About Lymphoma > Grades (indolent - aggressive)

Last update: 01/17/2013

TOPICS
Introduction | Indolent | Intermediate/Aggressive
Grading and Cell Type

Introduction

Grading

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 microscope.

"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 centroblasts.

("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."  

Source: PMID: 17350668

	According to the WHO criteria, 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 centroblasts) The clinical relevance of the grading system is still debated. Grade 3b is often treated as an aggressive (high grade) lymphoma.  Grade 3a can behave and is sometimes treated as a low grade lymphoma.
	low grade or indolent   Grade 1 = small cell 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 lymphoma.     The 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:   Small lymphocytic Follicular, predominantly small cleaved cell Follicular mixed, small and large cell
	intermediate- or high-grade  (see Grade 3 confusion below.)   (Today these are both often referred to as aggressive.)

Grade 3 confusion:  

"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 centroblasts/hpf)
	grade 2 (5-15 centroblasts/hpf)
	grade 3 (>15 centroblasts/hpf)

"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 Grade 3. 

Related articles
 

	A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival. Blood. 2003 Mar 15;101(6):2363-7. Epub 2002 Nov 07. PMID: 12424193 and related abstracts
	Grade 3 and anthracycline-containing treatments [such as CHOP] Commentary from Experts PAL
	Grade 3 follicular Lymphoma resource page PAL

Lay comment: 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 trials.

What 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 more slowly.  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 chemotherapy.
 
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  Medscape (free login req.)

Indolent
lymphomas

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This grouping  relates to the grade (relatively slow growth behavior) of the lymphoma, which includes a variety of cell types. 

Comprehensive review of  Cancernetwork

Intermediate/
 aggressive
lymphomas

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This grouping relates to the grade (relatively fast growth behavior) of the lymphoma, which includes a variety of cell types.  

	Aggressive NHL: Oncology Board Review Manual  yr 2000 PDF
	Overview Aggressive Non-Hodgkin's Lymphomas  Lymphoma InfoNet
	Treatment of Intermediate-and High-Grade Non-Hodgkin's Lymphoma  ACS

Grading and
 Lymphoma Cell
Types

Source

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Low-Grade Lymphomas (indolent):

Follicular, predominantly small cleaved. Most common non-Hodgkin's lymphomas, accounting for 30% of all NHLs and for 60% to 70% of low-grade tumors.

Follicular, mixed small cleaved and large cell lymphomas. Account for 20% to 30% of low-grade tumors.

Small lymphocytic, diffuse. Form well-differentiated tumors;  often wide spread when diagnosed. 

Intermediate-Grade Lymphomas (aggressive):

Diffuse, large cell lymphomas. Account for 85% of intermediate-grade lymphomas. Second most common NHL in  U.S. Further categorized into other types, including immunoblastic lymphomas. 

Follicular, predominantly large cell.

Diffuse, small cleaved cell.

Diffuse mixed, small cleaved and large cell.

High-Grade Lymphomas (aggressive):

Diffuse, small noncleaved cell (DSNC)

Large cell, immunoblastic

Small non-cleaved cell (Burkitt's or Burkitt-like)

Lymphoblastic

Other (indolent, intermediate, high grades)

Lymphoplasmacytoid lymphoma (categorized typically as low-grade)

Mantle cell lymphoma (categorized as intermediate grade, although cell histology itself is low-grade)

Mucosa-associated lymphoid tissue lymphomas (MALT) and monocytoid B-cell lymphoma (low-grade lymphomas typically involving tissue in gastrointestinal tract, thyroid, breast, and skin).

Splenic marginal zone lymphoma (typically low-grade)

Anaplastic large-cell lymphomas (typically intermediate)