Follicular Lymphoma Flashcards
(43 cards)
What are the common symptoms at presentation for FL?
B Symptoms
Fatigue
Local mass effect of LN
Cytopenias
Describe FL
Indolent Lymphoma
Follows a chronic, relapsing course
Median survival of 7-10 years
Minority little or no progressions
Spontaneous and prolonged remissions
20-30% transform to high grade
Incidence of 20-25% amongst B Cell lymphoma
Median age 60 yo
What are the main oncogenic events that occur in the development of FL?
Ectopic expression of B-cell lymphoma 2 (BCL2)
Changes in the epigenome
BCL2 - promotes an anti-apoptotic programme
- provides survival signals to the malignant cells
Changes in the epigenome due to:
- Genetic inactivation of the histo economy methyltransferase MLL2
- Genetic inactivation of the acetyltransferases CREB-binding protein (CREBBP)
- Genetic inactivation of the E1A-binding protein p300 (EP300)
- activation of his tone methyltransferase enhancer of zeste homologous (EZH2)
What is the immunophenotype of FL?
CD20+
CD10+
BCL2+
BCL6+
CD23+/-
CD5-
CD43-
CCND1+
Any characteristic chromosomal translocation of FL?
BCL2 t(14;18) in 90% of cases
What are the differential diagnosis for FL?
1) NLPHL
- small and scattered large cells
2) CLL
- CD5+, CD23+
- CD10-, BCL6-
3) MCL
- Cyclin D1 +, CD5+
4) MZL
- CD10-, BCL6-
Anything in particular about FL with 1p36 deletions?
- Predominant diffuse pattern in inguinal LN,
- large localized mass
- CD23+
- Typically G1 or G2
- good prognosis
Anything about IRF4 translocations?
Usually DLBCL, but occasionally pure FL Grade 3B;
And often could be DLBCL + FL Grade 3B
Typically present with Waldeyer’s ring involvement
Often children/young adults
Locally aggressive, but responds well to chemo +/- RT
BCL2-
Should NOT be treated as low-grade FL
What is the Waldeyer’s ring?
Ring of lymphoid tissue in the pharynx.
Formed by:
- Palatine tonsils ('tonsils)
- pharyngeal tonsils
- tubal tonsils
- lingual tonsil
- adenoidsWhat are the suggestions that a histologically transformation has occurred?
LDH rising
Single site growing disproportionately
Extranodal disease develops
New B symptoms
What are the indications for treatment in FL (Grades 1-2)?
Candidate for clinical trial Symptoms Threatened end-organ function Cytopenia secondary to lymphoma Bulky disease Steady progression
GELF Criteria:
1) LN
- 3 or more LN areas each 3 or more cm
- any nodal or Extranodal site 7cm or bigger
2) Blood
- Cytopenias (Plts, Leukocytes)
- Leukemia
3) Organ
- Splenomegaly
- Ascites/Pleural effusions
4) General
- B Symptoms
What is the GELF criteria?
1) Blood
- Cytopenias (Plt 5x10^9 malignant cells)
2) Organ
- Splenomegaly
- pleural effusions/ascites
3) LN
- 3 or more LN regions, each 3cm or bigger
- any LN or Extranodal site 7cm or bigger
4) General
- B symptoms
What is FLIPI-2 ?
Age >60 yo Long diameter of largest LN >6cm BM involvement (stage) Beta-2microglobulin increased (Serum marker) Hb
What are first-line treatments for fit FL patients?
R-Bendamustine RCHOP RCVP Rituximab (375mg/m2 weekly for 4 doses) R-Lenalidomide
Addition of R has shown to increase ORR, Response duration, PFS as well as possibly OS
What are first-line therapies for FL who are elderly or infirm ?
1) Rituximab (375mg/m2 weekly for 4 doses) - preferred
2) Single-agent alkylators +/- Rituximab
- Chlorambucil
- Cyclophosphamide
3) Radioimmunotherapy
What are 2nd-line and subsequent therapies approved for FL?
1) Chemoimmunotherapy
2) Rituximab
3) Lenalidomide +/- R
4) Idelalisib
5) Fludarabine + Rituximab
6) RFND
- Rituximab, Fludarabine, Mitoxantrone, Dexamethasone
How do we give Idelalisib?
Small molecule inhibitors
Recommended dose is 150mg PO BD
Possible s/e: - Fatal +/- serious hepatotoxicitis >> stop if ALT/AST >5xULN >> when transaminitis resolved, need to reduce dose to 100mg BD - severe diarrhea or colitis >> severe diarrhea/colitis can be managed with systemic or nonabsorbable steroids - pneumonitis - intestinal perforation
When used for CLL, upon initiation of Idelalisib, transient increase in absolute lymphocyte count is expected in most patients
- does not mean PD
- may persist for several weeks on treatment
What are the grades of FL?
Grading is performed according to the number of blasts per hpf
Grade 1: 5 or less than 5 blasts/hpf
Grade 2: 6-15 blasts/hpf
Grade 3A: >15 blasts/hpf, centroblasts with intermingled centrocytes
Grade 3B: >15 blasts/hpf, pure sheets of blasts
Tell me what you know about FL3B with cytogenetic abnormalities at BCL6 (3p27)
More similar to germinal center DLBCL than FL1-3A
A/w more aggressive clinical course
What are the other variants of FL?
1) Pediatric-type FL:
- Rare variant of FL
- lack of BCL2 rearrangement and t(14;18)
- better prognosis than adult FL
- often cured with minimal therapy
2) Primary intestinal FL:
- common in small intestine, usually duodenum
- similar to those of nodal FL
- clinically indolent, localized disease
- survival appears excellent even w/o tx.
3) Other Extranodal FL
- usually localized disease
- systemic relapses rare
4) FL-in-situ
- Preservation of LN architecture
- incidental finding of focal strongly positive staining for BCL2 restricted to germinal centers
- also has strong staining for CD10 in involved follicles
- detection of t(14;18) by FISH
- has been reported in patients with prior FL or concurrent FL at other sites
What is primary cutaneous follicle Centre lymphoma? (PC-FCL)
Defined as:
- tumor of neoplastic follicle center cells,
- includes centrocytes, variable number of centroblasts
- with a follicular and diffuse or a diffuse growth pattern
Most common B-cell lymphoma of the skin
Indolent, rarely disseminates to extra cutaneous sites
BCL6+, CD10+ likely
BCL2 often negative
Excellent prognosis, 5y OS 95%
What are the 3 trials that advocated for WW in advanced stage asymptomatic FL in the pre-Rituximab era?
1) Ardeshna 2003
- treatment arm: Chlorambucil
2) Brice 1997
- Arm 2: Prednimustine
- Arm 3: IFN
3) Young 1988
- ProMACE-MOPP + total nodal irradiation
Which 2 criteria can we use to assess if a FL patient is suitable for WW approach?
1) BNLI
2) GELF Criteria
What is the BNLI criteria?
Absence of any:
- pruritus or B symptoms
- rapid growth in 3 months
- life threatening organ involvement
- marrow infiltration causing Hb
