Hodgkin Lymphomas Flashcards
Hodgkin lymphomas generally affect which
organs and what is a common feature of
most of them?
- usually affect Lymph Nodes
- variable mixture of associated, non-neoplastic inflammatory cells
- sometimes associated with variable fibrosis (thick band like)
What are the 2 types of
Hodgkin’s Lymphomas?
- Nodular lymphocyte predominant (NLPHL)
- Classic Hodgkin Lymphoma
Which HL is the most common type and
what age groups is it often seen in?
- Classic Hodgkin Lymphoma
- 90% of all HL
- Two peaks
- 15-35 years old
- late life
- Has different subtypes that fall into these categories
How does HL (both types, general) present
clinically?
- peripheral lymphadenopathy
- usually localized to 1-2 lymph nodes
- generally cervical
- NLPHL prefers peripheral lymph nodes
- B symptoms
- fever, drenching night sweats, weight loss
- NLPHL does not present with B symptoms, in fact it is usually asymptomatic
At what stage of B cell maturation are
Hodgkin/R-S cells derived from?
- > 98% of cases are neoplastic B cells
- derived from mature B cells of the germinal centre stage
- clonal IG genes
What are the 4 subtypes of
Classical Hodgkin’s Lymphoma?
- Nodular Sclerosis Hodgkin Lymphoma
- Lymphocyte rich CHL
- Mixed Cellularity CHL
- Lymphocyte depleted CHL
What age group is preferentially affected
by Nodular Lymphocyte Predominant HL?
- generally 4th-5th decade
- also common in children
- M > F
CHL subtypes tend to have a male predominance, with the exception of which subtype?
- Nodular sclerosing HL
- slight female predominance
What two subtypes of CHL are often
associated with EBV infection?
- Mixed cellularity CHL
- Lymphocyte depleted CHL
Note: NLPHL is only rarely associated with EBV infection (<5%)
Which organ when involved by
HL increases the risk of extranodal dissemination?
- Splenic involvement increases risk
- usually Mixed cellularity CHL
- Usually cervical LN are involved by CHL
- NSCHL involves the mediastinum frequently
- Primary extranodal involvement is very rare
- Bone marrow involvement is rare (5%)
- bone marrow lacks lymphatics
- bone marrow infiltration indicates vascular dissemination (stage IV)
What is the morphology of Classic
Reed-Sternberg Cells?
- large with abundant and slightly basophilic cytoplasm
- have at least 2 nuclear lobes and 2 nuclei
- can have more than this
- nuclei are large, rounded contours
- prominent, irregular nuclear membrane
- pale chromatin, eosinophlic nucleolus
- perinuclear halo
- 2 prominent nucleoli in 2 separate nuclei in one cell
What is the morphology of the Hodgkin cell
and the Mummified Hodgkin cell?
- smudgy large nuclei (may be slightly eosinophilic)
- can be anaplastic and confused with ALCL
What is the immunophenotype of the HS
of CHL?
- CD15 and CD30- membranous pattern with accentuation in the Golgi region
- PAX5
- weaker than reactive B cells (IMP)
- IRF4/MUM1 - strongly positive
- CD20
- positive in 30% of cases
- CD79a
- not often expressed
- CD45 and CD68 - negative
What is the EBV expression of HS cells
of CHL ?
- EBV infected cells express LMP1 and EBNA1
- no expression of EBNA2
- this is characteristic of type II EBV infection
What is the expression of OCT2 and BOB1
in CHL HS cells?
- absence of the transcription factor (OCT2) and its cofactor (BOB1)
Note: EMA is also negative in most cases
How can CHL lymphoma be mistaken for ALCL
and what IHC helps differentiate the two well?
- if the CHL is rich in neopastic cells it can morphologically resemble ALCL
- IHC
- CHL = PAX5 (+)
- EMA and ALK protein (-)
- Detection of EBV (LMP1) favors CHL over ALCL as well
- CHL = PAX5 (+)
What is one of the most difficult d/d
with CHL to differentiate?
- DLBCL with anaplastic morphology and CD30 (+) cells
- especially if it is within the mediastinum
What is the IHC findings of
NLPHL?
- very different from CHL, preserve B cell programming
- Positive:
- CD20, CD79a, PAX5
- OCT2, BOB1
- Negative:
- CD30 (can have patchy, weak +)
- CD15
- EMA
In what subset of patients would you
more likely see IgD expression by the LP
cells in NLPHL?
- IgD expression is usually seen in the LP cells of young males
What T lymphocytes are found predominantly
in the cellular milieu of HL?
- T helper 2 cells
- thought to be a result of the abnormal cytokine production of CHL cells
What is the normal counterpart to the HRS
cells of CHL?
- clonal and Germinal center B cell derived
- based on IG studies
Note: LP cells are clonal expansions of GCB cells as well but they have the classic immunophenotype
What is the EBV expression/infection
pattern in the various types of HL?
- Highest:
- MCCHL
- LDCHL
- Lowest:
- NLPHL
Note: NSCHL shows an intermediate range of EBV positivity
IMP: HIV and in resource poor countries EBV + is almost 100%
What medications are part of the
ABVD protocol to treat CHL?
- Doxorubicin
- Bleomycin
- Vinblastine
- Dacarbazine
What medications are included in the
escalated BEACOPP treatment protocol?
- Bleomycin
- Etoposide
- Doxorubicin
- Cyclophosphamide
- Vincristine
- Procarbazine
- Prednisone
What is the current prognosis of CHL
with modern treatments?
- >85% of cases of CHL are curable
Note: in advanced stage disease the International Prognostic Index score correlates with prognosis
What is a new drug that has been approved
for treatment of relapsed/refractory CHL?
- Brentuximab vedotin
- CD30 directed antibody
Note: anti-PD1 antibodies have also been investigated and have promising results
What has been shown with tumor infiltrating
CD68+, histiocytes in CHL?
- a high content of macrophages correlated with reduced progression-free survival
- also a high content is a feature of some aggressive forms of CHL like lymphocyte-depleted subtype
