Pathology of Lymphoma

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B cell development	progenitor B cell --> pre-B cell --> immature B cell (IgM+, IgD-) --> Mature B cell (IgM+, IgD+) B cells produced in bone marrow from committed stem cell progenitor
T cell development	T cells originate in bone marrow from committed stem cell precursors. Precursor T cells migrate to thymus where they develop into mature T cells. in thymus: double positive thymocytes --> double negative thymocytes --> single positive thymocytes (CD4+/CD8- or CD4-/CD8+)
What is lymphoma?	Malignancy with distinct tissue masses derived from mature lymphocytes (B, T, NK) most commonly develops in lymph nodes (60%) autonomous, increased proliferation and reduced cell death
B cell neoplasms (3)	(ACUTE) B-LYMPHOBLASTIC LEUKAEMIA • Neoplastic precursor B-cells (blasts) in peripheral blood & bone marrow • Most cases in children • Aggressive but curable disease B-CELL CHRONIC LYMPHOCYTIC LEUKAEMIA - high white cell count due to neoplastic lymphocytes in bone marrow and peripheral blood - most patients elderly - usually a slowly progressive but incurable disease LYMPHOMA - tissue based masses - various types - various clinical courses
T cell neoplasms	(ACUTE) T-LYMPHOBLASTIC LEUKAEMIA/LYMPHOMA - usually adolescent males - often present with thymic/mediastinal mass (T-lymphoblastic lymphoma) +/- peripheral blood involvement (T-lymphoblastic leukaemia) - aggressive but curable disease T-CELL LEUKAEMIA - proliferation of mature T cells in peripheral blood - various type with different behaviours T-CELL LYMPHOMA - tissue based masses - various types - various clinical courses
How can immunohistochemistry be used in investigating possible leukaemia/lymphoma?	Antibodies raised against specific lymphocyte associated proteins can be used to test tissue sections for their presence or absence.
What is FISH? used to detect what?	FLUORESCENCE IN SITU HYBRIDIZATION fluorescence labelled oligonucleotide probes used to identify - entire chromosome - centromeric region of specific chromosome - specific alleles can be applied to: - cells in interphase - formalin fixed, paraffin embedded tissue sections Used to detect - chromosomal translocations - copy number changes (whole chromosomes, specific genes)
General categories of lymphoma	Non-Hodgkin (70%) - 90% B cell - can be nodal (60%) or extranodal (GIT, skin, brain) Hodgkin's - Classical - nodular lymphocyte predominant HL
Low grade lymphoma - size - proliferation and apoptosis - clinical presentation - prognosis	- small size - low rate of proliferation and apoptosis - widely disseminated at presentation and - often involving the marrow --> INCURABLE - indolent clinical course
High grade lymphoma - size and appearance - proliferation and apoptosis - spread - prognosis	- usually large cells with activated (blast-like) appearance, dispersed nuclear chromatin, prominent nucleoli - high proliferation, variable apoptosis - tend to be localised at presentation - often curable (up to 80-90%)
low grade vs high grade lymphoma using immunohistochemistry	Ki67 is a protein expressed by cells in cell-cycle (S-phase) i.e. dividing or proliferating cells express this protein expression of this protein can be detected in tissue sections using immunohistochemistry
Ann Arbor Staging	For staging lymphoma I: single LN region or lymphoid structure II: one or more LN regions on same side of diaphragm III: LN regions or structures involved on both sides of the diaphragm IV: diffuse involvement of >=1 extralymphatic organs or involvement of BM, pleura or CSF A= absence of constitutional symptoms B= constitutional symptoms; fever; sweats; weight loss
Follicular lymphoma - what - who - presentation - prognosis	neoplasm of follicle central G bells (centrocytes, centroblasts). 20% of all lymphomas predominantly affects adults aged 50-60 Presentation: - painless lymphadenopathy - bone marrow frequently involved incurable but indolent course
Morphology of follicular lymphoma	Morphological and phenotypic resemblance to normal counterpart (BCL6 and CD10 in immunohistochemistry)
Genetic abnormality in follicular lymphoma how detected?	t(14:18) --> BCL2/IGH present in 90% follicular lymphomas results in upregulation of BCL2 protein (anti-apoptotic) detected with immunohistochemistry
Treatment of follicular lymphoma	Aim of treatment is to ameliorate symptoms and prolong survival rather than cure - watch and wait if asymptomatic - Rituximab (anti-CD20) +/- low intensity chemo - radiotherapy
Burkitt lymphoma - what - 3 variants	Neoplasm of PROLIFERATING follicle centre B-cells (centroblasts) it is a 'high grade' neoplasm with an aggressive course 1. Endemic Burkitt lymphoma - equatorial Africa and Papua New Guinea - association with EBV - most common childhood malignancy in these areas (4-7yrs) 2. Sporadic Burkitt lymphoma - western Europe and north America, 1-2% all lymphoma - children and young adults (median age 30yrs) 3. Immunodeficiency associated Burkitt lymphoma - HIV - post-transplant
How does Burkitt lymphoma present?	With extranodal disease - jaws and facial bones (endemic BL) - ileocaecal region of GIT - ovaries lymph nodes and bone marrow more frequently affected in immunosuppression-associated BL CNS involvement is common in all types
Treatment of Burkitt lymphoma prognosis?	Intensive chemotherapy (CODOX-M/IVAC) aggressive but curable neoplasm (70-90% survival)
Microscopy of Burkitt lymphoma	morphological and phenotypic resemblance to normal counterpart (proliferating germinal centre cells) CD10 but no BCL2
Genetic abnormality in Burkitt Lymphoma	vast majority have chromosomal translocation involving MYC and IG gene partners - t(8:14) - t(2:8) MYC gene drives proliferation but is also linked to apoptosis (so high rate of both)
Treatment and prognosis of Burkitt Lymphoma	Short survival unless treated but responds well to chemotherapy. Aim of treatment is to cure. BUT not all patients able to tolerate treatment eg. this mostly explains poorer outcomes for elderly
Diffuse Large B-Cell Lymphoma - clinical course - % lymphoma - who - clinical presentation	aggressive 'high grade' lymphoma 40% of lymphomas heterogeneous group of lymphomas mostly adults (median age 60yrs) presents with: - RAPIDLY enlarging mass at single nodal or extranodal site (GIT, Waldeyers ring, skin, bone) - 50% early stage (I or II)
Microscopy of DLBCL	morphology: resemblance to activated B cells varied immunophenotype represents the heterogeneous nature of the category - MOST CASES BCL6 positive but variable CD10 and BCL2 some cases resemble activated B cells (CD10-, BCL6+/-, IRF4+) some cases resemble germinal centre B cells (CD10+, BCL6+, IRF4-) BCL2 usually positive but may be negative
Genetic abnormality in DLBCL	variety of chromosomal translocations may be found - t(14:18) - IGH/BCL2 in 30% t(8:14) - MYC in 10-20% t(3q27) - BCL6 in 20-30% unlike Burkitt lymphoma there is usually a complex karyotype and many other genetic abnormalities present (many of these resulting in reduced cell death eg. NFkB pathway)
Treatment and prognosis of lymphoma germinal centre B cell-like vs activated B-cell-like?	Requires aggressive chemotherapy with intention to cure. Variable response; subset of tumour resistant to conventional treatment 50% have long term survival Cases resembling germinal centre B-cells respond better to R-CHOP than those resembling activated B-cells
Hodgkin lymphoma - what - characterised by	lymphoid neoplasms affecting lymph nodes that, unlike NHL, do NOT present at extramodal sites. Characterised by: - very large neoplastic B-cell (1% tumour mass)--> Reed-Sternberg cell - prominent background of reactive WBCs (90% tumour mass)
Classic Hodgkin lymphoma - % lymphomas - age - presentation - unusual symptoms	15-20% of all lymphomas BIMODAL age incidence - young adults (15-35yrs) - older adults presentation - painless lymphadenopathy (localised, especially in young) - commonly mediastinal and cervical lymph nodes - spreads from one nodal group to immediately adacent nodes ("contiguous spread" unlike NHL) - may have B symptoms at advanced stage unusual phenomena - pain in involved nodes on consumption of alcohol - itch
Reed-Sternberg cells	neoplastic cell is very large B-cell with blast-like morphology --> REED-STERNBERG CELLS - abundant cytoplasm - binucleate - prominent nucleolus
Morphological subtypes of HL	- number and type of reactive cells - presence or absence of fibrosis 1. mixed cellularity (lymphocytes, histiocytes, neutrophils, eosinophils) 2. nodular sclerosing 3. lymphocyte predominant (Reed-Sternberg cells in background of small lymphocytes) 4. lymphocyte depleted (increased Reed-Sternberg cells, few lymphocytes, may be histiocytes)
REED Sternberg immunohistochemistry	They have defective B-cell signature = - CD20 negative - PAX5 positive They also strongly express CD30 ~40% cases are positive for EPV (express latent membrane protein 1 (LMP1) (more common in mixed cellularity variant)
Prognosis of HL	stage rather than histological subtype is most important determinant of outcome (5yr survival for stage I and II is 90%)
Where are Auer rods seen?	seen in the cytoplasm of myeloid leukemic blasts.

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	Erstellt von Ellie Britt vor etwa 7 Jahre