Week 4 Lecture 7 - Cases Involving Bone Marrow

Question 1

Hemophagocytic Syndrome (HPS)

Answer 1

A.k.a Haemophagocytic lymphohistiocytosis or Macrophage activation syndrome
Activated macrophages proliferate & exhibit extreme phagocytosis (of both white and red blood cells)
Promoted by excessive cytokine stimulation
May be life-threatening
HPS typically occurs with the occurrence of both immune dysfunction and a trigger event, e.g. exposure to infection, drug, toxin etc

Question 2

When Might Hemophagocytic Syndrome Occur?

Answer 2

Inherited
- e.g. Chediak-Higashi syndrome
- e.g. Hemansky-Pudlak syndrome
Acquired non-neoplastic
- pregnancy
- ITP
- IBD
- SLE
- rheumatoid arthritis
Acquired neoplastic
- wide range of neoplasms
- B-cell neoplasms
- T-cell neoplasms
- Hodgkin lymphoma
- carcinoma

Question 3

Histoplasmosis

Answer 3

Infection is associated with activities that disturb soil, particularly soil that contains bird or bat droppings
Many people exposed to the fungus Histoplasma never develop disease or may have self-limiting disease
Immunocompromised people are at higher risk for developing the severe forms of histoplasmosis
Symptoms of histoplasmosis include:
- fever
- cough
- fatigue
- chills
- headache
- chest pain
- body aches
Bone marrow histology shows:
- hypercellular
- granulomas (with epithelioid macrophages and Langerhans giant cells)

Question 4

Schistosomiasis

Answer 4

Schistosomiasis (Bilharziasis) is caused by some species of blood trematodes (flukes) in the genus Schistosoma
The three main species infecting humans are:
- Schistosoma haematobium
- S. japonicum
- S. mansoni
Dogs serve as the reservoir for S. mekongi
Intermediate hosts are snails
Many infections asymptomatic

Question 5

Schistosomiasis Clinical Presentation

Answer 5

A local cutaneous hypersensitivity reaction following skin penetration by cercariae may occur and appears as small, itchy maculopapular lesions
Acute schistosomiasis is a systemic hypersensitivity reaction that may occur weeks after the initial infection, especially by S. mansoni and S. japonicum
Symptoms
- fever
- cough
- abdominal pain
- diarrhoea
- hepatosplenomegaly
- eosinophilia

Question 6

Schistosomiasis - Bone Marrow Characteristics

Answer 6

Fragmented
Hypocellular
Trilineage hypoplasia
Atypical structures
Embryonated eggs
- size (48-51 μm) & morphology consistent with Schistosoma mekongi

Question 7

Post Transplant Lymphoproliferative Disorder (PTLD)

Answer 7

Lymphoid disorders ranging from indolent polyclonal proliferations to aggressive lymphomas that complicate solid organ or hematopoietic transplantation

Question 8

Non-Tuberculosis Mycobacteria (NTM)

Answer 8

NTM can be divided into two groups based on how long they take to grow in a culture:
- rapid-growing species: usually grow within 7 to 10 days
- slow-growing species: may need >14 days to grow
Rapidly growing species
- e.g. M. abscessus complex
- e.g. M. fortuitum
Slow growing species
- e.g. M. avium complex

Question 9

Q-Fever

Answer 9

Agent: Coxiella burnetii
People are infected by:
- contact with animal faeces, urine, milk, and birth fluids that contain Coxiella burnetii
- breathing in dust that has been contaminated with Coxiella burnetii
- eating contaminated, unpasteurised dairy products
Bone marrow findings:
- hypocellular
- trilineage hypoplasia
- granulomas with central lipid vacuole

Question 10

Granulomas

Answer 10

Found in the bone marrow in a wide variety of disorders
Morphological features:
- presence of giant cells
- epithelioid cell
- lymphocyte cuffing
- fibrosis
- caseation
- presence of organisms or infiltrates

Question 11

Parvovirus B19 Infection

Answer 11

Infects erythroid precursors
May have only mild, rash illness
Less common symptoms include:
- polyarthropathy (more common in adults)
- severe anaemia
Reticulocytes not increased = erythropoiesis is not increased
Have large increase in EPO level = marrow is not responding to erythropoietic stimulus
Shows population of large atypical cells with prominent intranuclear inclusions and vacuolated cytoplasm (erythroid origin)
- to confirm origin of these large cells, test with glycophorin and E-cadherin

Question 12

Parvovirus B19 Infection - FBP and Bone Marrow Findings

Answer 12

FBP:
- anaemia
- neutropenia
- lymphocytosis
- thrombocytopenia
BM:
- severe erythroid hypoplasia
- giant pronormoblasts
- population of large atypical cells with prominent intranuclear inclusions and vacuolated cytoplasm

Question 13

Leishmaniasis

Answer 13

Infection in people is caused by more than 20 species of Leishmania parasites, which are spread by about 30 species of sand flies
There are different forms of leishmaniasis in people:
- cutaneous leishmaniasis causes skin sores
- visceral leishmaniasis affects several internal organs
Transmission in nature is usually between sand flies & animals
On BM examination shows, small cells both intracellular and extracellular with small amount of cytoplasm
- consistent with Leishmania species amastigotes

Question 14

General Aspects of Inflammation of the Bone Marrow

Answer 14

Inflammation of bone marrow = Osteomyelitis
Cellular composition varies according to aetiology, magnitude, duration, etc.
Often reflects systemic disease
May be difficult to detect if lesions are focal => trephine biopsies are warranted (as well as aspirates)
Organisms may be evident

Question 15

Organisms in the Bone Marrow

Answer 15

Organisms found in the peripheral blood may be encountered in the bone marrow
May be:
- transient
- resident
Wide range
- bacteria
- fungi
- virus
- protozoa
- helminth

Question 16

Infectious Disease of the Bone Marrow

Answer 16

Trilineage hypoplasia (=> pancytopenia) makes patients susceptible to infectious agents
Some infectious agents can infect the bone marrow without immuno-compromise
Infection of the bone marrow can have effect on the composition/morphology of the bone marrow
- influences the composition of the peripheral blood