Case and Research Letter
Indeterminate Cell Histiocytosis in Children: A Case Report
Histiocitosis de células indeterminadas en edad pediátrica: a propósito de un caso
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Sahuquillo-Torralba, M.A. Navarro-Mira, M. Llavador-Ros, R. Botella-Estrada" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Sahuquillo-Torralba" "email" => array:1 [ 0 => "saucodos@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.A." "apellidos" => "Navarro-Mira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Llavador-Ros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Botella-Estrada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitari i Politécnic La Fe, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitari i Politécnic La Fe, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Histiocitosis de células indeterminadas en edad pediátrica: a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1200 "Ancho" => 1600 "Tamanyo" => 618007 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ulcerated epidermis with a nodular superficial and deep dermal infiltrate, with a predominance of mononuclear histiocytes accompanied by lymphocytes and eosinophils. A, Hematoxylin and eosin (H&E), original magnification<span class="elsevierStyleHsp" style=""></span>×40. B, H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×100; C, H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×200; D, Detail of a nodule. H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×400.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Indeterminate cell histiocytosis (ICH) is a rare disease characterized by a proliferation of histiocytes with a mixed immunohistochemical phenotype between Langerhans cells and non-Langerhans histiocytes. The behavior of the disease varies from exclusively cutaneous forms with a chronic benign or self-resolving clinical course to fulminant acute systemic forms.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a girl aged 16 months, with no personal or family history of interest. She was seen in outpatients for facial lesions that had appearance rapidly 15 days earlier and had not improved with amoxicillin–clavulanic acid, which was prescribed by her health area pediatrician because of the sudden onset of the condition. No manifestations of any associated disease were detected in the medical history. Physical examination revealed multiple erythematous-orange papules with an erythematous halo, some showing pseudovesiculation, umbilication, and the formation of a central scab (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The lesions mainly affected the face and there were no palpable lymph nodes. A smear was taken from the lesions for direct microscopy, microbiological culture, and polymerase chain reaction for varicella-zoster virus and coxsackieviruses. The results were normal or negative. A week later, all the lesions persisted in their papular phase, with the additional appearance of yellow-orange papules on the forearms and root of the limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, B and C). The patient remained in a good general state of health. With a suspected diagnosis of benign cephalic, generalized eruptive, or Langerhans cell histiocytosis (LCH), skin biopsy was taken from a lesion on the right forearm. Histology revealed an ulcerated epidermis with an infiltrate formed mainly of mononuclear and histiocytoid cells, accompanied by lymphocytes and occasional eosinophils, affecting the papillary dermis and deep dermis, where histiocytic nodules were observed (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Immunohistochemistry was intensely and diffusely positive for CD1a both in the epidermis and in the dermal nodules, with clear and intense but more scattered positivity for CD68 and S100 in the epidermis, interstitial dermis, and in the histiocytic nodules. In contrast, langerin (CD207) was positive in the epidermal control sample, and very focally, practically negative, in the interstitial dermis and dermal nodules. Based on these findings we made a diagnosis of ICH (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The workup was completed with blood biochemistry, complete blood count, plasma osmolarity, and urinary sediment, together with abdominal ultrasound, and x-rays of the chest, cranial vault, and vertebral column. The additional tests were within normal limits. After 2 months of follow-up, and on treatment with only topical methylprednisolone, the facial lesions started to resolve. However, bullous lesions appeared on the forearms and hands (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D), obliging us to start systemic corticosteroid treatment, which achieved good control of the new lesions. At the time of writing, no systemic complications have developed, but the patient has required a low maintenance dose of oral corticosteroids to prevent outbreaks of vesicular-bullous lesions on the trunk and limbs, and periodic follow-up has been continued due to the possibility of developing associated hematologic tumors or extracutaneous, multiorgan forms of her disease.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The histiocytoses are a heterogeneous group of disorders whose common feature is an excessive proliferation of histiocytes. They are traditionally classified according to their immunohistochemical phenotype as LCH (CD1a<span class="elsevierStyleSup">+</span>, S100<span class="elsevierStyleSup">+</span>, langerin<span class="elsevierStyleSup">+</span>, and CD68<span class="elsevierStyleSup">−</span>) and non-LCH (CD68<span class="elsevierStyleSup">+</span>, CD1a<span class="elsevierStyleSup">−</span>, S100<span class="elsevierStyleSup">−</span>, langerin<span class="elsevierStyleSup">−</span> and factor XIIIa<span class="elsevierStyleSup">±</span>). ICH is a rare group within this spectrum of histiocytoses, with markers of the 2 main groups, that is, CD1a<span class="elsevierStyleSup">+</span>, S100<span class="elsevierStyleSup">+</span>, CD68<span class="elsevierStyleSup">+</span>, with langerin<span class="elsevierStyleSup">−</span> (langerin is the immunohistochemical marker of Birbeck granules).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">ICH has been reported in patients of all ages and even as a congenital disease. It presents with brownish-red, occasionally ulcerated papular lesions on the trunk and limbs, and that may be widely distributed or occur as an isolated lesion; cases similar to ours, with predominantly or exclusively facial lesions, have been reported.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Although purely cutaneous involvement with an acute, chronic, or recurrent-remitting presentation and an indolent or even self-resolving clinical course are typical of ICH, eye or bone involvement can occasionally develop, or even multiorgan disease with a fatal outcome.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Clinical presentation can thus mimic LCH or non-LCH, especially the generalized eruptive forms and benign cephalic histiocytosis, and histology is essential to make the correct diagnosis.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The pathophysiology of the disease was described by Badalian-Very et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> in 2010 in a series of 61 patients with LCH, finding mutations in <span class="elsevierStyleItalic">BRAF V600E</span> in 57% of patients. Three cases were reported recently with translocations in genes <span class="elsevierStyleItalic">ETV3-NCOA2</span>, a genetic alteration not previously found in histiocytosis; <span class="elsevierStyleItalic">NCOA2</span> codes for the protein TIF2, a transcription cofactor for nuclear steroid receptors.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> These data support the clonal origin of histiocytosis, and in the future may have therapeutic implications. However, cases of histiocytosis with the immunohistochemical profile of ICH have been reported after inflammatory diseases such as scabies or pityriasis rosea and have shown a self-resolving clinical course.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> This allows us to propose the hypothesis that the histiocytoses are a spectrum of diseases defined only by their immunohistochemical pattern, and that they include truly neoplastic diseases as well as reactive inflammatory conditions. Molecular study will probably contribute to a better characterization of this entity in the near future.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Because of the low frequency of ICH, no clear drug of choice has yet emerged for its treatment. A wait-and-see approach is an option, given the indolent or even self-resolving course in the majority of cases, with support using topical corticosteroids in the cutaneous forms. However, a wide variety of treatments other than systemic corticosteroids have been reported in the literature, including phototherapy, thalidomide, isotretinoin, methotrexate, cyclophosphamide, pravastatin, electron beam therapy, and the excision of solitary lesions.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> Polychemotherapy is an option usually reserved for more serious cases with multiorgan disease and, as with other hematologic tumors, hematopoietic stem cell transplant may be considered in refractory cases that put the patient's life in danger.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, we would like to draw attention to the importance of follow-up in these patients for the early detection of possible organ involvement by the disease or the appearance of associated second hematologic tumors. In this regard, low grade B-cell lymphoma and acute leukemia are the most frequently reported in the literature, even years after onset of the ICH, requiring us to perform long-term clinical and laboratory follow-up.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sahuquillo-Torralba A, Navarro-Mira MA, Llavador-Ros M, Botella-Estrada R. Histiocitosis de células indeterminadas en edad pediátrica: a propósito de un caso. Actas Dermosifiliogr. 2017;108:871–874.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1249 "Ancho" => 1600 "Tamanyo" => 254270 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Erythematous-orange papules, some of which are umbilicated and show pseudovesiculation and the presence of scabs. B and C, A week later, all the lesions were in the papular phase, and yellow-orange papules had appeared on the forearms. D, Bullous lesions on the hands 2 months after onset of the condition.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1200 "Ancho" => 1600 "Tamanyo" => 618007 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ulcerated epidermis with a nodular superficial and deep dermal infiltrate, with a predominance of mononuclear histiocytes accompanied by lymphocytes and eosinophils. A, Hematoxylin and eosin (H&E), original magnification<span class="elsevierStyleHsp" style=""></span>×40. B, H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×100; C, H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×200; D, Detail of a nodule. H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×400.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1125 "Ancho" => 1500 "Tamanyo" => 629935 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemistry: A, Extensive and diffuse positivity for CD1a. Original magnification<span class="elsevierStyleHsp" style=""></span>×100. B and C, Detail of the nodules showing scattered but extensive positivity for CD68 and S100 in the epidermis, interstitial dermis, and dermal nodules. Original magnification<span class="elsevierStyleHsp" style=""></span>×200. D, Detail of the nodules showing weak positivity for langerin in the same areas that were positive for CD1a, CD68, and S100. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 7 | 14 |
| 2024 October | 99 | 46 | 145 |
| 2024 September | 108 | 30 | 138 |
| 2024 August | 155 | 62 | 217 |
| 2024 July | 115 | 41 | 156 |
| 2024 June | 149 | 24 | 173 |
| 2024 May | 103 | 42 | 145 |
| 2024 April | 128 | 38 | 166 |
| 2024 March | 107 | 34 | 141 |
| 2024 February | 107 | 35 | 142 |
| 2024 January | 106 | 34 | 140 |
| 2023 December | 89 | 17 | 106 |
| 2023 November | 116 | 27 | 143 |
| 2023 October | 99 | 24 | 123 |
| 2023 September | 98 | 33 | 131 |
| 2023 August | 66 | 22 | 88 |
| 2023 July | 112 | 30 | 142 |
| 2023 June | 99 | 23 | 122 |
| 2023 May | 110 | 24 | 134 |
| 2023 April | 105 | 22 | 127 |
| 2023 March | 93 | 57 | 150 |
| 2023 February | 90 | 23 | 113 |
| 2023 January | 54 | 29 | 83 |
| 2022 December | 78 | 36 | 114 |
| 2022 November | 89 | 20 | 109 |
| 2022 October | 70 | 34 | 104 |
| 2022 September | 66 | 43 | 109 |
| 2022 August | 50 | 32 | 82 |
| 2022 July | 68 | 43 | 111 |
| 2022 June | 50 | 19 | 69 |
| 2022 May | 104 | 31 | 135 |
| 2022 April | 125 | 47 | 172 |
| 2022 March | 79 | 47 | 126 |
| 2022 February | 89 | 20 | 109 |
| 2022 January | 116 | 39 | 155 |
| 2021 December | 90 | 41 | 131 |
| 2021 November | 85 | 51 | 136 |
| 2021 October | 110 | 57 | 167 |
| 2021 September | 82 | 39 | 121 |
| 2021 August | 88 | 42 | 130 |
| 2021 July | 158 | 34 | 192 |
| 2021 June | 72 | 35 | 107 |
| 2021 May | 74 | 53 | 127 |
| 2021 April | 173 | 102 | 275 |
| 2021 March | 124 | 29 | 153 |
| 2021 February | 84 | 37 | 121 |
| 2021 January | 62 | 33 | 95 |
| 2020 December | 53 | 24 | 77 |
| 2020 November | 54 | 23 | 77 |
| 2020 October | 64 | 21 | 85 |
| 2020 September | 50 | 27 | 77 |
| 2020 August | 42 | 23 | 65 |
| 2020 July | 34 | 21 | 55 |
| 2020 June | 43 | 38 | 81 |
| 2020 May | 28 | 11 | 39 |
| 2020 April | 25 | 17 | 42 |
| 2020 March | 30 | 20 | 50 |
| 2020 February | 1 | 0 | 1 |
| 2020 January | 4 | 0 | 4 |
| 2019 December | 4 | 0 | 4 |
| 2019 November | 80 | 2 | 82 |
| 2019 August | 4 | 0 | 4 |
| 2019 July | 4 | 0 | 4 |
| 2019 June | 4 | 0 | 4 |
| 2019 May | 5 | 1 | 6 |
| 2019 April | 2 | 0 | 2 |
| 2019 March | 2 | 0 | 2 |
| 2019 February | 4 | 0 | 4 |
| 2019 January | 6 | 0 | 6 |
| 2018 November | 3 | 0 | 3 |
| 2018 October | 5 | 0 | 5 |
| 2018 September | 3 | 0 | 3 |
| 2018 February | 36 | 6 | 42 |
| 2018 January | 41 | 7 | 48 |
| 2017 December | 53 | 16 | 69 |
| 2017 November | 69 | 33 | 102 |
| 2017 October | 3 | 5 | 8 |
| 2017 September | 3 | 8 | 11 |
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