Q. Can you explain a bit about the classification of B-cell lymphoma? I’m a teacher, and I’ve inherited a lecture on lymphomas. The previous lecturer’s PowerPoint says there are three types of B-cell lymphoma: 1. Small-cell B-cell lymphoma, 2. Large-cell B-cell lymphoma, and 3. Mixed cell type B-cell lymphoma. Have the names of these subtypes changed? I’m not finding the “Mixed-cell…”  Are there different names for the B-cell lymphomas?

A. Yes, there are different names now! It would seem the previous lecturer picked a few types of B-cell lymphoma out of the many that exist. There is a better way to list the B-cell lymphomas that I’ll get to in a bit. Lymphoma classification is one of those annoying areas of pathology where the terminology seems to change every time you turn around. Maybe a short review of how things have changed over the years is in order.

In the olden days (before lymphomas were even classified into B- and T-cell types), there were just three categories of lymphoma: well-differentiated (composed of small lymphocytes in a diffuse pattern), poorly differentiated (composed of small lymphocytes in a follicular pattern) and histiocytic (composed of large cells – now known to be lymphocytes, not histiocytes, but hey, how were they supposed to know that back then?). This was called the Rappaport Classification and it isn’t used anymore because we know a lot more about lymphomas now, and consequently the classification of lymphomas has been updated.

A later classification, put out in 1982, was the Working Formulation. It divided lymphomas into three groups based on how they behaved clinically: low-grade lymphomas, intermediate-grade lymphomas, and high grade lymphomas.

Low-grade lymphomas:
Small lymphocytic lymphoma
Follicular small cleaved cell lymphoma
Follicular mixed small cleaved and large cell lymphoma

Intermediate-grade lymphomas:
Follicular large-cell lymphoma
Diffuse small cleaved cell lymphoma
Diffuse mixed small and large cell lymphoma
Diffuse large cell lymphoma

High-grade lymphomas:
Large cell immunoblastic lymphoma
Lymphoblastic lymphoma
Small non-cleaved cell (Burkitt) lymphoma (that’s the diagnosis in the image above)

Notice how there is still no mention of B-cell vs. T-cell lymphomas! These lymphomas were classified not on their immunophenotype (B vs. T), or their cytogenetic abnormalities (like whether they had a t[8;14]), but just on how they behaved clinically (were they really bad? or just sort of bad?). Some of the lymphomas listed above are always B-cell in nature (small non-cleaved cell [Burkitt] lymphoma, for example), and some can be either B or T (like lymphoblastic lymphoma).

These days, we use a lymphoma classification put out by the World Health Organization. It categorizes all lymphoid neoplasms (not just lymphomas, but leukemias too) into three groups: B-cell neoplasms, T- and NK-cell neoplasms, and Hodgkin disease. Here is the B-cell section:

B-cell neoplasms
1. Precursor B-cell neoplasm (in other words, a neoplasm composed of cells that are B-lymphoblasts, which are precursors to the mature B cells we have floating around in our blood):
– Precursor B-lymphoblastic leukemia/lymphoma

2. Mature (peripheral) B-cell neoplasms (in other words, neoplasms composed of B-lineage cells that have matured past the lymphoblast stage):
– B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
– B-cell prolymphocytic leukemia
– Lymphoplasmacytic lymphoma
– Splenic marginal zone B-cell lymphoma
– Nodal marginal zone lymphoma
– Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
– Hairy cell leukemia
– Plasma cell myeloma/plasmacytoma
– Follicular lymphoma, follicle center
– Mantle cell lymphoma
– Diffuse large B-cell lymphoma
– Burkitt lymphoma/Burkitt cell leukemia

Notice how they put both lymphomas and leukemias under the same “B-cell neoplasms” heading. That’s because while lymphomas start in lymph nodes, and leukemias start in the bone marrow, both often spread to involve other sites. In fact, some “lymphomas” (like small lymphocytic lymphoma) and “leukemias” (like chronic lymphocytic leukemia) are now known to be exactly the same disease. It’s just that they were described in different places way back when names were given…but now, we have enough clinical experience to know that they have the same prognosis (relatively good, in the case of CLL/SLL), and the cells mark the same way (both are B-cell neoplasms). So these “pairs” are now lumped together.

Notice also that there are a TON of different B-cell neoplasms! It might be a good idea to pare the list down to just the more common neoplasms, and leave the rarities to the hematopathologists. So a shorter, more reasonable list might look like this:

B-cell neoplasms:
1. Precursor B-lymphoblastic leukemia/lymphoma
3. MALT lymphoma
4. Plasma cell myeloma
5. Follicular lymphoma
6. Diffuse large B-cell lymphoma
7. Burkitt lymphoma/leukemia

In case you need to teach about T-cell neoplasms too, which I imagine you do, here’s a shortened list of the more common T-cell neoplasms:

T-cell neoplasms:
1. Precursor T-lymphoblastic leukemia/lymphoma
2. Adult T-cell leukemia/lymphoma
3. Mycosis fungoides/Sezary syndrome

So there you have it. Taken as a whole, the classification schemes can seem a bit (okay, a lot) overwhelming. But if you focus on the 10 lymphomas above, that should be doable – for you and for your students.