseminated. Stage I disease is a relatively rare occurrence. With modern imaging, such as PET scans, we can determine that patients who we thought had stage I follicular lymphoma really don’t. However, because of the pathophysiology of marginal zone lymphomas, particularly the ones associated with infection, stage I disease is relatively common. You might have a patient who has an isolated lung lesion. Whether or not it’s resected, they may not develop disseminated disease for quite a long time.

One of the interesting aspects of marginal zone lymphoma is that it is associated with autoimmune diseases, most commonly Hashimoto’s thyroiditis and Sjögren’s syndrome. Someone who has Hashimoto’s thyroiditis may have developed marginal zone lymphoma in the thyroid. Similarly, someone who has Sjögren’s syndrome may develop marginal zone lymphoma in the carotid gland.

The assumption is that the autoimmune disease creates a milieu that invites the development of lymphoma through dysregulation of the normal B-cell development pathway. In addition, the treatments for autoimmune disease, if they are immune-modulatory therapies, can leave a patient susceptible to the development of lymphoma.

Transcript edited for clarity.

A 64-Year-Old Woman With Advanced Extranodal MZL

January 2016

• PH: At age 64, the patient presented with a fever of unknown origin, weight loss, and fatigue
  • PE: revealed 2 masses near left ear
  • PMH: Sjogren’s syndrome, symptoms managed on cevimeline
• CT revealed bilateral involvement in parotid glands and a 3.0-cm. mass in the left lung
• Biopsies confirmed presence of MALT lymphoma in salivary gland and lung with nodules of diffuse heterogeneous B-cell infiltrate
• IHC: B cell phenotype CD20
• HBC, HBV, and other infections ruled out

Treatment History

• After 6-month period of active monitoring/observation, salivary masses began to cause patient distress; she also developed a persistent cough
  • CT revealed an additional new mass in left lung
• Decision was made to start patient on a course of rituximab
• Follow-up imaging at 6 months and 9 months showed near complete remission

March 2018

• Imaging at 20 months showed disease progression in the lung  
• Patient started on treatment with rituximab monotherapy

June 2018

• Imaging at 3 months showed no response to therapy
• The patient was started on treatment with ibrutinib