Lymphoma Histology Flashcards

1
Q

What are the 3 divisions of the lymphoreticular system?

A

Generative LR tissue: BM + Thymus
Reactive LR tissue: LN + Spleen
Acquired LR tissue: extra nodal lymphoid tissue e.g skin, stomach, lung

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2
Q

What are the functions of each of the divisions of the lymphoreticular system?

A

Generative: generation + maturation of lymphoid cells
Reactive: development of immune reaction
Acquired: development of local immune system

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3
Q

What are the cells of the lymphoreticular system?

A

Lymphocytes (B + T)
Accessory cells: antigen presenting, macrophages, connective tissue cells

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4
Q

What are the functions of B and T lymphocytes?

A

B: express surface immunoglobulin + antibody production
T: express surface T cell receptor, regulation of B cell + macrophage function, cytotoxic function

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5
Q

Describe the appearance of a lymphoid follicle

A

Paracortical T cell zone
Mantle zone: naive unstimulated B cells, dark crescent shape appearance
Germinal center: B cells, APCs

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6
Q

What occurs in the germinal center?

A

B cells which bind antigen epitopes are selected + activated

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7
Q

What is found in the paracortex as well as T cells? What occurs here?

A

APCs
High endothelial vessels
T cells which bind antigen epitopes are selected + activated

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8
Q

How can mutation arise to contribute to the pathogenesis of lymphoma?

A
  1. Normal lymphocytes undergo controlled genomic “instability” of lymphoid cells: mistakes in this produce neoplastic mutations
  2. Inherited disorders resulting in increased/ abnormal genomic instability
  3. Viral agents: EBV, HTLV1
  4. Environmental agents: mutagens, chronic immune stimulation (e.g H pylori)
  5. Iatrogenic: radiotherapy, chemotherapy
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9
Q

How does immunosuppression predispose to development of lymphoma? Give an example

A

Infection e.g. HIV
Loss of surveillance

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10
Q

What is the most common type of lymphoma?

A

B cell non-hodgkin lymphoma (80-85%)

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11
Q

Why are lymphoid cells often disseminated at presentation?

A

Neoplastic lymphoid cells circulate in blood
(Exception = Hodgkins (presents as defined, localised) + some very early NHL)

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12
Q

Why do some patients with lymphoma develop immunodeficiencies?

A

Lymphoid neoplasms may disrupt normal immune system

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13
Q

How can pathologists assess cells for malignancy?

A

Cytology: single cells aspirated from a lump
Histology: tissue sections architecture + cell shape/ size

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14
Q

What may you suspect from finding small round lymphocytes on histology?

A

Naive B cells:
CLL or Mantle cell lymphoma

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15
Q

What may you suspect from finding small cleaved lymphocytes on histology?

A

Follicular lymphoma

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16
Q

What may you suspect from finding large lymphocytes with prominent nuclei on histology?

A

High grade lymphoma

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17
Q

What is immunohistochemistry used for? How?

A

Identifies proteins on/ in cells in tissue sections
Uses labelled antibody to cell surface receptor

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18
Q

Which markers indicate whether lymphomas are B cells or T cells?

A

B cell: stain +ve with antibodies to CD20
T cell: stain +ve with antibodies to CD3 or 5

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19
Q

What can be determined on immunohistochemistry?

A

Cell type
Cell distribution
Loss of normal surface proteins e.g. CD3 in neoplastic T cells
Abnormal expression of proteins e.g. Cyclin D1 (Mantle cell lymphoma)
Clonality of B cells (light chain expression)

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20
Q

What is meant by clonality of B cells?

A

A reactive population of B cells will express both Kappa + Lambda light chains
In lymphoma, a population will exclusively express kappa OR lambda

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21
Q

What molecular tools can be used in lymphoma?

A

FISH: identifies Chr translocations
PCR: identify Chr translocations + clonal T cell receptor or immunoglobulin gene rearrangement

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22
Q

Give an example of a diagnostic translocation that may be determined by FISH

A

11:14 Mantle cell lymphoma

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23
Q

Give an example of a prognostic translocation that may be determined by FISH

A

2:5 Anapaestic large cell lymphoma

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24
Q

Give 3 examples of low grade B cell non-hodgkin lymphomas

A

Follicular lymphoma
Small lymphocytic lymphoma/ CLL
Marginal zone lymphoma

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25
Q

Give 2 examples of high grade B cell non Hodgkin lymphoma

A

Diffuse large B cell lymphoma
Burrito’s lymphoma

26
Q

Is Mantle cell lymphoma categorised in B cell NHL?

A

Aggressive
Composed of small/ medium cells (as would be seen in low grade) but is aggressive

27
Q

What can be seen on histopathology in follicular lymphoma?

A

Follicular pattern
Express B cell markers: CD20
Germinal centre cell origin :CD10 + BCL6 +ve

28
Q

What translocation is found in molecular studies of follicular lymphoma?

A

14;18 translocation involving BCL2 gene
(BCL2 expressed in neoplastic follicle- should only be in mantle)

29
Q

Give 2 features of follicular lymphoma

A

Lymphadenopathy in MA/ elderly
Indolent but can transform to high grade

30
Q

How do small lymphocytic lymphoma and CLL differ in presentation?

A

Lymphadenopathy: small lymphocytic lymphoma
High WCC: CLL

31
Q

What can be seen on histopathology in small lymphocytic lymphoma / CLL?

A

Small lymphocytes: Naive or post germinal center memory B cells
Abnormal expression of CD5 + CD23 +ve

32
Q

What may be found in molecular studies in small lymphocytic lymphoma/ CLL?

A

Multiple genetic abnormalities

33
Q

Give 2 features of small lymphocytic lymphoma/ CLL

A

MA or elderly
Indolent but can transform to high grade= Richter transformation

34
Q

Where do marginal zone lymphomas (MALT) usually arise?

A

Extranodal sites e.g. gut, lung, spleen
In response to chronic antigen stimulation + inflammation

35
Q

What cells are present in MALT?

A

Post germinal centre memory B cells

36
Q

Describe the nature of MALT

A

Indolent but can transform to high grade
Can treat low grade with non-chemotherapeutic modalities- eradicate antigen

37
Q

Give 3 features of mantle cell lymphoma presentation

A

MA M > F
Lymphadenopathy + Weight loss
Disseminated disease at presentation

38
Q

What may be seen on histopathology in mantle cell lymphoma?

A

Pre-germinal center cells located in mantle zone
Aberrant CD5 + Cyclin D1 expression

39
Q

What is found in molecular studies in mantle cell lymphoma?

A

11;14 translocation
Cyclin D1 over-expression

40
Q

Give 2 features of Burkitt’s lymphoma presentation. Describe the aetiology

A

Jaw or abdo mass in children/ YA
Endemic: SS Africa
Sporadic
Immunodeficiency: in context of HIV
EBV associated

41
Q

What is found on histopathology in Burkitt’s lymphoma?

A

Germinal center cell origin
“Starry-sky” appearance

42
Q

What is found in molecular studies in Burkitt’s lymphoma?

A

C-yc translocation
8;14
2;8
8;22

43
Q

Give 2 clinical features of diffuse large B cell lymphoma

A

MA/ Elderly
Lymphadenopathy

44
Q

What is found on histopathology in diffuse large B cell lymphoma?

A

Germinal center/ post-GC B cells
Sheets of large lymphoid cells

45
Q

What histopathologic findings in diffuse large B cell lymphoma are prognostic?

A

GC phenotype (CD10 +ve) = GOOD
p53 +ve, high proliferation = POOR

46
Q

Give 5 features of peripheral T cll lymphomas NOS

A

MA/ elderly
Lymphadenopathy + extra nodal sites
Large T lymphocytes
Associated with reactive cell pop, esp. eosinophils
Aggressive

47
Q

List 4 special forms of T cell lymphoma

A

Adult T cell leukaemia/ lymphoma
Enteropathy associated T cell lymphoma
Cutaneous T cell lymphoma
Anapaestic large cell lymphoma

48
Q

In which populations are adult T cell leukaemia/ lymphoma more common?

A

Caribbean + Japan
Associated with HTLV-1 infection

49
Q

Give 3 clinical features of anapaestic large cell lymphoma

A

Children/ YA
Lymphadenopathy
Aggressive

50
Q

What is seen on histopathology in anapaestic large cell lymphoma?

A

Large “epitheliod” lymphocytes
T cell or null phenotype (express no T or B markers)

51
Q

Give 2 molecular findings in anapaestic large cell lymphoma

A

2;5 translocation
Alk-1 protein expression (better prognosis)

52
Q

Give a type of cutaneous T cell lymphoma. What happens?

A

Mycosis fungoides
CD4 +ve T cells infiltrate epidermis
Form micro-abscesses
Plaques + patch phase
Nodular stage: of abnormal T cells

53
Q

Differentiate between Hodgkins + non Hodgkins lymphoma

A

H: usually localised to single nodal site + spreads contiguously to adjacent LN
NHL” usually involves multiple LNs, spreads discontinuously

54
Q

List 4 subtypes of classical Hodgkins lymphoma

A

Nodular sclerosing
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted

55
Q

Name 1 non-classical type of Hodgkins lymphoma

A

Lymphocyte predominant (some relationship to NHL)

56
Q

Give 3 clinical features of classic Hodgkins lymphomas

A

Young + MA
Often just single LN group
EBV associated

57
Q

Where do cells originate in classical Hodgkins lymphoma?

A

Germinal center or Post GV B cells
CD30 +ve
CD15 +ve
CD20 -ve

58
Q

What is seen on histopathology in classical Hodgkins lymphoma?

A

Sclerosis
Reactive mixed cell population in which scattered Reed-Sternberg + Hodgkin cells with eosinophils

59
Q

Give 4 features of non classical lymphocyte predominant Hodgkins lymphoma

A

Lymphadenopathy
No association to EBV
Indolent
Can transform to high grade

60
Q

Where do cells originate in non classical lymphocyte predominant Hodgkins lymphoma?

A

Germinal center B cells (+ve for some GC B cell markers e.g. CD10, BCL6)
CD30 -ve
CD15 -ve
CD20 +ve

61
Q

What is seen on histopathology in non classical lymphocyte predominant Hodgkins lymphoma?

A

B cell rich nodules with scattered L+H cells