03. Lymphoreticular Pathology > 2. Lymphomas > Flashcards

2. Lymphomas Flashcards

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1
Q

Definition of lymphomas

A

Malignancies of the lymphoid system which primarily manifests themselves outside the bone marrow, at sites of normal lymphoid homing (lymph nodes, spleen, thymus, mucosa-associated lymphoid tissue)

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2
Q

Types of lymphomas

A
  1. Hodgkin Lymphoma
    a. Classical
    b. Non-classical
  2. Non-Hodgkin Lymphoma
    a. B-cell lymphoma
    b. T-cell & NK cell lymphomas
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3
Q

How is each disease entity characterised and defined?

A
  1. Morphology (histological appearance)
  2. Immunophenotype (surface cellular markers)
  3. Molecular signature (characteristic translocations)
  4. Clinical features (presentation, clinical course)
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4
Q

Types of Non-Hodgkin Lymphoma

A
  1. B-cell Lymphoma
    - Follicular lymphoma
    - Diffuse large B-cell lymphoma
    - Burkitt lymphoma
    - Mantle cell lymphoma
    - Marginal zone lymphoma: Splenic, extranodal & nodal
    - Multiple myeloma
    - B-cell acute lymphoblastic leukemia
    - Chronic lymphocytic leukemia
  2. T-cell & NK cell lymphoma
    - Anaplastic large cell lymphoma
    - Extranodal NK/T cell lymphoma
    - Peripheral T cell lymphoma
    - NOS T-cell acute lymphoblastic leukemia
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5
Q

What type of lymphomas constitute the majority?

A

B-cell lymphoma (85-90%)

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6
Q

How to classify Non-Hodgkin Lymphomas based on clinical course?

A
  1. Indolent lymphomas (small proliferation margin with low proliferation & low apoptosis rates)
    margin,
    a. Follicular lymphoma
    b. Marginal zone lymphoma
    c. Multiple myeloma
    d. Anaplastic large cell lymphoma (cutaneous
    CD30+ type)
  2. Aggressive lymphomas (large proliferation margin
    with high proliferation & high apoptosis rate)
    a. Diffuse large B-cell lymphoma
    b. Burkitt lymphoma
    c. Mantle cell lymphoma
    d. Anaplastic large cell lymphoma
    e. All peripheral T cell lymphomas
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7
Q

Clinical presentations in Non-Hodgkin Lymphoma

A
  1. Enlarging masses at sites of lymphoid tissue
    - Typically painless
  2. Hollow organ compression/infiltration
    - Pain, obstruction, perforation
  3. Solid organ infiltration
    - Renal insufficiency
    - Hepatic insufficiency
    - Bone marrow insufficiency
  4. Systemic symptoms (B symptoms)
    - Fever
    - Night sweats
    - Weight loss (> 10% body weight)
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8
Q

Clinical staging of Lymphomas (Ann Arbor Staging System)

A
  1. Stage I
    - Single lymph node group or contiguous lymph nodes on same side of diaphragm
    - 5-year survival = 90%
  2. Stage II
    - Two or more lymph node groups of lymphatic tissues on same side of diaphragm
    - 5-year survival = 70%
  3. Stage III
    - Involvement of lymphatic tissues on both sides of diaphragm
    - 5-year survival = 40%
  4. Stage IV
    - Involvement of extranodal sites (e.g. bone marrow, liver, lung, skin)
    - 5-year survival = 20%
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9
Q

Definition of Hodgkin Lymphoma

A

Encompasses a group of lymphoid neoplasms characterized by the presence of neoplastic Reed-Sternberg cells amongst other differences from non-Hodgkin lymphomas; cell of origin is an altered B cell, hence technically rendering Hodgkin lymphomas as B cell lymphomas, but with a very different biology from other types of B cell lymphomas

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10
Q

Pattern of spread in Hodgkin Lymphoma

A

Orderly spread by anatomical contiguity

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11
Q

Pattern of spread in Non-Hodgkin Lymphoma

A

Non-contiguous spread

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12
Q

Distribution of nodes involved in Hodgkin Lymphoma

A

Often localized to a single axial group of nodes (cervical, mediastinal, para-aortic)

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13
Q

Distribution of nodes involved in Non-Hodgkin Lymphoma

A

Often involves multiple peripheral nodes

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14
Q

Nodes involved in Hodgkin Lymphoma

A

Mesenteric nodes & Waldeyer’s ring rarely involved

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15
Q

Nodes involved in Non-Hodgkin Lymphoma

A

Mesenteric nodes & Waldeyer’s ring commonly involved

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16
Q

Extranodal presentation in Hodgkin Lymphoma

A

Rarely

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17
Q

Extranodal presentation in Non-Hodgkin Lymphoma

A

Frequently

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18
Q

Types of Hodgkin Lymphoma

A
  1. Classical Hodgkin Lymphoma
    a. 4 types:
    - Nodular sclerosis
    - Mixed cellularity
    - Lymphocyte rich
    - Lymphocyte depleted
    b. Features:
    - Classical Reed-Sternberg cells residing in a non-
    neoplastic inflammatory background
    - CD15+, CD30+
    - Negative for other B cell markers & CD45
    (leukocyte common antigen)
  2. Non-Classical Hodgkin Lymphoma
    a. 1 type:
    - Nodular lymphocyte predominant
    b. Features:
    - Lymphocytic & histiocytic (L&H) variant cell (aka popcorn cell)
    - CD20+, BCL6+
    - CD15-, CD30-
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19
Q

Histology of Nodular sclerosis Hodgkin Lymphoma

A
  1. Bands of fibrosis

2. Lacunar variant RS cells in inflammatory background

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20
Q

Frequency of Nodular sclerosis Hodgkin Lymphoma

A
  1. 60%
  2. Female > Male
  3. EBV uncommon
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21
Q

5-yr survival for Nodular sclerosis Hodgkin Lymphoma

A

70%

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22
Q

Histology of Mixed cellularity Hodgkin Lymphoma

A

RS cells in inflammatory background (mixed)

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23
Q

Frequency of Mixed cellularity Hodgkin Lymphoma

A
  1. 30%
  2. Old > Young
  3. EBV in 70%
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24
Q

5-yr survival for Mixed cellularity Hodgkin Lymphoma

A

70%

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25
Histology of Lymphocyte rich Hodgkin Lymphoma
RS cells in inflammatory background (many background lymphocytes)
26
Frequency of Lymphocyte rich Hodgkin Lymphoma
1. 5% | 2. EBV in 40%
27
5-yr survival for Lymphocyte rich Hodgkin Lymphoma
90%
28
Histology of Lymphocyte depleted Hogkin Lymphoma
RS cells in inflammatory background (many RS cells, few lymphocytes)
29
Frequency of Lymphocyte depleted Hogkin Lymphoma
1. <5% 2. Old > Young 3. EBV in 90%
30
5-yr survival for Lymphocyte depleted Hogkin Lymphoma
20%
31
Histology of Nodular lymphocyte predominant Hodgkin Lymphoma
L&H variant RS cells in background of reactive B cells
32
Frequency of Nodular lymphocyte predominant Hodgkin Lymphoma
1. 5% 2. Male > Female 3. < 35 years old
33
5-yr survival for Nodular lymphocyte predominant Hodgkin Lymphoma
90%
34
Morphology of classical Reed-Sternberg cell
- Large cell ( >45 micrometer diameter) - Multiple nuclei or single nucleus with multiple lobes - Each nucleus has a large inclusion nucleolus the size of a typical small lymphocyte - Abundant cytoplasm
35
Morphology of Lacunar variant Reed-Sternberg cell
Nucleus appears to sit in an empty space (lacuna)
36
Morphology of L&H variant Reed-Sternberg cell
- Multilobated nucleus resembling a popcorn kernel (hence also known as popcorn cell) - Nodular infiltrates of small lymphocytes & macrophages - Plasma cells & eosinophil scant
37
Clinical presentations in Hodgkin Lymphoma
1. Signs & symptoms: - Painless lymphadenopathy - B symptoms (more so for stage III-IV or mixed cellularity & lymphocyte depleted subtypes) - 2. Treatment: - Limited stage, low bulk disease treated with radiation therapy - Higher stage disease with B symptoms (Stage IIB-IV) treated with multi-agent chemotherapy & radiation therapy (but this predisposes to development of other malignancies) - Overall cure rate = 80%
38
Cell of origin of Follicular lymphoma
Germinal centre B cell
39
Frequency & associations of Follicular lymphoma
1. Most common type of indolent lymphoma in US 2. Second most common type of lymphoma overall 3. Occurs in adults >40 (median age = 59)
40
Morphology of Follicular lymphoma
1. Retains characteristic follicular structure 2. Monotonous accumulation of single cell type 3. Characteristically devoid of apoptotic cells
41
Immunophenotype of Follicular lymphoma
1. CD19+, CD10+, CD20+, BCL2+, BCL6+ | 2. CD5-, Cyclin D1-
42
Molecular signature of Follicular lymphoma
t(14;18): upregulates BCL2 (anti-apoptotic protein)
43
Clinical features of Follicular lymphoma
1. Indolent lymphoma 2. Usually widely disseminated at diagnosis, including bone marrow (takes form of paratrabecular lymphoid aggregates) 3. Presentation: painless generalized lymphadenopathy 4. Transformation into more aggressive lymphomas (DLBCL, Burkitt’s) in some cases 5. Will respond to gentle chemotherapy, but will relapse (essentially incurable short of bone marrow transplant) 6. Overall 5-year survival = 72%
44
Cell of origin of Diffuse Large B-cell Lymphoma
Germinal centre B cell
45
Frequency & associations of Diffuse Large B-cell lymphoma
1. Most common non-Hodgkin lymphoma | 2. Disease of adults & children (median age = 64)
46
Morphology of Diffuse Large B-cell lymphoma
1. Diffuse infiltration of lymph nodes 2. Relatively large neoplastic cells (4-5x the diameter of a typical small lymphocyte)
47
Immunophenotype of Diffuse Large B-cell lymphoma
CD10+, CD19+, CD20+, BCL6+
48
Molecular signature of Diffuse Large B-cell lymphoma
1. BCL6 mutations/overexpression → represses germinal centre B cell differentiation & growth arrest; silences p53 expression 2. t(14;18) → same as that for follicular lymphoma 3. Immunodeficiency-associated large B-cell lymphoma (occurs in setting of severe T cell deficiency; composed of EBV infected neoplastic B cells) 4. Primary effusion lymphoma (occurs in setting of KSHV infection; presents as a malignant ascetic or pleural effusion) KSHV: Kaposi sarcoma-associated herpesvirus
49
Clinical features of Diffuse Large B-cell lymphoma
1. Aggressive lymphoma 2. Presentation: rapidly enlarging masses (nodal: Waldeyer’s ring; extranodal: spleen, liver, GIT, skin, bone, brain) 3. Approximately 40% curable with aggressive chemotherapy or stem cell transplant
50
Cell of origin for Burkitt Lymphoma
germinal centre B cell
51
Frequency & associations of Burkitt Lymphoma
1. 3% of lymphomas 2. Endemic Burkitt lymphoma: all latently infected with EBV; seen in Africa; tumours found at mandible & abdominal viscera (kidney, ovary, adrenal gland) 3. Sporadic Burkitt lymphoma: tumours found at ileocecum, peritoneum
52
Morphology of Burkitt lymphoma
1. Diffuse infiltration of lymph nodes 2. Intermediate-sized neoplastic cells 3. Starry-sky appearance: pale areas due to macrophages phagocytosing cell debris from rapid cellular turnover (generally seen in aggressive lymphomas; also seen in acute lymphoblastic leukemia)
53
Immunophenotype of Burkitt Lymphoma
1. CD10+, CD19+, CD20+, BCL6+ | 2. CD5-
54
Molecular signature of Burkitt lymphoma
t(8;14) → upregulates cMYC (cell cycle oncogene)
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Clinical features of Burkitt lymphoma
Used to be very aggressive & rapidly fatal in earlier | eras, but now 70-80% of children & 40% of adults curable
56
Cell of origin of Mantle cell lymphoma
Naive B cell
57
Frequency & associations of Mantle cell lymphoma
1. 6% of lymphomas | 2. Disease of adults (median age = 63)
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Morphology of Mantle cell lymphoma
1. Nodal infiltration by homogenous population of small lymphocytes 2. Forms diffuse, vaguely nodular "mantle zone" around residual benign follicles
59
Immunophenotype of Mantle cell lymphoma
1. CD5+, CD19+, CD20+, Cyclin D+ | 2. CD10-, CD23-
60
Molecular signature of Mantle cell lymphoma
t(11;14) → upregulates Cyclin D (aka BCL1), a cell-cycle promoter
61
Clinical features of Mantle cell lymphoma
1. Usually widely disseminated 2. Presentation: painless lymphadenopathy, splenic & gut involvement (may produce GI polyp-like lesions) 3. Poor response to all attempted therapies 4. Potentially curable with transplant 5. Overall 5-year survival = 27%
62
Cell of origin of Marginal zone lymphoma
B cells found in lymph nodes, spleen or extranodal tissue (mucosa-associated lymphoid tissue)
63
Where does Marginal zone lymphoma arises from?
Arises within chronically-inflammed tissues: 1. Salivary gland in the setting of Sjögren disease 2. Thyroid gland in the setting of Hashimoto thyroiditis 3. Stomach in the setting of H. pylori chronic gastritis
64
Morphology of Marginal zone lymphoma
May grow in diffuse infiltrative pattern or as multifocal tumour nodules in extranodal site
65
Molecular signature of Marginal zone lymphoma
t(11;18) or t(1;14) → upregulates BCL10 (aka MALT1), a protein component of a signaling complex that promotes growth & survival of B cells
66
Clinical features of Marginal zone lymphoma
1. Remains localized for long periods, spreading only late in their course 2. Transformation to DLBCL may occur
67
Cell of origin of Multiple myeloma
Plasma cell
68
Morphology of Multiple myeloma
1. Destructive punched-out defects within the skeletal system (vertebrae, ribs, skull, pelvis, femur etc) 2. Bone marrow infiltrated by plasma cells, including variant forms with multiple nuclei, prominent nucleoli & cytoplasmic droplets containing Ig
69
Clinical features of Multiple myeloma
1. Multifocal involvement of the skeleton (may lead to pathological fractures) 2. Production of excessive immunoglobulins may result in increased amounts of renally excreted light chains causing renal epithelial cell toxicity (Bence Jones proteinuria)
03. Lymphoreticular Pathology
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