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1</a>c&#41;&#44; giving rise to suspicion of metastatic lesions&#46; Biopsy of one of the elements of the scalp revealed a well-delimited intradermal neoplasm&#44; made up of epithelial nodules surrounded by bands of fibrotic tissue and tumoral invasion of superficial skin lymph nodes &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a&#41;&#46; Neoplastic cells that formed follicular structures had a polygonal form with a clear cytoplasm and pleomorphic nuclei&#44; some of which had a ground-glass appearance &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>b&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Immunohistochemical study was positive for TTF-1 &#40;thyroid transcription factor 1&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c&#41; and galectin-3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>d&#41; but negative for thyroglobulin &#40;Tg&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">With these findings&#44; cutaneous metastasis of follicular variant of papillary thyroid carcinoma was diagnosed&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient received another dose of radioactive iodine&#44; but some months later neurologic symptoms occurred due to bilateral supratentorial and infratentorial brain metastases and osteolytic images were observed in the cranial vault&#46; Given this disease progression&#44; sorafenib was administered in combination with zoledronic acid in the compassionate use setting&#44; but the patient finally died 6 months later&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Cutaneous metastases of thyroid carcinomas are rare &#40;occurring in less than 1&#37; of primary thyroid carcinomas&#41;&#46; When they do occur&#44; they present as slow-growing erythematous lesions&#44; purpuric plaques&#44; or soft and mildly itchy erythematous nodules&#44; which may become ulcerated&#46; In 70&#37; of the cases&#44; these lesions are found on the scalp and the rest of the face or neck&#44; due to the extensive vascularization of the dermis at these sites&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#8211;3</span></a> The condition affects men and women equally and is most frequently associated with follicular thyroid carcinoma &#40;42&#37;&#41; even though papillary carcinoma is the most frequent primary carcinoma &#40;50&#37;-89&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> Metastases may present as the first manifestation of an occult papillary carcinoma &#40;worse prognosis&#41; or appear in advanced tumors&#44; as was the case with our patient&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The presence of vascular structures in dermoscopy of a nodular lesion in a patient with a history of cancer should require differential diagnosis with cutaneous metastases&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> The histological and immunohistochemical characteristics with TTF-1 in the present case&#44; in the clinical context of the patient&#44; suggested diagnosis of metastasis of thyroid carcinoma&#44; although the possibility of a pulmonary origin could not be ruled out given the absence of staining with Tg &#40;characteristically positive&#41;&#46; Immunostaining with galectin-3 enabled definitive diagnosis of metastasis of thyroid origin&#46; Galectin plays an important role in cell adhesion and in the interaction between matrix and cells&#46; In addition&#44; it is the primary potential tumor marker for local and distant metastases&#44; particularly in cases of papillary thyroid carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Anatomopathologic diagnosis of metastases of a well-differentiated follicular carcinoma of the thyroid glands is relatively simple given the presence of follicles with colloid material&#46; However&#44; in cases of the follicular variant of papillary thyroid carcinoma&#44; papillary architecture is usually absent and the nuclear characteristics are not always present&#44; and so immunohistochemical techniques are necessary using Tg &#40;sensitivity of close to 100&#37; in follicular cancer&#44; 95&#37; in papillary cancer&#44; and lower in poorly-differentiated carcinomas&#41;&#44; TTF-1&#44; RET&#47;PTC&#44; HBME-1&#44; CK19&#44; CD10&#44; and galectin-3&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#44;7&#44;8</span></a> The <span class="elsevierStyleItalic">BRAFV600E</span> mutation has been identified in cutaneous metastases of papillary thyroid carcinoma and its presence is associated with worse prognosis although new chemotherapeutic agents can be used&#46; Mean survival is 19 months after diagnosis of the cutaneous metastases in patients with advanced disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Differential diagnosis should be considered with primary apocrine tumors and other metastatic lesions&#44; with immunohistochemical study with TTF-1&#44; Tg&#44; and galectin-3 being particularly useful&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; despite the rarity of cutaneous metastases of thyroid carcinoma&#44; we should be aware of this possibility in the differential diagnosis of cutaneous metastases&#44; given that diagnosis and early treatment may improve prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a></p></span>"
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Case and Research Letters
Cutaneous metastases on the head and neck from a papillary thyroid carcinoma, follicular variant
Metástasis cutáneas craneocervicales de un carcinoma papilar de tiroides variedad folicular
A. Márquez Garcíaa,
Corresponding author
ana_marquez54@hotmail.com

Corresponding author.
, L. Ferrándiz Pulidoa, J.J. Ríos-Martínb, F.M. Camacho Martíneza
a Unidad de Gestión Clínica de Dermatología, Hospital Universitario Virgen Macarena, Sevilla, Spain
b Unidad de Gestión Clínica de Anatomía Patológica, Hospital Virgen Macarena, Sevilla, Spain
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Two years after surgery&#44; a cervical mass was detected and this was attributed to relapse of papillary thyroid carcinoma&#46; It was decided to excise the lesion and subsequently treat with I<span class="elsevierStyleSup">131</span>&#46; The patient remained stable&#44; but after 7 months&#44; constitutional symptoms occurred&#44; along with dyspnea and pain in the right side as a result of the presence of multiple bilateral pulmonary nodular metastases&#44; as well as a mediastinal conglomerate lymph nodal mass in both pulmonary hila &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46; The physical examination revealed indurated nodular lesions that were mildly itchy with a vascular appearance on the scalp in the frontal region and close to the thyroidectomy scar &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b-d&#41;&#46; They had appeared 6 months earlier and showed thick vessels with a mottled appearance on dermoscopic examination &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#44; giving rise to suspicion of metastatic lesions&#46; Biopsy of one of the elements of the scalp revealed a well-delimited intradermal neoplasm&#44; made up of epithelial nodules surrounded by bands of fibrotic tissue and tumoral invasion of superficial skin lymph nodes &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a&#41;&#46; Neoplastic cells that formed follicular structures had a polygonal form with a clear cytoplasm and pleomorphic nuclei&#44; some of which had a ground-glass appearance &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>b&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Immunohistochemical study was positive for TTF-1 &#40;thyroid transcription factor 1&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c&#41; and galectin-3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>d&#41; but negative for thyroglobulin &#40;Tg&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">With these findings&#44; cutaneous metastasis of follicular variant of papillary thyroid carcinoma was diagnosed&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient received another dose of radioactive iodine&#44; but some months later neurologic symptoms occurred due to bilateral supratentorial and infratentorial brain metastases and osteolytic images were observed in the cranial vault&#46; Given this disease progression&#44; sorafenib was administered in combination with zoledronic acid in the compassionate use setting&#44; but the patient finally died 6 months later&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Cutaneous metastases of thyroid carcinomas are rare &#40;occurring in less than 1&#37; of primary thyroid carcinomas&#41;&#46; When they do occur&#44; they present as slow-growing erythematous lesions&#44; purpuric plaques&#44; or soft and mildly itchy erythematous nodules&#44; which may become ulcerated&#46; In 70&#37; of the cases&#44; these lesions are found on the scalp and the rest of the face or neck&#44; due to the extensive vascularization of the dermis at these sites&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#8211;3</span></a> The condition affects men and women equally and is most frequently associated with follicular thyroid carcinoma &#40;42&#37;&#41; even though papillary carcinoma is the most frequent primary carcinoma &#40;50&#37;-89&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> Metastases may present as the first manifestation of an occult papillary carcinoma &#40;worse prognosis&#41; or appear in advanced tumors&#44; as was the case with our patient&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The presence of vascular structures in dermoscopy of a nodular lesion in a patient with a history of cancer should require differential diagnosis with cutaneous metastases&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> The histological and immunohistochemical characteristics with TTF-1 in the present case&#44; in the clinical context of the patient&#44; suggested diagnosis of metastasis of thyroid carcinoma&#44; although the possibility of a pulmonary origin could not be ruled out given the absence of staining with Tg &#40;characteristically positive&#41;&#46; Immunostaining with galectin-3 enabled definitive diagnosis of metastasis of thyroid origin&#46; Galectin plays an important role in cell adhesion and in the interaction between matrix and cells&#46; In addition&#44; it is the primary potential tumor marker for local and distant metastases&#44; particularly in cases of papillary thyroid carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Anatomopathologic diagnosis of metastases of a well-differentiated follicular carcinoma of the thyroid glands is relatively simple given the presence of follicles with colloid material&#46; However&#44; in cases of the follicular variant of papillary thyroid carcinoma&#44; papillary architecture is usually absent and the nuclear characteristics are not always present&#44; and so immunohistochemical techniques are necessary using Tg &#40;sensitivity of close to 100&#37; in follicular cancer&#44; 95&#37; in papillary cancer&#44; and lower in poorly-differentiated carcinomas&#41;&#44; TTF-1&#44; RET&#47;PTC&#44; HBME-1&#44; CK19&#44; CD10&#44; and galectin-3&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#44;7&#44;8</span></a> The <span class="elsevierStyleItalic">BRAFV600E</span> mutation has been identified in cutaneous metastases of papillary thyroid carcinoma and its presence is associated with worse prognosis although new chemotherapeutic agents can be used&#46; Mean survival is 19 months after diagnosis of the cutaneous metastases in patients with advanced disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Differential diagnosis should be considered with primary apocrine tumors and other metastatic lesions&#44; with immunohistochemical study with TTF-1&#44; Tg&#44; and galectin-3 being particularly useful&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; despite the rarity of cutaneous metastases of thyroid carcinoma&#44; we should be aware of this possibility in the differential diagnosis of cutaneous metastases&#44; given that diagnosis and early treatment may improve prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a></p></span>"
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