100 Marginal Zone B-Cell Lymphomas Flashcards
Most frequently involved anatomic compartment in Marginal zone lymphomas (MZLs)
Spleen and the mucosa-associated lymphoid tissues (MALT)
Lymph nodes may also be involved, albeit rarely
Three distinct subtypes of MZL
- Extranodal MZL of MALT type (also termed extranodal marginal zone lymphoma [EMZL])
- Splenic marginal zone lymphoma (SMZL)
- Nodal marginal zone lymphoma (NMZL)
In addition, three provisional entities are recognized by the current WHO classification: pediatric nodal MZL, splenic diffuse red pulp lymphoma, and hairy-cell leukemia variant.
In adults, MZLs account for approximately _____of all non-Hodgkin lymphomas (NHLs)
10%
The most frequent MZL, being the third most frequent NHL and representing approximately 7.5% of all B-cell neoplasms
MALT lymphoma
TRUE OR FALSE
MALT lymphoma mostly affects middle-aged adults, at a median age of 60 years, with a slight female preponderance and often in association with chronic antigenic stimulation, either as a consequence of a chronic infection or a gastric autoimmune disease
TRUE
MALT lymphoma mostly affects middle-aged adults, at a median age of 60 years, with a slight female preponderance and often in association with chronic antigenic stimulation, either as a consequence of a chronic infection or a gastric autoimmune disease
Sites of EMZL or MALT lymphoma
Gut, the nasopharynx, and the lung, salivary glands, the ocular adnexa, the skin, the thyroid, the genitourinary tract
MALT lymphoma accounts for at least _____ of primary gastric lymphomas
50%
Middle-aged adults, with a female predominance
Common in the Northeastern part of Italy, an area where there is an area of high prevalence of Helicobacter pylori infection
Ocular and adnexal MZLs are associated with infection by
Chlamydophila psittaci
Microbial species thought to be associated with MALT lymphoma
H. pylori and Helicobacter heilmannii, Campylobacter jejuni, Borrelia burgdorferi, and Chlamydophila psittaci
Helicobacter pylori can be demonstrated by
Helicobacter pylori has been documented as the etiologic agent in more than 90% of patients with gastric MALT lymphoma
Histology, PCR, or urea breath test, culture
An infection by hepatitis C virus (HCV) can be documented in at least ____ of gastric and ____of nongastric MALT lymphomas
it is also associated with SMZL and NMZL
Half of gastric MALT lymphomas
One-third of nongastric MALT lymphomas
Associated Autoimmune Diseases
Sjögren syndrome :
Hashimoto thyroiditis:
Sjögren syndrome :EMZL of the salivary gland (44x)
Hashimoto thyroiditis: thyroid lymphoma (70x)
A key transcription factor that regulates the expression of several survival- and proliferation-related genes in B cells during immune responses and has the potential to promote an uncontrolled B-cell proliferation
NF-κB
The inactivation of this protein, a negative controller of the NF-κB pathway, is frequently encountered in EMZL
TNF-α–induced protein 3 (TNFAIP3)
The most common structural chromosomal abnormality in MALT lymphoma
t(11;18)(q21;q21) translocation
Demonstrated in 15% to 40% of the cases, especially in gastric and lung MALT lymphoma
Other chromosomal translocations include t(14;18)(q32;q21), t(1;14)(p22;q32) and t(3;14)(p13;q32), all involving the immunoglobulin heavy chain variable region (IGHV) gene on chromosome 14, and displaying a specific anatomic distribution
EMZL mostly presents as Ann Arbor classification stage _______
Stage IE disease
The most commonly involved organ in EMZL, accounting for approximately one-third of cases.
Stomach
Most frequently involved portion of the stomach in EMZL
Antrum
Macroscopic features of Gastric MALT lymphoma
Intragastric nodularities, enlarged rugal folds, thickened gastric walls, irregularly shaped superficial erosions, and shallow ulcers
MALT lymphomas of the ocular adnexa most often arise in the __________
Orbit (40% of cases)
The ______________is the site of origin in approximately 35% to 40% of the cases of MALT lymphomas of the ocular adnexa
Conjunctiva
The conjunctiva is the site of origin in approximately 35% to 40% of the cases, with bilateral involvement observed in nearly 15% of patients.
More rarely, the lymphoma originates from the lacrimal gland (10% of the cases) or the eyelid.
Cutaneous MALT lymphoma generally presents with papules, plaques, or nodules mainly involving the __________________
Trunk and the upper limbs
Morphology: highly characteristic of MALT lymphoma, particularly gastric MALT lymphoma, although they are not pathognomonic
Invasion or necrotic destruction of the glandular epithelium by infiltrating lymphoma cells
Immunohistochemistry of MALT lymphoma
CD20+, CD79a+, CD21+, and CD35+
Expressing immunoglobulin (Ig) M (less often IgA or IgG), with an immunoglobulin light-chain restriction
Negative: CD5, CD23, and CD10
The outcome of H. pylori eradication must be confirmed by
Urea breath test at least 6 weeks after eradication therapy and at least 2 weeks after proton pump inhibitors withdrawal
Helicobacter pylori eradication therapy
Proton pump inhibitor, in association with either amoxicillin or metronidazole, and clarithromycin for 10–14 days
Gastrectomy can be considered in gastric MALT lymphoma in the ff cases
- Major hemorrhage
- Massive infiltration of the gastric walls (with an enhanced risk of perforation during chemotherapy)
- Pyloric stenosis
Treatment options for nongastric MALT lymphoma and gastric MALT lymphoma patients who fail to respond to H. pylori eradication or who have no evidence of H. pylori infection
Involved-field radiation therapy (25–35 Gy)
Chemotherapy or rituximab immunotherapy, or a combination of both
TRUE OR FALSE
Patients with the t(11;18) translocation are also usually responsive to alkylating drugs if administered as single agents
FALSE
Patients with the t(11;18) translocation are also usually unresponsive to alkylating drugs if administered as single agents
Treatment options for patients with the t(11;18) translocation
Fludarabine with rituximab
Rituximab and chlorambucil
Radioimmunotherapy used in patients with MALT lymphoma, being feasible and safe either at disease onset or at relapse
90Y-ibritumomab tiuxetan
A tetracycline antibiotic, has been evaluated as the upfront treatment of patients with stage I ocular or adnexal MZL, showing activity against C. psittaci and inducing lymphoma regression
Doxycycline
TRUE OR FALSE
MALT lymphoma has a favorable outcome, with a 5-year overall survival greater than 85% in most series
TRUE
MALT lymphoma has a favorable outcome, with a 5-year overall survival greater than 85% in most series
The reported median time to progression seems to be more favorable for GI MALT lymphomas than non-GI lymphomas; however, no significant differences in overall survival have been demonstrated between the two disease subgroups.
3 parameters used in the MALT Lymphoma International Prognostic Index
- Age 70 years or older
- Elevated LDH
- Ann Arbor stage III/IV
Three risk groups (low, 0 points; intermediate, 1 point; high, at least 2 points)
Histologic transformation to diffuse large B-cell lymphoma of MALT Lymphoma occurs in approximately _____%
6% to 10%
Risk factors for disease transformation to diffuse large B-cell lymphoma of MALT Lymphoma
- Elevated LDH
- Failure to achieve a complete remission after first-line course
- Involvement of more than four nodal sites
A mature B-cell neoplasm arising from postgerminal center lymphocytes and involving the white pulp follicles of the spleen, the splenic hilar lymph nodes, the marrow, and often the blood, showing characteristic neoplastic lymphoid elements referred to as “villous lymphocytes.”
SPLENIC MARGINAL ZONE LYMPHOMA
It accounts for 1% to 2% of all lymphomas, with a median age at diagnosis of nearly 65 years (range, 30–90 years) and a slight male predominance.
SMZL is associated with this chronic viral infection
HCV
Result of the interaction of the viral E2 glycoprotein with CD81 on B cells
SMZL associated with chronic HCV infection is often associated with
Mixed cryoglobulinemia
Cryoglobulinemic vasculitis
Most frequent cytogenetic abnormalities in SMZL patients
Complete or partial 3q trisomy (30–80% of cases) and gains of 12q (15–20% of patients)
The most significant karyotype aberrations, considered typical of SMZL, are ____________, which are reported in nearly 40% of the cases
Deletions or translocations involving 7q32
Most significant clinical characteristics of SMZL
Asymptomatic splenomegaly and cytopenias
In CBC,______________ is always present, and basophilic villous cells in blood may also be found
Lymphocytosis
Lymphocytosis is always present, and basophilic villous cells in blood may also be found
Morphology of SMZL
A micronodular lymphoid infiltrate of small lymphocytes typically surrounds and replaces the splenic white pulp germinal centers in SMZL, with involvement of the red pulp also consistently observed
Immunohistochemistry of SMZL
CD20+, CD23−, CD38−, CD5−, CD10−, cyclin D1−, IgD+
Distinction of both follicular lymphoma and mantle cell lymphoma from SMZL
Expression of both CD5 and cyclin D1 by mantle cell lymphoma
CD10 Expression of follicular lymphoma
Distinction of lymphoplasmacytic lymphoma (LPL) from SMZL
The presence of a very large IgM paraprotein spike (>10 g/L) favors the diagnosis of LPL rather than SMZL, though small IgM paraprotein spikes may also been seen in SMZL (usually <10 g/L).
Treatment indications in SMZL
Symptomatic SMZL patients with massive splenomegaly causing pain, early satiety or
Significant cytopenias, defined as
* hemoglobin less than 100 g/L
* platelets less than 80,000/μL, or
* neutrophils less than 1000/μL
Frontline treatment for SMZL
- Symptomatic SMZL patients with massive splenomegaly causing pain, early satiety or
- Significant cytopenias, defined as hemoglobin less than 100 g/L, platelets less than 80,000/μL, or neutrophils less than 1000/μ
Splenectomy
Does not influence marrow infiltration or blood lymphocytosis
Systemic therapy in SMZL is required when:
- Major contraindications to surgery exist,
- Older adult patients
- Those who relapse or progress after splenectomy
- Advanced disseminated nodal disease
- High-grade transformation
Options for systemic therapy in SMZL
Rituximab, used both as a single agent or combined with chemotherapy
Chemotherapy regimens are based on alkylating agents (eg, chlorambucil or cyclophosphamide), fludarabine, or bendamustine
Three variables used for prognostication in SMZL
- Hemoglobin concentration (< 120 g/L)
- LDH (if elevated at diagnosis)
- Albumin levels (<35 g/L)
Low-risk group (no risk factors): 88% 5-year cause-specific survival rate
Intermediate-risk group (one risk factor): 73% 5-year cause-specific survival rate
Hiigh risk group (at least two risk factors): 50% cause-specific survival rate
Nodal MZL is a mature, postgerminal center B cell lymphoma accounting for _________ % of all lymphomas, with a median age at onset of between 50 and 60 years
Less than 2%
TRUE OR FALSE
The association with autoimmune phenomena is strong for Nodal MZL, in contrast to other MZLs
FALSE
The association with autoimmune phenomena is weak for Nodal MZL, in contrast to other MZLs
Constitute a common marker of NMZL, occurring in 20% to 25% of patients and are shared with patients presenting with EMZL
Gain of several regions of chromosome 3
More than three-quarters of patients harbor somatic IGHV gene mutations and show a biased use of IGHV segments 3 and 4.
No typical cytogenetic aberrations have been demonstrated for NMZL
The majority of patients affected by NMZL present with ____________
Disseminated peripheral and abdominal nodal involvement
wlaa dapat extranodal at spleen, puro nodes!
Marrow infiltration is seen in fewer than half of the patients, and blood involvement is rare.
TRUE OR FALSE
In NMZL, extranodal disease is absent by definition, and the presence of splenomegaly should suggest a diagnosis of SMZL.
TRUE
In NMZL, extranodal disease is absent by definition, and the presence of splenomegaly should suggest a diagnosis of SMZL.
Type of NMZL that arises in adolescent patients, with a striking predominance in males.
Atypical cells within lymph nodes show a marked pleomorphism and an interfollicular distribution with the marginal zones considerably expanded.
Pediatric NMZL
Patients generally present with localized stage I disease, which can be managed conservatively (surgical excision and observation), with low rates of disease recurrence.
Treatment for limited-stage disease NMZL
Surgery and radiotherapy
No specific treatment consensus guidelines have been developed for NMZL, and patients are generally well managed using treatment paradigms developed for follicular lymphoma and other indolent NHLs.
Treatment for symptomatic advanced stage disease NMZL
Immunochemotherapy
Rituximab may be combined with cyclophosphamide, vincristine, and prednisone (R-CVP);
Fludarabine-containing and anthracycline-containing regimens (eg, R-CHOP, which is based on cyclophosphamide, doxorubicin, vincristine and prednisone); or
Bendamustine
Immunomodulatory and targeted agents used in immunomodulatory
Lenalidomide
Bortezomib
Ibrutinib
Inhibition of the Phosphatidylinositol 3-Kinase Pathway (Idelalisib, Duvelisib, Copanlisib, Parsaclisib, Umbralisib)
