histopathology of lymphoma Flashcards
what are the features of the lymphoreticular system
Generative LR tissue
* Bone marrow and thymus
* Function - generation/maturation of lymphoid cells
Reactive LR tissue
* Lymph nodes and spleen
* Function - development of immune reaction
Acquired LR tissue
* Extranodal lymphoid tissue
* E.g. Skin, stomach, lung
* Function - development of local immune reaction eg bacteria on skin surface
differentiate the lymphocytes
B lymphocytes
* Express surface immunoglobulin
* Antibody production
T lymphocytes
* Express surface T cell receptor
* Regulation of B cell and macrophage function
* Cytotoxic function – mainly viruses
what are the accessory cells of the lymphoreticular system
APC
macrophages
connective tissue cells
production of lymphocytes
B cells in lymphoid follicles in outer part of lymph node – go to germinal centre to PC or memory
T cells in interfollicular areas
T cell diff into CD 4 (produce cytokines) CD 8 cytotoxic – destruct virus
histology of normal lymph node
B cell follicles in the outer part of LN
Paler germinal centre
Pale pink is lymph node sinuses
describe the B cell area of a normal lymph node
Mantle zone – dark appearance
Germinal centre –pale – B cells are larger – interact withAPC – selected, activated, and proliferate
describe the normal T cell area of a lymph node
Comprises
T cells
Antigen presenting cells
High endothelial vessels
This is where T cells which bind antigen epitopes are selected and activated
T cell interact with APC undergo activation and selection
how do you identify the different lymphcoytes
immunohistochemistry - looking for the CD markers
Receptors linked to dye
CD 20 on B cells – stain +ve ie brown. Other cell types stain –ve
definition of lymphoma
Neoplastic proliferation of lymphoid cells forming discrete tissue masses.
site of lymphoma
lymphoid tissues (including acquired lymphoid tissue - extranodal lymphomas eg stomach/lung)
classification of lymphoma
Hodgkin lymphoma
Non-Hodgkin lymphoma
* B cell type (most common) - low and high grade
* T cell type (rarer)
* Other (v rare)
pathogenesis of lymphoma
mutation (mistake in the controlled genetic instability of lymphoid cells -> uncontrolled growth
inherited disorder -> increased/abnormal genomic instabilitry
env agents - mutagens, chronic immune stimulation (eg H pylori)
iatrogenic - radiotherapy/chemotherapy
viral - EBV, HTLV-1
immunosuppression predispose to lymphoma - infection, transplant, loss of surveillance
differentiate between WHO classification of lymphoma
hodgkin - classical, lymphocyte predominant
NHL
* B cell - precurser B cell, peripheral B cell (low or high grade)
* T cell - precurser or peripheral T cell neoplasm
what stage of lymphocyte development and activation does lymphoma occur
can be any stage
so cell can resemble normal in both morphology and CD markers
features of lymphomas
circ in blood - so disseminated at presentation - Exception is Hodgkin lymphoma and some very early NHL
may disrupt normal immune system -> immunodef
where in the maturation process do lymphomas arise
B lymphoblasts -> acute B lymphoblastic lymphomas
niave B cells -> small lymphocytic lymphoma, chronic lymphocytic leukaemia
plasma cells -> multiple myeloma (have clockface nuclei)
follicular lymphomas - neoplastic cells try and form follicles
diagnostics of lymphoma
cytology - look at single cells aspirated from a lump
histology - look at tissue sections
* architecture - nodular (suggest follicular lymphoma) or diffuse (chronic lymphocytic leukaemia or small lymphocytic leukaemia)
* cells - small round (and naive -> CLL or mantle cell lymphoma)/small cleaved (follicular lymphoma)/large (centroblastic, immunoblastic, plasmablastic)
large with prominant nuclei - high grade lymphoma
immunophenotyping
Molecular tools - FISH or PCR
immunophenotyping for lymphoma
immunohistochemistry to identify
* cell type (T= CD3 5 B= CD20)
* cell distribution
* loss of normal surface proteins eg neoplastic T cells
* abnormal expression of proteins (secondary to specific chr gene abnormalities) eg cyclin D1 (normal lymphocytes shouldnt express this)
* clonality of B cells - light chain expression
immunohistochem in follicular lymphoma
bcl-2 expression by neoplastic B cells in follicles
the gene translocation leads to overexpression of bcl-2
summarise Small lymphocytic lymphoma/CLL
clinically - middle age or elderly, nodes (SLL), blood (CLL)
Histopathology - Small lymphocytes, uniform nuclei, small nucleoli Naïve or post-germinal centre memory B cell
diffuse/slightly nodular
CD5, CD23 +
molecular - multiple genetic abnormalities - Indolent, but can transform to high grade lymphoma (Richter transformation)
summarise marginal zone lymphoma
extranodal sites - gut, lung, spleen
arise in response to chronic antigen stimulation ie chonic inflammation (e.g. by Helicobacter in stomach)
Post germinal centre memory B cell
Indolent but can transform to high grade lymphoma
Can treat low grade disease with non-chemotheraputic modalities - i.e. remove antigen
E.g Helicobacter eradication can treat MALT lymphoma of stomach
T cells small, pale cytoplasm, infiltrate between epithelial cells of gastric
summarise mantle cell lymphoma
clinical - middle age, male predominance, nodes, GIT, disseminated disease at presentation
histopath - mantle zone of B cell follicles, pre-germinal centre cell, aberrent CD5. cyclin d1 expression in nuclei (+ve staining)
molecular - 11;14 translocation, cyclin D1 overexpression
median survival 3-5yrs
histopathology of burkitt’s lymphoma
germinal centre origin
starry sky appearance - stars are the debriding macrophages
many apoptotic cells being mopped up by macrophages
Rapidly progressing and proliferating - proliferative index is very high
High proliferative fraction/rate
See many mitotic figures
lymphoma cells are dark with prominant nucleoli
can express B cell markers - CD10, CD20, bcl-6
histopathology for diffuse B cell lymphoma
Germinal center or post-germinal center B cell
Sheets of large lymphoid cells
high proliferative rate
Can see many mitotic figures
Necrosis
Stain for B cell markers
Can be terminal/non-terminal – CD10 is germinal centre = good prognosis
Germinal center phenotype = good prognosis
p53 positive, high proliferation fraction = poor prognosis
summarise T cell lymphomas
aggressive
arise in lymph nodes (lymphadenopathy) or extranodal sites
Neoplastic T cells atypical compared to normal lymphocytes –> larger nuclei, small nucleoli and irregular nuclear membranes
Accompanied by reactive subpopulation – eosinophils, macrophages
histopathology of anaplastic large cell lymphoma
Anaplastic looking T cells ie nuclei variable in size and shape
Large “epithelioid” lymphocytes
T cell (CD2 3 4) or null phenotype (-ve for B or T cell markers)
histopathology of classic HL
Neoplastic cells are few in number – most of infiltrate is reactive cells – plasma cells, neutrophils etc
Large nuclei
sclerosis
Reed Sternberg cells - Binuclei cells – owls eye
mixed cell population in which scattered Reed-Sternberg and Hodgkin cells with eosinophils
Are a B cell origin but –ve CD20 but have other B cell marker
thought to be germinal centre or post germinal centre B cell origin
histopathology of Nodular LP Hodgkins Lymphoma
Germinal centre B cell (positive for some germinal centre B cell markers)
No association with EBV
CD30-, CD15-, CD20 +
B cell rich nodules with scattered Lymphoid &H cells
few neoplastic cells
