Case and Research Letter
Neuroendocrine TumorWith an Atypical Clinical Course: A Description of 2 Cases
Tumor neuroendocrino: descripción de 2 casos de evolución atípica
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Tumor constituido por nidos de células poligonales (hematoxilina-eosina [H-E] × 5). B. Estas células eran irregulares y atípicas y no establecían conexión con la epidermis (H-E × 20). C. Se aprecian abundantes figuras de mitosis (H-E × 40). D. Estas células eran sinaptofisina positivas (H-E × 40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Arrue, M.A. Arregui, B. Catón, R. Soloeta" "autores" => array:4 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Arrue" ] 1 => array:2 [ "nombre" => "M.A." "apellidos" => "Arregui" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Catón" ] 3 => array:2 [ "nombre" => "R." 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Rosettes (indicated by a white circle in the lesion on the left; a larger number of rosettes are seen in the central area of the lesion on the right) are in evidence, along with irregularly shaped vessels and a clear rainbow pattern.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Pérez-Pérez, J. García-Gavín, F. Allegue, A. Zulaica" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Pérez-Pérez" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "García-Gavín" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Allegue" ] 3 => array:2 [ "nombre" => "A." 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Arrue, M.A. Arregui, B. Catón, R. Soloeta" "autores" => array:4 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "Arrue" "email" => array:1 [ 0 => "itziar.arruemichelena@osakidetza.net" ] "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" => "Arregui" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "B." "apellidos" => "Catón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Soloeta" "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 Santiago Apóstol, Vitoria, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Santiago Apóstol, Vitoria, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tumor neuroendocrino: descripción de 2 casos de evolución atípica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 598 "Ancho" => 900 "Tamanyo" => 96404 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Two erythematous plaques in the right paranasal-infrapalpebral region (image taken after excision of 1 of the lesions).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report 2 cases of cytokeratin-20 negative neuroendocrine tumors with skin involvement that were not Merkel cell carcinoma.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Patient 1. Patient 1 was a 72-year-old man with 3 asymptomatic papular, erythematous lesions measuring 2 to 3<span class="elsevierStyleHsp" style=""></span>mm in the right paranasal region (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The lesions had appeared 20 days earlier. One of the lesions was excised to reveal a diffuse epithelial tumor consisting of solid nests of irregular, atypical polygonal cells with abundant mitotic figures. There was no sign of morphologic differentiation and the epidermis was not involved. The tumor was composed of keratin cells positive for AE1-AE3, synaptophysin, chromogranin, and neuron-specific enolase and negative for cytokeratin 20, thyroid transcription factor 1, CD30, S100, and human melanoma marker (HMB45) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The tumor was diagnosed as intradermal carcinoma with neuroendocrine differentiation. Plasma levels of chromogranin A were elevated (124.2 ng/mL; normal range, 19.4-98.1<span class="elsevierStyleHsp" style=""></span>mg/mL). Other hormones were normal in both blood and urine. Chest radiography, abdominal magnetic resonance imaging, <span class="elsevierStyleSup">111</span>In-labeled octreotide scintigraphy and positron electron imaging findings were normal. There were no significant findings in gastroscopy and colonoscopy revealed an adenomatous polyp. The 3 lesions were excised without any adjuvant therapy and chromogranin A levels returned to normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The patient has remained asymptomatic during 5 years of follow-up.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patient 2. Patient 2 was a 62-year-old woman with a progressively growing sternal lesion that had appeared 2 years earlier. Examination revealed an erythematous-violaceous plaque measuring 3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>cm (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). In the biopsy, a tumor was detected in the dermis in the form of disperse nests of monomorphic cells of epithelial appearance and few atypical cells. They had a poorly defined cytoplasm with occasional microcalcifications and limited mitotic activity. These cells were positive for AE1-AE3 keratins, cytokeratin 8, synaptophysin, chromogranin, and neuron-specific enolase and negative for S100, MELAN-A, HMB45, and cytokeratin 20. Histologic diagnosis was of cutaneous metastasis of a well-differentiated neuroendocrine tumor. Elevated levels of plasma somatostatin were found (27.3<span class="elsevierStyleHsp" style=""></span>pmol/L; normal range, <16<span class="elsevierStyleHsp" style=""></span>pmol/L). Other hormones were normal in both blood and urine. In view of a suspected diagnosis of cutaneous metastasis of a somatostatin-secreting neuroendocrine tumor, octreotide scintigraphy was performed. Uptake was detected in the sternal region and the left axilla. In the other imaging tests, the only finding of note was biliary lithiasis and a hepatic lesion suggestive of hemangioma.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The sternal plaque was excised and 10 left axillary lymph nodes were dissected but no tumor infiltration was observed in any of these. After this procedure, somatostatin levels decreased to 19.9<span class="elsevierStyleHsp" style=""></span>pmol/L (a decrease of 16<span class="elsevierStyleHsp" style=""></span>pmol/L) but did not return to normal. Repeat octreotide scintigraphy still showed focal uptake in the upper external quadrant of the left breast, that is, the tail of the breast. Magnetic resonance imaging, X-ray radiography, and a breast ultrasound were requested to identify this lesion. The results were interpreted as corresponding to an intramammary lymph node measuring 9<span class="elsevierStyleHsp" style=""></span>mm. On review of the patient's medical records, we found that a mammography had detected a lesion of 4<span class="elsevierStyleHsp" style=""></span>mm in the same place 16 years earlier. At the time, benign lymph node enlargement had been diagnosed.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Under radiographic guidance, the lesion was excised to reveal infiltration by fibroadipose and lymph node tissue from a carcinoma of neuroendocrine origin. After excision, somatostatin levels returned to normal during the 2-year follow-up. During this time, the patient remained asymptomatic with no new lesions or increased uptake in octreotide scintigraphy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Cutaneous neuroendocrine tumors can originate from many different organs. They are usually Merkel cell tumors. Cutaneous metastasis of endocrine tumors and primary cutaneous neuroendocrine tumors of other origins are rare.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> These latter 2 types of tumor have certain neuroendocrine markers in common, such as synaptophysin, neuron-specific enolase, and chromogranin, and are negative for cytokeratin 20.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Diagnosis is based on clinical presentation, hormone levels, and imaging. Of particular importance among the imaging tests is <span class="elsevierStyleSup">111</span>In-labeled octreotide scintigraphy. Octreotide is an analogue of somatostatin, and given that somatostatin receptors are expressed in most of these tumors, this test can detect between 67% and 91% of tumors. The technique can be used for diagnosis, staging, and follow-up of these patients.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> Some tumors may follow an aggressive course, although most are slow-growing and indolent.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The main tumors to be included in the differential diagnosis are basal cell carcinoma and cutaneous lymphoma. Histologically, small cell tumors such as metastases from undifferentiated small cell carcinomas of the pulmonary oat cell carcinoma type and small cell neuroendocrine tumors such as Ewing sarcoma, rhabdomyosarcoma, and low-grade lymphomas should also be considered. Merkel cell carcinomas differ from neuroendocrine carcinomas with secondary cutaneous involvement in that their cells have basophilia and less cytoplasm, and often infiltrate the epidermis in the form of Bowen disease.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The treatment of choice for neuroendocrine tumors, whether or not there is cutaneous involvement, is surgery and indeed surgery is the only curative treatment.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">We reported 2 cases of neuroendocrine tumors with cutaneous involvement. In neither case did we find a primary neuroendocrine tumor at another site, though this does not mean that one might not be present because, for example, such a tumor might be too small to be detected in the imaging tests or endoscopy, as is the case with duodenal neuroendocrine tumors.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Multidisciplinary study and long-term follow-up are therefore important with these patients.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Arrue I, Arregui MA, Catón B, Soloeta R. Tumor neuroendocrino: descripción de 2 casos de evolución atípica. Actas Dermosifiliogr. 2014;105:94–96.</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" => 598 "Ancho" => 900 "Tamanyo" => 96404 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Two erythematous plaques in the right paranasal-infrapalpebral region (image taken after excision of 1 of the lesions).</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" => 1051 "Ancho" => 1402 "Tamanyo" => 387250 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Tumor consisting of nests of polygonal cells (hematoxylin-eosin [H-E], original magnification ×5). B, These cells were irregular and atypical and there was no epidermal involvement (H-E, original magnification ×20). C, Abundant mitotic figures are apparent (H-E, original magnification ×40). D, These cells were positive for synaptophysin (H-E, original magnification ×40).</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" => 1379 "Ancho" => 901 "Tamanyo" => 213125 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Sternal erythematous-violaceous plaque.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The diagnosis and medical management of advanced neuroendocrine tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 14 | 12 | 26 |
| 2024 Octubre | 83 | 41 | 124 |
| 2024 Septiembre | 88 | 27 | 115 |
| 2024 Agosto | 114 | 50 | 164 |
| 2024 Julio | 85 | 32 | 117 |
| 2024 Junio | 114 | 27 | 141 |
| 2024 Mayo | 89 | 23 | 112 |
| 2024 Abril | 89 | 25 | 114 |
| 2024 Marzo | 77 | 35 | 112 |
| 2024 Febrero | 91 | 25 | 116 |
| 2024 Enero | 59 | 38 | 97 |
| 2023 Diciembre | 79 | 14 | 93 |
| 2023 Noviembre | 86 | 33 | 119 |
| 2023 Octubre | 85 | 29 | 114 |
| 2023 Septiembre | 88 | 29 | 117 |
| 2023 Agosto | 53 | 21 | 74 |
| 2023 Julio | 56 | 32 | 88 |
| 2023 Junio | 56 | 25 | 81 |
| 2023 Mayo | 52 | 28 | 80 |
| 2023 Abril | 45 | 15 | 60 |
| 2023 Marzo | 39 | 13 | 52 |
| 2023 Febrero | 50 | 24 | 74 |
| 2023 Enero | 33 | 19 | 52 |
| 2022 Diciembre | 52 | 44 | 96 |
| 2022 Noviembre | 24 | 33 | 57 |
| 2022 Octubre | 29 | 21 | 50 |
| 2022 Septiembre | 31 | 31 | 62 |
| 2022 Agosto | 20 | 43 | 63 |
| 2022 Julio | 26 | 31 | 57 |
| 2022 Junio | 21 | 19 | 40 |
| 2022 Mayo | 36 | 49 | 85 |
| 2022 Abril | 60 | 44 | 104 |
| 2022 Marzo | 59 | 63 | 122 |
| 2022 Febrero | 42 | 34 | 76 |
| 2022 Enero | 59 | 44 | 103 |
| 2021 Diciembre | 41 | 54 | 95 |
| 2021 Noviembre | 41 | 54 | 95 |
| 2021 Octubre | 41 | 44 | 85 |
| 2021 Septiembre | 32 | 33 | 65 |
| 2021 Agosto | 27 | 19 | 46 |
| 2021 Julio | 44 | 22 | 66 |
| 2021 Junio | 25 | 35 | 60 |
| 2021 Mayo | 26 | 33 | 59 |
| 2021 Abril | 42 | 47 | 89 |
| 2021 Marzo | 68 | 36 | 104 |
| 2021 Febrero | 49 | 18 | 67 |
| 2021 Enero | 39 | 21 | 60 |
| 2020 Diciembre | 28 | 17 | 45 |
| 2020 Noviembre | 24 | 10 | 34 |
| 2020 Octubre | 5 | 12 | 17 |
| 2020 Septiembre | 32 | 9 | 41 |
| 2020 Agosto | 24 | 18 | 42 |
| 2020 Julio | 22 | 14 | 36 |
| 2020 Junio | 38 | 22 | 60 |
| 2020 Mayo | 28 | 12 | 40 |
| 2020 Abril | 39 | 19 | 58 |
| 2020 Marzo | 29 | 20 | 49 |
| 2020 Febrero | 2 | 1 | 3 |
| 2020 Enero | 4 | 2 | 6 |
| 2019 Diciembre | 8 | 2 | 10 |
| 2019 Noviembre | 2 | 0 | 2 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 10 | 1 | 11 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 4 | 8 |
| 2019 Junio | 5 | 2 | 7 |
| 2019 Mayo | 4 | 9 | 13 |
| 2019 Abril | 3 | 11 | 14 |
| 2019 Marzo | 2 | 4 | 6 |
| 2019 Febrero | 3 | 2 | 5 |
| 2019 Enero | 3 | 1 | 4 |
| 2018 Diciembre | 0 | 4 | 4 |
| 2018 Noviembre | 4 | 0 | 4 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Mayo | 0 | 1 | 1 |
| 2018 Marzo | 2 | 2 | 4 |
| 2018 Febrero | 22 | 5 | 27 |
| 2018 Enero | 27 | 4 | 31 |
| 2017 Diciembre | 36 | 8 | 44 |
| 2017 Noviembre | 18 | 6 | 24 |
| 2017 Octubre | 36 | 4 | 40 |
| 2017 Septiembre | 27 | 6 | 33 |
| 2017 Agosto | 29 | 6 | 35 |
| 2017 Julio | 34 | 5 | 39 |
| 2017 Junio | 35 | 6 | 41 |
| 2017 Mayo | 24 | 5 | 29 |
| 2017 Abril | 29 | 4 | 33 |
| 2017 Marzo | 22 | 31 | 53 |
| 2017 Febrero | 15 | 8 | 23 |
| 2017 Enero | 22 | 8 | 30 |
| 2016 Diciembre | 36 | 17 | 53 |
| 2016 Noviembre | 47 | 10 | 57 |
| 2016 Octubre | 39 | 17 | 56 |
| 2016 Septiembre | 43 | 11 | 54 |
| 2016 Agosto | 34 | 4 | 38 |
| 2016 Julio | 21 | 5 | 26 |
| 2016 Junio | 4 | 0 | 4 |
| 2016 Mayo | 13 | 7 | 20 |
| 2016 Abril | 9 | 5 | 14 |
| 2016 Marzo | 10 | 0 | 10 |
| 2016 Febrero | 4 | 4 | 8 |
| 2016 Enero | 16 | 1 | 17 |
| 2015 Diciembre | 14 | 3 | 17 |
| 2015 Noviembre | 13 | 0 | 13 |
| 2015 Octubre | 10 | 7 | 17 |
| 2015 Septiembre | 7 | 1 | 8 |
| 2015 Agosto | 10 | 2 | 12 |
| 2015 Julio | 61 | 4 | 65 |
| 2015 Junio | 38 | 3 | 41 |
| 2015 Mayo | 41 | 9 | 50 |
| 2015 Abril | 42 | 12 | 54 |
| 2015 Marzo | 25 | 4 | 29 |
| 2015 Febrero | 20 | 2 | 22 |
| 2015 Enero | 23 | 1 | 24 |
| 2014 Diciembre | 15 | 5 | 20 |
| 2014 Noviembre | 11 | 5 | 16 |
| 2014 Octubre | 16 | 2 | 18 |
| 2014 Septiembre | 18 | 3 | 21 |
| 2014 Agosto | 14 | 4 | 18 |
| 2014 Julio | 13 | 5 | 18 |
| 2014 Junio | 16 | 1 | 17 |
| 2014 Mayo | 21 | 7 | 28 |
| 2014 Abril | 12 | 5 | 17 |
| 2014 Marzo | 11 | 2 | 13 |
| 2014 Febrero | 4 | 1 | 5 |
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