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Bloc F - Defense > Mar23 M1,M2-Lymphadenopathy Lymphoma > Flashcards

Mar23 M1,M2-Lymphadenopathy Lymphoma Flashcards

1
Q

general approach to patient with lymphadenopathy (appearing as mass in the neck)

A
  1. non neoplastic vs neoplastic
  2. if neoplastic, benign vs malignant
    3a. if benign, mesenchymal or epithelial
    3b. if malignant, primary or metastasis
  3. if primary malignancy, mesenchymal, epithelial or mixed
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2
Q

ddx of lymphadenopathy (presenting as mass in the neck)

A
  • goiter (usually more central)
  • TB
  • neoplastic (benign or malignant). think of ENT CA or mesenchymal malignancy
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3
Q

main steps of lymphadenopathy or suspected lymphoma workup (5 things)

A
  1. hx (HPI + full hx, fam history or previous malignancy, all symptoms)
  2. physical (palpation, general system exam)
  3. imaging (XR, US, CT, MRI, PET)
  4. labs (RBC, WBC, platelets, biochemistry LDH liver electrolytes, microbio, serology, CA markers)
  5. cytopathology (fluid analysis, FNA, urine, ..)
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4
Q

lymphadenopathy or suspected lymphoma: later workup steps

A
  • endoscopic bx
  • core bx (take sample down a long hollow tube)
  • incisional bx (remove a part, used for large lesions)
  • excisional bx (remove entire lymph node)
  • resection of organ
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5
Q

what can be done with patho tissue for lymphadenopathy assessment

A
  • culture to check for infectious cause
  • microscopy (histology and cytology)
  • IHC (lineages, markers, malignancy)
  • flow cytometry (surface Ags + what light chain clone)
  • PCR to ID gene rearrangements
  • cytogenetics (see translocations)
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6
Q

lymphoma main markers

A
  1. CD5 + CD20 coexpression
  2. CD19,20 (for B cells) + CD10 (lymphoma). bcl6 specific to germinal center
  3. CD3,4,8 (T cells) + CD5 (lymphomas, mostly T cells and some B cell)
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7
Q

what CD10 and CD5 are specific for

A

CD10: lymphoblastic leuk-lymph. (ALL) (+ is a GC marker)
CD5: many T cell lymphomas + some B cell lymphomas (mantle cell, CLL-SLL (meaning chronic lymphocytic leukemia and small lymphocytic lymphoma))

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8
Q

other lymphoma specific markers

A
  • bcl2 (anti-apoptotic protein): follicular lymphomas
  • CD15 and CD30: + in Hogkin lympgoma
  • CD34: stem cells
  • CD138: used in myelomas plasma cells (kappa and lambda light chains).
  • Ki67 (prolif marker): determine subtypes (high grade B cell lymphoma vs Burkitt lymphoma)
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9
Q

common leukocyte marker to differentiate between lymphoma and CA, melanoma, wtv

A

CD45 (is a common leukocyte marker)

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10
Q

histological pattern of a reactive lymphadenopathy (NON NEOPLASTIC) caused by bacteria

A

acute non-specific lymphadenitis

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11
Q

histological pattern of a reactive lymphadenopathy caused by immune or connective tissue disorders like RA and SLE, toxoplasmosis or early HIV

A

chronic non-specific lymphadenitis.

  • follicular hyperplasia (B cells)
  • large germinal centers
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12
Q

histological pattern of a reactive lymphadenopathy caused by viral infections (CMV, EBV, vaccination), drugs (dilantin, etc.) and dermatopathic lymphadenopathy

A

chronic non-specific lymphadenitis
-paracortical hyperplasia (T cells)
OR
-diffuse pattern

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13
Q

histological pattern of a reactive lymphadenopathy caused by a lymphoma or a carcinoma

A 
sinus histiocytosis (=expansion of sinus histiocytes + increased number of sinuses in histiocytes) (can also not be cancer, but near cancer)
(is a non specific pattern)
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14
Q

histological pattern of a reactive lymphadenopathy caused by EBV specifically (specific things)

A
  • interfollicular area with numerous immunoblasts (T and B)

- paracortical hyperplasia (T cells) OR diffuse pattern

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15
Q

histological pattern of a reactive lymphadenopathy caused by mycobacteria, fungi and sarcoidosis

A

chronic specific lymphadenitis

-granulomatous

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16
Q

histological pattern of a reactive lymphadenopathy caused by cat scratch, tularemia, etc.

A

chronic specific lymphadenitis
-granulomatous with abcesses
(in cat scratch, stellate abcesses)

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17
Q

leukemia vs lymphoma def

A

leuk: 1. liquid, white blood 2. starts in BM and spreads to other sites + blood
lymph: 1. solid mass in soft tissues 2. start in lymphoid organs (lymph nodes or extranodal sites like GIT, skin, CNS)

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18
Q

leukemia vs lymphoma cells of origin

A

leuk: 1. mostly myeloid (less erythroid or mega) 2. some lymphoid cells (as in CLL, SLL, ALL)
lymph: 1. precursor B or T lymphoblasts 2. mature B or T lymphoblasts

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19
Q

leuk vs lymph 2 subgroups

A

leuk: acute vs chronic subgroups
lymph: Hodgkin vs non-Hodgkin subgroups

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20
Q

leukemia clinical presentation

A

bone marrow replacement effects

  • anemia: fatigue, dyspnea
  • neutropenia: infections
  • thrombocytopenia: bleeding
  • bone pain
  • abd pain (splenomegaly)
  • systemic symptoms (constitutional)
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21
Q

lymphomas clinical presentation

A
  • enlarged lymph node, mass, pain, bleeding, organ-related symptom
  • abd pain (splenomegaly or other)
  • systemic effects called ‘‘B’’ symptoms (fever, night sweats, weight loss), fatigue, …
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22
Q

important charact of lymphomas + most common ones

A
  • are clonal, arise from a single cell
  • most common = of B-cell origin, especially germinal center bc lot of prolif, genetic instab + somatic hypermutation + class switching there: follicular lymphoma (FL), subset of DLBCL (diffuse large B cell lymphoma), Burkitt, Hodgkin
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23
Q

basic principles of classification of leukemias and lymphomas by WHO

A
  • dx only in context of complete clinical history
  • morpho and immunophenotype enough to dx most but not all entities
  • genetics become important (FISH + cyto for transloc. PCR for B- T- cell clonality)
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24
Q

3 kinds of non-Hodgkin lymphomas (NHL)

A
  • precursor B, T cell (BM or thymus)
  • mature B cell (BM, lymph node)
  • mature T, NK cell (thymus, lymph node)
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25
Q

4 kinds of mature B cell NHLs

A
  1. low grade (CLL, FL, MZL)
  2. '’bogus low grade’’ (mantle cell) = aggressive
  3. fairly high grade (DLBCL)
  4. very high grade (Burkitt)
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26
Q

2 kinds of HLs

A
  1. nodular lymphocyte predominant

2. classical

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27
Q

NHL on microscopy (histology)

A
  • numerous malignant cells (is most of the field) forming many sheets of cells
  • reactive cells are NOT prominent
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28
Q

2 precursor leuk, lymph (put leuk because 2 entities here) in NHLs

A

B-cell: acute lymphoblastic leukemia (mostly)

T-cell: lymphoblastic leukemia (mostly)

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29
Q

mature B cell NHLs: give 4

A

-CLL/SLL (chronic lymphocytic leuk, small lymphocytic lymph) (2 entities) (low grade)
-FL (low grade)
-DLBCL (fairly high grade)
-plasma cell neoplasm/multiple myeloma
(also mantle cell (bogus low grade), marginal zone lymphoma (MZL) (low grade), Burkitt (very high grade)

30
Q

mature T cell NHLs and other NHLs

A
  • mature-T cell lymphoma

- mycosis fungoides and Sezary syndrome (2 entites leuk/lymph)

31
Q

HLs: 4 kinds in the classical category (other category is nodular lymphocytic predominance)

A

classical:

  • nodular sclerosis
  • mixed cellularity
  • lymphocyte-predominant
  • lymphocyte depleted
32
Q

histology of B-ALL/LBL (acute lymphoblastic leukemia or lymphoblastic lymphoma) and T-ALL/LBL

A
  • monotonous medium sized blasts, cells.

- medium sized lymphoid cells

33
Q

markers (IHC) of B-ALL/LBL and T-ALL/LBL (same as lymphoblasts markers bc are precursor T and B derived)

A
  • B-ALL/LBL: TdT, CD19, maybe CD10

- T-ALL/LBL: TdT, CD3, CD4, CD8, maybe CD10

34
Q

markers of mature B cell NHLs (remember this category includes a lot of malignancies)

A

CD20 (therapy with rituximab possible)

35
Q

markers of CLL/SLL NHLs + cells they are derived from

A

CD5, CD20, CD23 (are derived from mature B cells)

36
Q

CLL/SLL NHLs cells found on histology

A

-monomorphic small round B lymphocytes in the blood, BM, spleen, lymph nodes
MIXED WITH
-larger prolymphocytes, paraimmunoblasts proliferation centers in the lymph nodes

37
Q

CLL/SLL appearance on histology

A
  • architecture gone (no GC, no T zone, no B zone)

- pale pseudoproliferation centers

38
Q

follicular lymphoma appearance on histology

A

nodules of lymphocytes in the lymph nodes creating a follicular pattern (many follicles that are like GCs)

39
Q

follicular lymphoma markers (IHC)

A

CD10, CD20, Bcl2

40
Q

DLBCL appearance on histology

A

-large cells
-diffuse pattern
-high proliferation rate
(is an aggressive fairly high grade mature B cell NHL)

41
Q

DLBCL markers (IHC)

A
  • CD20+

- high Ki67 (high proliferation rate)

42
Q

plasma cell myeloma histological appearance

A
  • plasma cells infiltrate the BM perivascularly (near blood vessels)
  • atypical, big nucleoli
  • sheets of cells
  • excentric nuclei + abundant cytoplasm
  • paranuclear halo (produce IgG)
43
Q

plasma cell myeloma markers

A
  • CD138
  • ONE light chain (kappa or lambda)
  • ONE heavy chain (usually IgG but can be IgA­­»IgM, IgD)
44
Q

plasma cell myeloma histo appearance in bone and kidney

A

bone: osteoclasts breaking down bone (bc of cytokines released by the malignancy)
kidney: abnormal paraprotein deposits in the tubules with damage to epithelial cells (myeloma nephrosis)

45
Q

mature T and NK cells lymphomas: histo appearance

A
  • heterogeneous cell pop: atypical large, medium, small cells
  • cell polymorphism
  • reactive inflammatory cells (small lymphocytes, eosinophils, histiocytes)
  • all bc T cells make lot of cytokines*
46
Q

mature T and NK cells lymphomas markers

A

CD2, CD3 (T cell..), CD5, CD4 and or CD8 or none

47
Q

definition of HL

A
  • lymphoma derived from GC B-cells composed of 1. small pop of malignant cells 2. Reed-Sternberg or other Hodgkin cells 3. numerous reactive cells
  • clinically and pathologically distinctive lymphoma
48
Q

HL on histology

A

small number of malignant cells (Reed-Sternberg + Hodgkin cells) + sea of non neoplastic reactive cells (supporting the neoplastic cells) (T lymphocytes, eosinophils, plasma cells, histiocytes)

49
Q

classical HL histological pattern

A

Hodgkin, Reed-Sternberg cells, lacunar cells (nodular sclerosis)
BACKGROUND = T cells (CD4+)

50
Q

classical HL markers of neoplastic cells and of background cells

A

neoplastic cells: CD15+, CD30+, (CD20-), (CD45-)

background cells: CD4+

51
Q

nodular lymphocyte predominant HL histological appearance

A

-L and H (popcorn) look to cells and maybe Hodgkin and Reed-Sternberg cells
BACKGROUND = B cells

52
Q

nodular lymphocyte predominant HL markers of neoplastic cells

A

CD20+, CD45+, bcl6+, (CD15-, CD30-)

53
Q

Reed-Sternberg cells (malignant cells in HL) apperance on microscopy

A
  • large
  • multilobated or multinucleated
  • inclusion-like nucleolus
  • amphophilic cytoplasm
54
Q

two lymphomas with translocation of chromosomes

A
  • follicular lymphoma (low grade mature B cell NHL)

- Burkitt lymphoma (very high grade mature B cell NHL)

55
Q

chromosomal translocations in FL and consequence

A
  • IgH (Ig heavy chain) on 14 + bcl2 on 18

- bcl2 constitutively active and is an anti-apoptotic gene so cells are immortal

56
Q

chromosomal translocations in Burkitt lymphoma and consequence

A
  • IgH (Ig heavy chain) on 14 and MYC gene on chrom 8

- MYC becomes constitutively active and is a cell proliferation stimulator so cells proliferate a lot

57
Q

specific modality of FL and Burkitt lymphoma diagnosis

A

cytogenetics (FISH: fluorescence in situ hybridization) to look for translocations

58
Q

definition of plasma cell myeloma

A

clonal expansion of Ig secreting plasma cells: monoclonal Ig (M protein) peak in the serum and/or

59
Q

clinical findings in plasma cell myeloma

A
  • lytic, punched-out bone lesions and fractures
  • bone pain
  • anemia
  • lowered humoral immunity (recurrent infections **bacterial)
  • hypercalcemia and neurological signs
  • renal failure (nephrotic syndrome)
60
Q

causes of lytic punched out bone lesions, fractures, in multiple myeloma

A
  • BM infiltration by neoplastic plasma cells

- stimulation of osteoclastic bone resorption via secreted cytokines (IL6, IL-1b, TNF-alpha: fever cytokines)

61
Q

causes of anemia in multiple myeloma

A

BM infiltration by neoplastic plasma cells

62
Q

causes of recurrent infections (especially bacterial) in multiple myeloma

A

-suppressed production of other Ig heavy chains (other than the one produced in excess) (lower levels)

63
Q

cause of hypercalcemia and neurological signs in multiple myeloma

A

stimulation of osteoclastic bone resorption via secreted cytokines (IL6, IL-1b, TNF-alpha: fever cytokines) SO HIGHER BLOOD CALCIUM

64
Q

cause of renal failure and nephrotic syndrome in multiple myeloma

A
  • deposits of paraprotein in renal tubules with damage to epithelial cells (myeloma nephrosis)
  • stimulation of osteoclastic bone resorption via secreted cytokines (IL6, IL-1b, TNF-alpha: fever cytokines) SO HIGHER BLOOD CALCIUM
65
Q

prognostics factors in lymphomas

A
  • type of lymphoma (including grading)
  • stage (PET)
  • host-related factors (International prognostic index = IPI and also if pt immunosuppressed or not)
  • expression of markers, cytogenetic
66
Q

IPI (international prognostic index) for lymphomas description

A
  • determine score and then 5 year-survival depending on that score
  • risk factors in the score calculation: age>60, stage III or IV, high LDH, more than 1 extranodal site, ECOG/Zubrod performance status of 2,3 or 4
67
Q

staging of lymphomas (give stages and meaning)

A

I = one lymph node region
IE = one extra-lymphatic organ or tissue
II: two or more lymph node regions, one side of diaphragm
IIE: two or more extra-lymphatic organs or tissues
III: lymph node regions involvement on both sides of the diaphragm
IIIs: splenic involvement
IIIe: - (splenic + 3 lymph node regions both sides)
IV: multiple foci or disseminated extra-lymphatic involvement (liver, BM, etc.)
**In each, say if A vs B (B is if have B symptoms = fever, night sweats, weight loss)

68
Q

principal therapies in lymphomas

A
  • watch and wait
  • radiation
  • chemo (non specific, usually combinations)
  • specific biological agents and drugs like rituximab (CD20) or brentuximab (CD30), RTK inhibitors
  • permutations and combinations of these
  • HSC transplant
  • (surgery is RARE)
69
Q

examples of specific treatment modalities in HLs and NHLs

A

specific biological agents and drugs

  • Abs (anti-CD20, rituximab), brentuximab (anti-CD30)
  • RTK (tyrosine kinase) inhibitors
70
Q

example of lymphomas where rituximab (anti-CD20) is a good therapy

A

mature B cell NHLs (bc nearly all express CD20)

Bloc F - Defense (57 decks)

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