Haematology Flashcards
What nonreceptor tyrosine kinase is abnormal in chronic myeloid leukaemia. What is the nature of this abnormality
ABL
Abnormality involves a chromosomal translocation 9:22 to the BCR gene. This produces a chimeric, constitutively active tyrosine kinase
What is the genetic abnormality that results in Burkitt lymphoma
Chromosomal translocation of MYC gene 8:14, resulting in increased production of MYC protein
What type of malignancies are associated with JAK2 abnormalities, and by what mechanism? What type of protein is JAK2, and what what type of genetic abnormality is usually associated with it
Myeloid neoplasms. This is because JAK2 becomes constitutively active and no longer needs signalling from haematopoeitic growth factors such as EPO.
JAK2 is a nonreceptor tyrosine kinase (other non tyrosine receptors on the cell membrane receive the growth factor)
Point mutations
What are mature cells of lymphoid origin
NK cells
B cells
T cells
What are mature cells of myeloid origin
Platelets, erythrocytes (red cells), basophils, eosinophils, neutrophils, monocytes
What are the three categories of myeloid neoplasm
Acute myeloid leukaemia: immature progenor cells accumulate in the bone marrow
Myelodysplastic syndromes: ineffective haematologists resulting in peripheral cytopenias
Myeloproliferative syndromes: increased production of one or more terminally differentiated cell lines
How are lymphocytic lymphomas vs leukaemia defined in basic terms
By the usual distributions of the disease:
-leukaemia: starts in bone marrow, spills out into peripheral blood
-lymphoma: form discrete tissue masses
There can be cross over in presentations, particularly in advanced disease
What are the subtypes of Hodgkin lymphoma
Classical:
-nodular sclerosing
-mixed cellularity
-lymphocyte rich
-lymphocyte depleted
Nodular lymphocyte predominant
What type of lymphoid neoplasm is follicular lymphoma
A peripheral B cell neoplasm
What are the 5 classification groups of lymphoid neoplasms
- Precursor B-cell neoplasms (B-ALL)
- Peripheral B-cell neoplasms
- Precursor T-cell neoplasms (T-ALL)
- Peripheral T-cell neoplasms
- Hodgkin lymphoma
What is the difference between Hodgkin lymphoma and NHL in terms of their typical distribution at diagnosis and pattern of spread
Hodgkin lymphoma sometimes presents in a single group of lymph nodes only.
Tend to spread in an orderly fashion. Lymph nodes, then spleen, then liver, then bone marrow + other tissues
Extranodal presentation is rare. Rare to involve waldeyer ring or mesenteric nodes
NHL more likely to present as disseminated disease and unpredictable
What is included in the waldeyer ring
Adenoid bands
Tubal tonsils ( located posterior to the opening of Eustachian tubes)
Palatine tonsils
Pharyngeal tonsils/band
Lingual tonsils
What cells are characteristic of Hodgkin lymphoma
Reed Sternberg cells: neoplastic giant cells with owl eye appearance
What type of cell are Reed Sternberg cells derived from
Post germinal centre B cells
What makes up most of the cellularity of Hodgkin lymphoma
Lymphocytes, macrophages, granulocytes recruited by reed Sternberg cells
What is the average age of diagnosis of Hodgkin lymphoma
32 years old
Why is nodular lymphocyte predominant Hodgkin lymphoma not considered classical lymphoma
The reed Sternberg cells have a different immunophenotype
Do Reed-sternberg cells commonly express B-cell genes
No, presumably due to widespread epigenetic change
Why is T-cell immune response again Reed-Sternberg cells commonly not effective
Due to increased copy number (therefore expression) of PD-L1 and PD-L2 to inhibit T-cell activation
What is the appearance of Reed-Sternberg cells
Large cells with binucleation
Each nucleus has large inclusion-like nucleoli
Abundant eosinophilic cytoplasm
Prominent nuclear membrane
Perinuclear halo
Multiple variants exist
How is Hodgkin lymphoma distinguished from other conditions that have Reed-Sternbeg-like cells
The presence of Reed-Sternberg cells surrounded by background of non-neoplastic cells (confirmed by IHC)
What is the IHC profile of classical Hodgkin lymphomas
CD15+ CD30+ PAX5+
CD45-
What is the IHC profile of nodular lymphocyte predominant Hodgkin lymphoma
CD20+ BCL6+
CD15- CD30-
What is the most common subtype of Hodgkin lymphoma
Nodular sclerosis (65-70% of cases)