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<art><ui>1746-1596-7-28</ui><ji>1746-1596</ji><fm>
<dochead>Case Report</dochead>
<bibl>
<title>
<p>Renal cell carcinoma associated with peritumoral sarcoid-like reaction without intratumoral granuloma</p>
</title>
<aug>
<au id="A1"><snm>Ouellet</snm><fnm>Simon</fnm><insr iid="I1"/><email>simon.ouellet3@usherbrooke.ca</email></au>
<au id="A2"><snm>Albadine</snm><fnm>Roula</fnm><insr iid="I2"/><email>roula.albadine@usherbrooke.ca</email></au>
<au id="A3" ca="yes"><snm>Sabbagh</snm><fnm>Robert</fnm><insr iid="I1"/><email>robert.sabbagh@usherbrooke.ca</email></au>
</aug>
<insg>
<ins id="I1"><p>Department of Surgery, Division of Urology, Sherbrooke University, Centre hospitalier universitaire de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada</p></ins>
<ins id="I2"><p>Department of Pathology, Sherbrooke University, Centre hospitalier universitaire de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada</p></ins>
</insg>
<source>Diagnostic Pathology</source>
<issn>1746-1596</issn>
<pubdate>2012</pubdate>
<volume>7</volume>
<issue>1</issue>
<fpage>28</fpage>
<url>http://www.diagnosticpathology.org/content/7/1/28</url>
<xrefbib><pubidlist><pubid idtype="doi">10.1186/1746-1596-7-28</pubid><pubid idtype="pmpid">22424560</pubid></pubidlist></xrefbib>
</bibl>
<history><rec><date><day>21</day><month>1</month><year>2012</year></date></rec><acc><date><day>18</day><month>3</month><year>2012</year></date></acc><pub><date><day>18</day><month>3</month><year>2012</year></date></pub></history>
<cpyrt><year>2012</year><collab>Ouellet et al; licensee BioMed Central Ltd.</collab><note>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</note></cpyrt>
<kwdg>
<kwd>Sarcoid-like reaction</kwd>
<kwd>Granuloma</kwd>
<kwd>Renal cell carcinoma</kwd>
</kwdg>
<abs>
<sec>
<st>
<p>Abstract</p>
</st>
<p>Non-necrotizing epithelioid granulomas have been described in association with many primary tumors. In such cases, they are designated as sarcoid-like reaction. Although it is more seen in carcinomas than in sarcomas, it is very rarely reported in renal carcinoma. Here, we describe a rare association of prominent peritumoral sarcoid-like reaction without intratumoral granulomas and conventional clear cell renal carcinoma in a 62-year-old-male, without clinical or laboratory finding of sarcoidosis. At 30 months follow-up, he had no recurrence.</p>
<sec>
<st>
<p>Virtual Slides</p>
</st>
<p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/4054525336657922</url>
</p>
</sec>
</sec>
</abs>
</fm><bdy>
<sec>
<st>
<p>Background</p>
</st>
<p>Non-necrotizing granulomas have been described in association with several primary cancers. Histologically, this sarcoid-like reaction is undistinguishable from granulomas found in systemic sarcoidosis. It is composed of a focal accumulation of epitheloid cells and multinucleated giant cells <abbrgrp>
<abbr bid="B1">1</abbr>
</abbrgrp>. Few cases of association of sarcoid-like reaction with renal cell carcinoma have been described <abbrgrp>
<abbr bid="B2">2</abbr>
<abbr bid="B3">3</abbr>
<abbr bid="B4">4</abbr>
<abbr bid="B5">5</abbr>
<abbr bid="B6">6</abbr>
</abbrgrp>, and some in patients with a known or suspected systemic sarcoidosis <abbrgrp>
<abbr bid="B7">7</abbr>
<abbr bid="B8">8</abbr>
<abbr bid="B9">9</abbr>
<abbr bid="B10">10</abbr>
</abbrgrp>. Here, we describe a renal cell carcinoma associated with a peritumoral granulomatous reaction in a patient without systemic sarcoidosis.</p>
</sec>
<sec>
<st>
<p>Case presentation</p>
</st>
<sec>
<st>
<p>Case report</p>
</st>
<p>A 62-year-old caucasian male known for dyslipidemia and scalp psoriasis was admitted to the emergency room for right renal colic. The patients had no history of constitutional symptoms, gross hematuria or abdominal pain. Laboratory findings were unremarkable. A computerized tomography (CT) was performed, which showed a 3.3 cm heterogeneous enhancing lesion in the upper pole of the right kidney consistent with a renal carcinoma (Figure <figr fid="F1">1</figr>). Patient was then scheduled for a laparoscopic partial nephrectomy. The per- and post-operative periods were uneventful. Lymph nodes were explored during surgery and none were found. Nothing in the patient's clinical history or in the thoracic and abdominal CT scan performed suggested sarcoid granulomas involvement. No lymph node nor metastasis were present at the time of the surgery and at 30 months follow-up.</p>
<fig id="F1"><title><p>Figure 1</p></title><caption><p>CT of the abdomen</p></caption><text>
   <p><b>CT of the abdomen</b>. Heterogeneous enhancing lesion in the upper pole of the right kidney without invasion to surrounding tissues.</p>
</text><graphic file="1746-1596-7-28-1" hint_layout="single"/></fig>
</sec>
<sec>
<st>
<p>Pathologic findings</p>
</st>
<p>Macroscopically, the tumor lesion revealed a 3.5 cm encapsulated yellowish mass with bosselated surface with small foci of hemorrhage and necrosis.</p>
<p>Histological examination showed a conventional clear cell type renal carcinoma of Fuhrman nuclear grade III, without sarcomatoid features (Figure <figr fid="F2">2A</figr>). There was no perinephric, renal sinus fat, or renal vessel involvement. Surgical margins were negative. Neoplastic proliferation was delineated from normal renal parenchyma by a fibrous pseudocapsule where multiple non-necrotizing granulomas with multinucleated giant cells were found (Figure <figr fid="F2">2B, C, D</figr>). No granuloma was seen within the tumor. These granulomas did not contain centrally located malignant cells. These granulomas were associated with mild mononuclear, lymphocytic inflammatory infiltrate. No granuloma was seen in the adjacent renal parenchyma (Figure <figr fid="F3">3</figr>). Ziehl-Neelsen and Grocott stains did not detect the presence of mycobacteria or fungi.</p>
<fig id="F2"><title><p>Figure 2</p></title><caption><p>Partial right upper pole nephrectomy</p></caption><text>
   <p><b>Partial right upper pole nephrectomy</b>. A, Conventional clear cell type renal carcinoma of Fuhrman nuclear grade III, without sarcomatoid features (HE;&#215;100 original magnification). B, Epithelioid cell granulomas with Langhans-type giant cells (Sarcoid-like reaction) in the peritumoral fibrous pseudocapsule (&#215;40 original magnification). C, Sarcoid-like reaction with some peritumoral inflammatory reaction, without any contact with tumor cells (&#215;100 original magnification). D, Renal cell carcinoma with sarcoid-like reaction (&#215;200 original magnification)</p>
</text><graphic file="1746-1596-7-28-2" hint_layout="double"/></fig>
<fig id="F3"><title><p>Figure 3</p></title><caption><p>No granuloma was observed in the adjacent normal renal parenchyma (x40 original magnification)</p></caption><text>
   <p><b>No granuloma was observed in the adjacent normal renal parenchyma (x40 original magnification)</b>.</p>
</text><graphic file="1746-1596-7-28-3" hint_layout="single"/></fig>
</sec>
</sec>
<sec>
<st>
<p>Discussion</p>
</st>
<p>The frequency of sarcoid like reactions in certain tumor types and in different locations varies from 4% in carcinoma, to 20% in lymphoma <abbrgrp>
<abbr bid="B1">1</abbr>
</abbrgrp>. Non-caseating granulomas can be caused by chemical exposure, infections, foreign bodies, granulomatous diseases and tumors <abbrgrp>
<abbr bid="B1">1</abbr>
<abbr bid="B11">11</abbr>
</abbrgrp>. Therefore, before claiming an association between renal cell cancer and sarcoid-like reaction, the other causes must be excluded by a careful clinical history, diagnostic tests and pathologic examination <abbrgrp>
<abbr bid="B5">5</abbr>
</abbrgrp>.</p>
<p>Antigens expressed by the neoplastic cell or soluble tumor antigens trigger an immune response which leads to the formation of non-caseating granulomas. Such reaction, locally mediated by T-cell, can be found in involved or uninvolved remote site, in regional lymph nodes and less frequently in tumoral areas <abbrgrp>
<abbr bid="B1">1</abbr>
<abbr bid="B2">2</abbr>
<abbr bid="B3">3</abbr>
<abbr bid="B4">4</abbr>
<abbr bid="B5">5</abbr>
<abbr bid="B6">6</abbr>
<abbr bid="B7">7</abbr>
<abbr bid="B8">8</abbr>
<abbr bid="B9">9</abbr>
<abbr bid="B10">10</abbr>
<abbr bid="B11">11</abbr>
</abbrgrp>.</p>
<p>A certain number of cases in the literature reports sarcoid-like reaction associated with renal cell carcinoma in patient with sarcoidosis <abbrgrp>
<abbr bid="B7">7</abbr>
<abbr bid="B8">8</abbr>
<abbr bid="B9">9</abbr>
<abbr bid="B10">10</abbr>
</abbrgrp>. Renal involvement in sarcoidosis displays a wide range of clinical manifestations. Renal histopathology shows granulomatous interstitial nephritis. Alexandrescu et al <abbrgrp>
<abbr bid="B12">12</abbr>
</abbrgrp> reported one case of renal cancer with non-cutaneous sarcoidosis. Lucci et al <abbrgrp>
<abbr bid="B10">10</abbr>
</abbrgrp> described the 6<sup>th </sup>case of clear cell renal cell carcinoma associated with sarcoidosis, this association is very rare.</p>
<p>Few cases reported sarcoid-like reaction associated with renal cell carcinoma in patients without sarcoidoisis <abbrgrp>
<abbr bid="B2">2</abbr>
<abbr bid="B3">3</abbr>
<abbr bid="B4">4</abbr>
<abbr bid="B5">5</abbr>
<abbr bid="B6">6</abbr>
</abbrgrp>. We presented the sixth case of this reaction in conventional clear cell type renal carcinoma, in patients without sarcoidosis (Table <tblr tid="T1">1</tblr>). The prognostic factor of this association is still unclear. Kamiyoshihara et al <abbrgrp>
<abbr bid="B13">13</abbr>
</abbrgrp> found no difference regarding lung cancer prognosis. However, Pavic et al <abbrgrp>
<abbr bid="B14">14</abbr>
</abbrgrp> suggested that sarcoid-like reaction could play a role in preventing metastatic dissemination and may be associated with a better prognosis in Hodgkin's disease and gastric adenocarcinomas. Piscioli et al <abbrgrp>
<abbr bid="B6">6</abbr>
</abbrgrp> reported a case of a renal cell carcinoma with sarcomatoid and sarcoid-like reaction. The patient died from metastatic dissemination 6 months after the nephrectomy. The authors suggested that his poor prognostic was not influenced by the sarcoid-like reaction but rather the sarcomatoid features. However two other cases reported longer recurrence free survival of 15 <abbrgrp>
<abbr bid="B4">4</abbr>
</abbrgrp> and 48 <abbrgrp>
<abbr bid="B3">3</abbr>
</abbrgrp> months, respectively. In our case, the sarcoid like reaction was seen peritumoral, without sarcomatoid features, with a recurrence free survival at 30 months follow-up. Sarcoidosis and sarcoid-like granulomas have been associated with psoriasis treatments <abbrgrp>
<abbr bid="B15">15</abbr>
<abbr bid="B16">16</abbr>
</abbrgrp>. However, in our case the patient never had any treatment for his scalp psoriasis.</p>
<tbl id="T1"><title><p>Table 1</p></title><caption><p>Clinicopathological features of reported cases of sarcoid-like reaction associated with conventional clear cell type renal carcinoma in patients without sarcoidosis</p></caption><tblbdy cols="5">
      <r>
         <c ca="left">
            <p>
               <b>Reference</b>
            </p>
         </c>
         <c ca="left">
            <p>
               <b>Age (y)/Sex</b>
            </p>
         </c>
         <c ca="left">
            <p>
               <b>Histology</b>
            </p>
         </c>
         <c ca="left">
            <p>
               <b>Tumor size (cm)</b>
            </p>
         </c>
         <c ca="left">
            <p>
               <b>Follow-up</b>
            </p>
         </c>
      </r>
      <r>
         <c cspan="5">
            <hr/>
         </c>
      </r>
      <r>
         <c ca="left">
            <p>Hes et al. <abbrgrp><abbr bid="B3">3</abbr></abbrgrp> (2003)</p>
         </c>
         <c ca="left">
            <p>73 to 85 (mean 78.3)/2M, 1F</p>
         </c>
         <c ca="left">
            <p>Granulomatous reaction within tumorous stroma</p>
         </c>
         <c ca="left">
            <p>2.3 to 7.0 (mean 4.4)</p>
         </c>
         <c ca="left">
            <p>6 months to 4 years</p>
         </c>
      </r>
      <r>
         <c cspan="5">
            <hr/>
         </c>
      </r>
      <r>
         <c ca="left">
            <p>Kovacs et al. <abbrgrp><abbr bid="B4">4</abbr></abbrgrp> (2004)</p>
         </c>
         <c ca="left">
            <p>62/F</p>
         </c>
         <c ca="left">
            <p>Granulomatous reaction within tumorous stroma and fibrous stroma surrounding the tumor</p>
         </c>
         <c ca="left">
            <p>6.0</p>
         </c>
         <c ca="left">
            <p>15 months</p>
         </c>
      </r>
      <r>
         <c cspan="5">
            <hr/>
         </c>
      </r>
      <r>
         <c ca="left">
            <p>Shah et al. <abbrgrp><abbr bid="B5">5</abbr></abbrgrp> (2010)</p>
         </c>
         <c ca="left">
            <p>62/M</p>
         </c>
         <c ca="left">
            <p>Granulomatous reaction within tumorous stroma</p>
         </c>
         <c ca="left">
            <p>5.0</p>
         </c>
         <c ca="left">
            <p>12 months</p>
         </c>
      </r>
      <r>
         <c cspan="5">
            <hr/>
         </c>
      </r>
      <r>
         <c ca="left">
            <p>Present case</p>
         </c>
         <c ca="left">
            <p>62/M</p>
         </c>
         <c ca="left">
            <p>Peritumoral sarcoid-like reaction without intratumoral granulomas</p>
         </c>
         <c ca="left">
            <p>3.5</p>
         </c>
         <c ca="left">
            <p>30 months</p>
         </c>
      </r>
   </tblbdy></tbl>
<p>Interestingly, in our case we did not find granulomatous reaction within the tumor as described in some carcinoma, including breast <abbrgrp>
<abbr bid="B17">17</abbr>
</abbrgrp>, renal <abbrgrp>
<abbr bid="B2">2</abbr>
<abbr bid="B3">3</abbr>
<abbr bid="B4">4</abbr>
<abbr bid="B5">5</abbr>
</abbrgrp> and hepatocellular carcinomas <abbrgrp>
<abbr bid="B18">18</abbr>
</abbrgrp>. We presented the sixth case of this reaction in conventional clear cell type renal carcinoma, in patients without sarcoidosis. However, it is, to our knowledge the first case of conventional clear cell type renal carcinoma to show peritumoral sarcoid-like reaction without intratumoral involvement.</p>
</sec>
<sec>
<st>
<p>Conclusion</p>
</st>
<p>We report a rare association between conventional clear cell type renal carcinoma and peritumoral sarcoid-like granulomatous reaction in a patient without clinical, radiologic or laboratory finding of sarcoidosis. Due to the low number of published cases, prognostic value of peritumoral non-necrotizing epithelioid granulomas has yet to be determined. Further cases are needed to provide information on the mechanism and prognostic value of peritumoral granuloma reaction in renal cell carcinoma.</p>
</sec>
<sec>
<st>
<p>Consent</p>
</st>
<p>Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of written consent is available for review by the Editor-in-Chief of this journal.</p>
</sec>
<sec>
<st>
<p>Competing interests</p>
</st>
<p>The authors declare that they have no competing interests.</p>
</sec>
<sec>
<st>
<p>Authors' contributions</p>
</st>
<p>SO drafted the manuscript and provided clinical information. RA carried out the histological evaluation and helped drafted this manuscript. RS was the surgeon, supervised and helped drafted this manuscript. All authors read and approved the final manuscript.</p>
</sec>
</bdy><bm>
<ack>
<sec>
<st>
<p>Acknowledgements</p>
</st>
<p>We would like to thank Tania Fayad, Ph D for the critical reading of this article.</p>
</sec>
</ack>
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