The characteristic clinical presentation of all subtypes in the neonatal period is leukemia cutis and hepatosplenomegaly, with a majority of patients also demonstrating hyperleukocytosis and evidence of meningeal involvement. When leukemias present later in infancy, signs and symptoms are often less specific and include low-grade fever, pallor, lethargy, hepatosplenomegaly, bleeding diathesis, diarrhea, or failure to thrive. The prognosis of neonatal / infant leukemia is generally bleak, with or without chemotherapy.
C95.90 – Leukemia, unspecified not having achieved remission
93143009 – Leukemia, disease
- Transient myeloproliferative disorder (TMD) (synonyms: transient leukemia, transient abnormal myelopoiesis, transient congenital leukemia) – This condition is universally associated with Down syndrome. It is clinically and morphologically indistinguishable from leukemia, except that the disorder spontaneously remits within the first months of life. TMD is associated with significant morbidity, and as many as 30% of affected individuals will develop a subsequent leukemia, most commonly AMKL.
- Congenital infections due to toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus (HSV), or syphilis – These infections may show dermal erythropoiesis, leukocytosis, and circulating immature leukocytes but are differentiated from leukemia on the basis of normal bone marrow examination and immunohistochemical findings, positive serologies for specific infectious agents, as well as clinical findings such as intrauterine growth retardation, microcephaly, and hepatitis.
- Hemolytic disease of the newborn (Rh and ABO incompatibility) – When severe, affected neonates show hepatosplenomegaly, dermal erythropoiesis, numerous erythroblasts on peripheral smear, and even thrombocytopenia. Demonstration of Rh or ABO incompatibility with a direct antibody test or indirect Coombs test is necessary.
- Neuroblastoma, stage IV-A – This condition may show hepatosplenomegaly and cutaneous nodules, but peripheral counts are typically normal and bone marrow aspiration shows characteristic neuroblastoma cells.
- Congenital HIV
- Congenital Langerhans cell histiocytosis
- Juvenile xanthogranuloma