Scientific Letter
Skin infiltration as a presenting sign of congenital leukaemia: presentation of two cases
Infiltración cutánea como manifestación de leucemia congénita: presentación de dos casos
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=> array:2 [ "paginaInicial" => "105" "paginaFinal" => "107" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Novedades para el diagnóstico de la toxoplasmosis ocular: uso de la tomografía de coherencia óptica" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 578 "Ancho" => 1500 "Tamanyo" => 65220 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A) OCT image. 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Contrary to the pattern in the rest of childhood, two thirds of cases correspond to acute myeloid leukaemia (AML). It typically presents with cytopaenia, hyperleukocytosis, hepatosplenomegaly and coagulopathy and, in up to 60 % of patients, cutaneous infiltration.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This article presents 2 cases of CL managed in our hospital.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first was an infant aged 2 months that had onset with fever and malaise. From the first month of life, the patient exhibited a purplish, elastic lump in the anterior fontanelle, with subsequent development of nodules in a generalised distribution. This was associated with pallor of the skin and mucosae, hepatosplenomegaly, respiratory failure and generalised hypertonia. The salient findings of blood tests were anaemia (4.4 g/dL), thrombocytopenia (66,000/mm<span class="elsevierStyleSup">3</span>), leucocytosis (38,440/mm<span class="elsevierStyleSup">3</span>) with atypia, elevation of lactate dehydrogenase (LDH) (2357 U/L) and hyperuricemia (7.49 mg/dL). The acute phase reactants were negative. The diagnosis of CD10-B-precursor acute lymphoblastic leukaemia (ALL) was confirmed by bone marrow aspiration. Fluorescence in situ hybridization (FISH) detected rearrangement of the <span class="elsevierStyleItalic">MLL</span> gene (11q23) with the t(10;11) translocation, and chromosome analysis revealed a normal 46 XX karyotype. The findings of cerebrospinal fluid (CSF) analysis, fundoscopy and transfontanellar ultrasound examination were normal. The patient received chemotherapy following the Interfant-99 protocol for the high-risk group and achieved complete remission after the induction phase with persistence of MLL+. After completing the consolidation phase, the patient underwent a pretransplantation evaluation that revealed bone marrow infiltration with 80 % of myeloid blasts (M0–M1), infiltration of the CSF and additional skin lesions. Molecular tests once again detected the t(10:11) translocation. Following cytoreductive chemotherapy (hydroxyurea, cytarabine and tioguanine), the patient was treated with intravenous fludarabine and intrathecal chemotherapy, achieving a second complete remission. Later on, the patient underwent haematopoietic stem cell transplantation (HSCT) of peripheral cord blood cells from a matched unrelated donor after conditioning with busulfan, cyclophosphamide, thiotepa and thymoglobulin. Full donor chimerism was not achieved and the patient experienced a second marrow relapse with a myeloid immune phenotype, which was treated with a FLAG-Ida regimen (idarubicin, fludarabine and cytarabine). The patient experienced recurrence of massive infiltration by lymphoid blasts during haematologic recovery, and died at age 12 months.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient was an infant aged 7 weeks that developed indurated purplish nodular lesions in the skin with a generalised distribution starting at 20 days of age (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), accompanied by pallor of the skin and mucosae and splenomegaly. The salient findings of blood tests were leucocytosis (32,910/mm<span class="elsevierStyleSup">3</span>) with atypia, anaemia (8.7 g/dL), thrombocytopenia (100,000/mm<span class="elsevierStyleSup">3</span>), elevation of LDH (661 U/L) and coagulopathy. Examination of a bone marrow aspiration sample revealed infiltration with 90 % of blasts with an immune phenotype compatible with M0 AML, and FISH revealed MLL rearrangement with no evidence of translocation. There was no central nervous system infiltration. The patient received chemotherapy following the St Jude AML 02 protocol, with resolution of the skin lesions on day 8 and complete full remission with a minimal residual disease of less than 0.1 % after the first cycle of ADE (cytarabine, etoposide, daunorubicin). After a second cycle of ADE, the patient, in first complete remission, underwent HSCT of αβ/CD19-depleted peripheral blood from a haploidentical donor (the mother). The patient had achieved complete chimerism at 30 days post transplantation, and the only complication she experienced was grade 3 acute cutaneous graft versus host disease, which has since resolved. The patient is in complete remission 15 months after the diagnosis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The incidence of CL is estimated at 1–5 cases per million live births. Approximately 65 % of cases are cases of AML compared to 35 % of cases of ALL.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Due to the immaturity of haematopoietic stem cells in these patients, co-expression of myeloid and lymphoid markers is frequent in the neonatal period, and so is lineage switch, as illustrated by the first case presented here. The diagnosis of CL also requires the presence of blasts in blood or bone marrow and extramedullary haematopoietic organs, ruling out other diseases such as leukemoid reactions or transient myeloproliferative disorder of Down syndrome.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">As observed in the presented cases, cutaneous infiltration in CL is characterised by the presence of erythematous, purple papules, plaques or nodules, usually with a generalised distribution. Due to its appearance, this rash is referred to as “blueberry muffin syndrome”, a term that can be applied to lesions of different aetiologies such as neuroblastoma metastases, Langerhans cell histiocytosis or leukemoid reactions caused by congenital infections or haemolytic anaemia, all of which must be included in the differential diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> In up to 10 % of cases, leukaemia cutis is the sole manifestation of disease, with no bone marrow infiltration.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Although cases of spontaneous resolution of CL have been described,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> cutaneous infiltration does not have an impact on the course of disease. In general, the survival of patients with CL is poor, with the most representative case series reporting survival rates of 25 % in patients with AML and up to 17 % in patients with ALL.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-08-10" "fechaAceptado" => "2019-03-25" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Hernández MC, Catalán MA, Angulo BM, Robleda AC, López LM. Infiltración cutánea como manifestación de leucemia congénita: presentación de dos casos. An Pediatr (Barc). 2020;92:106–108.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1030 "Ancho" => 1250 "Tamanyo" => 138717 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Nodular skin lesions.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of neonatal leukaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.H. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 14 | 8 | 22 |
| 2024 September | 54 | 31 | 85 |
| 2024 August | 80 | 39 | 119 |
| 2024 July | 104 | 40 | 144 |
| 2024 June | 88 | 30 | 118 |
| 2024 May | 69 | 52 | 121 |
| 2024 April | 51 | 32 | 83 |
| 2024 March | 50 | 23 | 73 |
| 2024 February | 55 | 23 | 78 |
| 2024 January | 58 | 21 | 79 |
| 2023 December | 99 | 23 | 122 |
| 2023 November | 91 | 55 | 146 |
| 2023 October | 59 | 23 | 82 |
| 2023 September | 52 | 35 | 87 |
| 2023 August | 53 | 24 | 77 |
| 2023 July | 51 | 22 | 73 |
| 2023 June | 54 | 40 | 94 |
| 2023 May | 92 | 15 | 107 |
| 2023 April | 64 | 26 | 90 |
| 2023 March | 101 | 43 | 144 |
| 2023 February | 85 | 40 | 125 |
| 2023 January | 93 | 49 | 142 |
| 2022 December | 90 | 42 | 132 |
| 2022 November | 126 | 37 | 163 |
| 2022 October | 121 | 61 | 182 |
| 2022 September | 93 | 46 | 139 |
| 2022 August | 89 | 59 | 148 |
| 2022 July | 90 | 62 | 152 |
| 2022 June | 86 | 41 | 127 |
| 2022 May | 98 | 43 | 141 |
| 2022 April | 135 | 45 | 180 |
| 2022 March | 142 | 62 | 204 |
| 2022 February | 117 | 24 | 141 |
| 2022 January | 142 | 40 | 182 |
| 2021 December | 106 | 47 | 153 |
| 2021 November | 107 | 42 | 149 |
| 2021 October | 145 | 78 | 223 |
| 2021 September | 92 | 40 | 132 |
| 2021 August | 116 | 26 | 142 |
| 2021 July | 137 | 26 | 163 |
| 2021 June | 109 | 34 | 143 |
| 2021 May | 109 | 34 | 143 |
| 2021 April | 204 | 62 | 266 |
| 2021 March | 107 | 29 | 136 |
| 2021 February | 43 | 32 | 75 |
| 2021 January | 59 | 20 | 79 |
| 2020 December | 56 | 16 | 72 |
| 2020 November | 52 | 18 | 70 |
| 2020 October | 73 | 12 | 85 |
| 2020 September | 39 | 17 | 56 |
| 2020 August | 51 | 18 | 69 |
| 2020 July | 61 | 17 | 78 |
| 2020 June | 59 | 8 | 67 |
| 2020 May | 53 | 12 | 65 |
| 2020 April | 30 | 6 | 36 |
| 2020 March | 44 | 18 | 62 |
| 2020 February | 50 | 29 | 79 |
| 2020 January | 13 | 3 | 16 |
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