Myeloid Neoplasms II

Question 1

Explain AML.

Answer 1

• There is proliferation AND lack of maturation, which requires atleast 2 different mutations. Median onset 65 years.
• Auer rods (picture below)
• Myeloperoxidase ⊕ cytoplasmic inclusions seen mostly in APL (acute promyelocytic leukemia, formerly M3 AML)
• Circulating myeloblasts on peripheral smear. Risk factors: prior exposure to
• alkylating chemotherapy,
• topoisomerase II inhibitors
• radiation,
• myeloproliferative disorders,
• Down syndrome.
• t(15;17)Ž = APL subtype responds to all-trans retinoic acid (vitamin A), inducing differentiation of promyelocytes.
• DIC is a common presentation.

Question 2

What are the clinical features of AML?

Answer 2

• Anemia - can lead to fatigue, weakness, pallor.
• Thrombocytopenia - bleeding disorders.
• Hepatosplenomegaly - 1/3rd of the cases
• In the bone marrow we see increased number of blast cells (of lymphoid lineage unlike ALL), we also see Auer bodies

Question 3

What are some of the other organs involvement seen in AML?

Answer 3

Leukostasis and granulocytic sarcoma.

Question 4

How do we define Acute Promyeloid Leukemia?Explain this disease.

Answer 4

• AML with t(15;17) defines acute promyelocytic leukemia
• Disrupts retinoic acid receptor (RAR-α) gene
• Abnormal promyelocytes with multiple Auer rods
• Frequent association with DIC
• All trans retinoic acid (ATRA) used for treatment. However, this is not the cure, these patients still have t(15;17), ATRA only makes these immature cells become mature (neutrophils) and eventually die.
• Favorable to intermediate prognosis

Question 5

What are some of the other AML diseases that have good prognosis?

Answer 5

• t(8;21) - Favorable prognosis

* inv(16) or t(16;16) -Acute myelomonocytic leukemia with abnormal eosinophils (AML –M4Eo), also favorable prognosis

Question 6

What is the clinical course and prognosis of AML?

Question 7

Explain myelodysplastic syndromes.

Answer 7

• Ineffective hematopoiesis together with peripheral cytopenias + hypercellular marrow Etiologic associations
• Benzene
• Alkylating chemotherapeutic drugs
• Ionizing radiation
• Topoisomerase II inhibitors Clinical features –related to pancytopenia
• Variable course
• May smolder for years; some are transfusion dependent
• 10-40% transform to AML

Question 8

Explain Langerhan’s Cell Histiocytosis.

Answer 8

• Neoplastic proliferation of Langerhans cells
• BRAF mutations in 60% of cases
• Admixed eosinophils, plasma cells, neutrophils
• Variable clinical presentation

Question 9

What are the different diseases that are classified under Langerhan’s Cell Histiocytosis and seperated by age groups and presentation?

Question 10

How can we identify Langerhan cells under electronmicroscope?

Answer 10

By the presence of Birbeck Granules.