The most common variant of classical Hodgkin’s lymphoma (65–70% of cases), which is characterized by fibrous collagen bands that divide the lymph node into at least one nodule (fibrosis can range from scant to abundant) and neoplastic Hodgkin cells and Reed-Sternberg (HRS) cells with lacunar morphology (formalin fixation artifact with retraction of the cytoplasm).  The lymph node capsule is usually thickened.

 

Syncytial variant – prominent aggregates of neoplastic Hodgkin cells.

 

The immunophenotype of nodular sclerosing variant is shared with the other variants of classical Hodgkin lymphoma (PAX-5+, CD15+, CD30+, and CD45-).  EBV infection is not common in this subtype (10-40%).

 

Characteristic Immunohistochemical Features

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References

NF-κB transcription factor is a common event, which may occur through EBV infection (hence some cases positive for EBV) or other mechanism.  It is thought this process results in survival of germinal center B-cells, which would otherwise undergo apoptosis.  Hodgkin lymphoma cells typically represent a small number within the lesional tissue.  Hodgkin cells secrete varying cytokines that recruit other inflammatory cells, which make up the characteristic milieu (histiocytes, plasma cells, T-cell, and eosinophils).

 

Reed-Sternberg (HRS) cells are defined by two separate nuclear lobes with large nucleoli.  Mononuclear neoplastic cells are referred to as Hodgkin cells.  There is often a spectrum in appearance of the neoplastic cells with some HRS types but they may a minority.  Granulomatous inflammation may be present in biopsy specimens, and it important not to dismiss the granulomatous inflammation as the primary pathology (especially in small biopsy samples).

• Nodular Sclerosing CHL (65-70%), EBV-
• Lymphocyte-Rich CHL (~5%), ~40% EBV+
• Mixed-Cellularity CHL (20-25%), 70% EBV+
• Lymphocyte-Depleted CHL (<1%), >90% EBV+

Characteristic Immunohistochemical Features:

CD30	Positive in the malignant cells in almost all cases.  Membrane staining with Golgi area positivity.
CD15	Positive in the malignant cells in a majority of cases (75-85%).  The staining pattern is similar to CD30.  It should be noted that there is a lot a variability lab to lab in the performance of the antibody.
CD45	Usually negative
PAX_5	Dim expression in the lymphoma cells in >90% of the cases.  Helpful in differentiating cases from anapestic large cell lymphoma, which may be CD45 negative.
CD20	Usually negative, but may have dim variable subset expression in up to 20% of cases.
CD79a	Rarely positive in the lymphoma cells.
MUM1	Usually positive and usually intense.
EBV	Variable
EMA	Rarely positive and usually weak if positive.
OCT-2	Negative in 90% of cases.
BOB.1	Negative in 90% of cases.
ALK	Negative.

References

Nodular Lymphocyte Predominate Hodgkin Lymphoma (NLPHL) epresents approximately 5-10% of Hodgkin lymphoma cases (predominately male, 30-50 y/o) and has slightly different appearing neoplastic cells (popcorn cells – folded/multilobuated usually with multiple nucleoli).  The cellular background is typically composed of small lymphocytes and histiocytes.  Some plasma cells may be present at the peripheral of the nodule.  Neutrophils and eosinophils are not typically present.  The immunophenotype of lymphocyte predominate (LP) cells in NLPHL  is different from classical Hodgkin lymphoma.  The LP  cells express CD20 and BCL 6, but are typically negative for CD30 and CD15.  Dim expression of CD30 can be seen.