The term congenital leukemia was originally applied to cases of leukemia that developed at birth, whereas neonatal and infantile leukemia were used to describe leukemia developing within the first 4 weeks of life or from 4 weeks to 1 year of life, respectively. However, commonly congenital leukemia is diagnosed from birth to 6 weeks of life. Patients with congenital leukemia fulfill the following diagnostic criteria1
: First, a finding of immature cell proliferation in myelomonocytic, lymphoid, or erythroid series; and second, infiltration of these cells into extrahematopoietic tissue. Third, the absence of any other disease that might cause leukemoid reactions mimicking congenital leukemia, such as, TORCH syndrome, hemolytic disease of the newborn (ABO or Rh incompatibility), hereditary spherocytosis, twin-twin transfusion, other neoplastic infiltrates (metastatic neuroblastoma, rhabdomyosarcoma, Langerhans cell histiocytosis) and the absence of Down's syndrome or cytogenetic abnormalities of chromosome 21 with a transient abnormal myeloproliferative disorder. The majority of cases of congenital leukemia are of the myelogenous type, and the notable more common varieties of congenital leukemia are the myelomonocytic (M4) or monocytic (M5) FAB subtypes, and rarely the lymphoblastic subtypes7,8
Congenital leukemia is often associated with pallor, lethargy, hepatosplenomegaly, leukemia cutis, anemia, and leukocytosis. Leukemia cutis occurs in approximately 10% of adults with AML and in 1% of those with acute lymphoblastic leukemia (ALL)9
. On the other hand, it has been documented to occur in 25~30% of patients with congenital leukemia5,6
. According to the FAB system, most cases of congenital leukemia cutis are of the M5 subtypes8
. Congenital leukemia cutis has been reported in 11 cases in Korea10-12
, and of these, 6 were diagnosed by bone marrow biopsy. According to the FAB system, one of the six was M3, another was M4, and the others were M5. Our case was also M5, and thus, we believe that M5 is likely to be the most common type in Korea. The specific clinical morphology of leukemia cutis in congenital leukemia has been reported to be variable. However, the predominant morphology is of red to purple colored dermal nodules, though some reports mention additional tumors, papules, and macules. Lesions are typically multiple with a generalized distributed pattern. Involvements of the oral and ocular mucosa are quite rare.
The causes of congenital leukemia are unknown, but it has been associated with maternal exposure to radiation, maternal dietary exposure to bioflavonoid, maternal use of tobacco and illicit drugs, and inherited conditions, such as, Down's syndrome, neurofibromatosis, Bloom's syndrome, and Fanconi's anemia13
. Chromosomal instability is a hallmark of congenital leukemia, and the most common karyotypic abnormality involves the myeloid-lineage leukemia gene at the 11q23 translocation breakpoint7,14
. However, this translocation can involve several different chromosomal partners, such as, 4, 9 and 191
. Evaluations of infants suspected of having leukemia cutis should include skin biopsy, serology, peripheral smear, bone marrow aspirate, and cytogenetics1
, and the differential diagnosis should include congenital infections (rubella, Coxsackie's virus, CMV, and toxoplasmosis), hemolytic disease, transient myeloproliferative disorder and other infiltrative cutaneous processes, such as, metastatic neuroblastoma, malignant histiocytosis, and Langerhans cell histiocytosis15
Histopathologic analysis of leukemia cutis lesions may reveal different patterns of infiltration16
. Most commonly, a dense diffuse dermal infiltrate of pleomorphic leukemic cells is observed in a linearly array between collagen bundles in the reticular dermis. Some, band-like or compact nodular infiltrates may also be seen. These infiltrates show extension into the subcutis in most cases, but rarely infiltrate the epidermis. Malignant myeloid cells are the dominant cell type of acute myeloid leukemia cutis and tend to appear monotonous and homogeneous cytologically. Nuclei are round to oval, chromatin is likely to be evenly dispersed, and nucleoli are multiple but potentially inconspicuous. Despite these suggestive histological characteristics, histochemistry and immunohistochemistry are generally required for confirmation, in addition to examinations of peripheral blood and bone marrow.
Congenital leukemia has a poor prognosis with an overall survival rate of only 20% at 2 years of age6,7
. However, unlike leukemia cutis in adults, which confers a poor prognosis for 90% patients with extramedullary involvements, cutaneous involvement in congenital leukemia does not uniformly portend a poor prognosis17
, and a few reported patients have undergone spontaneous remissions of congenital AML without chemotherapeutic intervention1,18,19
. On the other hand, aggressive chemotherapy and bone marrow transplantation can result in high morbidity and mortality rates1
We report a male neonate born with congenital acute myeloid leukemia who presented with leukemia cutis. This case displayed highly aggressive skin infiltration with widespread dusky red papules to nodules from birth and a very poor prognosis.