MALT Lymphoma - ABHH Eventos

MALT Lymphoma
History - I
• A 45-year-old woman complains of dyspepsia
and epigastric pain over the last 2 years. An
upper
gastroendoscopic
examination
performed 1 year ago revealed chronic
gastritis. She has no other symptoms.
Recently, the symptoms worsened.
• No other relevant symptoms.
Physical examination
• Performance status: ECOG 0.
• No enlarged lymph nodes.
• No splenomegaly or hepatomegaly.
Diagnostic tests
• She was submitted to another upper
gastroendoscopic examination. A gastric
ulcer was observed and biopsied.
Histopathology
Histopathologic findings
Gastric biopsy – low power
Gastric biopsy – high power
Immunohistochemistry - keratin
Helicobacter pylori
Histopathologic findings
Gastric biopsy – low power
Gastric biopsy – high power
Immunohistochemistry - keratin
Helicobacter pylori
Histopathologic findings
Gastric biopsy – low power
Gastric biopsy – high power
Immunohistochemistry - keratin
Helicobacter pylori
Histopathologic findings
Gastric biopsy – low power
Gastric biopsy – high power
Immunohistochemistry - keratin
Helicobacter pylori
MALT CONCEPT
Helicobacter pylori
Isaacson has suggested that “acquired MALT” secondary
to autoimmune disease or infection in these sites may form
the substrate for lymphoma development.
DEFINITION OF MALT LYMPHOMA
Extranodal marginal zone lymphoma of mucosa-associated
lymphoid tissue (MALT lymphoma).
Destruição do epitélio glandular
Colonização do centro
germinativo e desaparecimento
da zona do manto
DEFINITION OF MALT LYMPHOMA
The infiltrate is in the marginal
zone of reactive B-cell follicules
and extends into the interfollicular
region.
Composed of morphologically
heterogeneous small B-cells
including marginal zone cells
(centrocyte-like) cells,
Cells resembling
monocytoid cells,
Small lymphocytes and
scattered immunoblasts
and centroblast-like cells.
There is a plasma cell
differentiation in a proportion of
the cases.
The most striking feature of MALT lymphoma
is the presence of a variable number of
lymphoepithelial lesions defined by evident
invasion and partial destruction of mucosal
glands by the tumor cells.
MALT lymphoma as defined is a
lymphoma composed
predominantly of small cells
When solid or sheet-like
proliferations of transformed cells
are present, the tumour should be
diagnosed as diffuse large B-cell
lymphoma and the accompanying
MALT lymphoma noted
THE TERM “HIGH-GRADE MALT LYMPHOMA” SHOULD NOT BE USED!
Immunophenotype
CD20 (+)
CD21 (+)
CD5 (–)
Very important
CD10 (–)
Ciclina D1 (-)
Others markers
CD35 (+)
CD79a (+)
There is no specific marker for MALT lymphoma at present
Classification
• MALT lymphoma accounts for 7-8% of all B-cell lymphomas and up to 50%
of the primary gastric lymphomas.
• In the World Health Organization (WHO) classification of tumors of
hematopoietic and lymphoid tissues, the group of marginal zone
lymphomas (MZL) comprises three different entities:
– Extranodal marginal zone B-cell lymphoma of mucosa- associated lymphoid
tissue ( ‘‘MALT lymphoma’’)
– Nodal marginal zone B-cell lymphoma
– Splenic marginal zone B-cell lymphoma (with or without circulating villous
lymphocytes)
Schematic model of the origin and progression of a mucosaassociated lymphoid tissue (MALT) lymphoma
Zucca, BJH, 2006.
Staging Procedures - I
• The traditional Ann Arbor staging system can be
misleading in MALT lymphomas.
• Alternative staging systems for extranodal
lymphomas have been proposed
• There might be asymptomatic dissemination in
patients with apparently localized disease - staging
is advised in all patients with MALT lymphoma.
Rohatiner, 1994
Recommended staging procedures -I
• Staging for all locations of MALT lymphoma should include:
– clinical history and the physical examination
– inspection of the upper airways and tonsils,
– thyroid examination, and clinical evaluation of the size of liver and spleen.
– CT scans of thorax, abdomen, and pelvis
– Bone marrow biopsy must be performed at diagnosis.
• LDH and beta-2-microglobulin levels, evaluation of renal and liver
function, serology for hepatitis C virus (HCV) and HIV infections.
Recommended staging procedures -II
• Initial staging procedures should include a gastroduodenal
endoscopy, with multiple biopsies from each region of the
stomach, duodenum, gastro-esophageal junction, and from
any abnormal-appearing site.
• Many authors also recommend a colonoscopy.
• If possible, endoscopic ultrasound is recommended to
evaluate the depth of infiltration and perigastric lymph
nodes enlargement
Staging procedures in the present case
• Thoracic and abdominal CAT scan: normal
• Bone marrow biopsy: normal
• WBC 7.5 x 109/l (68% N, 28% L, 3% M, 1% Eo), Hb 13g/L,
Ht 39, MCV 92 fl, Platelets 300 x 109/l .
• Biochemical workup: normal
• LDH and B2M: normal
• HCV, HBV, HIV: negative
• Protein electrophoresis: normal
Final Diagnosis
• Gastric MALT Lymphoma, stage IE
Treatment
• H. Pylori eradication with antibiotics is widely
accepted as initial standard treatment for stage I
gastric lymphoma of MALT type
Erradicação do Helicobacter pylori
Response evaluation and Follow-up studies
• Urea breath testing after 4-8 weeks
• Up to 20 percent of patients will require a second H pylori
eradication regimen
• Endoscopic follow-up is recommended, with multiple biopsies
3 months after treatment to document H. Pylori eradication.
• Subsequently, examinations should be done at least twice per
year for 2 years to monitor the histologic regression of
lymphoma.
Interpretation of a residual infiltrate
• The interpretation of residual infiltrates in posttreatment gastric biopsies can be difficult and there
are no uniform criteria for the definition of histologic
remission.
• In case of persistent but stable residual disease, a
watch and wait policy may be safe. Clinical and
endoscopic follow-up once per year is
recommended.
No difference was detected in
recurrence/progression rates and
recurrence/progression-free
survival or overall survival.
BJH, Hancock,BW,2009
Management of H. Pylori negative cases
• Response to antibiotic treatment can
sometimes be observed also in H. pylorinegative patients (sometimes the
lymphoma harbors H heilmannii or H
felis).
Second-line treatment
• Radiation therapy (IF radiotherapy 30–36 Gy
the stomach and perigastric nodes) is the
treatment of choice for patients with stage I-II
MALT lymphoma of the stomach without
evidence of H. pylori infection or with
persistent lymphoma after antibiotics -90% of
patients attained a CR.
Yahalom J, Ann Hematol 2001
Schecter NR, JCO, 1998
Tsang, JCO, 2003
Role of chemotherapy after antibiotic treatment
• Surgery is reserved for the treatment of complications, such
as perforation, haemorrhage or obstruction, which cannot be
managed conservatively.
• There is no consensus regarding chemotherapy after
antibiotic treatment (alkylating monotherapy and 2-CDA)
Treatment of advanced disease
• Chemotherapy or immunotherapy with anti CD20
mabs.
• Oral alkylating agents can result in a high rate of
disease control.
• Phase II studies demonstrated the antitumor activity
of the purine analogs fludarabine and cladribine.
• Aggressive anthracycline containing chemotherapy
should be reserved for patients with high tumor
burden (bulky masses, high IPI score)
•HP + 81%
Histological regression
•Histological
regression 76%
•Persistent
histological
remmision=33/74
•Transformation =2
Stathis and Zucca, Annals of Oncology, 2009
Stathis, Zucca,
Ann Oncol 2009