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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Skin metastases are a rare clinical finding&#44; with an incidence between 0&#46;7&#37; and 10&#37; in cancer patients and represent only 2&#37; of all skin tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> They usually occur in a clinical setting of known generalized metastatic disease&#59; however&#44; they can be the first sign of an underlying silent neoplasm&#44; as well as an early sign of the recurrence of a previously&#46; Because of this&#44; they usually indicate a poor prognosis and the mean survival of patients with metastatic cutaneous disease is 7&#46;5 months&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This is the report of a patient with a metastatic skin lesion that presented as the first manifestation of a pulmonary carcinoid tumor&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 64-year-old man&#44; an alcoholic and smoker since adolescence&#44; without previous comorbidities&#44; sought dermatological care due to the appearance of an erythematous lesion on the face showing progressive growth for seven months&#44; associated with cough with hemoptoic sputum&#44; dyspnea&#44; night fever&#44; and weight loss in the last three months&#46; Upon examination&#44; he had a tumor lesion on the nasal tip&#44; with a lobulated surface&#44; an infiltrated base&#44; which was intensely painful to the touch &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; No other findings were found upon physical examination&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">A biopsy of the skin lesion was performed and the histopathological study showed the dermis infiltrated by a malignant epithelial neoplasm of organoid pattern &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46; Immunohistochemistry showed reactivity with cytokeratin 40&#44; 48&#44; 50&#44; and 50&#46;6 in a Golgi pattern&#44; chromogranin A and synaptophysin &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; and was negative for TTF-1 and CK 20&#44; characterizing it as a neuroendocrine tumor&#46; The patient underwent computed tomography of the skull&#44; thorax and total abdomen&#44; which showed an extensively infiltrative pulmonary mass involving the main right bronchus&#44; in addition to multiple lesions suggestive of brain&#44; bone&#44; liver&#44; and adrenal metastasis&#46; Bronchoscopy was performed&#44; but the pulmonary mass biopsy was considered unfeasible due to heavy bleeding during the procedure&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">It was concluded that it was a pulmonary carcinoid tumor with metastases to the skin and other parts of the body&#46; The patient was classified as stage IV and referred to the oncologist and died within one month&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Cutaneous metastases &#40;CM&#41; result from the infiltration of the skin by neoplastic cells from distant malignant tumors and can develop by different routes&#44; including hematological and lymphatic dissemination&#44; invasion by contiguity&#44; in addition to iatrogenic implantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> CM develop months to years after the diagnosis of the primary tumor&#59; however&#44; in some cases &#40;37&#37; in men and 6&#37; in women&#41; metastatic cutaneous disease is diagnosed before the underlying internal neoplasia&#44; especially when the metastasis originates from lung&#44; stomach&#44; ovary and kidney cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The case reported herein belongs to this rare group of patients where the CM was recognized before the primary lung tumor&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">CM usually occur in older individuals and the most affected cutaneous sites are the anterior thoracic and abdominal regions&#44; with the involvement of the face and neck being rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> The frequency of neoplasms produce metastatic cutaneous disease varies according to gender and age group&#46; In adult women&#44; the most common primary tumor sites in decreasing order are as follows&#58; breast&#44; large intestine&#44; lung&#44; and ovary&#59; in adult men&#44; the most prevalent sites follow the sequences&#58; lung&#44; large intestine&#44; oral cavity&#44; and kidney&#59; in children&#44; they comprise neuroblastoma and rhabdomyosarcoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Determining the origin of the primary tumor&#44; if unknown&#44; can be a difficult and not always possible task&#46; In the case of a carcinoid tumor&#44; with a known histopathological subtype&#44; differentiating whether the skin tumor is primary or secondary is another major challenge for dermatologists and dermatopathologists&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Carcinoid tumors&#44; also called neuroendocrine neoplasms&#44; are derived from enterochromaffin cells and can affect several organs&#59; they are more commonly found in the gastrointestinal tract &#40;65&#37;&#41; and bronchopulmonary tract &#40;25&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Carcinoid tumor metastases to the skin are rare and&#44; when they occur&#44; the bronchus is the most common primary site&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Clinically&#44; they present as nodules&#44; which are usually multiple&#44; erythematous-violaceous&#44; and mostly asymptomatic&#59; however&#44; there are reports of painful lesions that can progress to ulceration&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The histopathological and immunohistochemical analyses help in the definitive diagnosis of carcinoid cutaneous metastases&#46; There is dermal and sometimes subcutaneous infiltration by uniform tumor nests and sheets of cells&#44; with hyperchromatic oval nuclei and scarce cytoplasm&#44; showing immunoreactivity for neuroendocrine markers&#44; including chromogranin&#44; synaptophysin&#44; and low molecular weight cytokeratin&#46; The metastatic cells do not express CK5&#47;6&#44; CK7&#44; CK20&#44; and p63&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The immunoexpression of TTF-1 and CDX2 may be useful in determining the primary site&#44; as the former has shown high sensitivity and specificity for carcinoid tumors originating in the lung&#44; whereas CDX2 expression is highly specific for tumors of gastrointestinal origin&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The differentiation between metastatic carcinoid and primary neuroendocrine tumors of the skin&#44; of which the main representative is Merkel Cell carcinoma &#40;MCC&#41;&#44; can also be made through histopathological and immunohistochemical studies&#46; In MCC&#44; subcutaneous involvement is more commonly found&#44; and aggressive neoplasia findings&#44; such as high mitotic index&#44; necrosis&#44; and ulceration are more frequent&#46; Moreover&#44; MCC is typically positive for CK-20&#44; unlike carcinoid tumors of internal origin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In the case described herein&#44; despite the fact that the tumor did not express TTF-1&#44; it was concluded that it was a metastatic cutaneous neuroendocrine carcinoma originating from the lung&#44; considering the immunohistochemical and imaging findings&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; although metastatic carcinoid cutaneous neoplasms are rare&#44; they may represent the first manifestation of a neuroendocrine tumor originating in another&#44; yet unknown organ&#46; Therefore&#44; it is worth noting that the high rate of clinical suspicion by dermatologists and their knowledge of histopathological and immunohistochemical findings allow an accurate diagnosis and prompt patient referral for adequate management&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors&#39; contributions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Lara Martins Fiorio&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Lucia Martins Diniz&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Elton Almeida Lucas&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Dermatopathology
Cutaneous metastasis on the nasal tip: first clinical sign of pulmonary carcinoid tumor
Lara Martins Fiorioa,
Corresponding author
laramfiorio@gmail.com

Corresponding author.
, Lucia Martins Dinizb, Elton Almeida Lucasb
a Hospital Universitário Cassiano Antônio de Moraes, Vitória, ES, Brazil
b Universidade Federal do Espírito Santo, Vitória, ES, Brazil
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Skin metastases are a rare clinical finding&#44; with an incidence between 0&#46;7&#37; and 10&#37; in cancer patients and represent only 2&#37; of all skin tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> They usually occur in a clinical setting of known generalized metastatic disease&#59; however&#44; they can be the first sign of an underlying silent neoplasm&#44; as well as an early sign of the recurrence of a previously&#46; Because of this&#44; they usually indicate a poor prognosis and the mean survival of patients with metastatic cutaneous disease is 7&#46;5 months&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This is the report of a patient with a metastatic skin lesion that presented as the first manifestation of a pulmonary carcinoid tumor&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 64-year-old man&#44; an alcoholic and smoker since adolescence&#44; without previous comorbidities&#44; sought dermatological care due to the appearance of an erythematous lesion on the face showing progressive growth for seven months&#44; associated with cough with hemoptoic sputum&#44; dyspnea&#44; night fever&#44; and weight loss in the last three months&#46; Upon examination&#44; he had a tumor lesion on the nasal tip&#44; with a lobulated surface&#44; an infiltrated base&#44; which was intensely painful to the touch &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; No other findings were found upon physical examination&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">A biopsy of the skin lesion was performed and the histopathological study showed the dermis infiltrated by a malignant epithelial neoplasm of organoid pattern &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46; Immunohistochemistry showed reactivity with cytokeratin 40&#44; 48&#44; 50&#44; and 50&#46;6 in a Golgi pattern&#44; chromogranin A and synaptophysin &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; and was negative for TTF-1 and CK 20&#44; characterizing it as a neuroendocrine tumor&#46; The patient underwent computed tomography of the skull&#44; thorax and total abdomen&#44; which showed an extensively infiltrative pulmonary mass involving the main right bronchus&#44; in addition to multiple lesions suggestive of brain&#44; bone&#44; liver&#44; and adrenal metastasis&#46; Bronchoscopy was performed&#44; but the pulmonary mass biopsy was considered unfeasible due to heavy bleeding during the procedure&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">It was concluded that it was a pulmonary carcinoid tumor with metastases to the skin and other parts of the body&#46; The patient was classified as stage IV and referred to the oncologist and died within one month&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Cutaneous metastases &#40;CM&#41; result from the infiltration of the skin by neoplastic cells from distant malignant tumors and can develop by different routes&#44; including hematological and lymphatic dissemination&#44; invasion by contiguity&#44; in addition to iatrogenic implantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> CM develop months to years after the diagnosis of the primary tumor&#59; however&#44; in some cases &#40;37&#37; in men and 6&#37; in women&#41; metastatic cutaneous disease is diagnosed before the underlying internal neoplasia&#44; especially when the metastasis originates from lung&#44; stomach&#44; ovary and kidney cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The case reported herein belongs to this rare group of patients where the CM was recognized before the primary lung tumor&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">CM usually occur in older individuals and the most affected cutaneous sites are the anterior thoracic and abdominal regions&#44; with the involvement of the face and neck being rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> The frequency of neoplasms produce metastatic cutaneous disease varies according to gender and age group&#46; In adult women&#44; the most common primary tumor sites in decreasing order are as follows&#58; breast&#44; large intestine&#44; lung&#44; and ovary&#59; in adult men&#44; the most prevalent sites follow the sequences&#58; lung&#44; large intestine&#44; oral cavity&#44; and kidney&#59; in children&#44; they comprise neuroblastoma and rhabdomyosarcoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Determining the origin of the primary tumor&#44; if unknown&#44; can be a difficult and not always possible task&#46; In the case of a carcinoid tumor&#44; with a known histopathological subtype&#44; differentiating whether the skin tumor is primary or secondary is another major challenge for dermatologists and dermatopathologists&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Carcinoid tumors&#44; also called neuroendocrine neoplasms&#44; are derived from enterochromaffin cells and can affect several organs&#59; they are more commonly found in the gastrointestinal tract &#40;65&#37;&#41; and bronchopulmonary tract &#40;25&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Carcinoid tumor metastases to the skin are rare and&#44; when they occur&#44; the bronchus is the most common primary site&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Clinically&#44; they present as nodules&#44; which are usually multiple&#44; erythematous-violaceous&#44; and mostly asymptomatic&#59; however&#44; there are reports of painful lesions that can progress to ulceration&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The histopathological and immunohistochemical analyses help in the definitive diagnosis of carcinoid cutaneous metastases&#46; There is dermal and sometimes subcutaneous infiltration by uniform tumor nests and sheets of cells&#44; with hyperchromatic oval nuclei and scarce cytoplasm&#44; showing immunoreactivity for neuroendocrine markers&#44; including chromogranin&#44; synaptophysin&#44; and low molecular weight cytokeratin&#46; The metastatic cells do not express CK5&#47;6&#44; CK7&#44; CK20&#44; and p63&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The immunoexpression of TTF-1 and CDX2 may be useful in determining the primary site&#44; as the former has shown high sensitivity and specificity for carcinoid tumors originating in the lung&#44; whereas CDX2 expression is highly specific for tumors of gastrointestinal origin&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The differentiation between metastatic carcinoid and primary neuroendocrine tumors of the skin&#44; of which the main representative is Merkel Cell carcinoma &#40;MCC&#41;&#44; can also be made through histopathological and immunohistochemical studies&#46; In MCC&#44; subcutaneous involvement is more commonly found&#44; and aggressive neoplasia findings&#44; such as high mitotic index&#44; necrosis&#44; and ulceration are more frequent&#46; Moreover&#44; MCC is typically positive for CK-20&#44; unlike carcinoid tumors of internal origin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In the case described herein&#44; despite the fact that the tumor did not express TTF-1&#44; it was concluded that it was a metastatic cutaneous neuroendocrine carcinoma originating from the lung&#44; considering the immunohistochemical and imaging findings&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; although metastatic carcinoid cutaneous neoplasms are rare&#44; they may represent the first manifestation of a neuroendocrine tumor originating in another&#44; yet unknown organ&#46; Therefore&#44; it is worth noting that the high rate of clinical suspicion by dermatologists and their knowledge of histopathological and immunohistochemical findings allow an accurate diagnosis and prompt patient referral for adequate management&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors&#39; contributions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Lara Martins Fiorio&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Lucia Martins Diniz&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Elton Almeida Lucas&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Article information
ISSN: 03650596
Original language: English
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