In the United States, the incidence of ALL is about 30 cases per million persons less than 20 years of age. The peak incidence occurs between the ages of 3 and 5 years. There is a slightly higher incidence in boys than in girls.³ Approximately 80% to 85% of cases are B-ALL and 10% to 15%⁴ are T-ALL.

Although several genetic factors, including Down syndrome, are associated with increased risk of ALL,³ most patients have no recognized inheritable factors. Genome-wide association studies have identified polymorphic variants in several genes (including ARID5B, CEBPE, GATA3, and IKZF1) that are associated with an increased risk of ALL or specific ALL subtypes.^5,6 Rare germline mutations in PAX5⁷ and ETV6⁸ are linked to familial ALL.⁴

It is estimated that approximately 5% of B-ALL cases will have associated cutaneous dissemination. Nearly 50 to 60 cases of B-ALL have been reported in children with skin involvement.^9,10,11,12 The frequency of cutaneous involvement in T-ALL is less well documented. However, Lee et al. reported an incidence of 4.3% in T-ALL and 15% in B-ALL.¹³ Approximately 33% of patients with the lymphomatous variants had cutaneous involvement, and only 1% in those with leukemic presentations. Cutaneous involvement by ALL presents as solitary (71%) or multiple, firm, painless, and erythematous to bluish nodules with overlying telangiectasia. The lesions present typically in the head and neck (the scalp is the most common location), and sometimes in the trunk.^14,15 They range in size from 1 to 8 cm.¹⁶ Millot et al.¹⁷ revealed cutaneous extension in 24 patients with ALL (n = 1,359 children). In their study, 62% of patients had cutaneous lesions preceding the diagnosis of ALL. Multiple lesions were associated with high-risk ALL. Cutaneous aleukemic variants of ALL have been described,^{18,19,20,21,22,23} including the presence of isolated forms confined to the skin without progression to systemic disease.^{16,17,18,19,20,21,22,23,24}

Rare cutaneous presentations include generalized purpuric maculopapular eruption in association with T-ALL,^25,26 limited involvement in the breasts and skin in T-ALL,^21,27 facial nerve palsy,²⁸ numb chin syndrome in B-ALL,²⁹ a nodule at a site of a catheter insertion on a patient with a previous diagnosis of B-ALL,³⁰ and intraocular and cutaneous lesions.³¹ Some cases of ALL with associated leukemia cutis could be congenital in nature.³²

The patient’s age and initial white blood cell (WBC) count are predictive of outcome, with older age or a higher WBC count portending a worse prognosis. The current consensus defines “standard risk” (age 1 to 9.99 years and initial WBC < 50,000/mm³) and “high-risk” (age > 10, initial WBC > 50,000/mm³, or both) ALL subgroups comprising, respectively, two-thirds and one-third of children with B-ALL.³ Supradiaphragmatic lymphadenopathy and involvement of the central nervous system and testis are also common. T-ALL patients, compared to those with B-ALL, are younger and have a higher rate of mediastinal tumors and bone marrow involvement. Patients are usually males in their teens to twenties and present with lymphadenopathy in cervical, supraclavicular, and axillary regions (50%), or with a mediastinal mass (50% to 75%). In most patients, the mediastinal mass is anterior, bulky, and associated with pleural effusions, superior vena cava syndrome, tracheal obstruction, and pericardial effusions. Bone pain is also typical in cases with bone marrow involvement.

The prognosis in ALL has changed substantially over the last 30 to 40 years. With contemporary systemic chemotherapeutic regimens and the use of craniospinal or cranial irradiation and intrathecal chemotherapy,³ the overall survival rates are 90% at 5 years.