<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="case-report" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.172051.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Case Report</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Case Report: Cutaneous Metastases from Colorectal Cancer: A Rare Case of Isolated Skin Recurrence</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: awaiting peer review]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Khedhiri</surname>
                        <given-names>Nizar</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-4512-4862</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mbarek</surname>
                        <given-names>Abdelhak</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Hlel</surname>
                        <given-names>Imen</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Jouini</surname>
                        <given-names>Raja</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Ben brahim</surname>
                        <given-names>Ihsen</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <xref ref-type="aff" rid="a5">5</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Haithem</surname>
                        <given-names>Zaafouri</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <xref ref-type="aff" rid="a6">6</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Haddad</surname>
                        <given-names>Dhafer</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <xref ref-type="aff" rid="a7">7</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Departement of surgery, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
                <aff id="a2">
                    <label>2</label>Departement of surgery, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
                <aff id="a3">
                    <label>3</label>Department of Pathology, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
                <aff id="a4">
                    <label>4</label>Department of Pathology, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
                <aff id="a5">
                    <label>5</label>Department of Pathology, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
                <aff id="a6">
                    <label>6</label>Department of Surgery, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
                <aff id="a7">
                    <label>7</label>Department of Surgery, Habib Thameur Hospital, Tunis, Tunis, 1008, Tunisia</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:nizar.khedhiri@fmt.utm.tn">nizar.khedhiri@fmt.utm.tn</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>28</day>
                <month>10</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>1172</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>22</day>
                    <month>10</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Khedhiri N et al.</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/14-1172/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Cutaneous metastases from colorectal cancer (CRC) are rare, occurring in fewer than 5% of metastatic cases, and typically indicate advanced disease with poor prognosis.</p>
                </sec>
                <sec>
                    <title>Case presentation</title>
                    <p>We report the case of a 42-year-old man previously treated with curative surgery and adjuvant chemotherapy for rectosigmoid adenocarcinoma. Eighteen months after completion of therapy, he presented with pruritic eczematous skin lesions in the right inguinal fold, gluteal region, and perianal area. Biopsy revealed metastatic adenocarcinoma of colorectal origin (CK20-positive/CK7-negative). Restaging CT scan demonstrated new non-necrotic lymphadenopathy at the aortic bifurcation and bilateral internal iliac chains, without visceral metastases. The disease was classified as unresectable metastatic recurrence (stage IV). The patient was referred for palliative systemic therapy, with molecular profiling (RAS/BRAF/MSI) to guide treatment.</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>Cutaneous metastases are an uncommon manifestation of CRC recurrence and may mimic benign dermatologic conditions. Prompt biopsy of atypical skin lesions in CRC survivors is crucial for early detection. Systemic therapy remains the cornerstone of management, guided by molecular features. Emerging immunotherapy and anti-angiogenic combinations offer potential benefit even in microsatellite-stable disease.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Colorectal cancer; Cutaneous metastasis; Skin metastasis; Rectosigmoid adenocarcinoma; Case report</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec4" sec-type="intro">
            <title>Introduction</title>
            <p>Cutaneous metastases from colorectal cancer (CRC) are rare, with reported incidences of 0.7&#x2013;4% among metastatic cases. Their presence generally reflects advanced disease and poor prognosis. Typical metastatic sites include the liver, lungs, and peritoneum; skin involvement is far less common.</p>
            <p>We present an unusual case of isolated cutaneous recurrence revealing systemic relapse after curative treatment for a rectosigmoid junction adenocarcinoma.</p>
        </sec>
        <sec id="sec5">
            <title>Case presentation</title>
            <p>A 42-year-old man with no prior medical history underwent surgery for a stenosing adenocarcinoma of the rectosigmoid junction.</p>
            <p>Initial locoregional and distant staging was negative. He underwent low anterior resection with stapled colorectal anastomosis and had an uncomplicated postoperative recovery.</p>
            <p>Histopathological examination of the resected specimen showed a moderately differentiated adenocarcinoma, staged as ypT3N1b. The patient received eight cycles of adjuvant capecitabine (Xeloda), completed 18 months after surgery.</p>
            <p>A follow-up CT scan performed three months after completion of chemotherapy showed no abnormalities. A completion colonoscopy, performed because a full preoperative evaluation had not been possible, was also normal.</p>
            <p>Approximately five months later, the patient presented with newly developed pruritic skin lesions. Clinical examination revealed erythematous eczematous plaques in the right inguinal fold, gluteal region, and perianal area (
                <xref ref-type="fig" rid="f1">
Figure 1</xref>). He was otherwise in good general condition (ECOG 0). Digital rectal examination was unremarkable, and serum tumor markers (CEA, CA 19-9) were within normal limits.</p>
            <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                <label>
Figure 1. </label>
                <caption>
                    <title>Clinical presentation of cutaneous metastases: infiltrating nodular lesions in inguinal and peri anal regions on examination.</title>
                </caption>
                <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/189736/64715e89-9464-4c45-ba2d-efa82f4b29c2_figure1.gif"/>
            </fig>
            <p>A punch biopsy of the skin lesion confirmed metastatic adenocarcinoma consistent with colorectal origin (CK20-positive, CK7-negative, CDX2-positive) (
                <xref ref-type="fig" rid="f2">
Figure 2A,B</xref>).</p>
            <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                <label>
Figure 2. </label>
                <caption>
                    <title>Histopathological and immunohistochemical features of the cutaneous metastasis: (A) Skin biopsy showing dermal infiltration by atypical glandular structures consistent with metastatic adenocarcinoma (Hematoxylin&#x2013;Eosin, &#x00d7;200). The asterisk (*) marks tumoral glands invading the dermis, while the arrow indicates adjacent uninvolved dermis. (B) Immunohistochemical staining showing diffuse cytoplasmic positivity for CK20 in tumor cells, confirming colorectal origin (CK20 IHC, &#x00d7;200).</title>
                </caption>
                <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/189736/64715e89-9464-4c45-ba2d-efa82f4b29c2_figure2.gif"/>
            </fig>
            <p>A thoraco-abdomino-pelvic CT scan revealed new, non-necrotic lymphadenopathy at the aortic bifurcation (22 &#x00d7; 9 mm) and in both internal iliac chains (
                <xref ref-type="fig" rid="f3">
Figure 3</xref>).</p>
            <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                <label>
Figure 3. </label>
                <caption>
                    <title>Contrast-enhanced CT scan shows non necrotic lymphadenopathy at the aortic bifurcation (22 &#x00d7; 9 mm).</title>
                </caption>
                <graphic id="gr3" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/189736/64715e89-9464-4c45-ba2d-efa82f4b29c2_figure3.gif"/>
            </fig>
            <p>The case was discussed in a multidisciplinary tumor board. The presence of cutaneous metastases and retroperitoneal lymph node involvement led to classification as unresectable stage IV disease. The patient was referred for palliative systemic chemotherapy, with RAS, BRAF, and MSI testing planned to guide targeted or immunotherapeutic options.</p>
        </sec>
        <sec id="sec6" sec-type="discussion">
            <title>Discussion</title>
            <p>Cutaneous metastases from CRC are uncommon but clinically significant indicators of systemic dissemination. The median time from initial diagnosis to skin involvement ranges from 18&#x2013;30 months, and median survival after diagnosis of skin metastasis is approximately 8 months.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <sec id="sec7">
                <title>Sites and mechanisms</title>
                <p>Skin metastases typically involve the abdominal wall, perineal, or perianal regions, often following surgical scars or areas of venous/lymphatic drainage from the primary tumor.
                    <sup>
                        <xref ref-type="bibr" rid="ref1">1</xref>,
                        <xref ref-type="bibr" rid="ref2">2</xref>
                    </sup> In our patient, the inguinal and perianal lesions likely reflected pelvic lymphatic spread from the rectosigmoid area.</p>
            </sec>
            <sec id="sec8">
                <title>Clinical presentation and diagnosis</title>
                <p>Cutaneous metastases may present as nodules, plaques, or inflammatory-like or eczematous lesions that mimic benign dermatoses, delaying diagnosis.
                    <sup>
                        <xref ref-type="bibr" rid="ref3">3</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref5">5</xref>
                    </sup>
                </p>
                <p>Histopathology with immunohistochemistry (CK20+, CK7&#x2013;, and CDX2+) is essential for confirming colorectal origin. Tumor markers such as CEA and CA 19-9 may remain normal, limiting their diagnostic value in isolation.</p>
            </sec>
            <sec id="sec9">
                <title>Management</title>
                <p>Treatment is mainly palliative and depends on molecular profile and disease extent:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>RAS/BRAF wild-type tumors:</bold> Chemotherapy (FOLFOX or FOLFIRI) plus anti-EGFR agents (cetuximab or panitumumab).</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>MSI-high/dMMR tumors:</bold> Immune checkpoint inhibitors (pembrolizumab, nivolumab &#x00b1; ipilimumab).</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>RAS/BRAF-mutant or MSS/pMMR tumors:</bold> Chemotherapy combined with anti-angiogenic therapy (e.g.
 bevacizumab).</p>
                        </list-item>
                    </list>
                </p>
                <p>For symptomatic relief, surgical excision or palliative radiotherapy can alleviate pain, bleeding, or ulceration, while topical or systemic antipruritic agents may improve comfort.</p>
            </sec>
            <sec id="sec10">
                <title>Emerging strategies</title>
                <p>Recent studies have reported clinical activity from combinations of immune checkpoint inhibitors with anti-angiogenic tyrosine kinase inhibitors (e.g. regorafenib, fruquintinib) in microsatellite-stable CRC, suggesting new therapeutic avenues.
                    <sup>
                        <xref ref-type="bibr" rid="ref6">6</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref8">8</xref>
                    </sup>
                </p>
            </sec>
        </sec>
        <sec id="sec11" sec-type="conclusion">
            <title>Conclusion</title>
            <p>Cutaneous metastases from colorectal cancer are rare and often signal systemic relapse. Awareness of this entity is essential, as lesions may mimic benign dermatologic conditions and occur even when tumor markers and imaging appear normal. Early biopsy and multidisciplinary evaluation are critical for accurate diagnosis and management.</p>
            <p>Systemic therapy guided by molecular profiling remains the mainstay of treatment, while novel immunotherapy&#x2013;anti-angiogenic combinations show promise in refractory microsatellite-stable disease. Continued reporting of such cases will aid in refining prognostic understanding and therapeutic strategies.</p>
        </sec>
        <sec id="sec12">
            <title>Patient consent</title>
            <p>Written informed consent was obtained from the patient for publication of this case report and any accompanying images.</p>
        </sec>
    </body>
    <back>
        <sec id="sec15" sec-type="data-availability">
            <title>Data availability</title>
            <sec id="sec16">
                <title>Underlying data</title>
                <p>All data underlying the results are included in this article.</p>
            </sec>
            <sec id="sec17">
                <title>Extended data</title>
                <p>All relevant supporting materials, including the completed CARE checklist, are openly available in Zenodo.</p>
                <p>This project contains the following extended data:</p>
                <p>&#x201c;CARE Checklist for case report on &#x201c;Cutaneous Metastases from Colorectal Cancer: A Case Report&#x201d;. DOI: 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.17368541">https://doi.org/10.5281/zenodo.17368541</ext-link>.
                    <sup>
                        <xref ref-type="bibr" rid="ref9">9</xref>
                    </sup>
                </p>
                <p>Data is available under the terms of the 
                    <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/publicdomain/zero/1.0/deed.en">Creative Commons Zero v1.0 Universal</ext-link> license.</p>
            </sec>
        </sec>
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