Myeloid sarcoma

by Jason Wasserman MD PhD FRCPC
January 12, 2025

Myeloid sarcoma is a type of cancer that develops from a group of blood-forming cells called myeloid blasts. These cells normally grow and mature in the bone marrow, which is the spongy tissue inside our bones. In myeloid sarcoma, abnormal myeloid blasts form a mass or tumour outside the bone marrow. This tumour can grow in almost any body part, including the skin, lymph nodes, bones, and internal organs.

Myeloid sarcoma is closely linked to acute myeloid leukaemia (AML), a type of blood cancer. It often occurs at the same time as AML or as a sign that AML has returned after treatment. In rare cases, myeloid sarcoma can develop before AML is diagnosed.

What are the symptoms of myeloid sarcoma?

The symptoms of myeloid sarcoma can vary widely depending on where the tumour forms in the body. For example, a tumour in the skin might cause a lump or swelling, while a tumour in the digestive system could cause pain or difficulty eating.

Myeloid sarcoma is seen in 2–9% of people with AML and in 5–12% of people who have had a stem cell transplant. It often appears at the same time as AML or as a recurrence of AML after treatment. In rare cases, it can develop before AML is diagnosed. Myeloid sarcoma can also arise from other types of myeloid diseases, such as myelodysplastic syndromes or myeloproliferative neoplasms, which are disorders that affect blood cell production.

In very rare cases, myeloid sarcoma occurs on its own without any apparent involvement of the bone marrow. This condition, called de novo isolated myeloid sarcoma, happens in about 1% of people with AML.

What causes myeloid sarcoma?

Myeloid sarcoma is caused by changes in the genetic material (DNA) of myeloid cells. These changes cause the cells to grow uncontrollably and form tumours. Many of the same genetic changes are seen in AML, which is why the two conditions are closely related.

Chromosomal changes are found in about half of all cases of myeloid sarcoma. These changes include:

• A rearrangement called t(8;21) is more common in children and often affects the area around the eyes.
• A rearrangement called inv(16), which is often seen in tumours in the abdominal area.
• Other changes include extra copies of specific chromosomes (trisomy 4 and trisomy 8) or missing pieces of chromosomes (monosomy 7, deletions in chromosome 5q or 20q).

In addition to chromosomal changes, more advanced testing called next-generation sequencing has shown that myeloid sarcoma often has specific mutations in its DNA. Some of the most common mutations include:

• Changes in the NPM1 gene occur in about 20–30% of cases, especially those with monocytic features.
• Changes in the KMT2A gene are found in about 10% of cases.
• Mutations in genes involved in the RAS pathway (a cell signalling pathway) and genes related to tumour suppression and DNA repair.

These genetic changes can influence where the tumour grows and how it behaves.

How is this diagnosis made?

The diagnosis of myeloid sarcoma is usually made through a combination of clinical, microscopic, and laboratory tests. A biopsy is performed to collect a small tumour sample, which is then examined under a microscope. Pathologists look for features typical of myeloid sarcoma and may use special tests like immunohistochemistry and flow cytometry to confirm the diagnosis.

In addition, a bone marrow biopsy and blood tests are often done to determine if the tumour is associated with acute myeloid leukaemia (AML) or another related condition. These tests help identify abnormal myeloid cells in the bone marrow or blood, which can provide important information about the underlying disease.

What are the microscopic features of myeloid sarcoma?

Under the microscope, myeloid sarcoma is a mass of abnormal myeloid blasts. The tumour cells are medium to large and have pale or slightly pink cytoplasm. Their nuclei, which contain the genetic material, can be round, oval, or irregular, with fine chromatin and small nucleoli.

In tumours with monocytic features, the cells may form single-file patterns, and some may have folded nuclei called promonocytes. Tumours with granulocytic features may show cells with pink cytoplasm, called eosinophilic myelocytes and metamyelocytes. Rarely do myeloid sarcomas show features of other myeloid lineages, such as erythroid or megakaryocytic differentiation.

Immunophenotype

The immunophenotype describes the unique set of proteins expressed on the surface of the tumour cells, which helps pathologists identify the type of cancer. This is determined using two main techniques:

• Immunohistochemistry involves staining tumour tissue with antibodies that bind to specific proteins. Under the microscope, these stains allow pathologists to see which proteins are present in the tumour cells.
• Flow cytometry is a test that uses a laser to analyze the proteins on the surface of individual cells in a liquid sample. This method provides detailed information about the types of cells in the tumour.

In myeloid sarcoma, common proteins expressed include CD13, CD33, CD43, CD68, and myeloperoxidase. Some tumours also express CD45. Immature tumours may express CD34 and KIT (CD117), while more mature tumours show other markers like CD14, CD64, and CD163. Tumours can also show features of other cell types, such as B cells (CD19), T cells (CD4, CD7), or natural killer cells (CD56). Specialized stains can detect mutations in genes like NPM1 and IDH1, which help guide treatment.

Molecular tests

Molecular tests look for specific genetic changes in the tumour cells. These tests include:

• Next-generation sequencing (NGS) can identify mutations in genes like NPM1, FLT3, and IDH.
• Fluorescence in situ hybridization (FISH) is a method for detecting chromosomal rearrangements, such as t(8;21) or inv(16).

These tests provide valuable information about the tumour’s behaviour and can guide treatment decisions. For example, FLT3 mutations may indicate a need for targeted therapy.

What is the prognosis for a person diagnosed with myeloid sarcoma?

The treatment for myeloid sarcoma is often the same as for acute myeloid leukaemia (AML), with chemotherapy being the mainstay of therapy. Radiation therapy may also be used in some instances to shrink the tumour.

The prognosis depends on several factors, including whether the tumour is associated with AML and its genetic changes. People with isolated myeloid sarcoma (without AML) tend to have a better prognosis, especially if the tumour is located in the skin or head and neck. In some cases, long-term remission can be achieved. On the other hand, tumours with complex or discordant genetic changes may behave more aggressively.