Steven H. Lin and John P. Plastaras
What does MALT stand for? Where is MALT generally located?
MALT stands for mucosa-associated lymphoid tissue. It is located in the Peyer patches of the bowel and lymphoid tissues of the H&N (nasopharynx [adenoids] or oropharynx [tonsils]), so it is not generally present in the stomach, lung, or salivary glands.
What is the etiology of MALT lymphomas?
The etiology of MALT lymphomas is chronic inflammation from infection or autoimmune disorder.
What are the most common locations of MALT lymphoma in the body?
The most common locations of MALT lymphoma are the GI tract (stomach > small intestine > colon), lung, thyroid, salivary gland, tonsil, breast, and orbit.
What types of infectious or autoimmune conditions are associated with MALT lymphoma in the stomach? Ocular adnexa? Salivary gland? Skin? Thyroid?
Infections or autoimmune conditions associated with MALT:
1. Stomach: Helicobacter pylori
2. Ocular adnexa: Chlamydia psittaci
3. Salivary gland: Sjögren
4. Skin: Borrelia burgdorferi
5. Thyroid: Hashimoto thyroiditis
What is the natural Hx of MALT lymphomas?
The natural Hx includes an indolent clinical course, as in low-grade lymphoma.
From where do MALT lymphomas typically arise in the lymphoid follicle?
MALT lymphomas typically arise from the marginal zone of the lymphoid follicle (and therefore are termed as extranodal marginal zone lymphoma).
What are some important cytogenetic abnormalities in MALT lymphomas?
Important cytogenetic abnormalities include t(11;18)(q21:q21) and trisomy 3.
What is the immuno-phenotype of MALT lymphoma?
MALT lymphoma is a low-grade B-cell lymphoma that is CD20 + , CD35 + , CD5 − , and CD10 −.
What is the typical stage of MALT lymphomas?
Stage IAE (80%) is typical for MALT lymphomas.
What is the typical presentation of a pt with gastric MALT?
The typical presentation of gastric MALT is dyspepsia (#1), epigastric pain or discomfort, n/v, GI bleed, and B Sx (rare).
What workup should be included in a pt with suspected MALT lymphoma of the stomach?
Suspected MALT lymphoma of the stomach workup: Complete H&P (with emphasis on B Sx and −evaluation of all LNs, including the Waldeyer ring [15% association; check hepatosplenomegaly]), CBC/CMP, LDH, CXR, CT abdomen/pelvis, esophagogastroduodenoscopy (EGD) with Bx, and EUS (to assess DOI). Test for H. pylori infection with a rapid urease test (RUT) on the Bx specimen. Consider BM Bx in pts with suspected systemic Dz.
What is the sensitivity and specificity of the RUT for H. pylori? What are other alternatives if the RUT is negative?
The sensitivity and specificity of RUT is >90%. However, if the test on the tissue sample is negative and the clinical suspicion is high, preferred noninvasive tests are (1) H. pylori serum serology (antibody), (2) urea breath test, or (3) stool antigen test.
How is the Ann Arbor system used for staging MALT lymphoma of the GI tract?
Ann Arbor staging for MALT lymphoma of the GI tract if no B Sx:
1. Stage IAE: confined to GI tract
2. Stage IIAE: GI confined + nodal involvement below diaphragm
3. Stage IIIAE: GI focus + nodes above diaphragm
4. Stage IVAE: GI + both sides of diaphragm + other extranodal involvement (BM, liver, etc.)
What is the 1st-line therapy used for the Tx of MALT lymphoma?
If there is documented H. pylori infection, use −antibiotics against H. pylori (triple therapy of Biaxin/Flagyl/proton-pump inhibitor [PPI] or Biaxin/amoxicillin/PPI).
If there is lymphoma but the pt is H. pylori–negative, consider RT as a primary therapeutic approach, −especially if there are chromosomal abnormalities.
How is the eradication of H. pylori determined?
To determine the eradication of H. pylori, a urea breath test should be done 1 mo after antibiotic use. If there is persistence of tumor and H. pylori infection, switch to a different antibiotic regimen.
What response rate is expected from 1st-line Tx of MALT lymphoma?
75%–80% of pts have a CR. (Wundisch T et al., JCO 2005)
What is the typical response period to antibiotics in MALT lymphoma?
In MALT lymphoma, regression is slow and can take from a median of 6 mos to 12–18 mos.
How should response be assessed when using antibiotics for MALT lymphoma?
Response to antibiotics in MALT lymphoma is assessed by EGD with visual inspection and Bx q3mos. Dz should at least be stable or responding. If Dz if progressing, consider RT. If Dz is stable or regressing and the pt is asymptomatic, repeat the EGD in 3 mos.
What are 3 tumor characteristics that portend a poor response to the use of antibiotics for the Tx of MALT lymphoma?
Tumor characteristics that portend a poor response with antibiotics for MALT lymphoma include t(11;18), trisomy 3, and DOI beyond the −submucosa (muscularis/serosa/adjacent organs) −(Sackmann M et al., Gastroenterology 1997). There is an 86% CR with DOI < submucosa and 0% if −invasion is beyond the submucosa.
What are the options for antibiotic-resistant MALT lymphomas?
Given the indolent nature of the Dz, there are many options. Involved-field radiation therapy (IFRT) can be considered upfront or single-agent chemo such as rituxan or chlorambucil. IFRT should be considered standard since the response is excellent and the pt can be potentially cured in the long term (~50% DFS at 10 yrs).
When should RT be considered for the Tx of MALT lymphoma?
RT for MALT lymphoma should be considered in the following situations:
1. H. pylori–negative with stage IAE lymphoma, with or without initial use of antibiotics, and pt has no documented response to Tx
3. Invasion beyond submucosa (muscularis/serosa/adjacent organs)
4. Documented progression after initial use of antibiotics
5. Documented failure of 2nd course of antibiotics
6. Rapid symptomatic progression of Dz
What are some important prognostic factors for MALT lymphomas?
Important prognostic factors for MALT lymphomas:
4. LN involvement
5. Tumor size, cytogenetics
What are the factors in the follicular lymphoma International Prognostic Index (FLIPI) used for predicting the prognosis in MALT?
FLIPI for predicting the prognosis in MALT:
1. Hgb <12 g/dL
2. Age >60 yrs
3. Stage III–IV Dz
4. Sites >3 nodal
5. LDH abnl
(Mnemonic: FLIPI is a HASSL)
Is there a benefit of adding chemo in low-risk (<1 FLIPI) MALT?
No. Trials have demonstrated no additional survival benefit. Thus, IFRT remains the standard 1st-line modality. Considerations are made with rituxan + IFRT or radioantibody therapy in the future.
What are some factors that would predict for poor response to RT alone?
Factors that predict for poor response to RT alone:
1. Stage II Dz
2. FLIPI >1 factor
3. B Sx
4. Tumor bulk
5. Age >60 yrs
How should pts with poor-risk MALT lymphoma be managed?
Pts with poor-risk MALT lymphoma should be −managed with a combined modality, using chemo + IFRT.
What is the 3rd-line therapy for Tx of MALT lymphoma?
The 3rd-line therapy for MALT lymphoma is chemo (rituxan, single-agent Cytoxan) or total gastrectomy + chemo.
What is the Tx paradigm for DLBCL of the stomach?
DLBCL of the stomach Tx paradigm: rituximab/cyclophosphamide/hydroxydaunomycin (Adriamycin)/Oncovin (vincristine)/prednisone (R-CHOP) + IFRT
What are the simulation procedures for RT planning for Tx of MALT lymphoma of the stomach?
1. CT plan pt in a fasting state, supine and with oral contrast. Use methods to determine respiratory excursion. The field should encompass the entire stomach + perigastric LNs +/− celiac nodes at T12-L1 + a 2-cm margin.
2. Use AP/PA or 4-field 3D-CRT (Princess Margaret Hospital technique) to reduce the dose to the kidneys (isocenter in stomach, with the sup field using AP (6 MV)/PA (15 MV), and the inf field using the opposed lat (15 MV and staying off kidney) and AP (6 MV) field.
3. Rx dose: 30 Gy in 1.5 Gy/fx for 20 fx. Consider boosting to the area of residual Dz to 36 Gy.
What are the long-term outcomes with the use of IFRT for Tx of MALT lymphoma?
Long-term outcomes with IFRT achieves 95% LC and 50% of pts relapsefree in 10 yrs. The natural Hx of low-grade lymphomas is high distant failure (40%–50%). 10-yr OS is 60%–80%.
What is the most common nongastric MALT?
Orbital MALT is the most common nongastric MALT and is generally in the elderly with a median age of 60 yrs.
With which areas of the eye is orbital MALT usually associated?
The conjunctiva, eyelids, lacrimal gland, and −retrobulbar areas are usually associated with orbital MALT.
What organism is often associated with orbital MALT?
C. psittaci is often associated with orbital MALT, with studies showing eradication of the organism with −antibiotics (doxycycline) to result in a CR.
How should RT be performed for the Tx of orbital MALT?
The whole orbit should be treated. For the ant orbital lesions in the conjunctiva, orthovoltage (250 kV), 4 MV photons, or electrons should be used. Consider hanging lens shielding (reduce the dose to 5%–10%). Wedge pair fields are considered for retrobulbar lesions.
25–30 Gy in 10–20 fx can be used, with 95% LC.
What is the typical natural Hx of orbital MALT?
The typical natural Hx of orbital MALT includes a high distant relapse rate, generally in the contralat eye or other MALT sites (20%–50%) but high −survival in the long term.
What is typically associated with MALT of the salivary gland?
Typical associations of MALT of the salivary gland include Sjögren syndrome, a median age of 50 yrs, and bilat parotids.
What are the fields, volumes, and doses used for MALT of salivary gland?
Treat the whole parotid (superficial and deep lobe) with IMRT or 3D-CRT to 30 Gy in 20 fx. For pts with IIE Dz (cervical nodal involvement), encompass the ipsi cervical LN stations. Treat the bilat parotid if there is bilat involvement. A dental evaluation should be performed.
What is typically offered for MALT of the lung?
Surgical resection is typically offered for MALT of the lung. Use observation for clear margins and no mediastinal nodal involvement. If the tumor is unresectable or there are +margins, consider IFRT. RT-induced 2nd malignancies (breast, lung) must be considered for a young person getting RT.
How is MALT of the skin managed?
MALT of the skin is managed by surgical excision for smaller lesions. If large, use electrons with bolus.
What is the regimen used for management of advanced low-grade lymphoma?
For advanced low-grade lymphoma, use systemic agents; however, no agents are curative. Palliative RT is very effective, especially for extensive symptomatic Dz. A high response rate (80%–90%) is seen with the use of 4 Gy (2 Gy × 2).
To what RT doses should the kidneys and liver be limited in MALT of the stomach?
Keep the mean dose to both kidneys to <20 Gy (or 20% of left kidney to <20 Gy). The dose to the liver should be V25 <50%.
What are some toxicities for using IFRT for Tx of MALT lymphoma of the stomach?
Anorexia and n/v are toxicities associated with IFRT for MALT lymphoma of the stomach. Very rarely is ulceration or outlet obstruction seen.