What is Leukemia Cutis?
Leukemia cutis is a condition where cancerous white blood cells, known as neoplastic leukocytes, infiltrate the skin. This accumulation of leukemia cells outside of the bone marrow is usually referred to as myeloid sarcoma. ‘Leukemia cutis’ is a general term used to describe cases where the disease specifically affects the skin. While any kind of leukemia can impact the skin, the types most often seen by doctors are chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), which can have either a ‘monocytic’ or ‘myelomonocytic’ form.
It’s quite uncommon to see skin symptoms in patients with chronic myeloid leukemia (CML), and if they do appear, it could signal an advanced stage of the disease known as the ‘blast phase’. Typically, patients already have a prior diagnosis of leukemia or a condition called myelodysplasia which affects the production of blood cells. However, in rare cases, the lesions, or abnormal changes in the skin, might be the first noticeable sign of the disease. If a patient has skin symptoms, this generally indicates that the disease is advanced and doctors will likely inspect other parts of the body for signs of the disease being present elsewhere.
Leukemia types that can potentially affect the skin are divided into two categories:
Myeloid or monocytic disorders, which include:
- Acute myeloid leukemia (monocytic or myelomonocytic) (AML)
- Chronic myeloid leukemia
- Chronic myelomonocytic leukemia (transformation)
- Myelodysplastic syndrome (transformation)
And lymphoproliferative disorders, or disorders in which lymphocytes (a type of white blood cell) are produced in excessive amounts, including:
- B-cell leukemias/lymphomas, such as:
- Precursor B-cell acute lymphoblastic leukemia
- Chronic lymphocytic leukemia (CLL)
- Hairy cell leukemia
- T-cell leukemias/lymphomas, like:
- Precursor T-cell acute lymphoblastic leukemia
- Adult T-cell leukemia/lymphoma (ATLL)
- T-cell prolymphocytic leukemia
What Causes Leukemia Cutis?
Leukemia, including a specific type called leukemia cutis, is caused by a combination of both genetic and environmental factors. These factors can cause early blood cells to stop developing properly and multiply uncontrollably.
The abnormal cancer cells in leukemia possess certain genetic changes. Some of the most noticeable changes in people with leukemia cutis involve certain chromosomes, such as chromosome 8, and specific rearrangements of chromosomes known as translocations.
Additionally, there are environmental risk factors that are the same for both leukemia cutis and other types of leukemia. These include exposure to benzene, ionizing radiation, substances called alkylating agents, and certain viruses. Moreover, the use of a specific drug, all-trans retinoic acid (ATRA), to treat a type of leukemia called acute promyelocytic leukemia might increase the risk of the disease spreading to other parts of the body, including the skin.
Risk Factors and Frequency for Leukemia Cutis
Leukemia cutis, a rare condition, is often seen in children with congenital leukemia, accounting for 25% to 30% of cases. Even though it is most prevalent in patients with an adult form of blood cancer called T-cell leukemia/lymphoma, this type of leukemia itself is quite rare. As such, the types most frequently seen in doctors’ offices are AML and CLL, making up 13% and 8% of all cases, respectively.
- Most skin lesions from leukemia cutis occur in patients who already have been diagnosed with leukemia, making up 55% to 77% of cases.
- About 23% to 44% of the time, these skin lesions are the first sign of systemic leukemia.
- In 2% to 3% of cases, patients may develop these skin lesions before the leukemia shows up in blood or bone marrow tests, a condition known as “aleukemic” cutis.
- These patients with “aleukemic” cutis eventually develop AML.
Signs and Symptoms of Leukemia Cutis
Leukemia cutis, a skin condition linked to leukemia, manifests a wide range of signs. The associated skin changes can be localized or widespread and present anywhere on the body, including isolated appearances or in combination. The condition may also show up as a widespread rash called “blueberry muffin syndrome” in infants.
Potential signs of Leukemia cutis include:
- Bumps and nodules (~60% of cases), which feel firm or rubber-like
- Flat, clearly defined patches known as plaques
More unusual signs can also occur, with various appearances and transitions between different types. These may include:
- Redness of the skin (Erythema)
- Widespread redness covering most of the body (Erythroderma)
- Skin sores (Ulcers)
- Fluid-filled bumps (Blisters)
- Variations in color, including red, brown, yellow, blue, gray, and purplish patches
- Blood spots beneath the skin (Purpura)
- Deep lesions, which may be the same color as the skin
The distribution of the skin changes in Leukemia cutis varies. They can appear anywhere on the body including the head, trunk, and limbs with no favored spots. They may occur as single spots, in groups, or spread widely over the body.
The oral mucosa can also be affected by Leukemia cutis, leading to
- Swelling of the gums (Gingival hyperplasia)
- Nodules or ulcers in the mouth
Testing for Leukemia Cutis
Diagnosing leukemia cutis, a condition where leukemia cells are found in the skin, can be quite challenging if you don’t already have a confirmed case of systemic leukemia (leukemia in the whole body). To correctly diagnose this condition, doctors have to carefully consider your symptoms, tissue examination results (histopathology), and the types of cells or proteins present (immunophenotyping).
Some tests your doctor might conduct include a complete blood count and a look at your peripheral smear. These tests look for abnormalities in your cell counts and check if there are circulating leukemia cells in your blood. If systemic leukemia is suspected, a bone marrow biopsy will be absolutely necessary for a definitive diagnosis. In addition to staining tests (immunohistochemistry), your biopsy samples should undergo tests to study the structure of chromosomes (cytogenetics) and measure the number of cells present and their characteristics (flow cytometry).
A skin biopsy and immunophenotyping should be done for all suspected patients, no matter if they have a history of leukemia or not. The reason being, transformations or developments of a different kind of leukemia may occur. Identification of the type of leukemia can be done based on marker (CD) proteins. Common CD proteins associated with each type of leukemia are outlined in table 1.
Some other tests you may need to take include coagulation studies (how your blood clots), a complete metabolic profile (how your body is functioning), liver and kidney function tests (to check how well these organs are working), uric acid, and lactate dehydrogenase tests. If you experience high, unrelenting fevers, especially while under treatment, an infectious disease examination might be necessary. People with leukemia cutis are more prone to infections due to an impaired immune system.
It’s very important to check if leukemia has spread to other parts of the body. Imaging tests like CTs, MRIs, or ultrasounds can assist in determining how extensive the disease is within the body.
Treatment Options for Leukemia Cutis
Leukemia cutis, a condition where leukemia cells invade the skin, is typically treated by addressing the underlying leukemia itself. This is often done via powerful systemic chemotherapy, a treatment which uses drugs to destroy cancer cells throughout the body. The type of chemotherapy used depends on the specific subtype of leukemia a patient has. It’s common for abnormalities in the blood to start improving at the same time as the skin lesions caused by leukemia cutis.
While chemotherapy is often the main method of treating leukemia cutis, in some cases radiation therapy may be used. This can be especially helpful for stubborn cases that don’t respond to other treatments, or in circumstances where the aim of treatment is to provide relief from symptoms rather than cure the disease. One specific type of radiation therapy that might be used is electron beam therapy.
What else can Leukemia Cutis be?
Leukemia cutis, a skin condition associated with leukemia, can be tricky to diagnose as many other skin issues resemble it, both in appearance and under microscopic examination. This means that doctors have to consider several other conditions when trying to diagnose leukemia cutis.
Some health conditions can appear similar to those caused by leukemia cutis. It’s also important to remember that this is not a complete list, and these conditions could also occur along with leukemia cutis:
- Lymphoma and pseudolymphoma
- Metastatic solid tumors
- Pyoderma gangrenosum (a rare skin condition causing large ulcers)
- Vasculitis (inflammation of blood vessels)
- Drug reactions
- Urticaria (hives)
- Viral exanthem (rash caused by viral infections)
- Hidradenitis (a chronic skin inflammation usually located around sweat glands)
- Erythema multiforme (skin disorder resulting from an allergic reaction or viral infection)
- Erythema nodosum (a skin condition causing red, painful lumps)
- Infections due to weakened immune system: cellulitis, herpes zoster (shingles), herpes simplex (cold sores or genital herpes)
- Graft vs. host disease (a complication that can occur after a bone marrow transplant)
What to expect with Leukemia Cutis
Leukemia cutis, a condition where leukemia shows up on the skin, is often considered a sign that the leukemia is affecting the whole body and it generally indicates a poor outlook. While some people may find that skin lesions disappear after undergoing systemic chemotherapy, having leukemia cutis is often linked with leukemia affecting other parts of the body outside the bone marrow. The most common place for it to spread to is the protective layers around the brain and spinal cord, known as the meninges, with the occurrence being about 40%.
A follow-up study conducted over two years on patients with a type of leukemia called Acute Myeloid Leukemia (AML), showed that the survival rate was 6% for those who had skin involvement, compared to 30% for those who did not have leukemia involving the skin.
Possible Complications When Diagnosed with Leukemia Cutis
The complications experienced by leukemia patients often stem from the disease itself or the treatments, rather than being due to the skin lesions that potentially develop.
- Leukemia patients are subject to a wide range of opportunistic infections due to pancytopenia, a condition that lowers their blood cell counts.
- Bleeding occurs either as a result of thrombocytopenia, which is a deficiency of platelets in the blood, or due to the erosion of skin lesions.
- Patients may also experience reactions to chemotherapy treatments.
- Leukemia cutis, a specific type of skin lesion associated with leukemia, can cause a mass effect if it forms a tumor.
