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Non-Hodgkin
Lymphoma
Jason Ryan, MD, MPH
Lymphomas
• Malignancies of lymphocytes (B cells, T cells)
• Often involve lymph nodes
• Also “extranodal” (skin, GI tract)

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Wikipedia/Public Domain
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Lymphomas
Tissue
Biopsy

Malignant Lymphocytes

Reed-Sternberg
Cells?
No Yes

Non-Hodgkin Hodgkin
Lymphoma Lymphoma
Hodgkin versus. Non-Hodgkin
Clinical Features

Hodgkin Non-Hodgkin
• Often localized • Often multiple
• Orderly spread from peripheral sites
node to node • Noncontiguous spread
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• Extranodal involvement • Extranodal involvement
rare common
• GI (thickened bowel wall)
• Skin
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Waldeyer’s Ring
• Lymphoid tissue in the pharynx
• Often involved in non-Hodgkin lymphoma
• Rare in Hodgkin lymphoma

Wikipiedia/Public Domain
Lymphocyte Antigens

Primarily Primarily
T-Cell Associated B-cell Associated
CD1
CD10
CD2
CD19
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CD3
CD20
CD4
CD21
CD5
CD22
CD7
CD23
CD8
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Non-Hodgkin Lymphoma
• B and T cell malignancies
• Most are B cell disorders
• Malignant cells obliterate lymph node architecture
• More than two dozen subtypes per WHO
• Classified by:
• B versus T cell
• Cell size (small versus large)
• Histologic appearance
• Expression of markers (“immunophenotype”)
• Genetics
Non-Hodgkin Lymphoma
• Follicular
• Marginal cell
• Mantle zone
• Diffuse Large B Cell
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• Small lymphocytic lymphoma
• Burkitt’s
• Adult T-cell Leukemia/Lymphoma
• Cutaneous T-cell Lymphomas
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Lymph Nodes Follicle

Cortex
Medulla
(cords)

Medulla
(sinus)
Paracortex
Artery/Vein

Afferent
Lymph
Vessel
Efferent
Lymph
Vessel
Lymphoid Follicles

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Gleiberg/Wikipedia
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Diffuse Large B-cell Lymphoma

• Most common NH lymphoma
• B cell malignancy
• Express CD19, CD20
• Most cells express surface immunoglobulin
Diffuse Large B-cell Lymphoma

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KGH/Wikipedia
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Diffuse Large B-cell Lymphoma

• Median age at presentation is 64 years
• Occurs in HIV
• AIDS defining malignancy
Diffuse Large B-cell Lymphoma
Prognosis

• Variable prognosis
• International Prognostic Index (IPI) score
• Age >60 years
• Increased LDH
• Patient functional status
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• Clinical stage
• Number of extranodal sites
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Rituximab
• Monoclonal CD20 antibody
• Used in CD20+ B cell lymphomas
• Diffuse large B cell
• Follicular

CD20
Follicular Lymphoma

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Patho/Wikipedia
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Follicular Lymphoma
• B cell malignancy
• Usually express CD19, CD20
• Most cells express surface immunoglobulin
Follicular Lymphoma
• Genetic hallmark: 14;18 translocation
• Overexpression of BCL2
• Blocks apoptosis (“antagonist” of apoptosis)
• Germinal center B cells usually lack BCL2
• Undergo apoptosis unless selected by somatic hypermutation
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IgG
H chain BCL2

14 18 14 18
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Follicular Lymphoma
• Median age at diagnosis: 65 years
• Indolent course: waxes/wanes for years
• Not all patients require treatment
• Difficult to cure
• Diffuse large B cell lymphoma (DLBCL)
• Histologic transformation: 10 to 70% cases over time
• Poor prognosis
Lymphoma vs. Reactive
• Follicular lymphoma vs. reactive lymphadenopathy
• Both have ↑ follicle growth
• Must distinguish in diagnosis of lymphoma
• Reactive lymphadenopathy (LAD)
• Somatic hypermutationAfraTafreeh.com
of B cells
• Apoptosis of many B cells
• B cell death → debris → macrophages
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Lymphoma vs. Reactive

Lymphoma Reactive LAD

Similar size/shape follicles Varying size/shape follicles
Tingible body
Relative absence of
(debris-laden)
macrophages
macrophages
++ BCL2 Staining -- BCL2 Staining
Mantle Cell Lymphoma
• B cell malignancy
• Follicle mantle or germinal center
• Usually express CD19,CD20
• Most cells express surface immunoglobulin
• Express CD5 (“Co-express CD20 and CD5”)
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• Median age at diagnosis: 68 years
• Median overall survival: 3 to 4 years (poor prognosis)
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Mantle Cell Lymphoma

• 50 to 65%: 11;14 translocation
• Overexpression of cyclin D1
• Promotes cell cycle transition from G1 to S phase

IgG
H chain Cyclin D1

14 11 14 11
Marginal Zone Lymphoma
• B cell malignancies
• Marginal zone forms from inflammation
• Often extranodal
• Lymphoma in chronic inflammatory disorders
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• Salivary glands in Sjogren’s
• Thyroid gland in Hashimoto’s thyroiditis
• Stomach in chronic H. Pylori infection (MALToma)
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Small Lymphocytic Lymphoma

• CD5+ B cells
• “Co-express CD20 and CD5”
• Similar markers to mantle cell lymphoma
• Typically negative for cyclin D1
• Same malignant cells as CLL
• Only difference is degree of lymphocytosis (↑WBC)
• Peripheral blood: normal or mild lymphocytosis
• SLL definition: lymphocyte count of <5000
• If >5000 → CLL
Burkitt’s Lymphoma
• B cell malignancy
• Usually express CD19, CD20
• Most cells express surface immunoglobulin
• Very aggressive – rapid proliferation
• Key distinctions: AfraTafreeh.com
• “Starry sky” morphology
• Epstein-Barr virus (EBV)
• C-myc translocation
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Burkitt’s Lymphoma

Wikipedia/Public Domain
Burkitt’s Lymphoma
• Endemic form
• Found in Africa and New Guinea
• 30 to 50% of childhood cancer in some regions
• Children four to seven years old
• Male to female ratio ~ 2:1
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• Commonly presents as mass in the mandible
• Sporadic form
• Also occurs in children
• Abdominal mass: ileocecum or peritoneum
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Burkitt’s Lymphoma

Mike Blyth/Wikipedia
Burkitt’s Lymphoma
Associations
• Epstein Barr virus (EBV) infection
• Nearly all endemic tumors associated with latent infection
• Express CD21 (EBV receptor)

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Burkitt’s Lymphoma
Associations
• C-myc translocation
• Growth promoter
• Activates transcription

IgG
H chain C-myc

14 8 14 8
T-Cell Leukemia/Lymphoma
• CD4+ T cell malignancy
• Occurs with HTLV-1 infection
• RNA Virus
• Infects CD4+ T cells
• Key diagnostic test: anti-HTLV1 antibodies
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T-Cell Leukemia/Lymphoma
• Clinical scenario
• Patient from Japan, Caribbean, West Africa (endemic regions)
• Lymphocytosis
• Lymphadenopathy
• Skin lesions (ulcers, nodules, papular rash)
• Rapidly progressive symptoms → usually fatal in months
• Lytic bone lesions with ↑ calcium
• Don’t confuse with multiple myeloma
Cutaneous T-cell Lymphoma
CTCL

• Skin disorder of malignant T-cells

• Variable expression of CD markers
• Presents with skin lesions
• Localized disease: Mycosis Fungoides
• Diffuse systemic disease: Sezary syndrome
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Cutaneous T-cell Lymphoma

CTCL

• Mycosis Fungoides
• Patches, plaques, tumors
• Varying size/shape
• Lesions progress slowly changing size/shape/appearance
• “Indolent”: Slowly developing
• Classically in a “bathing trunk” distribution
• Diagnosis: Skin biopsy shows lymphoid cells
• Upper dermis
• Epidermal aggregates (Pautrier microabscesses)
Cutaneous T-cell Lymphoma
CTCL

• Sezary syndrome
• T-cell lymphoma affecting skin of entire body
• Widespread erythema (skin bright red)
• Lymphadenopathy
• Malignant cells in bloodAfraTafreeh.com
(Sezary cells)

Multi-lobed nucleus
“Cerebriform”

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