9: Neoplastic Disease 3: Hodgkin Disease

Alston
4-25-17
Continue the use of the clinical-pathologic template for Hodgkin Lymphomas. (he said non?)
 Reed-Sternberg cells RS are characteristic of Hodgkin’s disease
(HD) and arise from B-cells germinal center
 CD15 and CD30 positive (except lymphocyte predominance)
 Negative for leukocyte common antigen (CD45)
 RS cells induce accumulation of lymphocytes, macrophages, and
granulocytes
 HD starts in single node or chainspreads in stepwise fashion
o Unique from other lymphomas
 EBV present in some RS cells
o 70% of mixed cellularity type
 Surrounding inflammatory infiltrate that plays active role in production
of growth factors
 Various cytokines produced by tumor (ex. NF-kB)
 Hodgkin lymphoma cardinal example of tumor that escapes from host immune response by expressing proteins
that inhibit T cell function (classical due high PD
ligandsantagonize T cell responses)
Clinical
 Painless lymphadenopathy
 Staging is VERY important for TTX and prognosis (pg. 3)
 Stage I and II:
o Young pts w/ less extensive disease
o favorable subtypes (nodular sclerosis and lymphocyte
predominance)
o Stage I and Ia have 90% of 5 year survival
 Advanced disease: more likely to have systemic complications
o 60-70% survival
o Use anti CD 30 treatment here
 Adverse factors: males, mixed cellularity or lymphocyte-depleted, advanced A. Diagnostic RS cell w/ 2
disease, constitutional symptoms, bulky tumor w/ multiple nodes involved nuclear lobes, large inclusion
 COMMON SIGN: disease spreads to contiguous nodes and chains early like nucleoli, abundant
 Stereotyped spread: starts in nodesmoves to spleen, hepaticfinally in cytoplasm, surrounded by
marrow and other tissues lymphocytes, macrophages, and
eosinophils.
 Treatments: include chemo and radiation together
B. RS cell; mononuclear variant.
o Genotoxic chemotherapeutic agents are minimized to reduce
C. RS cell, lacunar variant.
secondary tumors
D. RS cell, lymphohistiocytic
o Anti-CD30 antibodies used
variant.
Compare and contrast (e.g. construct a table) Hodgkin Disease vs. Non-
Hodgkin Lymphomas.

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 9: Neoplastic Disease 3: Hodgkin Disease
Alston
4-25-17
Non-Hodgkin Lymphoma Hodgkin Lymphoma Apply the pathologic template to
Overall frequency 60% 40% Hodgkin Disease including nodular
Malignant cells Lymphoid Reed-Sternberg sclerosis,
Composition of Lymphoid cell Predominantly reactive cells
Mass (inflammatory cells and fibrosis) mixed
Clinical Painless lymphadenopathy, Painless lymphadenopathy cellularity,
usually in late adulthood occasionally with “B” symptoms, lymphocyte-
usually in young adults rich,
Spread Diffuse, often extranodal Contiguous, rarely extranodal
Staging Limited importance Guides therapy; radiation is mainstay lymphocyte-
Leukemic phase Occurs Does not occur depleted,
and
lymphocyte-predominance forms. 
Nodular Sclerosis (Classical)
 Epi
o M=F
o Adolescents/young adults
o *most common subtype
o usually stage I or II
 Pathogenesis
o Lower cervical, supraclavicular, mediastinal nodes
 Morphology
o Lacunar cells (RS variant)
 Classic RS cells uncommon
o Collagen bands
o CD15+, CD30+, EBV-
 Natural course
o Excellent prognosis
Mixed cellularity (Classical)
 Epi
o most common form in adults > 50
o M>F
o usually stage III or IV
 Pathogenesis
o More likely to have disseminated and systemic
manifestation
o RS infected w/ EBV in 70% of cases
 Morphology
o Mononuclear and plentiful RS cells (Owl eye)
o w/in heterogeneous inflammatory infiltrate (T cells,
eosinophils (reddish granules), plasma cells, benign
macrophages)
o CD15+, CD30+, EBV+
 Natural course
o good prognosis
Lymphocyte Predominance
 Epi
o Uncommon
o 5% of all HL cases
o Young males (age 35)
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9: Neoplastic Disease 3: Hodgkin Disease
Alston
4-25-17
 Morphology
o Popcorn cell: Lymphohistiocytic (LH) variant RS cells
 have B markers (CD20 and BCL6)
 CD30-, CD15-
o Typical RS cells rare
 Pathogenesis
o Cervical or axillary lymphadenopathy
o Mediastinal
 Natural course
o Excellent prognosis

Lymphocyte Rich (Classical)

o Epi Uncommon
o M>F
o older adults
 Morphology
o Reactive lymphocytes make up majority of
cellular infiltrate
o Diffuse effacement of nodes
o Diagnostic RS cells w/ characteristic staining
 Pathogenesis
o 40% with EBV
 Natural course
o Good to excellent prognosis
Lymphocyte depletion (Classical)
 Epi
o uncommon overall—least common
o More common in elderly & HIV+ pts of any age
o Non-industrialized/developing countries
 Pathogenesis
o Paucity of lymphocytes (background cells) = limited
amt of lymphocytes in the background
o (relative) Abundance of RS cells
o EBV+ in 90% of cases
 Natural course
o Often presents w/ advanced disease
o Differential: Large cell NHL
 Treatment
o see pharm
o Radiation and chemo
o Anti CD30 antibodies promising

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9: Neoplastic Disease 3: Hodgkin Disease
Alston
4-25-17

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