Category Archives: WHO Classification

Organ Systems, WHO Classification

Hans’ Algorithm

Diffuse Large B-Cell Lymphoma represents a heterogeneous group of non-Hodgkin B-cell lymphoma cases that share a common architectural pattern and large cell size.  Subcategorization have been attempted with varying success based on morphology, immunophenotype, and molecular characteristics.  Gene expression profiling (GEP) has demonstrated two important groups for both prognosis and treatment.  Alizadeh, et al showed significant survival differences in cases of DLBCL with either a germinal center B-cell-like pattern or an activated B-cell-like pattern.
 
Unfortunately, GEP is not available in routine clinical practice, and multiple surrogate immunohistochemistry (IHC) based algorithms have been developed as a surrogate to GEP.  The Hans’ algorithm (classifier) has been one of the most popular methods because it uses only three IHC markers (CD10, Bcl-6, & MUM-1) that are commonly available in most pathology laboratories.  The following figure highlights the algorithm for the Hans’ classifier as described in the original paper.  The Hans’ algorithm appears to match GEP in 75-80% of cases.
 
Hans Classifier - CD10, Bcl-6, MUM-1
Hans classifier to subtype DLBCL as to germinal center B-cell-like (GCB) or non-germinal center B-cell-like (non-GCB) which has prognostic significance.
Alternative Algorithm(s)
The University of Nebraska group that originally developed the Hans algorithm has developed a new IHC stain algorithm that reportedly classifies cases of DLBCL more accurately compared to the corresponding molecular subtypes (~80% concordance).  This algorithm uses GCET1, CD10, BCL-6, MUM-1, and FOXP1 with differing cutoff values for positive/negative. (WW Choi, et al)  New algorithms with IHC markers not commonly used in many laboratories has probably limited popularity compared to the Hans’ algorithm.  The 2016 WHO hematopathology revision requires that cases of DLBCL be characterized at GCB vs. non-GCB by some acceptable methodology (molecular or IHC).
References
Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103: 275–282. doi:10.1182/blood-2003-05-1545
 
Haarer CF, Roberts RA, Frutiger YM, Grogan TM, Rimsza LM. Immunohistochemical classification of de novo, transformed, and relapsed diffuse large B-cell lymphoma into germinal center B-cell and nongerminal center B-cell subtypes correlates with gene expression profile and patient survival. Arch Pathol Lab Med. 2006;130: 1819–1824.
 
Chang C-C, McClintock S, Cleveland RP, Trzpuc T, Vesole DH, Logan B, et al. Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. Am J Surg Pathol. 2004;28: 464–470.
 
Choi WWL, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15: 5494–5502. doi:10.1158/1078-0432.CCR-09-0113
 
Alizadeh AA, Elsen MB, Davis RE, Ma C. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000.
 
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127: 2375–2390. doi:10.1182/blood-2016-01-643569 
Organ Systems, WHO Classification

Diffuse Large B-Cell Lymphoma (DLBCL)

DLBCL is the most common non-Hodgkin lymphoma in the US (25,000 new cases/year) and is an intermediate grade lymphoma consisting of a heterogeneous group of mature B-cell lymphoid neoplasms sharing the common characteristics of diffuse architectural pattern and (medium or large) neoplastic lymphoma cells (nuclei >2x normal lymphocyte or equal to / exceeding a macrophage nuclei).  DLBCL lymphoma can arise de novo or as transformation from another lymphoma (e.g. follicular lymphoma, CLL/SLL, marginal zone lymphoma).  

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Organ Systems, Breast, WHO Classification

Breast – Normal IHC Expression

Normal breast ducts and lobules are lined by a 2-cell layer composed of luminal and myoepithelial cells.  There are also interspersed “basal” cells, which probably represent the epithelial progenitor cells.
 
IHC Marker
Luminal Cells
Myoepithelial Cells
LMWCKs
(CK7/8/18)
Positive
Negative
Variable Expression
Negative
HMWCKs
(CK5/14/17)
Negative
Positive
SMA
Negative
Positive
Negative
Positive
Negative
Positive
SMA=Smooth Muscle Actin, SMM-HC=Smooth Muscle Myosin Heavy Chain
 
An understanding of the normal IHC expression pattern in breast ductal tissue is important when considering IHC use in the differential diagnosis of breast pathology.
References
Hicks DG. Immunohistochemistry in the diagnostic evaluation of breast lesions. Appl Immunohistochem Mol Morphol. 2011;19(6):501–505. doi:10.1097/PAI.0b013e31822c8a48.
 
Liu H. Application of immunohistochemistry in breast pathology: a review and update. Arch Pathol Lab Med. 2014;138(12):1629–1642. doi:10.5858/arpa.2014-0094-RA.