A rare cause of hemoptysis
Identifieur interne : 002696 ( Pmc/Corpus ); précédent : 002695; suivant : 002697A rare cause of hemoptysis
Auteurs : Meghan Aversa ; Sacha Bhinder ; Jeffrey Tanguay ; John ThenganattSource :
- Respiratory Medicine Case Reports [ 2213-0071 ] ; 2014.
Abstract
Angiosarcomas are rare, malignant, endothelial-cell tumors of vascular origin that can arise at any body site. They frequently metastasize to the lung, heralded by dyspnea, hemoptysis, chest pain, pneumothoraces, and diffuse pulmonary hemorrhage. However, in most cases lung metastases are discovered after the diagnosis of a primary angiosarcoma has already been established. Very rarely will an undiagnosed metastatic angiosarcoma present as diffuse pulmonary hemorrhage. We describe the case of a 59-year-old male who presented to hospital with dyspnea and hemoptysis. CT chest revealed rapidly progressing nodular changes and broncho-alveolar lavage returns were progressively bloody. Open lung wedge biopsy ultimately revealed metastatic angiosarcoma and extensive pulmonary hemorrhage. Our case highlights the key clinical, radiological, and pathological features of this rare malignancy that frequently metastasizes to the lung and reminds clinicians to consider it as a cause of hemoptysis and pulmonary hemorrhage.
Url:
DOI: 10.1016/j.rmcr.2014.08.001
PubMed: 26029560
PubMed Central: 4246356
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A rare cause of hemoptysis</title><author><name sortKey="Aversa, Meghan" sort="Aversa, Meghan" uniqKey="Aversa M" first="Meghan" last="Aversa">Meghan Aversa</name></author><author><name sortKey="Bhinder, Sacha" sort="Bhinder, Sacha" uniqKey="Bhinder S" first="Sacha" last="Bhinder">Sacha Bhinder</name></author><author><name sortKey="Tanguay, Jeffrey" sort="Tanguay, Jeffrey" uniqKey="Tanguay J" first="Jeffrey" last="Tanguay">Jeffrey Tanguay</name></author><author><name sortKey="Thenganatt, John" sort="Thenganatt, John" uniqKey="Thenganatt J" first="John" last="Thenganatt">John Thenganatt</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26029560</idno><idno type="pmc">4246356</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246356</idno><idno type="RBID">PMC:4246356</idno><idno type="doi">10.1016/j.rmcr.2014.08.001</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002696</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002696</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A rare cause of hemoptysis</title><author><name sortKey="Aversa, Meghan" sort="Aversa, Meghan" uniqKey="Aversa M" first="Meghan" last="Aversa">Meghan Aversa</name></author><author><name sortKey="Bhinder, Sacha" sort="Bhinder, Sacha" uniqKey="Bhinder S" first="Sacha" last="Bhinder">Sacha Bhinder</name></author><author><name sortKey="Tanguay, Jeffrey" sort="Tanguay, Jeffrey" uniqKey="Tanguay J" first="Jeffrey" last="Tanguay">Jeffrey Tanguay</name></author><author><name sortKey="Thenganatt, John" sort="Thenganatt, John" uniqKey="Thenganatt J" first="John" last="Thenganatt">John Thenganatt</name></author></analytic><series><title level="j">Respiratory Medicine Case Reports</title><idno type="eISSN">2213-0071</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Angiosarcomas are rare, malignant, endothelial-cell tumors of vascular origin that can arise at any body site. They frequently metastasize to the lung, heralded by dyspnea, hemoptysis, chest pain, pneumothoraces, and diffuse pulmonary hemorrhage. However, in most cases lung metastases are discovered after the diagnosis of a primary angiosarcoma has already been established. Very rarely will an undiagnosed metastatic angiosarcoma present as diffuse pulmonary hemorrhage. We describe the case of a 59-year-old male who presented to hospital with dyspnea and hemoptysis. CT chest revealed rapidly progressing nodular changes and broncho-alveolar lavage returns were progressively bloody. Open lung wedge biopsy ultimately revealed metastatic angiosarcoma and extensive pulmonary hemorrhage. Our case highlights the key clinical, radiological, and pathological features of this rare malignancy that frequently metastasizes to the lung and reminds clinicians to consider it as a cause of hemoptysis and pulmonary hemorrhage.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Patel, A M" uniqKey="Patel A">A.M. Patel</name></author><author><name sortKey="Ryu, J H" uniqKey="Ryu J">J.H. Ryu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ravi, V" uniqKey="Ravi V">V. Ravi</name></author><author><name sortKey="Patel, S" uniqKey="Patel S">S. Patel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adem, C" uniqKey="Adem C">C. Adem</name></author><author><name sortKey="Aubry, M C" uniqKey="Aubry M">M.C. Aubry</name></author><author><name sortKey="Tazelaar, H D" uniqKey="Tazelaar H">H.D. Tazelaar</name></author><author><name sortKey="Myers, J L" uniqKey="Myers J">J.L. Myers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zwaveling, J H" uniqKey="Zwaveling J">J.H. Zwaveling</name></author><author><name sortKey="Van Berkhout, F T" uniqKey="Van Berkhout F">F.T. van Berkhout</name></author><author><name sortKey="Haneveld, G T" uniqKey="Haneveld G">G.T. Haneveld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Edwards, R L" uniqKey="Edwards R">R.L. Edwards</name></author><author><name sortKey="Chalk, S M" uniqKey="Chalk S">S.M. Chalk</name></author><author><name sortKey="Mcevoy, J D S" uniqKey="Mcevoy J">J.D.S. McEvoy</name></author><author><name sortKey="Donald, K J" uniqKey="Donald K">K.J. Donald</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ebi, N" uniqKey="Ebi N">N. Ebi</name></author><author><name sortKey="Yamamoto, H" uniqKey="Yamamoto H">H. Yamamoto</name></author><author><name sortKey="Sakai, J" uniqKey="Sakai J">J. Sakai</name></author><author><name sortKey="Sugahara, K" uniqKey="Sugahara K">K. Sugahara</name></author><author><name sortKey="Arimura, H" uniqKey="Arimura H">H. Arimura</name></author><author><name sortKey="Nakanishi, K" uniqKey="Nakanishi K">K. Nakanishi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bic, J F" uniqKey="Bic J">J.F. Bic</name></author><author><name sortKey="Fade Schneller, O" uniqKey="Fade Schneller O">O. Fade-Schneller</name></author><author><name sortKey="Marie, B" uniqKey="Marie B">B. Marie</name></author><author><name sortKey="Neimann, J L" uniqKey="Neimann J">J.L. Neimann</name></author><author><name sortKey="Anthoine, D" uniqKey="Anthoine D">D. Anthoine</name></author><author><name sortKey="Martinet, Y" uniqKey="Martinet Y">Y. Martinet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Romero Menor, C" uniqKey="Romero Menor C">C. Romero-Menor</name></author><author><name sortKey="Vadillo, M" uniqKey="Vadillo M">M. Vadillo</name></author><author><name sortKey="Martin, F" uniqKey="Martin F">F. Martin</name></author><author><name sortKey="Romagosa, V" uniqKey="Romagosa V">V. Romagosa</name></author><author><name sortKey="Corbella, X" uniqKey="Corbella X">X. Corbella</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nara, M" uniqKey="Nara M">M. Nara</name></author><author><name sortKey="Sasaki, T" uniqKey="Sasaki T">T. Sasaki</name></author><author><name sortKey="Shimura, S" uniqKey="Shimura S">S. Shimura</name></author><author><name sortKey="Yamamoto, M" uniqKey="Yamamoto M">M. Yamamoto</name></author><author><name sortKey="Oshiro, T" uniqKey="Oshiro T">T. Oshiro</name></author><author><name sortKey="Kaiwa, Y" uniqKey="Kaiwa Y">Y. Kaiwa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rai, S" uniqKey="Rai S">S. Rai</name></author><author><name sortKey="Barthwal, M" uniqKey="Barthwal M">M. Barthwal</name></author><author><name sortKey="Bhattacharya, P" uniqKey="Bhattacharya P">P. Bhattacharya</name></author><author><name sortKey="Bhargava, S" uniqKey="Bhargava S">S. Bhargava</name></author><author><name sortKey="Pethe, M" uniqKey="Pethe M">M. Pethe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bocklage, T" uniqKey="Bocklage T">T. Bocklage</name></author><author><name sortKey="Leslie, K" uniqKey="Leslie K">K. Leslie</name></author><author><name sortKey="Yousem, S" uniqKey="Yousem S">S. Yousem</name></author><author><name sortKey="Colby, T" uniqKey="Colby T">T. Colby</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tateishi, U" uniqKey="Tateishi U">U. Tateishi</name></author><author><name sortKey="Hasegawa, T" uniqKey="Hasegawa T">T. Hasegawa</name></author><author><name sortKey="Kusumoto, M" uniqKey="Kusumoto M">M. Kusumoto</name></author><author><name sortKey="Yamazaki, N" uniqKey="Yamazaki N">N. Yamazaki</name></author><author><name sortKey="Iinuma, G" uniqKey="Iinuma G">G. Iinuma</name></author><author><name sortKey="Muramatsu, Y" uniqKey="Muramatsu Y">Y. Muramatsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krenke, R" uniqKey="Krenke R">R. Krenke</name></author><author><name sortKey="Klimiuk, J" uniqKey="Klimiuk J">J. Klimiuk</name></author><author><name sortKey="Korczynski, P" uniqKey="Korczynski P">P. Korczynski</name></author><author><name sortKey="Kupis, W" uniqKey="Kupis W">W. Kupis</name></author><author><name sortKey="Szolkowska, M" uniqKey="Szolkowska M">M. Szolkowska</name></author><author><name sortKey="Chazan, R" uniqKey="Chazan R">R. Chazan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Guo, L" uniqKey="Guo L">L. Guo</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name></author><author><name sortKey="Feng, W" uniqKey="Feng W">W. Feng</name></author><author><name sortKey="Zhang, X Q" uniqKey="Zhang X">X.Q. Zhang</name></author><author><name sortKey="Ling, C H" uniqKey="Ling C">C.H. Ling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penel, N" uniqKey="Penel N">N. Penel</name></author><author><name sortKey="Marreaud, S" uniqKey="Marreaud S">S. Marreaud</name></author><author><name sortKey="Robin, Y M" uniqKey="Robin Y">Y.M. Robin</name></author><author><name sortKey="Hohenberger, R" uniqKey="Hohenberger R">R. Hohenberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fury, M G" uniqKey="Fury M">M.G. Fury</name></author><author><name sortKey="Antonescu, C R" uniqKey="Antonescu C">C.R. Antonescu</name></author><author><name sortKey="Van Zee, K J" uniqKey="Van Zee K">K.J. Van Zee</name></author><author><name sortKey="Brennan, M F" uniqKey="Brennan M">M.F. Brennan</name></author><author><name sortKey="Maki, R G" uniqKey="Maki R">R.G. Maki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penel, N" uniqKey="Penel N">N. Penel</name></author><author><name sortKey="Bui, B N" uniqKey="Bui B">B.N. Bui</name></author><author><name sortKey="Bay, J O" uniqKey="Bay J">J.O. Bay</name></author><author><name sortKey="Cupissol, D" uniqKey="Cupissol D">D. Cupissol</name></author><author><name sortKey="Ray Coquard, I" uniqKey="Ray Coquard I">I. Ray-Coquard</name></author><author><name sortKey="Piperno Neumann, S" uniqKey="Piperno Neumann S">S. Piperno-Neumann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stacchiotti, S" uniqKey="Stacchiotti S">S. Stacchiotti</name></author><author><name sortKey="Palassini, E" uniqKey="Palassini E">E. Palassini</name></author><author><name sortKey="Sanfilippo, R" uniqKey="Sanfilippo R">R. Sanfilippo</name></author><author><name sortKey="Vincenzi, B" uniqKey="Vincenzi B">B. Vincenzi</name></author><author><name sortKey="Arena, M G" uniqKey="Arena M">M.G. Arena</name></author><author><name sortKey="Bochicchio, A M" uniqKey="Bochicchio A">A.M. Bochicchio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leu, K M" uniqKey="Leu K">K.M. Leu</name></author><author><name sortKey="Ostruszka, L J" uniqKey="Ostruszka L">L.J. Ostruszka</name></author><author><name sortKey="Shewach, D" uniqKey="Shewach D">D. Shewach</name></author><author><name sortKey="Zalupski, M" uniqKey="Zalupski M">M. Zalupski</name></author><author><name sortKey="Sondak, V" uniqKey="Sondak V">V. Sondak</name></author><author><name sortKey="Biermann, J S" uniqKey="Biermann J">J.S. Biermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="European Sarcoma Network Working Group" uniqKey="European Sarcoma Network Working Group">European Sarcoma Network Working Group</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maki, R G" uniqKey="Maki R">R.G. Maki</name></author><author><name sortKey="D Adamo, D R" uniqKey="D Adamo D">D.R. D'Adamo</name></author><author><name sortKey="Keohan, M L" uniqKey="Keohan M">M.L. Keohan</name></author><author><name sortKey="Saulle, M" uniqKey="Saulle M">M. Saulle</name></author><author><name sortKey="Schuetze, S M" uniqKey="Schuetze S">S.M. Schuetze</name></author><author><name sortKey="Undevia, S D" uniqKey="Undevia S">S.D. Undevia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chugh, R" uniqKey="Chugh R">R. Chugh</name></author><author><name sortKey="Wathen, J K" uniqKey="Wathen J">J.K. Wathen</name></author><author><name sortKey="Maki, R G" uniqKey="Maki R">R.G. Maki</name></author><author><name sortKey="Benjamin, R S" uniqKey="Benjamin R">R.S. Benjamin</name></author><author><name sortKey="Patel, S R" uniqKey="Patel S">S.R. Patel</name></author><author><name sortKey="Meyers, P A" uniqKey="Meyers P">P.A. Meyers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agulnik, M" uniqKey="Agulnik M">M. Agulnik</name></author><author><name sortKey="Yarber, J L" uniqKey="Yarber J">J.L. Yarber</name></author><author><name sortKey="Okuno, S H" uniqKey="Okuno S">S.H. Okuno</name></author><author><name sortKey="Von Mehren, M" uniqKey="Von Mehren M">M. von Mehren</name></author><author><name sortKey="Jovanovic, B D" uniqKey="Jovanovic B">B.D. Jovanovic</name></author><author><name sortKey="Brockstein, B E" uniqKey="Brockstein B">B.E. Brockstein</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="other"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Respir Med Case Rep</journal-id><journal-id journal-id-type="iso-abbrev">Respir Med Case Rep</journal-id><journal-title-group><journal-title>Respiratory Medicine Case Reports</journal-title></journal-title-group><issn pub-type="epub">2213-0071</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26029560</article-id><article-id pub-id-type="pmc">4246356</article-id><article-id pub-id-type="publisher-id">S2213-0071(14)00041-0</article-id><article-id pub-id-type="doi">10.1016/j.rmcr.2014.08.001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Report</subject></subj-group></article-categories><title-group><article-title>A rare cause of hemoptysis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Aversa</surname><given-names>Meghan</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bhinder</surname><given-names>Sacha</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tanguay</surname><given-names>Jeffrey</given-names></name></contrib><contrib contrib-type="author"><name><surname>Thenganatt</surname><given-names>John</given-names></name><email>john.thenganatt@uhn.ca</email><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1">Division of Respirology, Department of Medicine, Toronto General Hospital, 585 University Avenue, 9N-965, Toronto ON, M5G 2N2, Canada</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Tel.: +1 (416) 340 4800x4591; fax: +1 (416) 340 3109. <email>john.thenganatt@uhn.ca</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>28</day><month>9</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>28</day><month>9</month><year>2014</year></pub-date><volume>13</volume><fpage>48</fpage><lpage>50</lpage><permissions><copyright-statement>© 2014 The Authors</copyright-statement><copyright-year>2014</copyright-year><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).</license-p></license></permissions><abstract><p>Angiosarcomas are rare, malignant, endothelial-cell tumors of vascular origin that can arise at any body site. They frequently metastasize to the lung, heralded by dyspnea, hemoptysis, chest pain, pneumothoraces, and diffuse pulmonary hemorrhage. However, in most cases lung metastases are discovered after the diagnosis of a primary angiosarcoma has already been established. Very rarely will an undiagnosed metastatic angiosarcoma present as diffuse pulmonary hemorrhage. We describe the case of a 59-year-old male who presented to hospital with dyspnea and hemoptysis. CT chest revealed rapidly progressing nodular changes and broncho-alveolar lavage returns were progressively bloody. Open lung wedge biopsy ultimately revealed metastatic angiosarcoma and extensive pulmonary hemorrhage. Our case highlights the key clinical, radiological, and pathological features of this rare malignancy that frequently metastasizes to the lung and reminds clinicians to consider it as a cause of hemoptysis and pulmonary hemorrhage.</p></abstract><kwd-group><title>Keywords</title><kwd>Metastatic angiosarcoma</kwd><kwd>Diffuse pulmonary hemorrhage</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="sec1"><label>1</label><title>Introduction</title><p>We describe the case of a 59-year-old male who presented to hospital with diffuse pulmonary hemorrhage caused by an undiagnosed metastatic angiosarcoma. We highlight the key clinical, radiological, and pathological features of this rare malignancy that frequently metastasizes to the lung.</p></sec><sec id="sec2"><label>2</label><title>Case presentation</title><p>A 59-year-old non-smoking male of Chinese origin presented to hospital with a one-month history of worsening dyspnea and hemoptysis after recent travel to rural China. He denied fever or other constitutional symptoms. His symptoms had persisted despite completing two courses of antibiotics. His past medical history was significant for hypertension, type 2 diabetes mellitus, dyslipidemia, and thalassemia trait.</p><p>On presentation to hospital, the patient was hypoxic on room air and he had a low-grade fever. Physical examination was remarkable only for bilateral crackles on lung auscultation. No abnormal ocular, joint, or skin findings were noted. Blood work was remarkable only for microcytic anemia. Anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), and anti-glomerular basement membrane (anti-GBM) antibody testing were negative. Chest CT revealed bilateral, multifocal, nodular changes with surrounding ground-glass attenuation and consolidation (<xref rid="fig1" ref-type="fig">Figure 1</xref>A).</p><p>Bronchoscopy with broncho-alveolar lavage (BAL) was performed and the BAL returns were progressively bloody. BAL cultures were negative for acid-fast bacilli, viral, bacterial, and fungal pathogens; cytology was negative for malignant cells and hemosiderin-laden macrophages.</p><p>The case was reviewed at the weekly Respirology-Radiology rounds, and it was decided to send the patient for an open lung biopsy via video-assisted thoracic surgery (VATS). Shortly after the biopsy was performed, the patient became more hypoxic and a repeat CT chest was performed. Compared to the CT chest just two weeks prior, there was significant interval worsening of the nodular changes and ground-glass opacities. There was no evidence of pulmonary embolus (<xref rid="fig1" ref-type="fig">Figure 1</xref>B).</p><p>The biopsies revealed multiple foci of highly mitotically active spindle cells with enlarged nuclei within the lumen of multiple pulmonary arteries. At multiple sites these cells invaded through the pulmonary artery and infiltrated the surrounding lung parenchyma. Extensive pulmonary hemorrhage, acute and organizing diffuse alveolar damage, and pulmonary infarcts were also noted. The spindle cells stained positive for CD31, CD34, and vimentin (<xref rid="fig2" ref-type="fig">Figure 2</xref>). The histological features, immunohistochemical staining pattern, intravascular nature, and multifocality of the tumor were consistent with a metastatic angiosarcoma.</p><p>The patient was seen by Medical Oncology, but was not a candidate for chemotherapy due to his poor clinical status and rapid deterioration. Further imaging to identify the primary angiosarcoma or other areas of metastasis prior to his death was also deferred. The patient expired twenty-two days after admission. The patient's family declined autopsy.</p></sec><sec sec-type="discussion" id="sec3"><label>3</label><title>Discussion</title><p>Angiosarcomas are rare, malignant, endothelial-cell tumors of vascular origin that represent less than 2% of all sarcomas <xref rid="bib1" ref-type="bibr">[1]</xref>. Although they most commonly arise in the skin, angiosarcomas can originate at any site, including the breast, liver, bone, spleen, heart, and lung. Patients with chronic lymphedema or a history of radiation exposure are at increased risk of developing angiosarcomas. Less common risk factors include exposure to vinyl chloride, thorium dioxide, arsenic, and immunosuppression (post liver and kidney transplantation) <xref rid="bib2" ref-type="bibr">[2]</xref>.</p><p>Pulmonary angiosarcomas represent metastases in the vast majority of cases. Angiosarcomas from all sites frequently metastasize via hematologic spread to the lung, heralded by dyspnea, hemoptysis, chest pain, pneumothoraces, or diffuse pulmonary hemorrhage <xref rid="bib1" ref-type="bibr">[1]</xref>. However, in most cases lung metastases are discovered after the diagnosis of a primary angiosarcoma has already been established <xref rid="bib3" ref-type="bibr">[3]</xref>. Very rarely will an undiagnosed metastatic angiosarcoma present as diffuse pulmonary hemorrhage, as in the case of our patient <xref rid="bib3 bib4 bib5 bib6 bib7 bib8 bib9 bib10" ref-type="bibr">[3–10]</xref>. In these rare cases, the occult primary angiosarcoma is usually not identified ante-mortem but is most often found to be in the right atrium on autopsy <xref rid="bib3" ref-type="bibr">[3]</xref>. There are no histological features of the pulmonary metastases that may portend the primary site <xref rid="bib11" ref-type="bibr">[11]</xref>.</p><p>As demonstrated in our patient's CT, key radiographic features of a metastatic angiosarcoma in the lung can include multiple bilateral, solid nodules, ground-glass opacities representing pulmonary hemorrhage, and interlobular septal thickening indicating lymphangitic spread. Metastases have also been reported as multiple thin-walled cysts, or as a mixed pattern of solid nodules and thin-walled cysts <xref rid="bib12" ref-type="bibr">[12]</xref>.</p><p>Exceedingly rare cases of primary pulmonary angiosarcomas have been reported. Not surprisingly, primary pulmonary angiosarcomas present very similarly to metastatic angiosarcomas in the lung, with dyspnea and hemoptysis being the most commonly cited symptoms <xref rid="bib13" ref-type="bibr">[13]</xref>. On chest CT, a primary pulmonary angiosarcoma appears as either a solitary mass or multiple nodules in cases of multifocal growth <xref rid="bib14" ref-type="bibr">[14]</xref>. If the tumor invades the pleural space, pleural effusions or pneumothoraces can be seen <xref rid="bib13" ref-type="bibr">[13]</xref>. Differentiating a primary pulmonary angiosarcoma from metastases can be challenging, especially in cases of widespread organ involvement. As primary pulmonary angiosarcomas are typically characterized by more insidious growth <xref rid="bib14" ref-type="bibr">[14]</xref>, we felt that the extremely rapid progression of our patient's disease as captured with CT imaging was more in keeping with a metastatic angiosarcoma.</p><p>As demonstrated in this case, patients with metastatic angiosarcomas usually deteriorate quickly; the average survival from time of diagnosis is 9 months <xref rid="bib1" ref-type="bibr">[1]</xref>. Palliative chemotherapy is the mainstay of treatment for metastatic angiosarcomas, although current recommendations are based on limited evidence from small retrospective or phase 2 studies <xref rid="bib15" ref-type="bibr">[15]</xref>. Doxorubicin-based regimens have been shown to yield progression-free survival of 3.7–5.4 months in patients with unresectable angiosarcomas <xref rid="bib16" ref-type="bibr">[16]</xref>, and are considered first-line treatment <xref rid="bib15" ref-type="bibr">[15]</xref>. Specifically, doxorubicin plus ifosfamide is often used as this combination was shown to increase progression-free survival by an average of 1.7 months compared to doxorubicin alone <xref rid="bib16" ref-type="bibr">[16]</xref>. In 2008, a phase 2 study showed that weekly administration of paclitaxel achieved a nonprogression rate of 74% at two months and 42% at four months in patients with metastatic or unresectable angiosarcomas <xref rid="bib17" ref-type="bibr">[17]</xref>. Two retrospective case series have also indicated that gemcitabine, with or without the addition of docetaxel, may confer a clinical response in patients with metastatic angiosarcomas <xref rid="bib18 bib19" ref-type="bibr">[18,19]</xref>. As such, the 2012 European Society for Medical Oncology Clinical Practice Guidelines recommend a doxorubicin-based regimen for metastatic angiosarcomas, but consider taxanes or gemcitabine (with or without docetaxel) to be acceptable alternatives <xref rid="bib20" ref-type="bibr">[20]</xref>.</p><p>Molecular targeted therapies have recently come into light as potentially promising treatment options for metastatic angiosarcomas. In two phase 2 studies, the tyrosine kinase inhibitors sorafenib and imatinib yielded progression-free survival of 3.8 and 2.76 months, respectively, in patients with metastatic angiosarcomas <xref rid="bib21 bib22" ref-type="bibr">[21,22]</xref>. Very recently, a phase 2 study demonstrated that bevacizumab, a monoclonal antibody to circulating vascular endothelial growth factor (VEGF), achieves a median progression-free survival of 12 weeks in patients with metastatic or locally advanced angiosarcomas <xref rid="bib23" ref-type="bibr">[23]</xref>.</p></sec><sec sec-type="conclusions" id="sec4"><label>4</label><title>Conclusion</title><p>As our case illustrates, metastatic angiosarcomas in the lung can present with dyspnea, hemoptysis, chest pain, pneumothoraces, or diffuse pulmonary hemorrhage <xref rid="bib1" ref-type="bibr">[1]</xref>. Angiosarcomas most commonly arise in the skin, breast, liver, bone, spleen, and heart. The lung is the most frequent site of metastatic spread but is rarely the site of the primary tumor <xref rid="bib2" ref-type="bibr">[2]</xref>. Chest CT may reveal multiple bilateral, solid nodules with ground-glass opacities, multiple thin-walled cysts, or a mixed pattern of solid nodules and thin-walled cysts <xref rid="bib12" ref-type="bibr">[12]</xref>. The prognosis of metastatic angiosarcoma averages 9 months <xref rid="bib1" ref-type="bibr">[1]</xref>. Palliative chemotherapy using doxorubicin, taxanes, or gemcitabine (with or without docetaxel) is the treatment of choice <xref rid="bib20" ref-type="bibr">[20]</xref>. Further phase 3 studies are needed to determine the role of molecular targeted therapies in the management of patients with metastatic angiosarcomas in the future.</p></sec></body><back><ref-list><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Patel</surname><given-names>A.M.</given-names></name><name><surname>Ryu</surname><given-names>J.H.</given-names></name></person-group><article-title>Angiosarcoma in the lung</article-title><source>Chest</source><volume>103</volume><year>1993</year><fpage>1531</fpage><lpage>1535</lpage><pub-id pub-id-type="pmid">8486039</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="journal" id="sref2"><person-group person-group-type="author"><name><surname>Ravi</surname><given-names>V.</given-names></name><name><surname>Patel</surname><given-names>S.</given-names></name></person-group><article-title>Vascular sarcomas</article-title><source>Curr Oncol Rep</source><volume>15</volume><year>2013</year><fpage>347</fpage><lpage>355</lpage><pub-id pub-id-type="pmid">23852636</pub-id></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal" id="sref3"><person-group person-group-type="author"><name><surname>Adem</surname><given-names>C.</given-names></name><name><surname>Aubry</surname><given-names>M.C.</given-names></name><name><surname>Tazelaar</surname><given-names>H.D.</given-names></name><name><surname>Myers</surname><given-names>J.L.</given-names></name></person-group><article-title>Metastatic angiosarcoma masquerading as diffuse pulmonary hemorrhage: clinicopathologic analysis of 7 new patients</article-title><source>Arch Pathol Lab Med</source><volume>125</volume><year>2001</year><fpage>1562</fpage><lpage>1565</lpage><pub-id pub-id-type="pmid">11735690</pub-id></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal" id="sref4"><person-group person-group-type="author"><name><surname>Zwaveling</surname><given-names>J.H.</given-names></name><name><surname>van Berkhout</surname><given-names>F.T.</given-names></name><name><surname>Haneveld</surname><given-names>G.T.</given-names></name></person-group><article-title>Angiosarcoma of the heart presenting as pulmonary disease</article-title><source>Chest</source><volume>94</volume><year>1988</year><fpage>216</fpage><lpage>218</lpage><pub-id pub-id-type="pmid">3383642</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sref5"><person-group person-group-type="author"><name><surname>Edwards</surname><given-names>R.L.</given-names></name><name><surname>Chalk</surname><given-names>S.M.</given-names></name><name><surname>McEvoy</surname><given-names>J.D.S.</given-names></name><name><surname>Donald</surname><given-names>K.J.</given-names></name></person-group><article-title>Pulmonary haemorrhage in disseminated cardiac haemangiosarcoma</article-title><source>Br J Dis Chest</source><volume>71</volume><year>1977</year><fpage>127</fpage><lpage>131</lpage><pub-id pub-id-type="pmid">558787</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sref6"><person-group person-group-type="author"><name><surname>Ebi</surname><given-names>N.</given-names></name><name><surname>Yamamoto</surname><given-names>H.</given-names></name><name><surname>Sakai</surname><given-names>J.</given-names></name><name><surname>Sugahara</surname><given-names>K.</given-names></name><name><surname>Arimura</surname><given-names>H.</given-names></name><name><surname>Nakanishi</surname><given-names>K.</given-names></name></person-group><article-title>Angiosarcoma of the heart presenting as fatal pulmonary hemorrhage</article-title><source>Intern Med</source><volume>36</volume><year>1997</year><fpage>191</fpage><lpage>193</lpage><pub-id pub-id-type="pmid">9144011</pub-id></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="journal" id="sref7"><person-group person-group-type="author"><name><surname>Bic</surname><given-names>J.F.</given-names></name><name><surname>Fade-Schneller</surname><given-names>O.</given-names></name><name><surname>Marie</surname><given-names>B.</given-names></name><name><surname>Neimann</surname><given-names>J.L.</given-names></name><name><surname>Anthoine</surname><given-names>D.</given-names></name><name><surname>Martinet</surname><given-names>Y.</given-names></name></person-group><article-title>Cardiac angiosarcoma revealed by lung metastases</article-title><source>Eur Respir J</source><volume>7</volume><year>1994</year><fpage>1194</fpage><lpage>1196</lpage><pub-id pub-id-type="pmid">7925894</pub-id></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal" id="sref8"><person-group person-group-type="author"><name><surname>Romero-Menor</surname><given-names>C.</given-names></name><name><surname>Vadillo</surname><given-names>M.</given-names></name><name><surname>Martin</surname><given-names>F.</given-names></name><name><surname>Romagosa</surname><given-names>V.</given-names></name><name><surname>Corbella</surname><given-names>X.</given-names></name></person-group><article-title>Cardiac angiosarcoma presenting as diffuse pulmonary disease</article-title><source>Eur Heart J</source><volume>16</volume><year>1995</year><fpage>2005</fpage><lpage>2006</lpage><pub-id pub-id-type="pmid">8682042</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sref9"><person-group person-group-type="author"><name><surname>Nara</surname><given-names>M.</given-names></name><name><surname>Sasaki</surname><given-names>T.</given-names></name><name><surname>Shimura</surname><given-names>S.</given-names></name><name><surname>Yamamoto</surname><given-names>M.</given-names></name><name><surname>Oshiro</surname><given-names>T.</given-names></name><name><surname>Kaiwa</surname><given-names>Y.</given-names></name></person-group><article-title>Diffuse alveolar hemorrhage caused by lung metastasis of ovarian angiosarcoma</article-title><source>Intern Med</source><volume>35</volume><year>1996</year><fpage>653</fpage><lpage>656</lpage><pub-id pub-id-type="pmid">8894742</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal" id="sref10"><person-group person-group-type="author"><name><surname>Rai</surname><given-names>S.</given-names></name><name><surname>Barthwal</surname><given-names>M.</given-names></name><name><surname>Bhattacharya</surname><given-names>P.</given-names></name><name><surname>Bhargava</surname><given-names>S.</given-names></name><name><surname>Pethe</surname><given-names>M.</given-names></name></person-group><article-title>Metastatic angiosarcoma presenting as diffuse alveolar hemorrhage</article-title><source>Lung India</source><volume>25</volume><year>2008</year><fpage>14</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">20396655</pub-id></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sref11"><person-group person-group-type="author"><name><surname>Bocklage</surname><given-names>T.</given-names></name><name><surname>Leslie</surname><given-names>K.</given-names></name><name><surname>Yousem</surname><given-names>S.</given-names></name><name><surname>Colby</surname><given-names>T.</given-names></name></person-group><article-title>Extracutaneous angiosarcomas metastatic to the lungs: clinical and pathologic features of twenty-one cases</article-title><source>Mod Pathol</source><volume>14</volume><year>2001</year><fpage>1216</fpage><lpage>1225</lpage><pub-id pub-id-type="pmid">11743043</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal" id="sref12"><person-group person-group-type="author"><name><surname>Tateishi</surname><given-names>U.</given-names></name><name><surname>Hasegawa</surname><given-names>T.</given-names></name><name><surname>Kusumoto</surname><given-names>M.</given-names></name><name><surname>Yamazaki</surname><given-names>N.</given-names></name><name><surname>Iinuma</surname><given-names>G.</given-names></name><name><surname>Muramatsu</surname><given-names>Y.</given-names></name></person-group><article-title>Metastatic angiosarcoma of the lung: spectrum of CT findings</article-title><source>AJR Am J Roentgenol</source><volume>180</volume><year>2003</year><fpage>1671</fpage><lpage>1674</lpage><pub-id pub-id-type="pmid">12760941</pub-id></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal" id="sref13"><person-group person-group-type="author"><name><surname>Krenke</surname><given-names>R.</given-names></name><name><surname>Klimiuk</surname><given-names>J.</given-names></name><name><surname>Korczynski</surname><given-names>P.</given-names></name><name><surname>Kupis</surname><given-names>W.</given-names></name><name><surname>Szolkowska</surname><given-names>M.</given-names></name><name><surname>Chazan</surname><given-names>R.</given-names></name></person-group><article-title>Hemoptysis and spontaneous hemothorax in a patient with multifocal nodular lung lesions</article-title><source>Chest</source><volume>140</volume><year>2011</year><fpage>245</fpage><lpage>251</lpage><pub-id pub-id-type="pmid">21729897</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="journal" id="sref14"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>Y.</given-names></name><name><surname>Guo</surname><given-names>L.</given-names></name><name><surname>Yang</surname><given-names>L.</given-names></name><name><surname>Feng</surname><given-names>W.</given-names></name><name><surname>Zhang</surname><given-names>X.Q.</given-names></name><name><surname>Ling</surname><given-names>C.H.</given-names></name></person-group><article-title>Angiosarcoma of the lung: 2 case reports and literature reviewed</article-title><source>Lung Cancer</source><volume>70</volume><year>2010</year><fpage>352</fpage><lpage>356</lpage><pub-id pub-id-type="pmid">20952087</pub-id></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal" id="sref15"><person-group person-group-type="author"><name><surname>Penel</surname><given-names>N.</given-names></name><name><surname>Marreaud</surname><given-names>S.</given-names></name><name><surname>Robin</surname><given-names>Y.M.</given-names></name><name><surname>Hohenberger</surname><given-names>R.</given-names></name></person-group><article-title>Angiosarcoma: state of the art and perspectives</article-title><source>Crit Rev Oncol Hematol</source><volume>80</volume><year>2011</year><fpage>257</fpage><lpage>263</lpage><pub-id pub-id-type="pmid">21055965</pub-id></element-citation></ref><ref id="bib16"><label>16</label><element-citation publication-type="journal" id="sref16"><person-group person-group-type="author"><name><surname>Fury</surname><given-names>M.G.</given-names></name><name><surname>Antonescu</surname><given-names>C.R.</given-names></name><name><surname>Van Zee</surname><given-names>K.J.</given-names></name><name><surname>Brennan</surname><given-names>M.F.</given-names></name><name><surname>Maki</surname><given-names>R.G.</given-names></name></person-group><article-title>A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy</article-title><source>Cancer J</source><volume>11</volume><year>2005</year><fpage>241</fpage><lpage>247</lpage><pub-id pub-id-type="pmid">16053668</pub-id></element-citation></ref><ref id="bib17"><label>17</label><element-citation publication-type="journal" id="sref17"><person-group person-group-type="author"><name><surname>Penel</surname><given-names>N.</given-names></name><name><surname>Bui</surname><given-names>B.N.</given-names></name><name><surname>Bay</surname><given-names>J.O.</given-names></name><name><surname>Cupissol</surname><given-names>D.</given-names></name><name><surname>Ray-Coquard</surname><given-names>I.</given-names></name><name><surname>Piperno-Neumann</surname><given-names>S.</given-names></name></person-group><article-title>Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the AngioTax study</article-title><source>J Clin Oncol</source><volume>26</volume><year>2008</year><fpage>5269</fpage><lpage>5274</lpage><pub-id pub-id-type="pmid">18809609</pub-id></element-citation></ref><ref id="bib18"><label>18</label><element-citation publication-type="journal" id="sref18"><person-group person-group-type="author"><name><surname>Stacchiotti</surname><given-names>S.</given-names></name><name><surname>Palassini</surname><given-names>E.</given-names></name><name><surname>Sanfilippo</surname><given-names>R.</given-names></name><name><surname>Vincenzi</surname><given-names>B.</given-names></name><name><surname>Arena</surname><given-names>M.G.</given-names></name><name><surname>Bochicchio</surname><given-names>A.M.</given-names></name></person-group><article-title>Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network</article-title><source>Ann Oncol</source><volume>23</volume><year>2012</year><fpage>501</fpage><lpage>508</lpage><pub-id pub-id-type="pmid">21464156</pub-id></element-citation></ref><ref id="bib19"><label>19</label><element-citation publication-type="journal" id="sref19"><person-group person-group-type="author"><name><surname>Leu</surname><given-names>K.M.</given-names></name><name><surname>Ostruszka</surname><given-names>L.J.</given-names></name><name><surname>Shewach</surname><given-names>D.</given-names></name><name><surname>Zalupski</surname><given-names>M.</given-names></name><name><surname>Sondak</surname><given-names>V.</given-names></name><name><surname>Biermann</surname><given-names>J.S.</given-names></name></person-group><article-title>Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma</article-title><source>J Clin Oncol</source><volume>22</volume><year>2004</year><fpage>1706</fpage><lpage>1712</lpage><pub-id pub-id-type="pmid">15117993</pub-id></element-citation></ref><ref id="bib20"><label>20</label><element-citation publication-type="journal" id="sref20"><person-group person-group-type="author"><name><surname>European Sarcoma Network Working Group</surname></name></person-group><article-title>Soft tissue and visceral sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up</article-title><source>Ann Oncol</source><volume>23</volume><issue>Suppl. 7</issue><year>2012</year><fpage>vii92</fpage><lpage>vii99</lpage><pub-id pub-id-type="pmid">22997462</pub-id></element-citation></ref><ref id="bib21"><label>21</label><element-citation publication-type="journal" id="sref21"><person-group person-group-type="author"><name><surname>Maki</surname><given-names>R.G.</given-names></name><name><surname>D'Adamo</surname><given-names>D.R.</given-names></name><name><surname>Keohan</surname><given-names>M.L.</given-names></name><name><surname>Saulle</surname><given-names>M.</given-names></name><name><surname>Schuetze</surname><given-names>S.M.</given-names></name><name><surname>Undevia</surname><given-names>S.D.</given-names></name></person-group><article-title>Phase II study of sorafenib in patients with metastatic or recurrent sarcomas</article-title><source>J Clin Oncol</source><volume>27</volume><year>2009</year><fpage>3133</fpage><lpage>3140</lpage><pub-id pub-id-type="pmid">19451436</pub-id></element-citation></ref><ref id="bib22"><label>22</label><element-citation publication-type="journal" id="sref22"><person-group person-group-type="author"><name><surname>Chugh</surname><given-names>R.</given-names></name><name><surname>Wathen</surname><given-names>J.K.</given-names></name><name><surname>Maki</surname><given-names>R.G.</given-names></name><name><surname>Benjamin</surname><given-names>R.S.</given-names></name><name><surname>Patel</surname><given-names>S.R.</given-names></name><name><surname>Meyers</surname><given-names>P.A.</given-names></name></person-group><article-title>Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a Bayesian hierarchial statistical model</article-title><source>J Clin Oncol</source><volume>27</volume><year>2009</year><fpage>3148</fpage><lpage>3153</lpage><pub-id pub-id-type="pmid">19451433</pub-id></element-citation></ref><ref id="bib23"><label>23</label><element-citation publication-type="journal" id="sref23"><person-group person-group-type="author"><name><surname>Agulnik</surname><given-names>M.</given-names></name><name><surname>Yarber</surname><given-names>J.L.</given-names></name><name><surname>Okuno</surname><given-names>S.H.</given-names></name><name><surname>von Mehren</surname><given-names>M.</given-names></name><name><surname>Jovanovic</surname><given-names>B.D.</given-names></name><name><surname>Brockstein</surname><given-names>B.E.</given-names></name></person-group><article-title>An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas</article-title><source>Ann Oncol</source><volume>24</volume><year>2013</year><fpage>257</fpage><lpage>263</lpage><pub-id pub-id-type="pmid">22910841</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="fig1"><label>Fig. 1</label><caption><p>CT chest showing bilateral, multifocal, nodulor changes with surrounding ground-glass attenuation and consolidation (A). CT chest obtained two weeks later showing interval worsening of the nodular changes, ground-glass attenuation, and consolidation bilaterally (B).</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Fig. 2</label><caption><p>A low-magnification photomicrograph illustrating several pulmonary vessels containing the highly mitotically active spindle cells with enlarged nuclei (A,arrows). A high-magnification view illustrating a single branching pulmonary vessels containing the spindle cell lesion (B,arrows).</p></caption><graphic xlink:href="gr2"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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