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Hematopathology WHO > Hodgkin Lymphomas > Flashcards

Hodgkin Lymphomas Flashcards

1
Q

Hodgkin lymphomas generally affect which

organs and what is a common feature of

most of them?

A
  • usually affect Lymph Nodes
  • variable mixture of associated, non-neoplastic inflammatory cells
  • sometimes associated with variable fibrosis (thick band like)
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2
Q

What are the 2 types of

Hodgkin’s Lymphomas?

A
  • Nodular lymphocyte predominant (NLPHL)
  • Classic Hodgkin Lymphoma
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3
Q

Which HL is the most common type and

what age groups is it often seen in?

A
  • Classic Hodgkin Lymphoma
    • 90% of all HL
  • Two peaks
    • 15-35 years old
    • late life
  • Has different subtypes that fall into these categories
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4
Q

How does HL (both types, general) present

clinically?

A
  • 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
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5
Q

At what stage of B cell maturation are

Hodgkin/R-S cells derived from?

A
  • > 98% of cases are neoplastic B cells
  • derived from mature B cells of the germinal centre stage
  • clonal IG genes
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6
Q

What are the 4 subtypes of

Classical Hodgkin’s Lymphoma?

A
  • Nodular Sclerosis Hodgkin Lymphoma
  • Lymphocyte rich CHL
  • Mixed Cellularity CHL
  • Lymphocyte depleted CHL
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7
Q

What age group is preferentially affected

by Nodular Lymphocyte Predominant HL?

A
  • generally 4th-5th decade
  • also common in children
  • M > F
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8
Q

CHL subtypes tend to have a male predominance, with the exception of which subtype?

A
  • Nodular sclerosing HL
    • slight female predominance
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9
Q

What two subtypes of CHL are often

associated with EBV infection?

A
  • Mixed cellularity CHL
  • Lymphocyte depleted CHL

Note: NLPHL is only rarely associated with EBV infection (<5%)

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10
Q

Which organ when involved by

HL increases the risk of extranodal dissemination?

A
  • 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)
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11
Q

What is the morphology of Classic

Reed-Sternberg Cells?

A
  • 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
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12
Q

What is the morphology of the Hodgkin cell

and the Mummified Hodgkin cell?

A
  • smudgy large nuclei (may be slightly eosinophilic)
  • can be anaplastic and confused with ALCL
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13
Q

What is the immunophenotype of the HS

of CHL?

A
  • 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
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14
Q

What is the EBV expression of HS cells

of CHL ?

A
  • EBV infected cells express LMP1 and EBNA1
    • no expression of EBNA2
    • this is characteristic of type II EBV infection
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15
Q

What is the expression of OCT2 and BOB1

in CHL HS cells?

A
  • absence of the transcription factor (OCT2) and its cofactor (BOB1)

Note: EMA is also negative in most cases

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16
Q

How can CHL lymphoma be mistaken for ALCL

and what IHC helps differentiate the two well?

A
  • 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
17
Q

What is one of the most difficult d/d

with CHL to differentiate?

A
  • DLBCL with anaplastic morphology and CD30 (+) cells
    • especially if it is within the mediastinum
18
Q

What is the IHC findings of

NLPHL?

A
  • very different from CHL, preserve B cell programming
  • Positive:
    • CD20, CD79a, PAX5
    • OCT2, BOB1
  • Negative:
    • CD30 (can have patchy, weak +)
    • CD15
    • EMA
19
Q

In what subset of patients would you

more likely see IgD expression by the LP

cells in NLPHL?

A
  • IgD expression is usually seen in the LP cells of young males
20
Q

What T lymphocytes are found predominantly

in the cellular milieu of HL?

A
  • T helper 2 cells
  • thought to be a result of the abnormal cytokine production of CHL cells
21
Q

What is the normal counterpart to the HRS

cells of CHL?

A
  • 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

22
Q

What is the EBV expression/infection

pattern in the various types of HL?

A
  • 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%

23
Q

What medications are part of the

ABVD protocol to treat CHL?

A
  • Doxorubicin
  • Bleomycin
  • Vinblastine
  • Dacarbazine
24
Q

What medications are included in the

escalated BEACOPP treatment protocol?

A
  • Bleomycin
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Vincristine
  • Procarbazine
  • Prednisone
25
Q

What is the current prognosis of CHL

with modern treatments?

A
  • >85% of cases of CHL are curable

Note: in advanced stage disease the International Prognostic Index score correlates with prognosis

26
Q

What is a new drug that has been approved

for treatment of relapsed/refractory CHL?

A
  • Brentuximab vedotin
  • CD30 directed antibody

Note: anti-PD1 antibodies have also been investigated and have promising results

27
Q

What has been shown with tumor infiltrating

CD68+, histiocytes in CHL?

A
  • 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
28
Q
A

Hematopathology WHO (29 decks)

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