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<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="letter" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JDERM</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Dermatol</journal-id>
      <journal-title>JMIR Dermatology</journal-title>
      <issn pub-type="epub">2562-0959</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v4i2e33241</article-id>
      <article-id pub-id-type="pmid">37632877</article-id>
      <article-id pub-id-type="doi">10.2196/33241</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Letter</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Surgical Surprise: Cutaneous Metastasis Presenting for Mohs Micrographic Surgery Without a Prior Diagnostic Biopsy</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Dellavalle</surname>
            <given-names>Robert</given-names>
          </name>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Sivesind</surname>
            <given-names>Torunn</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Mytle</surname>
            <given-names>Nutan</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Li</surname>
            <given-names>Yang</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Dunaway</surname>
            <given-names>Spencer</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-6731-7219</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Aggarwal</surname>
            <given-names>Pushkar</given-names>
          </name>
          <degrees>MBA</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <address>
            <institution>University of Cincinnati College of Medicine</institution>
            <addr-line>3230 Eden Avenue</addr-line>
            <addr-line>Cincinnati, OH, 45267</addr-line>
            <country>United States</country>
            <phone>1 240 200 0896</phone>
            <email>aggarwpr@mail.uc.edu</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-5271-8127</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Shaughnessy</surname>
            <given-names>Cristin</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1937-8188</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Neltner</surname>
            <given-names>Scott</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9342-650X</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Department of Dermatology</institution>
        <institution>University of Cincinnati College of Medicine</institution>
        <addr-line>Cincinnati, OH</addr-line>
        <country>United States</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>University of Cincinnati College of Medicine</institution>
        <addr-line>Cincinnati, OH</addr-line>
        <country>United States</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Pushkar Aggarwal <email>aggarwpr@mail.uc.edu</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <season>Jul-Dec</season>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>1</day>
        <month>11</month>
        <year>2021</year>
      </pub-date>
      <volume>4</volume>
      <issue>2</issue>
      <elocation-id>e33241</elocation-id>
      <history>
        <date date-type="received">
          <day>29</day>
          <month>8</month>
          <year>2021</year>
        </date>
        <date date-type="rev-request">
          <day>6</day>
          <month>10</month>
          <year>2021</year>
        </date>
        <date date-type="rev-recd">
          <day>7</day>
          <month>10</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>11</day>
          <month>10</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Spencer Dunaway, Pushkar Aggarwal, Cristin Shaughnessy, Scott Neltner. Originally published in JMIR Dermatology (http://derma.jmir.org), 01.11.2021.</copyright-statement>
      <copyright-year>2021</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology Research, is properly cited. The complete bibliographic information, a link to the original publication on http://derma.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://derma.jmir.org/2021/2/e33241" xlink:type="simple"/>
      <kwd-group>
        <kwd>cutaneous metastasis</kwd>
        <kwd>Mohs surgery</kwd>
        <kwd>biopsy</kwd>
        <kwd>micrographic surgery</kwd>
        <kwd>dermatology</kwd>
        <kwd>dermatologist</kwd>
        <kwd>skin cancer</kwd>
        <kwd>melanoma</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title>Case Report</title>
      <p>A 60-year-old Caucasian woman presented for Mohs micrographic surgery (MMS) after being referred for a clinically presumed basal cell carcinoma of the scalp. Three months prior, while living abroad, the patient developed a nodule on the vertex of her scalp. The patient’s primary care physician initially treated the lesion as a cyst with antibiotics. However, after no improvement, she received a second opinion and was told it was a basal cell carcinoma. The patient returned to the United States for treatment and was seen by a plastic surgeon, who subsequently referred her to a Mohs micrographic surgeon.</p>
      <p>Upon presentation, the patient had a 1.7-cm violaceous, slightly scaly nodule on the vertex of the scalp (<xref rid="figure1" ref-type="fig">Figure 1</xref>).</p>
      <fig id="figure1" position="float">
        <label>Figure 1</label>
        <caption>
          <p>A 1.7-cm violaceous, slightly scaly nodule at the vertex of the patient’s scalp, revealed through preoperative evaluation.</p>
        </caption>
        <graphic xlink:href="derma_v4i2e33241_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <p>The patient also complained of a tender subcutaneous nodule on her right flank that was noted after a bicycle accident, also approximately 3 months prior. Pertinent history included  10 pack-years of smoking in her 20s. Prior to initiating Mohs surgery, a shave biopsy was performed, revealing a basaloid proliferation with adenomatous differentiation diffusely involving the dermis and subcutis. Given the diagnostic ambiguity regarding this lesion, it was sent for permanent section processing.</p>
      <p>Evaluation of the permanent section was consistent with metastatic adenocarcinoma. Immunohistochemical studies were performed and revealed the neoplastic cells to be positive for CK7 (cytokeratin 7) and TTF-1 (thyroid transcription factor-1) consistent with lung origin (<xref rid="figure2" ref-type="fig">Figures 2</xref>-<xref rid="figure5" ref-type="fig">5</xref>).</p>
      <fig id="figure2" position="float">
        <label>Figure 2</label>
        <caption>
          <p>Frozen section with basaloid proliferation with adenomatous differentiation.</p>
        </caption>
        <graphic xlink:href="derma_v4i2e33241_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <fig id="figure3" position="float">
        <label>Figure 3</label>
        <caption>
          <p>Permanent section with proliferation of variably shaped and sized islands with a central lumen lined by crowded, hyperchromatic, and large columnar cells with many atypical mitotic figures.</p>
        </caption>
        <graphic xlink:href="derma_v4i2e33241_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <fig id="figure4" position="float">
        <label>Figure 4</label>
        <caption>
          <p>CK7 (cytokeratin 7) positive.</p>
        </caption>
        <graphic xlink:href="derma_v4i2e33241_fig4.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <fig id="figure5" position="float">
        <label>Figure 5</label>
        <caption>
          <p>TTF-1 (thyroid transcription factor-1) positive.</p>
        </caption>
        <graphic xlink:href="derma_v4i2e33241_fig5.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <p>The patient was referred to oncology and was found to have stage IV adenocarcinoma of the lung with extensive bony metastasis and involvement of the adrenals, pelvis, and parietal lobe. Excision of the abdominal mass by plastic surgery revealed similar histology.</p>
    </sec>
    <sec>
      <title>Discussion</title>
      <p>Cutaneous metastases develop in 0.7% to 9% of patients with cancer. In men, the most frequent sources of metastases are the lung (24%), colon (19%), melanoma (13%), and oral cavity (12%). In women, the most frequent sources of metastases are the breast (69%), colon (9%), melanoma (5%), ovaries (4%), and lung (4%) [<xref ref-type="bibr" rid="ref1">1</xref>]. Cutaneous metastasis is rather uncommon and has been reported to occur in approximately 5% of all cancer patients [<xref ref-type="bibr" rid="ref2">2</xref>]. In lung cancer, it is usually a sign of late disease, and concomitant poor prognosis, with a median survival of 3.9 months [<xref ref-type="bibr" rid="ref3">3</xref>]. In a recent retrospective study of 2130 patients with nonsmall cell carcinoma, only 2.8% had cutaneous metastasis at the time of diagnosis [<xref ref-type="bibr" rid="ref3">3</xref>]. Our case describes an even rarer occurrence in which cutaneous metastasis manifested as the presenting sign of an underlying malignancy.</p>
      <p>Despite the rarity, dermatologists should always consider cutaneous metastasis in their differential for solitary nodules. Our case demonstrates the characteristic lesion of a cutaneous metastasis, which has been described as a flesh-colored or violaceous, nonpainful nodule [<xref ref-type="bibr" rid="ref2">2</xref>]. The lesion also was located in a high-risk area, the scalp, which makes up 6.9% of cases of cutaneous metastasis [<xref ref-type="bibr" rid="ref4">4</xref>]. A study of 398 Taiwanese patients with scalp malignancies reported that other than squamous cell carcinoma and basal cell carcinoma, metastatic cutaneous tumors were most common, making up 12.8% of cases. Lung cancer was the leading primary lesion, causing almost a quarter of the cases [<xref ref-type="bibr" rid="ref5">5</xref>].</p>
      <p>This case also demonstrates the critical importance of performing a biopsy and establishing a firm diagnosis prior to initiating MMS. One recent study reported that in 450 patients presenting for MMS with a clinical diagnosis only, 13 of the diagnoses changed following examination of the Mohs debulk specimen. In these patients, a skin biopsy would have changed the management of 9 patients (1%). In 6 of these cases, MMS would not have been performed due to precancerous or benign histology, and in 3 cases, MMS would have been expedited due to the histological presentation of squamous cell carcinoma rather than basal cell carcinoma [<xref ref-type="bibr" rid="ref6">6</xref>].</p>
      <p>In summary, it is rare for an underlying malignancy to present as a cutaneous metastasis. Despite this, it is essential for dermatologists to recognize the classic features and have a high index of suspicion. A timely biopsy can significantly expedite definitive diagnosis, which was delayed in our case by 3 months, potentially impacting the long-term prognosis. Confirmation of a clinical diagnosis with a biopsy prior to MMS can avoid unnecessary procedures and may reveal a more serious pathology. In situations of histologic ambiguity on frozen sections, diagnostic certainty is paramount prior to initiating MMS.</p>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">CK7</term>
          <def>
            <p>cytokeratin 7</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">MMS</term>
          <def>
            <p>Mohs micrographic surgery</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">TIF-1</term>
          <def>
            <p>thyroid transcription factor-1</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <fn-group>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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