07 - Myeloma / Lymphoma / MDS / Sarcomas Flashcards
Multiple Myeloma involves which cell type?
plasma cells - mature B lymphocytes
what at the 3 stages in Multiple Myeloma
1) Monoclonal gammopathy of undetermined significance
2) Smouldering myeloma
3) Myeloma
what are the presenting features in Multiple Myeloma
CRAB:
C - hypercalcaemia
R - Renal failure
A - Anaemia
B - Bone disease
what are the typical cytogenetic findings in Multiple Myeloma
> Hyperdiploid - favourable
non-hyperdiploid - non-favourable
the latter typically involves structural rearrangements of the IgH locus
> t(4;14)
> t(14;16)
Lymphoma is a solid tumour of the immune systems. What structures/organs could be involved?
> Lymph nodes
Spleen
thymus
Bone Marrow
Lymphoma can be characterised into….
> Hodgkins Lymphoma (have characteristic Reed Sternberg cell
> Non-hodgkins lymphoma (more common)
- this can be B-Cell or T-Cell
- B-cell can be further distinguished between:
- AGGRESSIVE (inc: diffuse large B cell lymphoma; Burkitt; mantle)
- INDOLENT (inc: follicular; marginal zone; hairy cell)
What types of lymphoma are considered aggressive?
> diffuse large B cell lymphoma
Burkitt lymphoma
lymphoma mantle
What types of lymphoma are considered INDOLENT?
> follicular lymphoma
marginal zone lymphoma
hairy cell lymphoma
Hodgkins Lymphoma is associated with a _____ prognosis
good
What is the characteristic in Hodgkins Lymphoma
Reed Sternberg cell - looks like a face
What are the features of INDOLENT non-Hodgkins Lymphoma
> late presentation
slow progression
compatible with long life
What are the features of AGGRESSIVE non-Hodgkins Lymphoma
> early presentation
rapid progression
fatal without treatment
Tell me about Burkitt Lymphoma
> type of aggressive non-Hodgkins Lymphoma
more common children
MYC rearrangements are the hallmark of BL
‘starry sky’ appearance on historical
common translocation t(8;14) - MYC / IgH
Tell me about Diffuse Large B-Cell Lymphoma (DLBCL)
> most common type of aggressive non-Hodgkins Lymphoma > IgH rearrangements common: - t(14;18) - IgH / BCL2 - t(3;14) - BCL6 / IgH - t(8;14) - IgH / MYC
Tell me about Follicular Lymphoma
> type of INDOLENT non-Hodgkins Lymphoma
t(14;18) common - 80% cases
BCL2 / IgH = overexpression of BCL2 (inhibits apoptosis)
this rearrangement alone is insufficient to drive malignancy as 70% healthy adults have t(14;18) in this circulating clonal memory B-cells
typically also have 6q21 del (60% patients)
or 17p13 del (20% patients)
Tell me about MDS
> MDS = myelodysplastic syndrome
disorder of haematopoetic stem cell
affects more than one myeloid cell lineage (= cytopenia)
elevated blast count, but importantly less than 20%
risk of progression into AML
more common in elderly
What cytogenetic findings are seen in MDS
> translocations rare, mostly copy number alterations > GOOD prognosis: - -Y - del(20q) - isolated del5q > POOR prognosis - complex (> 3 abs) - Chr7 abs
Tell me about MPN
> MPN = Myeloproliferative neoplasms
proliferation of >1 myeloid cell lineage in BM
enlargement of organs common (organomegaly)
progression of disorder leads to BM failure OR transformation into AML
What are the cytogenetic findings seen in MPN
> +8 > +9 > del(20q) > del(13q) > del(5q)
What are the molecular genetic findings seen in MPN
> JAK2 mutations - tyrosine kinase in JAK/STAT pathway - JAK2 mutations found in 95% patients with polycythaemia vera (PV) type MPN and 50% of Essential Thrombocythaemia (ET) type MPN > V617F common mutations > after that, exon 12
> MPL mutations:
- Myeloproliferative leukaemia virus oncogene
- seen in 5% patients with Essential Thrombocythaemia (ET) type MPN
> CALR mutations:
- calreticulin
- 80% frameshift mutations in ex9
- found in 60-80% cases -ve for JAK2 / MPL
Name 3 types of Sarcoma
1) Rhabdomyosarcoma - sarcoma of connective tissue
2) Ewing Sarcoma - sarcoma of bone
3) Synovial Sarcoma - sarcoma of the joints
What are the types of Rhabdomyosarcoma? what are the common genetics findings?
1) Embryonal Rhabdomyosarcoma (ERMS)
- 70-80% of RMS in young patients
- often gain of Chromosomes (eg +2, +8, +11)
- hyperdiploidy ERMS = GOOD prognosis
2) Alveolar Rhabdomyosarcoma (ARMS)
- 20-30% of RMS
- translocations involving FOXO1:
- t(2;13) - PAX3/FOXO1 (60%)
- t(1;13) - PAX7/FOXO1 (20%)
note: MYCN amplification often seen in RMS = BAD prognosis
What translocations are associated with Alveolar Rhabdomyosarcoma
- translocations involving FOXO1:
- t(2;13) - PAX3/FOXO1 (60%)
- t(1;13) - PAX7/FOXO1 (20%)
What are the symptoms of Ewing sarcoma? what are the common genetics findings?
Symptoms:
- bone pain
- fatigue
- weight loss
Genetics:
- t(11;22) - FLI1/EWSR1
note: many other translocation, but almost all involve fusion of the EWSR1 gene
