Pocket Oncology (Pocket Notebook Series), 1st Ed.


Andrew M. Intlekofer and Andrew D. Zelenetz


• Indolent neoplasm of mature, post-germinal center B lymphocytes whose nl counterparts reside in the marginal zone of lymphoid follicles in the spleen, LN, & lymphoid tissues

• 3 subtypes: Splenic MZL, nodal MZL, & ENMZL (also referred to as MALT lymphoma) (JNCCN 2006;4:311)


• Thought to arise from chronic Ag stimulation due to infectious pathogens or other causes of inflammation, including autoimmune diseases

• Variety of chromosomal translocations can result in Ag-independent activation of NF-kB pathway (important signal for B cell survival)

• Whole genome sequencing of splenic MZL has identified recurrent somatic Mts of genes encoding chromatin-modifying enzymes & proteins in the NOTCH, NF-κB, & MYD88 pathways (JEM 2012;209:1537; NEJM 2012;367:826)


• Comprise approximately 10% of all NHLs

Clinical Presentation

• MZL can affect diverse anatomical sites & presentation varies accordingly

• Localized sx: Epigastric pain (gastric), abdominal pain or bowel obstruction (intestine), cough (bronchial), orbital mass, salivary gland mass, thyroid mass, breast mass, skin nodules or rash, abdominal distension or early satiety due to splenomegaly (splenic MZL), LAN (nodal MZL)

• Systemic sx: B sx (wt loss >10%, fevers, sweats) uncommon, fatigue, bruising

Diagnostic Evaluation

• Bx required: Either excisional/incisional or core plus FNA w/flow cytometry, splenic MZL often diagnosed on splenectomy specimen

• Histology: Polymorphous infiltrate of small lymphocytes, centrocyte-like B cells, & plasma cells; reactive follicles; lymphoepithelial lesions (epithelial tissues)

• Immunophenotype: CD19+, CD20+, CD22+, κ or λ restricted, surface Ig+, often cytoplasmic Ig+, CD5−, CD10−, CD23−/+, CD43−/+, CD103−, CyclinD1−

• Cytogenetics/FISH: Most common t(11;18) (BIRC3:MALT1) → a/w H. pylori neg gastric ENMZL; t(1;14), t(14;18) (note this is IgH:MALT1), t(3;14); del13q; del7q

• Molecular diagnostics for clonal IgH rearrangement (proves malignancy)

• Lab evaluation: CBC w/diff, CMP, LDH, HBV sAg/cAb, HCV Ab, HCV PCR, HIV, SPEP/IFE (paraprotein often present), quant immunoglobulins

• BM aspirate & core bx: Send for flow cytometry, splenic MZL classically shows “intrasinusoidal” lymphocytic infiltrations

• Imaging: CT C/A/P w/contrast; may need MRI orbits (ocular) or neck (salivary); FDG PET not routinely required

• Special considerations for gastric ENMZL:

→ Endoscopy ± EUS w/core bx required, stain specimen for H. pylori

→ If H. pylori negative by histopath, then perform H. pylori stool Ag test, urea breath test, or H. pylori blood Ab test


• Ann Arbor Staging (for nodal, splenic, & nongastric ENMZL):

Stage I = single LN region or single extranodal site (IE)

Stage II = multiple LN on one side of diaphragm

Stage III = multiple LN on both sides of diaphragm

Stage IV = LN plus extranodal sites or multiple extranodal sites

A = no B sx, B = B sx (fevers, drenching sweats, wt loss >10% BW)

X = mass >10 cm

• Lugano Staging System (for gastric ENMZL) (Ann Oncol, 1994; 5:397):

Stage IE = confined to GI tract

Stage IIE = regional LN or adjacent organ involvement

Stage IIIE–IV = disseminated extranodal or supradiaphragmatic LN involvement

Principles of Treatment

• In some cases, tx of underlying etiology can result in MZL regression

→ H. pylori eradication w/abx for gastric ENMZL (not effective if translocations present or if there is muscularis or perigastric LN involvement)

→ HCV Rx for splenic MZL

→ Doxycycline for ocular or cutaneous ENMZL

• Localized disease is common in MZL, so RT is an important tx modality (usu IFRT = involved field RT)

• Localized disease is potentially curable so treat even asx pts

• Adv stage MZL is a chronic disease (not curable), therefore decision to treat is based on presence of 1 or more GELF criteria (same as follicular lymphoma): ≥3 nodal sites each ≥3 cm in size, any involved site ≥7 cm in size, B sx, splenomegaly, pleural effusion or ascites, cytopenias (WBC <1, Plt <100), malignant cells in blood (>5000)

• Transformation: 5–10% pts transform to aggressive large cell lymphoma, heralded by rapid ↑ LN, new B sx, or ↑↑ LDH, dx by FDG PET scan & bx LN w/ ↑ SUV, tx like DLBCL (eg, R-CHOP)

Supportive Care

• Vaccinations: Pneumococcal & meningococcal 2 wks prior to splenectomy

• Endoscopy: Surveillance EGD w/biopsies for pts w/gastric ENMZL treated by H. pylori eradication, not necessary after IFRT (Ann Oncol 2009;20 Suppl 4:113)