Lymphoma Histology Flashcards
What are the 3 divisions of the lymphoreticular system?
Generative LR tissue: BM + Thymus
Reactive LR tissue: LN + Spleen
Acquired LR tissue: extra nodal lymphoid tissue e.g skin, stomach, lung
What are the functions of each of the divisions of the lymphoreticular system?
Generative: generation + maturation of lymphoid cells
Reactive: development of immune reaction
Acquired: development of local immune system
What are the cells of the lymphoreticular system?
Lymphocytes (B + T)
Accessory cells: antigen presenting, macrophages, connective tissue cells
What are the functions of B and T lymphocytes?
B: express surface immunoglobulin + antibody production
T: express surface T cell receptor, regulation of B cell + macrophage function, cytotoxic function
Describe the appearance of a lymphoid follicle
Paracortical T cell zone
Mantle zone: naive unstimulated B cells, dark crescent shape appearance
Germinal center: B cells, APCs
What occurs in the germinal center?
B cells which bind antigen epitopes are selected + activated
What is found in the paracortex as well as T cells? What occurs here?
APCs
High endothelial vessels
T cells which bind antigen epitopes are selected + activated
How can mutation arise to contribute to the pathogenesis of lymphoma?
- Normal lymphocytes undergo controlled genomic “instability” of lymphoid cells: mistakes in this produce neoplastic mutations
- Inherited disorders resulting in increased/ abnormal genomic instability
- Viral agents: EBV, HTLV1
- Environmental agents: mutagens, chronic immune stimulation (e.g H pylori)
- Iatrogenic: radiotherapy, chemotherapy
How does immunosuppression predispose to development of lymphoma? Give an example
Infection e.g. HIV
Loss of surveillance
What is the most common type of lymphoma?
B cell non-hodgkin lymphoma (80-85%)
Why are lymphoid cells often disseminated at presentation?
Neoplastic lymphoid cells circulate in blood
(Exception = Hodgkins (presents as defined, localised) + some very early NHL)
Why do some patients with lymphoma develop immunodeficiencies?
Lymphoid neoplasms may disrupt normal immune system
How can pathologists assess cells for malignancy?
Cytology: single cells aspirated from a lump
Histology: tissue sections architecture + cell shape/ size
What may you suspect from finding small round lymphocytes on histology?
Naive B cells:
CLL or Mantle cell lymphoma
What may you suspect from finding small cleaved lymphocytes on histology?
Follicular lymphoma
What may you suspect from finding large lymphocytes with prominent nuclei on histology?
High grade lymphoma
What is immunohistochemistry used for? How?
Identifies proteins on/ in cells in tissue sections
Uses labelled antibody to cell surface receptor
Which markers indicate whether lymphomas are B cells or T cells?
B cell: stain +ve with antibodies to CD20
T cell: stain +ve with antibodies to CD3 or 5
What can be determined on immunohistochemistry?
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)
What is meant by clonality of B cells?
A reactive population of B cells will express both Kappa + Lambda light chains
In lymphoma, a population will exclusively express kappa OR lambda
What molecular tools can be used in lymphoma?
FISH: identifies Chr translocations
PCR: identify Chr translocations + clonal T cell receptor or immunoglobulin gene rearrangement
Give an example of a diagnostic translocation that may be determined by FISH
11:14 Mantle cell lymphoma
Give an example of a prognostic translocation that may be determined by FISH
2:5 Anapaestic large cell lymphoma
Give 3 examples of low grade B cell non-hodgkin lymphomas
Follicular lymphoma
Small lymphocytic lymphoma/ CLL
Marginal zone lymphoma
Give 2 examples of high grade B cell non Hodgkin lymphoma
Diffuse large B cell lymphoma
Burrito’s lymphoma
Is Mantle cell lymphoma categorised in B cell NHL?
Aggressive
Composed of small/ medium cells (as would be seen in low grade) but is aggressive
What can be seen on histopathology in follicular lymphoma?
Follicular pattern
Express B cell markers: CD20
Germinal centre cell origin :CD10 + BCL6 +ve
What translocation is found in molecular studies of follicular lymphoma?
14;18 translocation involving BCL2 gene
(BCL2 expressed in neoplastic follicle- should only be in mantle)
Give 2 features of follicular lymphoma
Lymphadenopathy in MA/ elderly
Indolent but can transform to high grade
How do small lymphocytic lymphoma and CLL differ in presentation?
Lymphadenopathy: small lymphocytic lymphoma
High WCC: CLL
What can be seen on histopathology in small lymphocytic lymphoma / CLL?
Small lymphocytes: Naive or post germinal center memory B cells
Abnormal expression of CD5 + CD23 +ve
What may be found in molecular studies in small lymphocytic lymphoma/ CLL?
Multiple genetic abnormalities
Give 2 features of small lymphocytic lymphoma/ CLL
MA or elderly
Indolent but can transform to high grade= Richter transformation
Where do marginal zone lymphomas (MALT) usually arise?
Extranodal sites e.g. gut, lung, spleen
In response to chronic antigen stimulation + inflammation
What cells are present in MALT?
Post germinal centre memory B cells
Describe the nature of MALT
Indolent but can transform to high grade
Can treat low grade with non-chemotherapeutic modalities- eradicate antigen
Give 3 features of mantle cell lymphoma presentation
MA M > F
Lymphadenopathy + Weight loss
Disseminated disease at presentation
What may be seen on histopathology in mantle cell lymphoma?
Pre-germinal center cells located in mantle zone
Aberrant CD5 + Cyclin D1 expression
What is found in molecular studies in mantle cell lymphoma?
11;14 translocation
Cyclin D1 over-expression
Give 2 features of Burkitt’s lymphoma presentation. Describe the aetiology
Jaw or abdo mass in children/ YA
Endemic: SS Africa
Sporadic
Immunodeficiency: in context of HIV
EBV associated
What is found on histopathology in Burkitt’s lymphoma?
Germinal center cell origin
“Starry-sky” appearance
What is found in molecular studies in Burkitt’s lymphoma?
C-yc translocation
8;14
2;8
8;22
Give 2 clinical features of diffuse large B cell lymphoma
MA/ Elderly
Lymphadenopathy
What is found on histopathology in diffuse large B cell lymphoma?
Germinal center/ post-GC B cells
Sheets of large lymphoid cells
What histopathologic findings in diffuse large B cell lymphoma are prognostic?
GC phenotype (CD10 +ve) = GOOD
p53 +ve, high proliferation = POOR
Give 5 features of peripheral T cll lymphomas NOS
MA/ elderly
Lymphadenopathy + extra nodal sites
Large T lymphocytes
Associated with reactive cell pop, esp. eosinophils
Aggressive
List 4 special forms of T cell lymphoma
Adult T cell leukaemia/ lymphoma
Enteropathy associated T cell lymphoma
Cutaneous T cell lymphoma
Anapaestic large cell lymphoma
In which populations are adult T cell leukaemia/ lymphoma more common?
Caribbean + Japan
Associated with HTLV-1 infection
Give 3 clinical features of anapaestic large cell lymphoma
Children/ YA
Lymphadenopathy
Aggressive
What is seen on histopathology in anapaestic large cell lymphoma?
Large “epitheliod” lymphocytes
T cell or null phenotype (express no T or B markers)
Give 2 molecular findings in anapaestic large cell lymphoma
2;5 translocation
Alk-1 protein expression (better prognosis)
Give a type of cutaneous T cell lymphoma. What happens?
Mycosis fungoides
CD4 +ve T cells infiltrate epidermis
Form micro-abscesses
Plaques + patch phase
Nodular stage: of abnormal T cells
Differentiate between Hodgkins + non Hodgkins lymphoma
H: usually localised to single nodal site + spreads contiguously to adjacent LN
NHL” usually involves multiple LNs, spreads discontinuously
List 4 subtypes of classical Hodgkins lymphoma
Nodular sclerosing
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
Name 1 non-classical type of Hodgkins lymphoma
Lymphocyte predominant (some relationship to NHL)
Give 3 clinical features of classic Hodgkins lymphomas
Young + MA
Often just single LN group
EBV associated
Where do cells originate in classical Hodgkins lymphoma?
Germinal center or Post GV B cells
CD30 +ve
CD15 +ve
CD20 -ve
What is seen on histopathology in classical Hodgkins lymphoma?
Sclerosis
Reactive mixed cell population in which scattered Reed-Sternberg + Hodgkin cells with eosinophils
Give 4 features of non classical lymphocyte predominant Hodgkins lymphoma
Lymphadenopathy
No association to EBV
Indolent
Can transform to high grade
Where do cells originate in non classical lymphocyte predominant Hodgkins lymphoma?
Germinal center B cells (+ve for some GC B cell markers e.g. CD10, BCL6)
CD30 -ve
CD15 -ve
CD20 +ve
What is seen on histopathology in non classical lymphocyte predominant Hodgkins lymphoma?
B cell rich nodules with scattered L+H cells
