Leukemia is a cancer of myelogenous and lymphatic precursor blood-forming cells. These leukemic blast cells develop in the bone marrow and spread into the circulation. Several types of leukemia are based on whether the disease is acute or chronic, and whether it involves myeloid cells or lymphoid cells. According to the Surveillance, Epidemiology, and End Results (SEER) Program database, the estimated number of new cases of leukemia in the United States in 2022 is 60,650, or 5 3.2% of all new cancers. Of these, the estimated number of tumor-related deaths will be 24,000. The age-adjusted incidence is 12.9/100,000 population.¹

Peripheral circulating leukemic cells possess the ability to leave the circulation and pass through soft tissues as a cellular infiltration, resulting in extramedullary leukemia. Myeloid sarcoma (MS), also known as chloroma or granulocytic sarcoma, is an extramedullary form of acute myeloid leukemia (AML) that can infiltrate soft tissues, bone, periosteum, and lymph nodes.²,³,⁴,⁵ Because several variants of AML are not of granulocytic lineage, the term myeloid sarcoma is preferred over granulocytic sarcoma.⁶ When the infiltration of neoplastic leukocytes is limited to the epidermis, dermis, and subcutis, and when this results in clinical cutaneous lesions, it is often referred to as leukemia cutis (LC). The latter is mostly seen with AML and acute lymphocytic leukemia (ALL), where it can occur in up to 10% of cases, but it can also be seen less commonly with other leukemia subtypes. In pediatric patients with acute leukemia, Russo et al identified specific orbital and ocular lesions (papilledema, Roth spots, leukemic hypopyon, optic nerve infiltration, exophthalmos, optic pallor, retinal infiltration, vitreal opacities) in 16.1% of 180 patients.⁷ Orbital and ocular lesions occurred in 66.6% (10/15) of children with AML and 11.5% (19/159) with ALL.⁷ The eyelid skin is very thin, and it has been suggested that this may predispose the patient to leukemic infiltrates.⁸ Cutaneous infiltrates may develop during therapy for systemic leukemia or may signify relapse. Rarely, extramedullary cutaneous MS by a leukemic infiltrate may be the initial manifestation of disease, where it occurs in the absence of peripheral blood or bone marrow involvement by leukemia, a condition referred to as aleukemic leukemia.⁹ Approximately one-third of patients with adult MS are cases of de novo aleukemic disease, with the skin being the most common site of involvement.¹⁰,¹¹

In the periorbital region, the orbit is the most common site for MS, followed in frequency by the conjunctiva and eyelid.¹²,¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸ It has been suggested that the higher frequency of cutaneous lesions in AML is a reflection of the more aggressive behavior of AML.¹⁹ Bilaterality is reported in about 10% of cases. Many of the reported cases of orbital, conjunctival, or eyelid MS are lesions presenting as the initial manifestation of the disease, preceding the development of systemic leukemia.⁶

MS is reported in 2.5% to 21.2% of patients with AML²⁰,²¹ and can occur before, concurrent with, or following the onset of systemic bone marrow leukemia. Isolated MS may occur in the absence of leukemia, and these patients are often misdiagnosed with lymphoma.²²,²³ MS can also develop during a relapse or after allogeneic hematopoietic cell transplantation.²⁴,²⁵

LC is much less common than MS, occurring in about 3% of patients with AML,²⁶ and is even less frequent in chronic leukemias.²⁷ Certain subtypes of AML are more commonly associated with skin infiltration, the most frequent associations being with acute myelomonocytic and monocytic differentiation with involvement in up to 50% of patients.²⁶,²⁸,²⁹ The incidence of LC may be higher in children, particularly infants with myeloid leukemia.³⁰

Leukemia is a cancer of myelogenous and lymphatic precursor blood-forming cells. In most patients, LC occurs after a diagnosis of leukemia has been established.³¹ However, LC can develop before the onset of systemic leukemia, and most of these patients eventually will develop AML. The cutaneous lesions produced by different leukemia subtypes may
develop distinctly different morphologies over the course of the disease.¹⁹,³² The most commonly involved anatomic locations are the lower extremities, followed by the upper extremities, back, trunk, and face.³³ Interestingly, LC may have a predilection for sites of previous or current inflammation.³⁴