Week 3 Lecture 5 - Neoplastic Disorders of Bone Marrow

Question 1

Effect of Neoplastic Disorders of the Bone Marrow

Answer 1

Proliferation of neoplastic cells => circulating in the peripheral blood
Myelophthisis (replacement of normal haematopoietic tissue)
- anaemia
- leukopenia/neutropenia
- thrombocytopenia
- bicytopenia
- pancytopenia

Question 2

Myeloproliferative Neoplasms - General Characteristics of the BM

Answer 2

Hypercellularity
Haematopoietic maturation
Megakaryocytic hyperplasia & dysmegakaryopoiesis
Hypervascularity
Reticulin fibrosis
Osteosclerosis

Question 3

Myelodysplastic Syndromes

Answer 3

General characteristics of the BM:
- variable cellularity
- M:E variable (often ↓)
- left-shift
- blasts < 20%
- dysplastic change affecting ≥ 1 cell line
=> Atypical morphology
- Erythroid: ↑ size, multinucleation, nuclear budding, cytoplasmic basophilia etc.
- Granulocyte: ↑ size, atypically shaped nucleus, atypical cytoplasmic granulation

Question 4

Hypocupraemia

Answer 4

Elevated copper levels
Associated with gastric surgery, malabsorption, and excess copper chelation
Impairs iron absorption & insertion into the protoporphyrin ring, causing iron accumulation with ringed sideroblasts, dysplastic changes, & vacuolisation

Question 5

Acute Myeloid Leukaemia - General Characteristics of BM Aspirate vs BM Histology

Answer 5

Aspirate:
- typically > 20% blast cell
- admixed with haematopoietic cells, lymphocytes, plasma cells
- differentiated haematopoietic cells may exhibit dysplastic features
Histology:
- hypercellular (for site & age)
- blast cells
- reactive plasmacytosis
- granulomas
- fibrosis
- bone abnormalities

Question 6

Refractory Anaemia with Ring Sideroblasts Associated with Thrombocytosis (RARS-T)

Answer 6

Characterised by:
- erythroid dysplasias
- ring sideroblasts constituting 15% or more of all erythroid precursors
- thrombocytosis
- atypical large megakaryocytes
Approximately 60% of patients with RARS-T demonstrate the JAK2-V617F mutation, and 90% exhibit mutations in SF3B1

Question 7

Lymphoglandular Bodies

Answer 7

Cytoplasmic fragments, commonly seen in FNA or cytology preparations of lymphoid tissue
- often in association with lymphoid malignancies
Their pale, lightly basophilic colour with smooth borders, occasional blebs, and lack of granulation allow them to be distinguished from platelets

Question 8

Acute Lymphoblastic Leukaemia - General Characteristics of Bone Marrow

Answer 8

Typically > 20% blast cells; often > 50% blasts
Admixed with haematopoietic cells, lymphocytes, plasma cells
Differentiated haematopoietic cells may persist & typically do not exhibit dysplastic features

Question 9

Findings with B Acute Lymphoblastic Leukaemia (B-ALL)

Answer 9

Sheets of blasts with basophilic cytoplasm, variable numbers of nucleoli & cytoplasmic vacuolations (panel A)
Flow immunophenotyping of the peripheral blood showed 13% blasts, which were
CD19+/CD10+/Tdt+/CD22+/HLA−DR+/partial CD20+, but were negative for CD45−/CD34−
Biopsy was hypercellular with blasts having irregular nuclear- contour (panel B)

Question 10

B-Lymphoblastic Leukaemia - Chromosomal Abnormalities

Answer 10

Hyperdiploidy
- 51-65 chromosomes
- ~25% childhood ALL; ~7- 8% of adult ALL
- relatively good prognosis
Hypodiploidy
- 30-39 chromosomes
- uncommon, 1-5% of B- ALL cases
- typically have a poor prognosis
Near-triploidy
- 60-78 chromosomes

Question 11

AML IHC Staining

Answer 11

Immature myeloid cells stain positively for CD13, CD33, CD41, CD61, and factor VIII and negatively for MPO and CD3