About Lymphoma > Grades

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

Introduction

Follicular NHL grading:
 
 "In the proposed schema (system), follicular lymphomas were categorized under “follicle center lymphomas” with cytologic (cell study) grades referring to the proportion of large cells in the follicle. 

Thus, grades I, II, and III form a continuum (gradual change) from follicular small cleaved-cell to large-cell predominance, without specific recommendations being made about cutoff criteria between grades."
 
   cancernetwork.com

About mixed large and small cell:
 
"All follicle center cell lymphomas contain centrocytes, which are small, cleaved follicle center cells, and centroblasts, which are larger noncleaved cells.
 
The centroblasts are usually in the minority; however, the variability seen in the proportions of cell types determines the grade of the tumor." 
 
  John E. Seng

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 (click illustration on the right), and sometimes other tests:

"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 these centroblasts is limited by certain cells (large centrocytes, follicular dendritic cells, and histiocytes) that could mimic centroblasts morphology (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."  

Utility of SKP2 and MIB-1 in grading follicular lymphoma using quantitative imaging analysis. Hum Pathol. 2007 Jun;38(6):878-82. Epub 2007 Mar 12. PMID: 17350668

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
 

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 more tailored to an individual's tumor will be identified.  This will take research and will be 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 will therefore tend to divide and grow 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 so many stages of differentiation. 

When cancer occurs it locks the cell and all it's descendants into the stage (and behavior of the stage) at which they became cancerous. Bottom line: well-differentiated = lower grade; poorly differentiated = higher grade. 

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. 

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.  

Grading and Lymphoma Cell Types

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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)