Lymph Nodes, Spleen & Thymus pathology Flashcards

1
Q

What are primary immune organs?

A

Sites of initial maturation -> immune competent cells
- bone marrow (for B cells)
- thymus (for T cells)

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2
Q

What are secondary immune organs?

A

Sites of antigen driven replication and differentiation into committed effector cells
- lymph nodes
- spleen
- Mucosal Associated Lymphoid System (MALT) -> lymphoid cells lining the respiratory and GI tracts
- everywhere else

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3
Q

Which part of the lymph node does metastatic cancer usually go to?

A

Subcapsular sinus

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4
Q

Eg of non neoplastic lymph node pathology

A

Infective
- acute non-specific lymphadenitis -> staphylococcus
- granulomatous inflammation
- mycobacterium
- fungal infection
- cat-scratch
- lymphogranuloma venereum
- sarcoidosis
-viral
infectious mononucleosis

Necrotising lymphadenitis (Kikuchi’s lymphadenitis)

Drug related lymphadenopathy

Autoimmune
- SLE
- RA

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5
Q

Histological findings of mycobacterial infection

A

“Cheesy” yellow appearance

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6
Q

Histological findings of granulomatous inflammation

A

Langhans giant cells

Caseating necrosis

Multi-nucleated giant cells

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7
Q

Eg of non-neoplastic pathology of lymph nodes

A

Candida

PCP

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8
Q

Histological findings if candida is the cause

A

Pseudohyphae

Spores

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9
Q

Trait seen in PCP

A

Boat-shaped cysts

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10
Q

Histological findings if CMV is the cause

A

Cytoplasmic inclusions

Nuclear inclusions

Owl’s eye inclusion

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11
Q

Definition of lymphomas

A

Malignancies of the lymphoid system which primarily manifest themselves outside the bone marrow, at the sites of normal lymphoid homing
- lymph nodes
- spleen
- MALT
- anywhere

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12
Q

Clinical presentation of lymphomas

A

Enlarging mass
- typically painless
- sites of nodal tissue
- lead to compression, infiltration of hollow organs -> pain, obstruction, perforation

Interference w/ normal organ fn
- solid organ infiltration -> kidneys, liver, bone marrow

Systemic symptoms
- fever
- night sweats
- weight loss

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13
Q

How to stage for lymphomas?

A

Stage 1
- involvement of single lymph node region/extralymphatic site

Stage 2
- involvement of 2/more lymph node regions on same side of diaphragm
- may include localised extralymphatic

Stage 3
- involvement of lymph node regions on both sides of the diaphragm
- may include spleen/localised

Stage 4
- everywhere
- diffuse extralymphatic disease

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14
Q

What is the International Prognostic Index (IPI)?

A

Clinical tool to predict the prognosis of pts w/ aggressive NHL

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15
Q

How is lymphomas classified?

A

Clinical behavior: aggressive vs indolent

Pathological diagnosis: WHO classification

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16
Q

Traits of malignant lymphoma

A

High proliferation rate and cell death rate
- but proliferate&raquo_space;> death -> net proliferation
- large proliferation margin

More often localised at presentation

Shorter natural hist

Curable in some w/ aggressive therapy

All childhood lymphomas of this type

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17
Q

Traits of indolent lymphoma

A

Grow very slowly but cells don’t die
- small proliferation margin

Widespread at diagnosis

Prolonged natural hist

Currently incurable
- exceptions:
- localised disease
- marrow ablation w/ stem cell transplant

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18
Q

What does clinical behaviour/natural hist of a disease mean?

A

It refers to usual course of development of a disease in the absence of treatment

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19
Q

Does pt with aggressive or indolent lymphoma have better response to treatment? Why?

A

Aggressive

Chemo targets rapidly dividing cells
- aggressive lymphoma divide very fast -> susceptible to chemo
- indolent -> slow-growing -> chemo don’t work very well

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20
Q

What are the principle of WHO classification of lymphomas?

A

Classification based on cell of origin: B, T, NK

3 major categories of lymphoid malignancies can be defined based on combination of morphology and cell lineage
- Non-Hodgkin lymphoma
- B cell neoplasms
- T/NK cell neoplasms
- Hodgkin lymphoma

Each disease is a distinct entity defined by a combination of
- clinical features
- morphology
- immunophenotype
- genetic/molecular features

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21
Q

How is the pathological diagnosis of lymphomas made?

A

Multiparameter approach and integration of clinical features, histology, surface antigen expression and molecular features

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22
Q

What are the clinical features we look out for when diagnosing lymphomas?

A

Nodal vs extranodal

Primary site

Immune deficiency conditions
- eg: HIV+ pts -> Burkitt lymphoma

Infection

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23
Q

What is morphology of a lymphoma?

A

Disruption of normal lymph node architecture
- growth pattern
- lymphoma cell size

Certain morphological features are characteristic of specific subtypes of lymphoma
- starry sky appearance in Burkitt’s lymphoma

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24
Q

What is surface antigens expression?

A

Cluster of differentiation (CD) antigens/markers characteristic of specific subtypes of lymphoma

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25
Q

How is surface antigens expression detected?

A

Immunochemistry

Flow cytometry

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26
Q

What are the diff markers of surface antigens expression?

A

Markers indicating cell of origin/lineage

Markers characteristic of specific subtypes of lymphoma

Markers of specific molecular abnormalities in specific subtypes

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27
Q

What are molecular signatures of lymphomas?

A

Certain DNA alterations characteristic of specific subtypes of lymphoma, usually translocations

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28
Q

Is diffuse large B cell lymphoma aggressive?

A

Yes

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29
Q

Clinical features of large B cell lymphoma

A

Most common non-hodgkin lymphoma (NHL)

Disease of adults and children

Presents w/ rapidly enlarging masses

Curable w/ aggressive chemotherapy

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30
Q

Pathogenesis of large B cell lymphoma

A

No defining genetic abnormalities

Several cytogenetic abnormalities associated w/ large cell lymphoma

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31
Q

Morphology of large B cell lymphoma

A

Diffuse infiltration of lymph node
- cannot see follicles -> sheet of lymphoid cell -> diffuse growth pattern

Large lymphoid cells

32
Q

Surface antigens of diffuse large B cell lymphoma

A

B cell markers

33
Q

Is Burkitt’s lymphoma aggressive?

A

Yes

34
Q

Clinical features of Burkitt’s lymphoma

A

Disease of adults and children

3 subtypes
- endemic (Africa) -> affect children, EBV+, jaw
- sporadic (western countries) -> affect children and young adults, common site is ileocaecal region
- immunodeficiency related -> HIV+

Very aggressive and rapidly fatal

35
Q

Pathogenesis of Burkitt’s lymphoma

A

t(8;14) -> upregulation of MYC oncogene (cell cycle regulation gene)

36
Q

Morphology of Burkitt’s lymphoma

A

Diffuse infiltration of lymph node

High cell turnover -> attracts macrophages to phagocytose -> starry sky appearance

37
Q

Surface antigens of Burkitt’s lymphoma

A

Positive:
- CD20 (B cell marker)
- CD10 (follicle centre marker)

38
Q

Molecular signature of Burkitt’s lymphoma

A

t(8;14)

39
Q

Is follicular lymphoma aggressive?

A

No

40
Q

Clinical features of follicular lymphoma

A

Affects adults

Usually widely disseminated at diagnosis, incl. bone marrow

Will respond to gentle chemotherapy but will relapse
- incurable short of bone marrow transplant, unless rare limited disease

41
Q

Pathogenesis of follicular lymphoma

A

t(14;18)(q32, q21)
- upregulates expression of anti-apoptotic protein Bcl2 -> immortalise lymphoma cells

42
Q

Morphology of follicular lymphoma

A

Retain characteristic follicular (nodular) structure but monotonous accumulation of single cell type

43
Q

Surface antigens of follicular lymphoma

A

Characteristic immunophenotype

44
Q

Molecular signature of follicular lymphoma

A

Translocation detected by cytogenetics, FISH and/or polymerase chain rxn

45
Q

Definition of classic Hodgkin lymphoma (CHL)

A

Lymphoid neoplasm composed of Reed-Sternberg cells (neoplastic) residing in an inflammatory (non-neoplastic) background, including lymphocytes, histiocytes, eosinophils and plasma cells

46
Q

What is the basis of diagnosis of CHL?

A

Background rich in inflammatory cells, especially eosinophils

Presence of Reed-Sternberg cells (lacunar cells)

47
Q

What is the pattern of spread of CHL?

A

Contiguously via lymphatics

48
Q

Treatment for CHL

A

Limited stage, low bulk (small tumor) disease treated w/ radiation therapy

Higher stage, B symptoms treated w/ multi-agent chemotherapy +/- radiation therapy

49
Q

Is CHL curable?

A

Yes

50
Q

Why does CHL have a separate category in the classification sys?

A

Molecular studies indicate that the R-S cell in the majority of cases is an altered B cell -> HL is a type of B cell lymphoma but w/ a very diff biology from other types of B cell lymphoma

51
Q

Tests to do if you suspect lymphoma

A

FNAC

Biopsy
- flow cytometry (fresh specimen)
- histology
- immunochemistry
- cytogenetics (fresh specimen)
- molecular tests

52
Q

Tests to do if you suspect infection

A

FNAC

Biopsy

Culture

Serology

53
Q

What are the commonest organs where pri neoplasms metastasize?

A

Lymph nodes

54
Q

What is the most impt prognostic indicator in cancer?

A

Lymph node metastasis

55
Q

Pathologist role in LN metastases

A

Identify presence of tumor

Microscopic type of tumor

Identify source of metastatic tumor

56
Q

What is the difference btw lymphomas and leukemia?

A

Lymphomas:
- malignancies of the lymphoid sys which primarily manifest themselves outside the bone marrow, at sites of normal lymphoid homing
- arise as discrete tumor masses

Leukemias:
- malignancies of hematopoietic sys which are primarily disorders of the bone marrow
- present w/ widespread involvement of bone marrow
- usually w/ large no. of tumor cells circulating in peripheral blood

57
Q

Definitions of leukemia

A

Leukemic cells originate in bone marrow

Leukemic cells usually spill from the bone marrow into the blood (may be seen in large no.)

Leukemic cells may also infiltrate lymph nodes, liver, spleen and other tissues

58
Q

What are the 3 main hematopoietic cell lines?

A

Erythroid series -> erythrocytes

Myeloid series -> polymorphs

Megakaryocytic series -> platelets

59
Q

How is leukemia classified?

A

Acute leukemia -> aggressive

Chronic leukemia -> slow growth, survival better in absence of treatment

60
Q

Symptoms of acute leukemia

A

Result from suppression of normal marrow fn
- anemia w/ accompanying fatigue
- fever, usually reflecting an infection
- bleeding, caused by thrombocytopenia
- fatal within weeks if untreated

61
Q

Symptoms of chronic leukemia

A

Non-specific symptoms
- fatigue
- weight loss
- anemia
- abnormal sensation in abdomen caused by splenomegaly
- pts w/ untreated chronic leukemia usually survive much longer

62
Q

Pathological characteristics of acute and chronic leukemias

A

Acute -> presence of immature, blast cells

Chronic -> more mature and well-differentiated cells

63
Q

Origins of lymphoid leukemia

A

Precursor of B/T lymphocyte

64
Q

Origins of myeloid leukemia

A

Precursor of granulocytes, monocytes, erythrocytes/megakaryocytes

65
Q

4 general classifications of leukemia

A

Acute lymphoblastic leukemia (ALL)

Chronic lymphoid leukemia (CLL)

Acute myeloblastic leukemia (AML)

Chronic myeloid leukemia (CML)

66
Q

How is the pathological diagnosis of leukemia made?

A

Clinical -> abnormal blood counts, symptoms and signs, sites of involvement

Morphology -> indicate degree of differentiation/maturation; characteristic of specific subtypes of leukemia
- not definitive

Surface antigens -> certain Ab characteristic of specific subtypes of leukemia

Molecular/genetic abnormalities -> certain DNA alterations are characteristic of specific subtypes of leukemia, usually translocations

67
Q

Histological features of spleen

A

Red pulp
- venous sinusoids
- macrophages

White pulp
- arteries
- T cells
- B cells

68
Q

Is spleen vascular or lymphoreticular?

A

Both

69
Q

Fns of spleen

A

Filtration of unwanted elements of blood

Major secondary organ in immune sys

Source of lymphoreticular/hematopoietic cells

Reserve pool and storage space

70
Q

What is the key symptom in spleen diseases

A

Splenomegaly

71
Q

Causes of splenomegaly

A

Infections
- any infective agent that can cause blood-borne infection
- transient, non-specific enlargements

Congestion (portal hypertension)

Lympho-hematogenous disorders
- pri/sec lymphomas
- splenic involvements by leukemias
- anemias

Immunologic-inflammatory conditions

Storage diseases

72
Q

What kind of tissue is the thymus?

A

Lymphoid tissue

73
Q

What happens to the thymus as an individual ages?

A

Lymphoid tissue replaced by fat

74
Q

Histological features of thymus

A

Lymphoid component

Epithelial component

Hassall corpuscles

75
Q

What is the fn of the thymus?

A

T cell production

76
Q

Pathology of thymus

A

Developmental disorders

Thymic hyperplasias

Myasthenia gravis

Thymic (mediastinal) neoplsms