Congenital aleukemic leukemia cutis mimicking infantile hemangioma

Dear Editors, Leukemia cutis is a rare manifestation of hematologic neoplasms, characterized by skin infiltration by neoplastic leukemic cells.1 It may occur in myeloid or lymphoid leukemias, both in acute and chronic forms in 3 to 30 % of cases.1, 2 Clinically, it presents as erythematous nodules, papules, or plaques, but may also appear less commonly as macules, ulcers, or blisters.2, 3 An even rarer variant is aleukemic leukemia cutis, defined as cutaneous infiltration without evidence of circulating blasts in peripheral blood or bone marrow.2, 3 This presentation may precede systemic leukemia by several months, representing a diagnostic challenge.1-3 In the pediatric context, congenital leukemia is defined as leukemia present at birth or manifesting within the first weeks of life, and especially when limited to the skin, can be misdiagnosed as infantile hemangiomas or other benign vascular anomalies. We report the case of a male infant, 2-months old, who presented with an erythematous macule on the right malar region, first noticed 20 days earlier, initially diagnosed as an infantile hemangioma. At four months of age, infiltrated nodules appeared on the forehead and feet, in addition to a macule in the diaper area, prompting a histological examination (Figure 1). Histopathology revealed a diffuse infiltrate throughout the dermis, composed of atypical mononuclear cells, and immunohistochemistry showed positivity for Ki67, CD43, CD68, and negativity for CD20, CD3, CD34, and myeloperoxidase, consistent with acute myeloid leukemia infiltration (Figure 2). The patient was referred to Pediatric Oncology. Complete blood count, chest CT, bone marrow aspirate, and cerebrospinal fluid examination were unremarkable. Bone marrow immunophenotyping for hematologic neoplasia showed no phenotypic changes compatible with acute leukemia infiltration, establishing the diagnosis of congenital aleukemic leukemia cutis. He achieved complete regression of skin lesions after the first chemotherapy cycle, with normal follow-up exams. At four years old, on oncology follow-up, he developed CNS and abdominal leukemic infiltration, with no cutaneous relapse, and passed away six months later due to disease progression. Leukemia cutis occurs more frequently in AML, mainly acute myelomonocytic and monocytic leukemia.1 Prognosis is variable, with reports ranging from poor outcomes to spontaneous resolution. In general, treatment follows acute leukemia protocols.4 Congenital leukemia cutis may mimic infantile hemangiomas, posing a significant diagnostic challenge at initial evaluation.4 Some physical examination findings may aid in distinction: leukemia cutis lesions tend to be more infiltrated on palpation, may present with petechiae or purpuric macules, and follow a different clinical course, whereas infantile hemangiomas usually exhibit a predictable pattern of growth and involution.4 The reason why, in aleukemic leukemia cutis, malignant leukemic cells may be detected in the skin before becoming apparent in the peripheral blood or bone marrow likely involves multiple, non–mutually exclusive mechanisms. Emerging evidence suggests that the skin may act as a permissive microenvironment for early leukemic cell homing and local expansion, supported by mesenchymal niches and mediated by skin-tropic chemokine receptors and adhesion molecules, thereby facilitating selective migration and retention of leukemic cells within the skin prior to overt systemic dissemination.5, 6 Concurrently, bone marrow involvement may be focal or display a patchy distribution, potentially escaping detection by conventional bone marrow biopsies that sample limited regions, such as the posterior iliac crest.7 These factors may collectively explain the aleukemic presentation observed in some cases, including the present case. This case highlights the diagnostic difficulty of aleukemic leukemia cutis. Clinical evolution, absence of blasts in peripheral blood and bone marrow, together with histopathological and immunohistochemical confirmation, allowed the diagnosis to be established. The outcome underscores both the importance of early recognition and the potential aggressive nature of the disease. None.