Defines how aggressive or slow growing the malignant cells are
likely to be. This is sometimes called histologic
grade, which is determined by the appearance of cells under the
"Follicular lymphoma is
classified into grades Grade 1, 2, and 3 based on the number of
centroblasts in neoplastic follicles.
However, the accuracy of manually counting centroblasts is
limited because certain cells mimic or look very much like
("morphology" is the study of the shape and form of things in general).
The reproducibility of follicular lymphoma grading is dependent
upon observer experience; therefore, significant variations occur."
According to the WHO
follicular lymphoma is graded as follows:
grade 1 (< 5 centroblasts (larger cells) per high-power field (hpf))
grade 2 (6 – 15 centroblasts/hpf)
grade 3 (> 15 centroblasts/hpf)
Grade 3 is further subdivided into:
grade 3A (centrocytes (smaller cells) still present)
grade 3B (the follicles consist almost entirely of
The clinical relevance of the grading system is still
Grade 3b is often treated as an aggressive (high grade)
Grade 3a can behave and is sometimes treated as a low grade
grade or indolent
Grade 1 =
Grade 2 =
mixed small and large cell
Note: both grade 1 & 2 are considered the same
diagnosis - are monitored and treated the same as indolent
determination of these grades can depend on the sample
evaluated under the microscope - it is not an exact science.
Sometimes grades of
indolent lymphoma are subdivided in this way:
Follicular, predominantly small cleaved cell
Follicular mixed, small and large cell
or high-grade (see
Grade 3 confusion below.)
are both often referred to as aggressive.)
"The WHO classification system recommends separating FL
(follicular lymphoma) into three different grades according to the number of centroblasts per high-power field (hpf):
grade 1 (<5
grade 2 (5-15
grade 3 (>15
"Also, it is recommended that in addition to a grade the biopsy be scored for the amount of
diffuse component present. The clinical importance of grade and diffuseness are unclear and generate much debate."
~ Halaas, et. al. (ASH
2003 - abstract)
The study suggests that most cases
(roughly 85%) previously classified as Follicular Large
Cell Lymphoma would currently be classified as Follicular
Grade 3a but that many of the cases currently classified as
Follicular Grade 3 would not have
been classified as Follicular Large Cell
in the old system.
The authors of this study concluded that
research regarding Follicular Large Cell should
not be assumed to apply to the newer system's Follicular
A significant diffuse
component predicts for inferior survival in grade 3
follicular lymphoma, but cytologic subtypes do not predict
Blood. 2003 Mar 15;101(6):2363-7. Epub 2002 Nov 07. PMID: 12424193
3 and anthracycline-containing treatments [such as CHOP]
Commentary from Experts PAL
Grade 3 follicular
Lymphoma resource page PAL
As tumor classification systems evolve, research using
older systems may show different results than newer classification
systems. As insights into genetic and molecular aspects of
tumors are discovered it is hoped that treatment strategies better
tailored to an individual's tumor will be identified. Such research
is facilitated by participation in research
is well-differentiated lymphoma?
Differentiation refers to the maturation level of the cells in question, which often defines how fast they are
likely to grow.
Think of a fetus as lacking differentiation
- organs not fully developed or fully functioning -- but rapidly growing to become so. A fully differentiated (mature) adult does not grow nearly as fast.
Cells that are well differentiated closely resemble mature cells and therefore tend to divide and grow
Therefore malignant cells that are well differentiated, like their normal
counterparts, will tend to grow slowly.
Cells that are poorly differentiated are less mature, more likely to grow fast, and also generally more susceptible to
The reason we have so many kinds of lymphomas is that immune cells have many stages
of maturation ... or differentiation.
When cancer occurs it locks the cell and all it's descendants into the stage (and behavior of the stage)
the stage at which they became cancerous. So in general: well-differentiated = lower grade; poorly differentiated = higher grade.
Also see Fine-Needle Aspiration in Non-Hodgkin Lymphoma: Evaluation of Cell Size by Cytomorphology and Flow Cytometry
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