Leukemia cutis is the infiltration of

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

s or their precursors into the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

resulting in clinically identifiable cutaneous lesions. This condition may be contrasted with leukemids, which are skin lesions that occur with leukemia, but which are not related to leukemic cell infiltration. Leukemia cutis can occur in most forms of

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

, including

chronic myeloid leukemia Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumula ...

acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympt ...

, and prolymphocytic leukemia. Aleukemic leukemia cutis occurs when cancerous

white blood cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

penetrate the skin before they are detected in the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

or peripheral circulation.

Signs and symptoms

The clinical appearance of leukemia cutis varies, with the most common lesions being

erythematous Erythema (, ) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology incl ...

to violaceous

papules A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some ...

nodules Nodule may refer to: *Nodule (geology), a small rock or mineral cluster *Manganese nodule, a metallic concretion found on the seafloor *Nodule (medicine), a small aggregation of cells *Root nodule Root nodules are found on the roots of plants, p ...

(60%), followed by infiltrating plaques, generalized cutaneous eruption, and

erythroderma Erythroderma is an inflammatory skin disease with erythema, redness and scaling that affects nearly the entire cutaneous surface.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. p. 436. . This te ...

. Oftentimes, they have no symptoms. Usually having a solid or rubbery consistency, the

might turn

purpuric Purpura () is a condition of red or purple discolored spots on the skin that do not Blanch (medical), blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagul ...

in patients who are

thrombocytopenic In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coa ...

. Unusual presentations include those that resemble

ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...

stasis dermatitis Stasis dermatitis refers to the skin changes that occur in the leg as a result of "stasis" or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins. Insuffi ...

guttate psoriasis Guttate psoriasis (also known as eruptive psoriasis) is a type of psoriasis that presents as small (0.5–1.5 cm in diameter) lesions over the upper trunk and proximal extremities; it is found frequently in young adults. The term " guttate" ...

, and figurate erythemas. Leukemia cutis has also been reported to localize to injuries, intravenous catheters,

herpes Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herp ...

lesions, and recent surgical procedures.

Causes

Leukemia cutis may develop concurrently with the diagnosis of systemic

, come first, or come later. Most cases of leukemia cutis occur in the context of an existing

(44–77%) or at the time of systemic

presentation (23–44%). On rare occasions, leukemia cutis may occur before

in the

or peripheral blood becomes observable. Leukemia cutis is linked to a number of gene abnormalities, such as

chromosome 8 Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 146 million base pairs (the building material of DNA) and represents between 4.5 and 5.0% of the total DNA i ...

numerical anomalies, translocation (8; 21) (q22; q22), and inversion (16) (p13; q22).

Mechanism

Leukemic skin involvement's pathogenic mechanism is poorly understood. Nonetheless, it's thought that

chemokine receptors Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7-transm ...

adhesion molecules Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

, and the genetic features of

all have an impact.

Adhesion molecules Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

, specifically

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...

, may have a role in the migration of leukemic cells into the skin through processes known as skin-selective homing.

and

may also have significant effects. On the dermal post-capillary venules, TARC (thymus- and activation-regulated chemokine)/

CCL17 CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an im ...

(CC chemokine ligand 17) and/or

E-selectin E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endotheli ...

may interact with the cutaneous leucocyte-associated antigen (CLA) receptor and CC chemokine receptor 4 (

CCR4 C-C chemokine receptor type 4 is a protein that in humans is encoded by the ''CCR4'' gene. CCR4 has also been designated CD194 ( cluster of differentiation 194). The protein encoded by this gene belongs to the G protein-coupled receptor family. ...

) on the leukemic cells. Leukemic cell migration and binding into the

dermis The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...

may be facilitated by this process. Additionally,

integrins Integrins are transmembrane receptors that help cell–cell and cell– extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

and endothelial-bound

chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

may interact to promote leukemic cell migration into the dermis.

Diagnosis

Leukemia cutis is diagnosed by looking at the morphologic pattern of skin infiltration, cytologic characteristics, and most importantly the tumor cells'

immunophenotype Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose. This can be done on tissue section (fresh or fixed tissue), cell suspensio ...

. The diagnosis is frequently confirmed by correlation with peripheral blood and

results as well as clinical data.

Treatment

Leukemia cutis is a localized symptom of a systemic underlying disease that requires systemic therapy tailored to the individual subtype of

. Hematologic remission typically happens in tandem with a full or partial response to cutaneous infiltrations in the majority of individuals. Local

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

, however, may be employed in patients with resistant leukemia cutis or recurrent skin infiltration. The treatment of refractory cutaneous leukemia has led to the proposal of simultaneous integrated boost with helical arc radiotherapy of total skin (HEARTS) for cutaneous symptoms.

Outlook

The prognosis is poor, with many patients suffering from additional extramedullary diseases and low survival rates. Most patients pass away months after being diagnosed. Patients without skin lesions who have

acute myelogenous leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...

had a 30% survival rate after two years, but those with skin lesions have a 6% survival rate, which indicates an unfavorable prognosis for leukemia cutis.

Epidemiology

Leukemia cutis can occur anywhere between 2% and 30% of the time, depending on the underlying

diagnosis.

References

External links

DermNet

StatPearls
{{Lymphoid malignancy Lymphoid-related cutaneous conditions