Week 4 Lecture 8 - Cases Involving Bone Marrow 2

Question 1

What is Filgrastim

Answer 1

It is a granulocyte colony-stimulating factor (G-CSF)

Question 2

Congenital Dyserythropoietic Anaemia

Answer 2

There are three main types of CDA (CDA-I, CDA-II and CDA-III) and although each has specific morphological and clinical features, blood films show overlapping abnormalities
All subtypes show anisocytosis and poikilocytosis and CDA I has macrocytic red cells while types II and III are usually normocytic
~90% of CDA-I cases are caused by bi-allelic mutations in CDAN1 or C15orf41
CDA-II is caused by biallelic mutations in SEC23B
CDA-III is a dominant disorder caused by the P916R mutation of KIF23
The disease is characterised by intravascular haemolysis in combination with dyserythropoiesis with large multinucleated erythroblasts in the bone marrow

Question 3

Gelatinous Transformation of Bone Marrow (GTBM)

Answer 3

Features include:
- adipocyte atrophy
- hematopoietic tissue hypoplasia
- extracellular deposition of gelatinous substance
Exclusively in adults
78% showed weight loss
81% were anaemic
Anorexia nervosa, acute febrile states, & AIDS in younger ages (<40 years)
Alcoholism and lymphomas in middle ages
Carcinomas, lymphomas, & chronic heart failure in older ages (>60 years)

Question 4

Cystinosis

Answer 4

Rare lysosomal storage disorder caused by a defect in cystine transport
Results from mutations in CTNS gene
CTNS encodes for protein ‘cystinosin’
Cystinosin is a transmembrane protein for active transport of cystine molecules out of the lysosome
This poorly soluble amino acid accumulates in the lysosomes of various organs, especially kidneys, inducing progressive kidney failure
Patients often suffer cytopenia associated with cystine crystals in the bone marrow, decreased renal production of erythropoietin, splenomegaly & portal hypertension

Question 5

Crystals in Bone Marrow

Answer 5

A number of crystal types may be encountered in
the bone marrow
- cystine
- haematoidin
- Charcot-Leyden (CL)
- lipofuscin
- crystal storing histiocytosis
- immunoglobulin chain crystals in myeloma

Question 6

Expression of Cell-Surface and Cytoplasmic Markers - AML

Answer 6

Precursors - CD13, CD33, CD34, CD117, HLA-DR
Granulocytic Markers - CD65, cytoplasmic MPO
Monocytic Markers - CD14, CD36, CD64
Megakaryocytic Markers - CD41 (glycoprotein IIb/IIIa), CD61 (glycoprotein IIIa)
Erythroid Markers - CD36, CD235a (glycophorin A)

Question 7

Bone Marrow Necrosis

Answer 7

A diagnosis of bone marrow necrosis is made when:
- areas of the trephine biopsy lack normal bone marrow architecture
- affected areas containing either amorphous granular eosinophilic staining debris or shadows of cells (ghost cells) with indistinct cellular margins
- debris and hemosiderin-laden histiocytes are also frequently seen
Clinical findings associated with BM necrosis include:
- bone pain
- fever
- cytopenias
- leukoerythroblastosis
- elevated LDH & ferritin