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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">MCO</journal-id>
<journal-title-group>
<journal-title>Molecular and Clinical Oncology</journal-title>
</journal-title-group>
<issn pub-type="ppub">2049-9450</issn>
<issn pub-type="epub">2049-9469</issn>
<publisher>
<publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3892/mco.2016.825</article-id>
<article-id pub-id-type="publisher-id">MCO-0-0-825</article-id>
<article-categories>
<subj-group>
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Metastatic prostate cancer initially presenting as chylothorax: A case report</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>YANG</surname><given-names>YU-JIN</given-names></name>
<xref rid="af1-mco-0-0-825" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>SEO</surname><given-names>MINJUNG</given-names></name>
<xref rid="af2-mco-0-0-825" ref-type="aff">2</xref></contrib>
<contrib contrib-type="author"><name><surname>JEON</surname><given-names>HEE-JEONG</given-names></name>
<xref rid="af1-mco-0-0-825" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>NOH</surname><given-names>JIN-HEE</given-names></name>
<xref rid="af1-mco-0-0-825" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>PARK</surname><given-names>SEOL HOON</given-names></name>
<xref rid="af2-mco-0-0-825" ref-type="aff">2</xref></contrib>
<contrib contrib-type="author"><name><surname>CHOI</surname><given-names>YUNSUK</given-names></name>
<xref rid="af3-mco-0-0-825" ref-type="aff">3</xref></contrib>
<contrib contrib-type="author"><name><surname>JO</surname><given-names>JAE-CHEOL</given-names></name>
<xref rid="af3-mco-0-0-825" ref-type="aff">3</xref>
<xref rid="c1-mco-0-0-825" ref-type="corresp"/></contrib>
<contrib contrib-type="author"><name><surname>BAEK</surname><given-names>JIN HO</given-names></name>
<xref rid="af3-mco-0-0-825" ref-type="aff">3</xref></contrib>
<contrib contrib-type="author"><name><surname>KOH</surname><given-names>SU-JIN</given-names></name>
<xref rid="af3-mco-0-0-825" ref-type="aff">3</xref></contrib>
<contrib contrib-type="author"><name><surname>KIM</surname><given-names>HAWK</given-names></name>
<xref rid="af3-mco-0-0-825" ref-type="aff">3</xref></contrib>
<contrib contrib-type="author"><name><surname>MIN</surname><given-names>YOUNG JOO</given-names></name>
<xref rid="af3-mco-0-0-825" ref-type="aff">3</xref></contrib>
</contrib-group>
<aff id="af1-mco-0-0-825"><label>1</label>Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea</aff>
<aff id="af2-mco-0-0-825"><label>2</label>Department of Nuclear Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea</aff>
<aff id="af3-mco-0-0-825"><label>3</label>Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea</aff>
<author-notes>
<corresp id="c1-mco-0-0-825"><italic>Correspondence to</italic>: Professor Jae-Cheol Jo, Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-Doro, Dong-Gu, Ulsan 44033, Republic of Korea, E-mail: <email>jcjo97@hanmail.net</email>; <email>jcjo@uuh.ulsan.kr</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>06</month>
<year>2016</year></pub-date>
<pub-date pub-type="epub">
<day>21</day>
<month>03</month>
<year>2016</year></pub-date>
<volume>4</volume>
<issue>6</issue>
<fpage>1009</fpage>
<lpage>1012</lpage>
<history>
<date date-type="received"><day>19</day><month>06</month><year>2015</year></date>
<date date-type="accepted"><day>23</day><month>11</month><year>2015</year></date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2016, Spandidos Publications</copyright-statement>
<copyright-year>2016</copyright-year>
</permissions>
<abstract>
<p>Chylothorax is caused by disruption or obstruction of the thoracic duct, which results in leakage of chyle in the pleural space. The most common etiologies are malignancy and trauma. Among the causative malignancies, lymphoma is the most common, followed by primary lung cancer, mediastinal tumors, and other metastatic malignancies. Conversely, prostate cancer has rarely been reported as the cause of chylothorax. We herein report a case of metastatic prostate cancer initially presenting as chylothorax, with disappearance of the pleural effusion after the initiation of androgen deprivation therapy. Moreover, we also discuss the various rare manifestations of metastatic prostate cancer, including chylothorax.</p>
</abstract>
<kwd-group>
<kwd>chylothorax</kwd>
<kwd>metastasis</kwd>
<kwd>prostate cancer</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Prostate cancer is the most common cancer among men in Western countries. The 5-year survival rate of localized and regional prostate cancer is ~100&#x0025;, whereas that of metastatic prostate cancer is only 27&#x2013;28&#x0025; (<xref rid="b1-mco-0-0-825" ref-type="bibr">1</xref>). As serum prostate-specific antigen (PSA) screening has become widespread, the proportion of cases presenting with lymph node involvement or advanced disease has decreased considerably (<xref rid="b2-mco-0-0-825" ref-type="bibr">2</xref>). However, ~20&#x0025; of patients present with metastatic disease. Metastatic prostate cancer usually involves the pelvic lymph nodes, bones, and lungs (<xref rid="b2-mco-0-0-825" ref-type="bibr">2</xref>), with bone pain being a common symptom in SUCH patients. However, there are other rare manifestations of metastatic prostate cancer. HereIN, we present a rare case of prostate cancer metastasis initially presenting as chylothorax.</p>
</sec>
<sec sec-type="cases">
<title>Case report</title>
<p>A 64-year-old Asian man visited the emergency room with dyspnea. The patient&#x0027;s medical history was unremarkable, with the exception of being a current smoker with a 20 pack-year history. Radiographic images, including computed tomography scan of the chest, revealed a left pleural effusion, pericardial effusion, and enlarged lymph nodes in the left supraclavicular/posterior neck/axillary area, right upper paratracheal area, subcarinal area, and bilateral lower paratracheal areas (<xref rid="f1-mco-0-0-825" ref-type="fig">Fig. 1A and B</xref>). Thoracentesis was performed and fluid analysis revealed a chylothorax, in which the triglyceride level was 244 mg/dl (normal range, &#x003C;50 mg/dl). Whole-body lymphoscintigraphy revealed faint tracer accumulation activity in the medial portion of the left hemithorax, where the pleural effusion was present (<xref rid="f1-mco-0-0-825" ref-type="fig">Fig. 1C</xref>). Considering that the patient had never received thoracic surgery or experienced trauma, malignancy was suspected. Pleural fluid cytology revealed numerous mononuclear leukocytes and some reactive mesothelial cells, but did not show any evidence of malignancy. The serum PSA level was elevated to 194.6 ng/ml (normal range, 0&#x2013;3 ng/ml).</p>
<p>A prostate biopsy revealed adenocarcinoma of the prostate gland. A bone scan was performed for staging, which revealed multiple bone metastases (<xref rid="f1-mco-0-0-825" ref-type="fig">Fig. 1D</xref>). Therefore, the chylothorax was considered to have resulted from thoracic duct obstruction by enlarged lymph node metastasis from prostate cancer. Androgen deprivation therapy (ADT) was initiated, with simultaneous administration of goserelin and anti-androgen. After 3 months, the amount of pleural effusion had decreased (<xref rid="f2-mco-0-0-825" ref-type="fig">Fig. 2A</xref>) and the serum PSA level decreased from 194.6 to 31.68 ng/ml following ADT. A bone scan performed 8 months after the initiation of ADT revealed that the intensities of multiple bone uptakes had decreased significantly when compared to the initial scan (<xref rid="f2-mco-0-0-825" ref-type="fig">Fig. 2B</xref>). The patient is undergoing regular follow-up at our outpatient clinic for 1 year after diagnosis and has not reported experiencing any further discomfort.</p>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>In Korea, among males aged &#x2265;65 years, prostate cancer is the fourth most common type of cancer and its incidence is increasing with advancing age. The crude mortality of prostate cancer is 2.8/10,000 and the 5-year relative survival rate by year of diagnosis from 2007&#x2013;2011 was 92&#x0025;, indicating that it is a highly treatable cancer (<xref rid="b3-mco-0-0-825" ref-type="bibr">3</xref>).</p>
<p>There is some controversy regarding the efficacy of serum PSA screening. Randomized trials have demonstrated that serum PSA screening reduces metastatic prostate cancer incidence and disease-related mortality (<xref rid="b4-mco-0-0-825" ref-type="bibr">4</xref>). However, other STUDIEs have reported that, due to the unnecessary biopsies following false-positive serum PSA results, cancer risk-adapted serum PSA screening is required (<xref rid="b5-mco-0-0-825" ref-type="bibr">5</xref>). In the United States, the proportion of patients presenting with metastatic disease decreased from 17&#x0025; in 1988&#x2013;1990 to 4&#x0025; in 1996-1998, while the proportion presenting with stage T1 tumors conversely increased from 14 to 51&#x0025; (<xref rid="b6-mco-0-0-825" ref-type="bibr">6</xref>).</p>
<p>As stated above, metastatic prostate cancer usually involves the pelvic lymph nodes, bones and lungs (<xref rid="b2-mco-0-0-825" ref-type="bibr">2</xref>) and it may present as a skin lesion, endobronchial mass, ascites, or renal mass. <xref rid="tI-mco-0-0-825" ref-type="table">Table I</xref> summarizes some of the rare manifestations of prostate cancer (<xref rid="b7-mco-0-0-825" ref-type="bibr">7</xref>&#x2013;<xref rid="b19-mco-0-0-825" ref-type="bibr">19</xref>). Although our patient was not the first case of metastatic prostate cancer presenting as chylothorax, initial presentation of prostate cancer as chylothorax is quite rare (<xref rid="b18-mco-0-0-825" ref-type="bibr">18</xref>,<xref rid="b19-mco-0-0-825" ref-type="bibr">19</xref>).</p>
<p>Lymphoscintigraphy, which functionally assesses the lymphatic transport and regional lymph nodes, is an easy, non-invasive method for detecting abnormalities in the lymphatic system, including leakages such as chylothorax, chyloperitoneum and chyluria. Positive findings include tracer activity at the site where lymphatic fluid is accumulated, as seen in our case (<xref rid="b20-mco-0-0-825" ref-type="bibr">20</xref>,<xref rid="b21-mco-0-0-825" ref-type="bibr">21</xref>). ADT is the mainstay of treatment for patients with metastatic prostate cancer. Luteinizing hormone-releasing hormone agonists have become the standard of care in hormonal therapy, as these agents have the potential of reversibility and enable the use of intermittent androgen deprivation (<xref rid="b22-mco-0-0-825" ref-type="bibr">22</xref>). Moreover, with ADT, patients avoid the physical and psychological discomfort associated with orchiectomy (<xref rid="b23-mco-0-0-825" ref-type="bibr">23</xref>). Intermittent androgen deprivation alternates androgen blockade with treatment cessation, in order to allow hormonal recovery between the treatment cycles, thus potentially improving the tolerability and quality of life. Hence, for older patients, intermittent androgen deprivation may generally be applied (<xref rid="b24-mco-0-0-825" ref-type="bibr">24</xref>).</p>
<p>In summary, chylothorax is an uncommon condition. If there is no history of chest/neck injury or surgery, exclusion of malignancy is crucial. Despite its low probability, prostate cancer with mediastinal lymph node metastasis may result in chylothorax. Therefore, when we evaluate the causes of non-traumatic chylothorax, prostate cancer should be considered, and serum PSA screening is recommended to exclude this possibility.</p>
</sec>
</body>
<back>
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<floats-group>
<fig id="f1-mco-0-0-825" position="float">
<label>Figure 1.</label>
<caption><p>Chest radiography, chest computed tomography (CT), whole-body lymphoscintigraphy and bone scan images at diagnosis. (A) Chest radiography showing left pleural effusion. (B) Chest CT revealing mediastinal lymph node metastatic nodules (arrows) and left pleural effusion. (C) Whole-body lymphoscintigraphy image CAPTURED 2 h after radiotracer injection, revealing faint tracer accumulation activity in the medial portion of the left hemithorax, where pleural effusion was present (arrows). Tracer activity is absent in the left ilioinguinal chain (arrowheads). (D) Bone scan showing multiple bone metastases in the left clavicle, right ribs, thoracolumbar spine, bilateral pelvic bones and right femur.</p></caption>
<graphic xlink:href="mco-04-06-1009-g00.tif"/>
</fig>
<fig id="f2-mco-0-0-825" position="float">
<label>Figure 2.</label>
<caption><p>(A) Chest radiography and (B) bone scan at 3 and 8 months after initiation of androgen deprivation therapy, respectively. THE chest radiography image showS disappearance of the previous left pleural effusion. The intensities of the multiple bone metastases are decreased on the follow-up bone scan.</p></caption>
<graphic xlink:href="mco-04-06-1009-g01.tif"/>
</fig>
<table-wrap id="tI-mco-0-0-825" position="float">
<label>Table I.</label>
<caption><p>Review of cases of rare manifestations from metastatic prostate cancer.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Authors</th>
<th align="center" valign="bottom">Presentation</th>
<th align="center" valign="bottom">Onset of manifestation</th>
<th align="center" valign="bottom">Age, years</th>
<th align="center" valign="bottom">Treatment</th>
<th align="center" valign="bottom">Outcome</th>
<th align="center" valign="bottom">REFS.</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Mak <italic>et al</italic></td>
<td align="center" valign="top">Skin</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">73</td>
<td align="center" valign="top">Radiotherapy</td>
<td align="center" valign="top">Pain relief</td>
<td align="center" valign="top">(<xref rid="b7-mco-0-0-825" ref-type="bibr">7</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Garai <italic>et al</italic></td>
<td align="center" valign="top">Endobronchial mass</td>
<td align="center" valign="top">Initial</td>
<td align="center" valign="top">84</td>
<td align="center" valign="top">Not stated</td>
<td align="center" valign="top">Not stated</td>
<td align="center" valign="top">(<xref rid="b8-mco-0-0-825" ref-type="bibr">8</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Ani <italic>et al</italic></td>
<td align="center" valign="top">Ascites</td>
<td align="center" valign="top">Initial</td>
<td align="center" valign="top">57</td>
<td align="center" valign="top">ADT</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b9-mco-0-0-825" ref-type="bibr">9</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Sakata <italic>et al</italic></td>
<td align="center" valign="top">Kidney</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">67</td>
<td align="center" valign="top">Nephrectomy</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b10-mco-0-0-825" ref-type="bibr">10</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Ibinaiye <italic>et al</italic></td>
<td align="center" valign="top">Kidney</td>
<td align="center" valign="top">Initial</td>
<td align="center" valign="top">55</td>
<td align="center" valign="top">ADT</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b11-mco-0-0-825" ref-type="bibr">11</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Grenader <italic>et al</italic></td>
<td align="center" valign="top">Brain</td>
<td align="center" valign="top">Initial</td>
<td align="center" valign="top">70</td>
<td align="center" valign="top">Radiotherapy &#x002B; ADT</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b12-mco-0-0-825" ref-type="bibr">12</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Rahmathulla <italic>et al</italic></td>
<td align="center" valign="top">Brain</td>
<td align="center" valign="top">Initial</td>
<td align="center" valign="top">70</td>
<td align="center" valign="top">Surgical resection</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b13-mco-0-0-825" ref-type="bibr">13</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Patel <italic>et al</italic></td>
<td align="center" valign="top">Pituitary gland</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">66</td>
<td align="center" valign="top">Radiotherapy</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b14-mco-0-0-825" ref-type="bibr">14</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Kaswala <italic>et al</italic></td>
<td align="center" valign="top">Small bowel</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">42</td>
<td align="center" valign="top">Chemotherapy</td>
<td align="center" valign="top">Not stated</td>
<td align="center" valign="top">(<xref rid="b15-mco-0-0-825" ref-type="bibr">15</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Kusaka <italic>et al</italic></td>
<td align="center" valign="top">Testis</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">56</td>
<td align="center" valign="top">Radiotherapy &#x002B; ADT</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b16-mco-0-0-825" ref-type="bibr">16</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Mortensen <italic>et al</italic></td>
<td align="center" valign="top">Testis</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">89</td>
<td align="center" valign="top">Bilateral orchiectomy</td>
<td align="center" valign="top">Not stated</td>
<td align="center" valign="top">(<xref rid="b17-mco-0-0-825" ref-type="bibr">17</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Tabba <italic>et al</italic></td>
<td align="center" valign="top">Chylothorax</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">69</td>
<td align="center" valign="top">Chemotherapy</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b18-mco-0-0-825" ref-type="bibr">18</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">Quinonez <italic>et al</italic></td>
<td align="center" valign="top">Chylothorax</td>
<td align="center" valign="top">Late</td>
<td align="center" valign="top">78</td>
<td align="center" valign="top">Bilateral orchiectomy &#x002B; chemotherapy</td>
<td align="center" valign="top">PR</td>
<td align="center" valign="top">(<xref rid="b19-mco-0-0-825" ref-type="bibr">19</xref>)</td>
</tr>
<tr>
<td align="left" valign="top">PRESENT case</td>
<td align="center" valign="top">Chylothorax</td>
<td align="center" valign="top">Initial</td>
<td align="center" valign="top">64</td>
<td align="center" valign="top">ADT</td>
<td align="center" valign="top">PR</td>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1-mco-0-0-825"><p>ADT, androgen deprivation therapy; PR, partial response.</p></fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</article>
