Episode 136: Follicular Lymphoma Series, Pt. 1 - Introduction
This week, we kick off a new series, this time focusing on follicular lymphoma! This series will build on a lot of fundamentals that we discussed in our prior series. In this first episode, we start with an introduction to how to approach management of this disease.
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What are different modalities for biopsy in lymphoma?
Fine needle aspiration cytology, core biopsy and excisional biopsy.
Refer to previous episodes on The Fellow on Call- hemepath series, carcinoma of unknown primary and DLBCL episodes.
When is a fine needle aspiration (FNA) cytology favored/sufficient?
FNA is often used in the workup for solid tumors due to its rapid turnaround. This can be done through direct visualization and and ability to be obtained same day via bronchoscopy or endobronchial ultrasound (EBUS). It provides small samples of cells allowing for:
Morphological assessment (ie lymphoid vs epithelia vs carcinoma)
Immunohistochemistry (subtype and protein expression)
Flow cytometry (specifically for differentiating lymphoid cells)
However, FNA is not recommended for diagnosing lymphoma, as it lacks information about nodal architecture which is critical for accurate diagnosis.
Core needle Biopsy: When is it sufficient?
Core needle biopsy can be useful when surgical excision is not feasible or urgent diagnosis is required. Multiple core samples are recommended to ensure adequate tissue samples to be able to send FISH and other molecular studies.
If diffuse large B-cell lymphoma is found, a core biopsy can be sufficient for diagnosis and planning (but not guaranteed).
However, for indolent lymphoma, (ie follicular) core biopsy may miss areas of high grade transformation, which has important treatment implications.
Excisional Biopsy: When is it preferred?
Excisional biopsy is considered the gold standard when evaluating and diagnosing lymphoma.
Hodgkin lymphoma: Typically few Reed sternberg cells embedded in a dense inflammatory infiltrate, requiring excisional biopsy to look for these pathognomonic cells
Indolent lymphomas: Core biopsy may miss areas of higher grade histologic transformation
Handling and processing Lymph Node Tissue
If lymphoma is suspected:
Do not place tissue in formalin if flow cytometry is needed
Communicate with the team performing the biopsy and the pathology team to ensure proper processing and transportation
What are the differentials when cells express surface CD10 antigen ?
CD10 antigen expressing cells indicate origin from the germinal center. Common CD10+ lymphomas include:
Follicular lymphoma
Diffuse large B-Cell lymphoma
Burkitt Lymphoma
Increased forward scatter indicates large cells, likely large cell aggressive lymphoma.
No increase in forward scatter indicates follicular pattern.
What is pathobiology of Follicular Lymphoma?
In histology, a nodular growth pattern and cell morphology consisting of a mixture of centrocytes and centroblasts is characteristic. The proportion of centroblasts found in the sample determines the tumor grade.
The tumor cells express monotypic immunoglobulin light chain, CD20 (or CD19), CD10, and BCL-6 and are negative for CD5 and CD23. The vast majority (>85 percent) of tumors express BCL-2.
How is Follicular Lymphoma classified?
Per WHO 4th edition: grading was mandatory.
Grades 1-2: 0-15 centroblasts/0.159 mm2.
Grade 3a: >15 centroblasts/0.159 mm2.
Grade 3b: diffuse area with solid sheets of centroblasts. Treated as aggressive large cell lymphoma.
Per WHO 5th edition: grading no longer mandatory
Classic FL (cFL), FL with predominantly follicular growth pattern, FL with unusual cytological features (uFL), Follicular Large B-cell Lymphoma (FLBCL)
Renamed Follicular lymphoma grade 3b to FLBCL for consistency.
Emphasis on t(14;18)(q32;q21) in cFL; variant immunophenotypic and genotypic features in uFL.
Table source: Follicular Lymphoma in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms—Updated Classification and New Biological Data. No copyright infringement intended.
Important Subtypes in FL
Predominantly Diffuse Follicular Lymphoma
This variant may mimic DLBCL, however it retains follicular features and typically presents with early stage disease.
Key diagnostic feature: Lack the hallmark t(14:18) translocation involving BCL2
Primary cutaneous follicle center lymphoma
Arises in the skin, typically confined to cutaneous sites without systemic involvement
Often responds to localized radiation therapy or rituximab monotherapy if in multiple locations
How do you work up for a newly suspected follicular lymphoma?
Labs: CBC, CMP, LDH (prognostic purpose; if >400 more concern for large cell), uric acid
Infectious/Pre-treatment workup: Hepatitis B/C, HIV
Hepatitis B reactivation risk → prophylaxis if positive
Imaging: PET/CT for staging
Image source: lymphoma research foundation. No copyright infringement intended.
What is the role for bone marrow aspiration and biopsy in lymphoma?
In 2012, El Galey et al evaluated the use of PET/CT by looking at patients undergoing initial staging with both PET/CT and bone marrow biopsy.
Their study showed 99% negative predictive value for lack of bone marrow involvement using PET/CT alone in stage I/II disease.
In stage III/IV disease, bone marrow biopsy upstaged 5 patients but did not result in change in treatment.
In general, there is no need for a bone marrow biopsy unless cytopenias are present.
What is the natural history of follicular lymphoma?
FL has a relapsing remitting course over a decade or more and given its indolent nature, it is incurable.
Overall favourable prognosis with a median OS of ~20 years.
There is a subset that may never need treatment and some very aggressive necessitating treatment.
For localized disease, radiation alone could be used to cure.
Obtain PET/CT (higher SUV) and biopsy for every relapse to assess for transformation to large cell lymphoma (MYC rearrangement for example, divergent clones).
While a transformed lymphoma can be cured with aggressive regimen, it is not uncommon for indolent lymphoma to recur given the persistence of clone.
What is the significance of POD24 (progression of disease within 24 months) in patients with follicular lymphoma?
POD24 is associated with poor overall survival (OS) and indicates a higher risk of early death.
Studies have shown that approximately 15-20% of FL patients experience POD24, and these patients have markedly worse outcomes compared to those who do not progress within this timeframe.
What are the key points about when to use core needle biopsy versus excisional biopsy in follicular lymphoma, specifically considering the standardized uptake value (SUV) from PET/CT imaging?
Core needle biopsy is appropriate for lesions with SUV ≤10, as lower SUV values are associated with indolent disease.
Excisional biopsy is preferred for lesions with SUV >10, as higher SUV values may indicate histologic transformation or aggressive disease.
***This episode is sponsored by our global research partners! Click here to get paid to participate in market research surveys!***
The crew behind the magic:
Show outline: Vivek Patel
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Resonate Recordings
Shownotes: Megan Connor, Srijan Valasapalli
Social media management: Ronak Mistry
We are proud to partner with HemOnc.org!
Want to learn more about the trials that lead to the regimens discussed today? What about dosing schedules? See links in the show notes for a link to HemOnc.org
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