Case and Research Letters
Granulocyte Colony-Stimulating Factor (G-Csf)–Producing Giant Squamous Cell Carcinoma of the Scrotum
Carcinoma en escroto de células escamosas gigantes productor de factor estimulante de colonias de granulocitos (G-CSF)
M. Takako
, K. Yasunobu, Y. Toshiyuki
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Departamento de Dermatología, Universidad de Medicina de Fukushima, Fukushima, Japón
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Takako, K. Yasunobu, Y. Toshiyuki" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Takako" "email" => array:1 [ 0 => "m-takako@fmu.ac.jp" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "K." "apellidos" => "Yasunobu" ] 2 => array:2 [ "nombre" => "Y." "apellidos" => "Toshiyuki" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Dermatología, Universidad de Medicina de Fukushima, Fukushima, Japón" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Carcinoma en escroto de células escamosas gigantes productor de factor estimulante de colonias de granulocitos (G-CSF)" ] ] "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" => 1887 "Ancho" => 2500 "Tamanyo" => 709976 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histologic examination of the fully resected tumor showed undifferentiated atypical squamous cells with extravasation and multiple thrombi (A) (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200). The cells were positive for p40 (B) and AE1/AE3 (C) and negative for CD31 (D) (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 72-year-old man presented with a painful tumor of 1 year's duration on the scrotum. Physical examination showed a cauliflower-like 9.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>8.0-cm mass with a surface that was mostly hemorrhagic and necrotic (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Biopsy showed squamous cell carcinoma (SCC) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Biopsy of the inguinal lymph nodes also showed metastasis from SCC. The white blood cell count (WBC) in blood was 19<span class="elsevierStyleHsp" style=""></span>700/μL, with 86% neutrophils. Evaluation of SCC antigen levels in serum using the chemiluminescent enzyme immunoassay (Abbott Japan Co. Ltd.) showed elevated levels (8.7<span class="elsevierStyleHsp" style=""></span>ng/dL; normal value, <<span class="elsevierStyleHsp" style=""></span>1.5). No other metastases were detected. The patient was treated with complete tumor resection and bilateral inguinal lymph node dissection. Histology showed massive infiltration of undifferentiated atypical squamous cells with abundant vascularization and multiple microthrombi extending from the dermis to the subcutaneous tissue (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Immunohistochemical staining was positive for p40, keratin (AE1/AE3), and vimentin, and negative for CD31 (Fig. 2B-D). The tumor cells were also positive for granulocyte colony-stimulating factor (G-CSF) and the G-CSF receptor (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> A, B). Serum levels of the SCC antigen returned to normal after surgery, but 4 days after the operation, the patient developed a high fever. Three weeks postsurgery, the leukocyte count increased suddenly to 85<span class="elsevierStyleHsp" style=""></span>700/μL and serum G-CSF levels rose to 70.4<span class="elsevierStyleHsp" style=""></span>pg/mL (normal range, 4.7-18.1). Computed tomography of the chest showed multiple pulmonary metastases and the patient suddenly developed pleural effusions. His blood calcium levels were extremely high (19.5<span class="elsevierStyleHsp" style=""></span>mg/dL; normal range, 8.4-10.2<span class="elsevierStyleHsp" style=""></span>mg/dL). Three weeks after resection of the tumor, the patient died of respiratory failure. His WBC count was 189<span class="elsevierStyleHsp" style=""></span>600/μL. An autopsy was not performed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">G-CSF-producing tumors are rare and have been reported for SSC, anaplastic large-cell lymphoma,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> and angiosarcoma.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Just 5 cases of G-CSF-producing SCCs, including ours, have been described to date (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3–6</span></a> All the patients had WBC counts of over 20 000/μL, but the count in our case was much higher. Hypercalcemia is a common complication of SCC and is believed to be caused by the stimulation of peptide parathyroid hormone–related peptide (PTH-rP) by tumor cells. In our patient, the immunohistochemistry study showed weak expression of PTH-rP (data not shown), but unfortunately, serum levels were not measured.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">According to the criteria for leukocytosis in cancer,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> WBC counts should improve after tumor resection. In the case reported, however, the count did not improve. What is more, it remained high. Some authors have reported that primary tumors do not produce G-CSF, unlike recurrent tumors, which produce large amounts of this growth factor.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> In our patient, however, both the primary lesion and the lymph node metastasis showed high G-CSF expression. We unfortunately did not measure serum G-CSF levels during the course of the patient's disease so are unable to determine whether or not there was a correlation with disease activity. In addition, further studies of G-CSF levels in genital SCC are needed. G-CSF-producing SCCs often have an undifferentiated histologic phenotype, with a loss of epithelial features and epithelial-mesenchymal transition.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> In our case, the tumor cells were positive for keratin and vimentin, indicating induction of this transition. According to an earlier study, G-CSF gene expression can result in autocrine/paracrine stimulation of local invasion and angiogenesis in SCC.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> Serum SCC antigen levels were high in our patient, coinciding with previous reports for cutaneous SCC.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10,11</span></a> Angiosarcoma was ruled out in all cases, as even though the tumors were highly vascularized, they were negative for CD31 staining. In addition, the tumor cells expressed both G-CSF and its receptor, indicating autocrine proliferation. In conclusion, and as indicated by the case described, G-CSF-producing tumors carry a poor prognosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0020" 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: Takako M, Yasunobu K, Toshiyuki Y. Carcinoma en escroto de células escamosas gigantes productor de factor estimulante de colonias de granulocitos (G-CSF). Actas Dermosifiliogr. 2019;110:57–59.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1131 "Ancho" => 2084 "Tamanyo" => 283000 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, A giant, dark erythematous, indurated cauliflower-like mass on the scrotum. B, Biopsy of the mass showed squamous cell carcinoma (hematoxylin-eosin, original magnification ×40).</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" => 1887 "Ancho" => 2500 "Tamanyo" => 709976 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histologic examination of the fully resected tumor showed undifferentiated atypical squamous cells with extravasation and multiple thrombi (A) (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200). The cells were positive for p40 (B) and AE1/AE3 (C) and negative for CD31 (D) (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100).</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" => 950 "Ancho" => 2500 "Tamanyo" => 420547 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The tumor cells in the primary scrotal mass and the lymph node metastases were strongly immunoreactive for granulocyte-colony stimulating factor (G-CSF) (A) and the G-CSF receptor (B).</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: F, female; M, male; ND, no data.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age, y/Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Location \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Size, cm \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Leukocyte Count, /μL \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Calcium, mg/dL \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">G-CSF, pg/mL \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ref. \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Arm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">117 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nara et al. (2007) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vulva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 740 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">430 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ito et al. (2011) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Foot \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 440 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14,6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">402 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Miura et al. (2011) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cheek \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 290 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">307 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yamasaki et al. (2013) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Scrotum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">85 700 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19,5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70,4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Current case \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1933253.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Cases of Granulocyte Colony-Stimulating Factor (G-CSF)–Producing Squamous Cell Carcinomas in the English-Language Literature.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Granulocyte-colony stimulating factor-producing primary cutaneous anaplastic large cell lymphoma with cerebral metastasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. 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| año/Mes | Html | Total | |
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| 2023 Septiembre | 79 | 30 | 109 |
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| 2023 Marzo | 82 | 25 | 107 |
| 2023 Febrero | 52 | 29 | 81 |
| 2023 Enero | 46 | 35 | 81 |
| 2022 Diciembre | 48 | 42 | 90 |
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| 2022 Junio | 24 | 33 | 57 |
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| 2022 Marzo | 51 | 60 | 111 |
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| 2021 Diciembre | 43 | 51 | 94 |
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| 2021 Septiembre | 50 | 39 | 89 |
| 2021 Agosto | 52 | 43 | 95 |
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| 2020 Octubre | 15 | 19 | 34 |
| 2020 Septiembre | 28 | 22 | 50 |
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| 2020 Julio | 24 | 17 | 41 |
| 2020 Junio | 28 | 32 | 60 |
| 2020 Mayo | 23 | 19 | 42 |
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