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Patient With Leukocytosis and Persistent Dry Cough
Discussion
An interdisciplinary discussion regarding the diagnosis considered the clinical features of the patient along with the imaging characteristics. The histological examination demonstrating sarcomatoid features with the supporting immunohistochemistry that confirmed both mesenchymal and epithelioid presence and was used to make the diagnosis of pulmonary sarcomatoid carcinoma (PSC).
The incidence of PSC ranges between 0.1% and 0.4% of all lung malignancies.1,4-7 PSC usually occurs in older men whose weight is moderate to heavy and who smoke. PSC appears to have an upper lobe predilection; also, these tumors tend to be bulky with invasive tendency, early recurrence, and systemic metastases. PSC frequently involves the adjacent lung, chest wall, diaphragm, pericardium, and other tissues.1-5 The source of the sarcoma component of the PSC remains uncertain. However, prior research suggests that it is associated with a clonal evolution that induces epidermal and mesenchymal tumor histological characteristics.1,8,9 The tumor cell epithelial-mesenchymal transition may induce transformation of the carcinoma component of PSC to into a sarcoma component. The epithelial-mesenchymal transition is associated with the PSC high risk for invasiveness and induces metastasis sites, such as the esophagus, colon, rectum, kidneys, and the common sites of NSCLC.
The most common symptoms include productive cough, chest congestion, and chest pain.1,7 In view of PSC’s clinical presentation and imaging, numerous differential diagnoses should be considered, such as sarcomatoid carcinomas, primary or secondary metastatic sarcomas, malignant melanoma, and pleural mesothelioma.6,10
The tumor is initially identified by a chest CT, confirmed by histology and immunohistochemistry. Several biomarkers are useful for diagnosis and classification of an undifferentiated neoplasm/tumor of uncertain origin. Those biomarkers help to understand the tumor pathobiology, to select the therapeutic regimen, and to predict the patient’s outcome. Although immunohistochemical staining of epithelial and mesenchymal markers can be helpful, a reliable diagnosis requires a precise histopathological examination. This is often difficult on small biopsy samples, such as fine-needle aspiration, as all the histological elements of PSC required to make the correct evaluation may not be present. Adequate sampling to generate a considerable number of histological slides is essential for an accurate diagnosis, which can be reached only with surgical resection.5
Due to rarity, rapid progression, short survival, and heterogeneous pathological qualities, PSC has been difficult to formulate treatment recommendations. Compared with other histological subtypes of NSCLC, PSC is more aggressive and has a poor prognosis. Survival time on average is about 13.3 months due to early metastasis, lower than other types of NSCLC. The greatest overall survival (OS) benefit has been shown with surgery in early-stage operable PSC, which remains the standard of care. Because most patients with PSC present in the advanced stage, they lose their opportunity for curative surgery. Auxiliary methods of treatment include radiotherapy and chemotherapy. Prior studies have shown that systemic chemotherapy efficacy has varied, some showing no OS benefit; others showing a modest benefit. It has also been noted that advanced-stage PSC has minimal response to chemotherapy. Further larger prospective studies are needed to outline the efficacy and role of systemic chemotherapy and other therapeutic agents, including targeted therapies and immunotherapy.1,4,11-13 However, two-thirds of patients are not sensitive to conventional chemotherapy. In comparison with other types of NSCLC, PSC carries a poor prognosis even in early-stage disease or if tumor metastasis is present. Therefore, further research on novel treatment options is needed to improve long-term survival.1,3-8
Conclusions
PSC is diagnostically challenging because it is rare and has an aggressive progression. Identification of this tumor requires knowledge of histological criteria to identify their subtypes. Immunohistochemistry has an important role in the classification and to rule out differential diagnoses, including metastatic spread. Nevertheless, a reliable diagnosis requires precise histopathological examination, reached with surgical resection. Therefore, a detailed history, physical examination, systematic investigation, and correlation with chest imaging are needed to avoid misdiagnosis.
Our case highlights the importance of keeping this rare, aggressive tumor as part of the differential diagnosis. In view of its natural history, heterogeneity, and low incidence, published cases of PSC are limited. Thus, further investigation could optimize rapid identification and treatment options.
1. Qin Z, Huang B, Yu G, Zheng Y, Zhao K. Gingival metastasis of a mediastinal pulmonary sarcomatoid carcinoma: a case report. J Cardiothorac Surg. 2019;14(1):161. Published 2019 Sep 9. doi:10.1186/s13019-019-0991-y
2. Travis WD, Brambilla E, Nicholson AG, et al; WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-1260. doi:10.1097/JTO.0000000000000630
3. Yendamuri S, Caty L, Pine M, et al. Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis. Surgery. 2012;152(3):397-402. doi:10.1016/j.surg.2012.05.007
4. Karim NA, Schuster J, Eldessouki I, et al. Pulmonary sarcomatoid carcinoma: University of Cincinnati experience. Oncotarget. 2017;9(3):4102-4108. Published 2017 Dec 18. doi:10.18632/oncotarget.23468
5. Weissferdt A. Pulmonary sarcomatoid carcinomas: a review. Adv Anat Pathol. 2018;25(5):304-313. doi:10.1097/PAP.0000000000000202
6. Roesel C, Terjung S, Weinreich G, et al. Sarcomatoid carcinoma of the lung: a rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages. Interact Cardiovasc Thorac Surg. 2017;24(3):407-413. doi:10.1093/icvts/ivw392
7. Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med. 2010;134(1):49-54. doi:10.5858/2008-0547-RAR.1
8. Thomas VT, Hinson S, Konduri K. Epithelial-mesenchymal transition in pulmonary carcinosarcoma: case report and literature review. Ther Adv Med Oncol. 2012;4(1):31-37. doi:10.1177/1758834011421949
9. Chang YL, Wu CT, Shih JY, Lee YC. EGFR and p53 status of pulmonary pleomorphic carcinoma: implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy. Ann Surg Oncol. 2011;18(10):2952-2960. doi:10.1245/s10434-011-1621-7
10. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, eds. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. International Agency for Research on Cancer; 2015:88-94.
11. Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases. World J Surg Oncol. 2013;11:252. Published 2013 Oct 2. doi:10.1186/1477-7819-11-252
12. Pelosi G, Sonzogni A, De Pas T, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol. 2010;18(2):103-120. doi:10.1177/1066896908330049
13. Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med. 2014;138(12):1583-1610. doi:10.5858/arpa.2014-0061-RA
Discussion
An interdisciplinary discussion regarding the diagnosis considered the clinical features of the patient along with the imaging characteristics. The histological examination demonstrating sarcomatoid features with the supporting immunohistochemistry that confirmed both mesenchymal and epithelioid presence and was used to make the diagnosis of pulmonary sarcomatoid carcinoma (PSC).
The incidence of PSC ranges between 0.1% and 0.4% of all lung malignancies.1,4-7 PSC usually occurs in older men whose weight is moderate to heavy and who smoke. PSC appears to have an upper lobe predilection; also, these tumors tend to be bulky with invasive tendency, early recurrence, and systemic metastases. PSC frequently involves the adjacent lung, chest wall, diaphragm, pericardium, and other tissues.1-5 The source of the sarcoma component of the PSC remains uncertain. However, prior research suggests that it is associated with a clonal evolution that induces epidermal and mesenchymal tumor histological characteristics.1,8,9 The tumor cell epithelial-mesenchymal transition may induce transformation of the carcinoma component of PSC to into a sarcoma component. The epithelial-mesenchymal transition is associated with the PSC high risk for invasiveness and induces metastasis sites, such as the esophagus, colon, rectum, kidneys, and the common sites of NSCLC.
The most common symptoms include productive cough, chest congestion, and chest pain.1,7 In view of PSC’s clinical presentation and imaging, numerous differential diagnoses should be considered, such as sarcomatoid carcinomas, primary or secondary metastatic sarcomas, malignant melanoma, and pleural mesothelioma.6,10
The tumor is initially identified by a chest CT, confirmed by histology and immunohistochemistry. Several biomarkers are useful for diagnosis and classification of an undifferentiated neoplasm/tumor of uncertain origin. Those biomarkers help to understand the tumor pathobiology, to select the therapeutic regimen, and to predict the patient’s outcome. Although immunohistochemical staining of epithelial and mesenchymal markers can be helpful, a reliable diagnosis requires a precise histopathological examination. This is often difficult on small biopsy samples, such as fine-needle aspiration, as all the histological elements of PSC required to make the correct evaluation may not be present. Adequate sampling to generate a considerable number of histological slides is essential for an accurate diagnosis, which can be reached only with surgical resection.5
Due to rarity, rapid progression, short survival, and heterogeneous pathological qualities, PSC has been difficult to formulate treatment recommendations. Compared with other histological subtypes of NSCLC, PSC is more aggressive and has a poor prognosis. Survival time on average is about 13.3 months due to early metastasis, lower than other types of NSCLC. The greatest overall survival (OS) benefit has been shown with surgery in early-stage operable PSC, which remains the standard of care. Because most patients with PSC present in the advanced stage, they lose their opportunity for curative surgery. Auxiliary methods of treatment include radiotherapy and chemotherapy. Prior studies have shown that systemic chemotherapy efficacy has varied, some showing no OS benefit; others showing a modest benefit. It has also been noted that advanced-stage PSC has minimal response to chemotherapy. Further larger prospective studies are needed to outline the efficacy and role of systemic chemotherapy and other therapeutic agents, including targeted therapies and immunotherapy.1,4,11-13 However, two-thirds of patients are not sensitive to conventional chemotherapy. In comparison with other types of NSCLC, PSC carries a poor prognosis even in early-stage disease or if tumor metastasis is present. Therefore, further research on novel treatment options is needed to improve long-term survival.1,3-8
Conclusions
PSC is diagnostically challenging because it is rare and has an aggressive progression. Identification of this tumor requires knowledge of histological criteria to identify their subtypes. Immunohistochemistry has an important role in the classification and to rule out differential diagnoses, including metastatic spread. Nevertheless, a reliable diagnosis requires precise histopathological examination, reached with surgical resection. Therefore, a detailed history, physical examination, systematic investigation, and correlation with chest imaging are needed to avoid misdiagnosis.
Our case highlights the importance of keeping this rare, aggressive tumor as part of the differential diagnosis. In view of its natural history, heterogeneity, and low incidence, published cases of PSC are limited. Thus, further investigation could optimize rapid identification and treatment options.
Discussion
An interdisciplinary discussion regarding the diagnosis considered the clinical features of the patient along with the imaging characteristics. The histological examination demonstrating sarcomatoid features with the supporting immunohistochemistry that confirmed both mesenchymal and epithelioid presence and was used to make the diagnosis of pulmonary sarcomatoid carcinoma (PSC).
The incidence of PSC ranges between 0.1% and 0.4% of all lung malignancies.1,4-7 PSC usually occurs in older men whose weight is moderate to heavy and who smoke. PSC appears to have an upper lobe predilection; also, these tumors tend to be bulky with invasive tendency, early recurrence, and systemic metastases. PSC frequently involves the adjacent lung, chest wall, diaphragm, pericardium, and other tissues.1-5 The source of the sarcoma component of the PSC remains uncertain. However, prior research suggests that it is associated with a clonal evolution that induces epidermal and mesenchymal tumor histological characteristics.1,8,9 The tumor cell epithelial-mesenchymal transition may induce transformation of the carcinoma component of PSC to into a sarcoma component. The epithelial-mesenchymal transition is associated with the PSC high risk for invasiveness and induces metastasis sites, such as the esophagus, colon, rectum, kidneys, and the common sites of NSCLC.
The most common symptoms include productive cough, chest congestion, and chest pain.1,7 In view of PSC’s clinical presentation and imaging, numerous differential diagnoses should be considered, such as sarcomatoid carcinomas, primary or secondary metastatic sarcomas, malignant melanoma, and pleural mesothelioma.6,10
The tumor is initially identified by a chest CT, confirmed by histology and immunohistochemistry. Several biomarkers are useful for diagnosis and classification of an undifferentiated neoplasm/tumor of uncertain origin. Those biomarkers help to understand the tumor pathobiology, to select the therapeutic regimen, and to predict the patient’s outcome. Although immunohistochemical staining of epithelial and mesenchymal markers can be helpful, a reliable diagnosis requires a precise histopathological examination. This is often difficult on small biopsy samples, such as fine-needle aspiration, as all the histological elements of PSC required to make the correct evaluation may not be present. Adequate sampling to generate a considerable number of histological slides is essential for an accurate diagnosis, which can be reached only with surgical resection.5
Due to rarity, rapid progression, short survival, and heterogeneous pathological qualities, PSC has been difficult to formulate treatment recommendations. Compared with other histological subtypes of NSCLC, PSC is more aggressive and has a poor prognosis. Survival time on average is about 13.3 months due to early metastasis, lower than other types of NSCLC. The greatest overall survival (OS) benefit has been shown with surgery in early-stage operable PSC, which remains the standard of care. Because most patients with PSC present in the advanced stage, they lose their opportunity for curative surgery. Auxiliary methods of treatment include radiotherapy and chemotherapy. Prior studies have shown that systemic chemotherapy efficacy has varied, some showing no OS benefit; others showing a modest benefit. It has also been noted that advanced-stage PSC has minimal response to chemotherapy. Further larger prospective studies are needed to outline the efficacy and role of systemic chemotherapy and other therapeutic agents, including targeted therapies and immunotherapy.1,4,11-13 However, two-thirds of patients are not sensitive to conventional chemotherapy. In comparison with other types of NSCLC, PSC carries a poor prognosis even in early-stage disease or if tumor metastasis is present. Therefore, further research on novel treatment options is needed to improve long-term survival.1,3-8
Conclusions
PSC is diagnostically challenging because it is rare and has an aggressive progression. Identification of this tumor requires knowledge of histological criteria to identify their subtypes. Immunohistochemistry has an important role in the classification and to rule out differential diagnoses, including metastatic spread. Nevertheless, a reliable diagnosis requires precise histopathological examination, reached with surgical resection. Therefore, a detailed history, physical examination, systematic investigation, and correlation with chest imaging are needed to avoid misdiagnosis.
Our case highlights the importance of keeping this rare, aggressive tumor as part of the differential diagnosis. In view of its natural history, heterogeneity, and low incidence, published cases of PSC are limited. Thus, further investigation could optimize rapid identification and treatment options.
1. Qin Z, Huang B, Yu G, Zheng Y, Zhao K. Gingival metastasis of a mediastinal pulmonary sarcomatoid carcinoma: a case report. J Cardiothorac Surg. 2019;14(1):161. Published 2019 Sep 9. doi:10.1186/s13019-019-0991-y
2. Travis WD, Brambilla E, Nicholson AG, et al; WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-1260. doi:10.1097/JTO.0000000000000630
3. Yendamuri S, Caty L, Pine M, et al. Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis. Surgery. 2012;152(3):397-402. doi:10.1016/j.surg.2012.05.007
4. Karim NA, Schuster J, Eldessouki I, et al. Pulmonary sarcomatoid carcinoma: University of Cincinnati experience. Oncotarget. 2017;9(3):4102-4108. Published 2017 Dec 18. doi:10.18632/oncotarget.23468
5. Weissferdt A. Pulmonary sarcomatoid carcinomas: a review. Adv Anat Pathol. 2018;25(5):304-313. doi:10.1097/PAP.0000000000000202
6. Roesel C, Terjung S, Weinreich G, et al. Sarcomatoid carcinoma of the lung: a rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages. Interact Cardiovasc Thorac Surg. 2017;24(3):407-413. doi:10.1093/icvts/ivw392
7. Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med. 2010;134(1):49-54. doi:10.5858/2008-0547-RAR.1
8. Thomas VT, Hinson S, Konduri K. Epithelial-mesenchymal transition in pulmonary carcinosarcoma: case report and literature review. Ther Adv Med Oncol. 2012;4(1):31-37. doi:10.1177/1758834011421949
9. Chang YL, Wu CT, Shih JY, Lee YC. EGFR and p53 status of pulmonary pleomorphic carcinoma: implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy. Ann Surg Oncol. 2011;18(10):2952-2960. doi:10.1245/s10434-011-1621-7
10. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, eds. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. International Agency for Research on Cancer; 2015:88-94.
11. Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases. World J Surg Oncol. 2013;11:252. Published 2013 Oct 2. doi:10.1186/1477-7819-11-252
12. Pelosi G, Sonzogni A, De Pas T, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol. 2010;18(2):103-120. doi:10.1177/1066896908330049
13. Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med. 2014;138(12):1583-1610. doi:10.5858/arpa.2014-0061-RA
1. Qin Z, Huang B, Yu G, Zheng Y, Zhao K. Gingival metastasis of a mediastinal pulmonary sarcomatoid carcinoma: a case report. J Cardiothorac Surg. 2019;14(1):161. Published 2019 Sep 9. doi:10.1186/s13019-019-0991-y
2. Travis WD, Brambilla E, Nicholson AG, et al; WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-1260. doi:10.1097/JTO.0000000000000630
3. Yendamuri S, Caty L, Pine M, et al. Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis. Surgery. 2012;152(3):397-402. doi:10.1016/j.surg.2012.05.007
4. Karim NA, Schuster J, Eldessouki I, et al. Pulmonary sarcomatoid carcinoma: University of Cincinnati experience. Oncotarget. 2017;9(3):4102-4108. Published 2017 Dec 18. doi:10.18632/oncotarget.23468
5. Weissferdt A. Pulmonary sarcomatoid carcinomas: a review. Adv Anat Pathol. 2018;25(5):304-313. doi:10.1097/PAP.0000000000000202
6. Roesel C, Terjung S, Weinreich G, et al. Sarcomatoid carcinoma of the lung: a rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages. Interact Cardiovasc Thorac Surg. 2017;24(3):407-413. doi:10.1093/icvts/ivw392
7. Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med. 2010;134(1):49-54. doi:10.5858/2008-0547-RAR.1
8. Thomas VT, Hinson S, Konduri K. Epithelial-mesenchymal transition in pulmonary carcinosarcoma: case report and literature review. Ther Adv Med Oncol. 2012;4(1):31-37. doi:10.1177/1758834011421949
9. Chang YL, Wu CT, Shih JY, Lee YC. EGFR and p53 status of pulmonary pleomorphic carcinoma: implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy. Ann Surg Oncol. 2011;18(10):2952-2960. doi:10.1245/s10434-011-1621-7
10. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, eds. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. International Agency for Research on Cancer; 2015:88-94.
11. Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases. World J Surg Oncol. 2013;11:252. Published 2013 Oct 2. doi:10.1186/1477-7819-11-252
12. Pelosi G, Sonzogni A, De Pas T, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol. 2010;18(2):103-120. doi:10.1177/1066896908330049
13. Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med. 2014;138(12):1583-1610. doi:10.5858/arpa.2014-0061-RA
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>0923 FED PSC</fileName> <TBEID>0C02DE61.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02DE61</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname/> <articleType>1</articleType> <TBLocation>Copyfitting-FED</TBLocation> <QCDate/> <firstPublished>20230915T135142</firstPublished> <LastPublished>20230915T135142</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20230915T135142</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline/> <bylineText/> <bylineFull/> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>An 83-year-old man who was a nonsmoker with no history of systemic disease was transferred to the Veterans Affairs Caribbean Healthcare System from an outside h</metaDescription> <articlePDF/> <teaserImage/> <title>Patient With Leukocytosis and Persistent Dry Cough</title> <deck/> <eyebrow>What’s Your Diagnosis?</eyebrow> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2023</pubPubdateYear> <pubPubdateMonth>September</pubPubdateMonth> <pubPubdateDay/> <pubVolume>40</pubVolume> <pubNumber>9</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>3639</CMSID> </CMSIDs> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>FED</publicationCode> <pubIssueName>September 2023</pubIssueName> <pubArticleType>Feature Articles | 3639</pubArticleType> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Fed Pract</journalTitle> <journalFullTitle>Federal Practitioner</journalFullTitle> <copyrightStatement>Copyright 2017 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">16</term> </publications> <sections> <term canonical="true">58390</term> </sections> <topics> <term canonical="true">27442</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Patient With Leukocytosis and Persistent Dry Cough</title> <deck/> </itemMeta> <itemContent> <p class="by"> <b>Mariela M. Rivera-Agosto, MD</b> <b> <sup>a</sup> </b> <b>; Onix Cantres-Fonseca, MD</b> <b> <sup>a</sup> </b> <b>; Luis E. Irizarry-Nieves</b> <b> <sup>a</sup> </b> <b>; William Rodr</b> <b>í</b> <b>guez-Cintr</b> <b>ó</b> <b>n, MD, MACP</b> <b> <sup>a</sup> </b> </p> <p>An 83-year-old man who was a nonsmoker with no history of systemic disease was transferred to the Veterans Affairs Caribbean Healthcare System from an outside hospital due to marked leukocytosis (white blood cell [WBC] count, 22.5 × 10<sup>3</sup>/μL). He reported a 3-month history of persistent dry cough, which required several primary care physician (PCP) evaluations. He was initially treated for an upper respiratory tract infection without adequate response. Instead, his symptoms progressed, and he presented with associated hoarseness and unintentional 26-pound weight loss. </p> <p>The patient’s physical examination was remarkable for left-sided decreased breath sounds. Laboratory tests confirmed leukocytosis (WBC, 20.0 × 10<sup>3</sup>/μL), and his radiographic chest X-ray (Figure 1) showed a left upper lobe mass, confirmed by computed tomography (CT) (Figure 2) in which mediastinal lymphadenopathy also was seen. The abdominal/pelvic CT showed renal and bilateral adrenal lesions suggestive of metastatic disease. A core needle biopsy from the anterior component of the mediastinal mass showed pleomorphic cells with hyperchromatic nuclei, spindle configuration, and mitotic figures (Figure 3). Immunohistochemistry was positive for pancytokeratin, CK7, and vimentin. </p> <h2>Discussion</h2> <p>An interdisciplinary discussion regarding the diagnosis considered the clinical features of the patient along with the imaging characteristics. The histological examination demonstrating sarcomatoid features with the supporting immunohistochemistry that confirmed both mesenchymal and epithelioid presence and was used to make the diagnosis of pulmonary sarcomatoid carcinoma (PSC). </p> <p>PSC is a very rare aggressive subtype of poorly differentiated non–small cell lung carcinoma (NSCLC). This tumor is clinically characterized by tumor cells with molecular, histological, and cytological properties of epithelial and mesenchymal tumors, distinguishing it from other types of NSCLC. PSC has a sarcoma-like differentiation (spindle and/or giant cell) or a component of sarcoma (malignant bone, cartilage, or skeletal muscle).<sup>1-5</sup> The World Health Organization (WHO) has classified PSC based on morphological characteristics (Table). <br/><br/>The incidence of PSC ranges between 0.1% and 0.4% of all lung malignancies.<sup>1,4-7</sup> PSC usually occurs in older men whose weight is moderate to heavy and who smoke. PSC appears to have an upper lobe predilection; also, these tumors tend to be bulky with invasive tendency, early recurrence, and systemic metastases. PSC frequently involves the adjacent lung, chest wall, diaphragm, pericardium, and other tissues.<sup>1-5</sup> The source of the sarcoma component of the PSC remains uncertain. However, prior research suggests that it is associated with a clonal evolution that induces epidermal and mesenchymal tumor histological characteristics.<sup>1,8,9</sup> The tumor cell epithelial-mesenchymal transition may induce transformation of the carcinoma component of PSC to into a sarcoma component. The epithelial-mesenchymal transition is associated with the PSC high risk for invasiveness and induces metastasis sites, such as the esophagus, colon, rectum, kidneys, and the common sites of NSCLC.<br/><br/>The most common symptoms include productive cough, chest congestion, and chest pain.<sup>1,7</sup> In view of PSC’s clinical presentation and imaging, numerous differential diagnoses should be considered, such as sarcomatoid carcinomas, primary or secondary metastatic sarcomas, malignant melanoma, and pleural mesothelioma.<sup>6,10</sup> <br/><br/>The tumor is initially identified by a chest CT, confirmed by histology and immunohistochemistry. Several biomarkers are useful for diagnosis and classification of an undifferentiated neoplasm/tumor of uncertain origin. Those biomarkers help to understand the tumor pathobiology, to select the therapeutic regimen, and to predict the patient’s outcome. Although immunohistochemical staining of epithelial and mesenchymal markers can be helpful, a reliable diagnosis requires a precise histopathological examination. This is often difficult on small biopsy samples, such as fine-needle aspiration, as all the histological elements of PSC required to make the correct evaluation may not be present. Adequate sampling to generate a considerable number of histological slides is essential for an accurate diagnosis, which can be reached only with surgical resection.<sup>5<br/><br/></sup>Due to rarity, rapid progression, short survival, and heterogeneous pathological qualities, PSC has been difficult to formulate treatment recommendations. Compared with other histological subtypes of NSCLC, PSC is more aggressive and has a poor prognosis. Survival time on average is about 13.3 months due to early metastasis, lower than other types of NSCLC. The greatest overall survival (OS) benefit has been shown with surgery in early-stage operable PSC, which remains the standard of care. Because most patients with PSC present in the advanced stage, they lose their opportunity for curative surgery. Auxiliary methods of treatment include radiotherapy and chemotherapy. Prior studies have shown that systemic chemotherapy efficacy has varied, some showing no OS benefit; others showing a modest benefit. It has also been noted that advanced-stage PSC has minimal response to chemotherapy. Further larger prospective studies are needed to outline the efficacy and role of systemic chemotherapy and other therapeutic agents, including targeted therapies and immunotherapy.<sup>1,4,11-13</sup> However, two-thirds of patients are not sensitive to conventional chemotherapy. In comparison with other types of NSCLC, PSC carries a poor prognosis even in early-stage disease or if tumor metastasis is present. Therefore, further research on novel treatment options is needed to improve long-term survival.<sup>1,3-8</sup></p> <h2>Conclusions</h2> <p>PSC is diagnostically challenging because it is rare and has an aggressive progression. Identification of this tumor requires knowledge of histological criteria to identify their subtypes. Immunohistochemistry has an important role in the classification and to rule out differential diagnoses, including metastatic spread. Nevertheless, a reliable diagnosis requires precise histopathological examination, reached with surgical resection. Therefore, a detailed history, physical examination, systematic investigation, and correlation with chest imaging are needed to avoid misdiagnosis. </p> <p>Our case highlights the importance of keeping this rare, aggressive tumor as part of the differential diagnosis. In view of its natural history, heterogeneity, and low incidence, published cases of PSC are limited. Thus, further investigation could optimize rapid identification and treatment options.</p> <p class="isub">Author affiliations</p> <p> <em><sup>a</sup>Veterans Affairs Caribbean Healthcare System, San Juan, Puerto Rico</em> </p> <p class="isub">Author disclosures </p> <p> <em>The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.</em> </p> <p class="isub">Disclaimer</p> <p> <em>The opinions expressed herein are those of the authors and do not necessarily reflect those of <i>Federal Practitioner</i>, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.</em> </p> <p class="isub">Ethics and consent</p> <p class="isub"> The patient died before he could provide written consent and relatives were unavailable despite attempts. No personal identifiers were used to maintain the patient's privacy. </p> <p class="isub">References</p> <p class="reference"> 1. Qin Z, Huang B, Yu G, Zheng Y, Zhao K. Gingival metastasis of a mediastinal pulmonary sarcomatoid carcinoma: a case report. <i>J Cardiothorac Surg</i>. 2019;14(1):161. Published 2019 Sep 9. doi:10.1186/s13019-019-0991-y <br/><br/> 2. Travis WD, Brambilla E, Nicholson AG, et al; WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. <i>J Thorac Oncol</i>. 2015;10(9):1243-1260. doi:10.1097/JTO.0000000000000630<br/><br/> 3. Yendamuri S, Caty L, Pine M, et al. Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis. <i>Surgery</i>. 2012;152(3):397-402. doi:10.1016/j.surg.2012.05.007<br/><br/> 4. Karim NA, Schuster J, Eldessouki I, et al. Pulmonary sarcomatoid carcinoma: University of Cincinnati experience. <i>Oncotarget</i>. 2017;9(3):4102-4108. Published 2017 Dec 18. doi:10.18632/oncotarget.23468<br/><br/> 5. Weissferdt A. Pulmonary sarcomatoid carcinomas: a review. <i>Adv Anat Pathol</i>. 2018;25(5):304-313. doi:10.1097/PAP.0000000000000202<br/><br/> 6. Roesel C, Terjung S, Weinreich G, et al. Sarcomatoid carcinoma of the lung: a rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages. <i>Interact Cardiovasc Thorac Surg</i>. 2017;24(3):407-413. doi:10.1093/icvts/ivw392<br/><br/> 7. Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis. <i>Arch Pathol Lab Med</i>. 2010;134(1):49-54. doi:10.5858/2008-0547-RAR.1<br/><br/> 8. Thomas VT, Hinson S, Konduri K. Epithelial-mesenchymal transition in pulmonary carcinosarcoma: case report and literature review. <i>Ther Adv Med Oncol</i>. 2012;4(1):31-37. doi:10.1177/1758834011421949<br/><br/> 9. Chang YL, Wu CT, Shih JY, Lee YC. EGFR and p53 status of pulmonary pleomorphic carcinoma: implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy.<i> Ann Surg Oncol</i>. 2011;18(10):2952-2960. doi:10.1245/s10434-011-1621-7<br/><br/>10. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, eds. <i>WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart</i>. 4th ed. International Agency for Research on Cancer; 2015:88-94.<br/><br/>11. Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases. <i>World J Surg Oncol</i>. 2013;11:252. Published 2013 Oct 2. doi:10.1186/1477-7819-11-252<br/><br/>12. Pelosi G, Sonzogni A, De Pas T, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. <i>Int J Surg Pathol</i>. 2010;18(2):103-120. doi:10.1177/1066896908330049<br/><br/>13. Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. <i>Arch Pathol Lab Med</i>. 2014;138(12):1583-1610. doi:10.5858/arpa.2014-0061-RA</p> </itemContent> </newsItem> </itemSet></root>
Misleading Diagnosis of Idiopathic Pulmonary Fibrosis: A Clinical Concern
Sjogren syndrome (SS) is a chronic inflammatory autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands causing sicca syndrome.¹ The disease can extend beyond the exocrine glands, and systemic manifestations, including vasculitis, lung, renal or neurologic involvement, can occur.² Lung disease associated with SS is more commonly seen in women aged ≥ 60 years. The most common symptoms include dry cough, chest pain, and dyspnea on exertion. Sjogren syndrome also may produce several respiratory complications, including bronchial hyperresponsiveness, bronchiolitis, bronchiectasis, pulmonary infections, pulmonary amyloidosis, pulmonary embolism, pulmonary hypertension, lymphomas, and interstitial lung diseases (ILD).² Although ILD typically occurs 5 to 10 years after the onset of SS, lung disease can precede SS.
[embed:render:related:node:141649]
Pulmonary involvement is associated with systemic manifestations, hypergammaglobulinemia, and anti-SSA and anti-SSB antibodies.² Laboratory tests that confirm a diagnosis of SS include antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB antibodies.² Pulmonary function test (PFT) results appear to reflect impairment of either the lung (restrictive syndrome) or airways (obstructive syndrome).² Imaging abnormalities may include ground-glass attenuation, subpleural small nodules, nonseptal linear opacities, interlobular septal thickening, bronchiectasis, and cysts.³ Therefore, many ILD cases show similar imaging and pathologic findings; nevertheless, they have identifiable etiology that are not idiopathic.
Case Presentation
A 67-year-old man with a medical history of hypertension, peripheral vascular disease, and keratoconjunctivitis sicca (treated with eye drops) developed progressive shortness of breath, dyspnea on exertion, and weight loss (40 pounds) over the course of 6 months. A pulmonary function test showed a restrictive abnormality with decreased diffusing capacity of the lungs for carbon monoxide (eFigure available online at www.fedprac.com). A chest computed tomography (CT) scan showed the presence of significant thickening of the interlobular septi that was more pronounced in the subpleural regions of the lungs and lower lobes, which was consistent with usual interstitial pneumonia. A chest X-ray conducted 4 months prior showed no significant acute cardiopulmonary abnormalities (Figure 1). An open lung wedge biopsy revealed chronic organizing pneumonia with mild interstitial chronic inflammation, smooth muscle hypertrophy, and honeycomb changes consistent with usual interstitial pneumonia. 
The patient had been diagnosed with idiopathic pulmonary fibrosis (IPF) by a private physician and started pirfenidone and oxygen therapy. Three months later the patient presented to the VA Caribbean Healthcare System in San Juan Puerto Rico when he developed an exacerbation of IPF. The patient reported having fever, chills, dry cough, night sweats, and marked shortness of breath. He was found hypoxemic (partial pressure of O2 was 50 mm Hg) and required a venturi mask set to 50% fractioned of inspired O2 to maintain a peripheral oxygen saturation around 90%. A chest X-ray showed decreased lung volume with bilateral interstitial and alveolar disease (Figure 2). Leukocytosis was present at 17×10-3/µl. The chest CT scan showed interval worsening of diffuse ground-glass airspace opacities and worsening of interstitial opacities; there 
After careful clinical assessment (+ dry eyes) and radiographic pattern evaluation (diffuse bilateral interstitial and ground-glass opacities), the clinical diagnosis of IPF was queried after the patient’s rheumatologic workup came back positive for ANA and anti-Ro/SSA tests. Since the etiology of ILD was secondary to SS, pirfenidone was discontinued, and the patient was started on steroid therapy with subsequent marked clinical improvement. Parotid biopsy revealed the presence of inflammatory cells supporting the diagnosis of ILD associated to SS. The patient was discharged home on a tapering dose of steroids. Four months after therapy with steroids, a follow-up chest CT scan without contrast showed a chronic ILD with improved ground-glass opacities (Figure 4). The patient currently is in good health without oxygen supplementation.
[embed:render:related:node:135726]
Discussion
Diagnosis of SS is challenging, since it may mimic other conditions such as IPF. The most common type of SS-associated ILD is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can be visualized, as in this case study. Usual interstitial pneumonia
Diagnosing IPF cannot be solely based on a lung biopsy consistent with UIP. Appropriate diagnosis should consider the clinical presentation; PFT, laboratory findings (including rheumatologic workup), imaging (especially radiographic patterns), and biopsies. Moreover, the pathologic characteristic of IPF, which is UIP, can be found with other diseases, such as SS. Thus, it is important to make an accurate diagnosis to provide the appropriate treatment available. Patients with ILD associated with SS who have worsening symptoms, PFT, and radiographic abnormalities may be treated with oral prednisone (daily dose: 1 mg/kg).
[embed:render:related:node:103978]
Conclusion
This case highlights the importance of making an adequate diagnosis of ILD considering that available treatments differ for all possible etiologies other than IPF. This is a true clinical concern taking into account that many patients might be receiving inappropriate therapy for IPF diagnosis, as illustrated in the case study.
1. Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjogren’s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med. 2005;171(6):632-638.
2. Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren’s syndrome. Eur Respir Rev. 2016;25(140):110-123.
3. Koyama M, Johkoh T, Honda O, et al. Pulmonary involvement in primary Sjögren’s syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients. J Thorac Imaging. 2001;16(4):290-296.
4. Wuyts WA, Cavazza A, Rossi G, Bonella F, Sverzellati N, Spagnolo P. Differential diagnosis of usual interstitial pneumonia: when is it truly idiopathic? Eur Respir Rev. 2014;23(133):308-319.
Sjogren syndrome (SS) is a chronic inflammatory autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands causing sicca syndrome.¹ The disease can extend beyond the exocrine glands, and systemic manifestations, including vasculitis, lung, renal or neurologic involvement, can occur.² Lung disease associated with SS is more commonly seen in women aged ≥ 60 years. The most common symptoms include dry cough, chest pain, and dyspnea on exertion. Sjogren syndrome also may produce several respiratory complications, including bronchial hyperresponsiveness, bronchiolitis, bronchiectasis, pulmonary infections, pulmonary amyloidosis, pulmonary embolism, pulmonary hypertension, lymphomas, and interstitial lung diseases (ILD).² Although ILD typically occurs 5 to 10 years after the onset of SS, lung disease can precede SS.
[embed:render:related:node:141649]
Pulmonary involvement is associated with systemic manifestations, hypergammaglobulinemia, and anti-SSA and anti-SSB antibodies.² Laboratory tests that confirm a diagnosis of SS include antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB antibodies.² Pulmonary function test (PFT) results appear to reflect impairment of either the lung (restrictive syndrome) or airways (obstructive syndrome).² Imaging abnormalities may include ground-glass attenuation, subpleural small nodules, nonseptal linear opacities, interlobular septal thickening, bronchiectasis, and cysts.³ Therefore, many ILD cases show similar imaging and pathologic findings; nevertheless, they have identifiable etiology that are not idiopathic.
Case Presentation
A 67-year-old man with a medical history of hypertension, peripheral vascular disease, and keratoconjunctivitis sicca (treated with eye drops) developed progressive shortness of breath, dyspnea on exertion, and weight loss (40 pounds) over the course of 6 months. A pulmonary function test showed a restrictive abnormality with decreased diffusing capacity of the lungs for carbon monoxide (eFigure available online at www.fedprac.com). A chest computed tomography (CT) scan showed the presence of significant thickening of the interlobular septi that was more pronounced in the subpleural regions of the lungs and lower lobes, which was consistent with usual interstitial pneumonia. A chest X-ray conducted 4 months prior showed no significant acute cardiopulmonary abnormalities (Figure 1). An open lung wedge biopsy revealed chronic organizing pneumonia with mild interstitial chronic inflammation, smooth muscle hypertrophy, and honeycomb changes consistent with usual interstitial pneumonia.
The patient had been diagnosed with idiopathic pulmonary fibrosis (IPF) by a private physician and started pirfenidone and oxygen therapy. Three months later the patient presented to the VA Caribbean Healthcare System in San Juan Puerto Rico when he developed an exacerbation of IPF. The patient reported having fever, chills, dry cough, night sweats, and marked shortness of breath. He was found hypoxemic (partial pressure of O2 was 50 mm Hg) and required a venturi mask set to 50% fractioned of inspired O2 to maintain a peripheral oxygen saturation around 90%. A chest X-ray showed decreased lung volume with bilateral interstitial and alveolar disease (Figure 2). Leukocytosis was present at 17×10-3/µl. The chest CT scan showed interval worsening of diffuse ground-glass airspace opacities and worsening of interstitial opacities; there
After careful clinical assessment (+ dry eyes) and radiographic pattern evaluation (diffuse bilateral interstitial and ground-glass opacities), the clinical diagnosis of IPF was queried after the patient’s rheumatologic workup came back positive for ANA and anti-Ro/SSA tests. Since the etiology of ILD was secondary to SS, pirfenidone was discontinued, and the patient was started on steroid therapy with subsequent marked clinical improvement. Parotid biopsy revealed the presence of inflammatory cells supporting the diagnosis of ILD associated to SS. The patient was discharged home on a tapering dose of steroids. Four months after therapy with steroids, a follow-up chest CT scan without contrast showed a chronic ILD with improved ground-glass opacities (Figure 4). The patient currently is in good health without oxygen supplementation.
[embed:render:related:node:135726]
Discussion
Diagnosis of SS is challenging, since it may mimic other conditions such as IPF. The most common type of SS-associated ILD is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can be visualized, as in this case study. Usual interstitial pneumonia
Diagnosing IPF cannot be solely based on a lung biopsy consistent with UIP. Appropriate diagnosis should consider the clinical presentation; PFT, laboratory findings (including rheumatologic workup), imaging (especially radiographic patterns), and biopsies. Moreover, the pathologic characteristic of IPF, which is UIP, can be found with other diseases, such as SS. Thus, it is important to make an accurate diagnosis to provide the appropriate treatment available. Patients with ILD associated with SS who have worsening symptoms, PFT, and radiographic abnormalities may be treated with oral prednisone (daily dose: 1 mg/kg).
[embed:render:related:node:103978]
Conclusion
This case highlights the importance of making an adequate diagnosis of ILD considering that available treatments differ for all possible etiologies other than IPF. This is a true clinical concern taking into account that many patients might be receiving inappropriate therapy for IPF diagnosis, as illustrated in the case study.
Sjogren syndrome (SS) is a chronic inflammatory autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands causing sicca syndrome.¹ The disease can extend beyond the exocrine glands, and systemic manifestations, including vasculitis, lung, renal or neurologic involvement, can occur.² Lung disease associated with SS is more commonly seen in women aged ≥ 60 years. The most common symptoms include dry cough, chest pain, and dyspnea on exertion. Sjogren syndrome also may produce several respiratory complications, including bronchial hyperresponsiveness, bronchiolitis, bronchiectasis, pulmonary infections, pulmonary amyloidosis, pulmonary embolism, pulmonary hypertension, lymphomas, and interstitial lung diseases (ILD).² Although ILD typically occurs 5 to 10 years after the onset of SS, lung disease can precede SS.
[embed:render:related:node:141649]
Pulmonary involvement is associated with systemic manifestations, hypergammaglobulinemia, and anti-SSA and anti-SSB antibodies.² Laboratory tests that confirm a diagnosis of SS include antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB antibodies.² Pulmonary function test (PFT) results appear to reflect impairment of either the lung (restrictive syndrome) or airways (obstructive syndrome).² Imaging abnormalities may include ground-glass attenuation, subpleural small nodules, nonseptal linear opacities, interlobular septal thickening, bronchiectasis, and cysts.³ Therefore, many ILD cases show similar imaging and pathologic findings; nevertheless, they have identifiable etiology that are not idiopathic.
Case Presentation
A 67-year-old man with a medical history of hypertension, peripheral vascular disease, and keratoconjunctivitis sicca (treated with eye drops) developed progressive shortness of breath, dyspnea on exertion, and weight loss (40 pounds) over the course of 6 months. A pulmonary function test showed a restrictive abnormality with decreased diffusing capacity of the lungs for carbon monoxide (eFigure available online at www.fedprac.com). A chest computed tomography (CT) scan showed the presence of significant thickening of the interlobular septi that was more pronounced in the subpleural regions of the lungs and lower lobes, which was consistent with usual interstitial pneumonia. A chest X-ray conducted 4 months prior showed no significant acute cardiopulmonary abnormalities (Figure 1). An open lung wedge biopsy revealed chronic organizing pneumonia with mild interstitial chronic inflammation, smooth muscle hypertrophy, and honeycomb changes consistent with usual interstitial pneumonia.
The patient had been diagnosed with idiopathic pulmonary fibrosis (IPF) by a private physician and started pirfenidone and oxygen therapy. Three months later the patient presented to the VA Caribbean Healthcare System in San Juan Puerto Rico when he developed an exacerbation of IPF. The patient reported having fever, chills, dry cough, night sweats, and marked shortness of breath. He was found hypoxemic (partial pressure of O2 was 50 mm Hg) and required a venturi mask set to 50% fractioned of inspired O2 to maintain a peripheral oxygen saturation around 90%. A chest X-ray showed decreased lung volume with bilateral interstitial and alveolar disease (Figure 2). Leukocytosis was present at 17×10-3/µl. The chest CT scan showed interval worsening of diffuse ground-glass airspace opacities and worsening of interstitial opacities; there
After careful clinical assessment (+ dry eyes) and radiographic pattern evaluation (diffuse bilateral interstitial and ground-glass opacities), the clinical diagnosis of IPF was queried after the patient’s rheumatologic workup came back positive for ANA and anti-Ro/SSA tests. Since the etiology of ILD was secondary to SS, pirfenidone was discontinued, and the patient was started on steroid therapy with subsequent marked clinical improvement. Parotid biopsy revealed the presence of inflammatory cells supporting the diagnosis of ILD associated to SS. The patient was discharged home on a tapering dose of steroids. Four months after therapy with steroids, a follow-up chest CT scan without contrast showed a chronic ILD with improved ground-glass opacities (Figure 4). The patient currently is in good health without oxygen supplementation.
[embed:render:related:node:135726]
Discussion
Diagnosis of SS is challenging, since it may mimic other conditions such as IPF. The most common type of SS-associated ILD is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can be visualized, as in this case study. Usual interstitial pneumonia
Diagnosing IPF cannot be solely based on a lung biopsy consistent with UIP. Appropriate diagnosis should consider the clinical presentation; PFT, laboratory findings (including rheumatologic workup), imaging (especially radiographic patterns), and biopsies. Moreover, the pathologic characteristic of IPF, which is UIP, can be found with other diseases, such as SS. Thus, it is important to make an accurate diagnosis to provide the appropriate treatment available. Patients with ILD associated with SS who have worsening symptoms, PFT, and radiographic abnormalities may be treated with oral prednisone (daily dose: 1 mg/kg).
[embed:render:related:node:103978]
Conclusion
This case highlights the importance of making an adequate diagnosis of ILD considering that available treatments differ for all possible etiologies other than IPF. This is a true clinical concern taking into account that many patients might be receiving inappropriate therapy for IPF diagnosis, as illustrated in the case study.
1. Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjogren’s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med. 2005;171(6):632-638.
2. Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren’s syndrome. Eur Respir Rev. 2016;25(140):110-123.
3. Koyama M, Johkoh T, Honda O, et al. Pulmonary involvement in primary Sjögren’s syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients. J Thorac Imaging. 2001;16(4):290-296.
4. Wuyts WA, Cavazza A, Rossi G, Bonella F, Sverzellati N, Spagnolo P. Differential diagnosis of usual interstitial pneumonia: when is it truly idiopathic? Eur Respir Rev. 2014;23(133):308-319.
1. Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjogren’s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med. 2005;171(6):632-638.
2. Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren’s syndrome. Eur Respir Rev. 2016;25(140):110-123.
3. Koyama M, Johkoh T, Honda O, et al. Pulmonary involvement in primary Sjögren’s syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients. J Thorac Imaging. 2001;16(4):290-296.
4. Wuyts WA, Cavazza A, Rossi G, Bonella F, Sverzellati N, Spagnolo P. Differential diagnosis of usual interstitial pneumonia: when is it truly idiopathic? Eur Respir Rev. 2014;23(133):308-319.
Unusual Congenital Pulmonary Anomaly in an Adult Patient With Dyspnea
Anatomic variations may result in abnormal return from the pulmonary veins to the right side of the heart. This group of congenital anomalies, also known as partial anomalous pulmonary venous return (PAPVR), may connect oxygenated blood from the pulmonary vein to a systemic vein before reaching the right atrium. The most common PAPVR is derived from the left upper pulmonary vein, which then connects to the left innominate vein and drains into the superior vena cava (SVC).
Scimitar syndrome is a rare PAPVR variant in which part of or the entire right lung is drained by the pulmonary vein into the inferior vena cava (IVC), giving the curvilinear dimension the appearance of a Middle Eastern sword (scimitar). The syndrome is frequently associated with other abnormalities, such as right lung hypoplasia and abnormal right lung lobation, dextroposition of the heart, right pulmonary artery hypoplasia, systemic arterial blood supply to the right lower lung from the infradiaphragmatic aorta, atrial septal defects of the secundum type, right-sided diaphragmatic hernia, and horseshoe lung.1,2 The syndrome was first described in 1836 by Cooper during an autopsy of an infant, and Dotter diagnosed the first symptomatic patient in 1949.3,4
Case Report
A 62-year-old man, former smoker (40 pack-year), with a past medical history of arterial hypertension and asthma visited the clinic, reporting exertional dyspnea. He also reported oppressive, retrosternally located exertional chest pain, 6/10 in intensity, of 3 minutes’ duration that radiated to the right chest and ameliorated with rest. Symptoms had occurred every other day for the past year. His physical exam was remarkable for central obesity. Lung auscultation was essentially clear. There was no jugular vein distention. The patient’s heart showed a regular rate and rhythm without evidence of murmurs or gallops. There was no evidence of leg edema or cyanosis. The patient’s resting oxygen saturation of 98% remained unchanged after exercise.
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An electrocardiogram showed normal sinus rhythm with no ischemic changes. A pulmonary function test showed a forced expiratory volume (FEV1) of 1.44 L (61% of predicted), forced vital capacity (FVC) of 1.99 L (68% of predicted), and slow vital capacity (SVC) of 2.09 L (60% of predicted), with an FEV1/SVC ratio of 68% of predicted. These results suggested moderate-to-severe obstructive ventilatory impairment.
There was no response to bronchodilator therapy. Lung volumes were measured by plethysmography. The residual volume (RV), total lung capacity (TLC), and RV/TLC ratio were 2.57 L (147% of predicted), 4.66 L (88% of predicted), and 55%, respectively, suggesting severe air trapping. Diffusion lung capacity (DLCO) testing revealed 16.95 mL/min/mm Hg (73% of predicted) when corrected by hemoglobin and DLCO/alveolar volume of 4.97 mL/min/mm Hg/L (114% of predicted). This result was consistent with a mild reduction of gas transfer, which normalized when corrected by alveolar volume.
A posteroanterior chest radiograph image was remarkable for mediastinal shifting toward the right side, volume loss of the right lung, and evidence of a previous gunshot on the right chest wall (Figure 1). Previous chest imaging done in October 2009 showed an opacification of the right lower lung with indistinctness of the right cardiac border and partial obliteration of the right hemidiaphragm. The patient was treated with inhaled steroids and long- acting bronchodilators with partial improvement in dyspnea symptoms.
Myocardial perfusion imaging revealed scintigraphic evidence of heart rate-induced ischemia on the inferior and apical wall segments of the left ventricular myocardium. A transthoracic echocardiogram showed a very poor echocardiographic window. Left ventricular function seemed preserved. Transesophageal echocardiography was scheduled, but the patient missed the appointment.
Cardiac catheterization was only remarkable for 40% to 50% obstruction of the mid-left anterior descending artery, which did not explain the patient’s dyspnea or chest pain. Right side pressures were described as follows: right atrial mean, 10 mm Hg; right ventricle, 36/8 mm Hg; pulmonary artery, 33/16 mm Hg; pulmonary artery mean, 23 mm Hg; pulmonary capillary wedge pressure, 12 mm Hg; and a mean arterial pressure of 100 mm Hg. He had a left ventricle ejection fraction of 60%.
Because images suggested dextroposition of the heart and right lung hypoplasia, a chest computed tomography (CT) and angiography were done (Figure 2). The images showed hypoplasia of the right lung field with an anomalous venous return from the right midlung, having a vertical contour that drained into the supradiaphragmatic IVC. In addition, CT reconstruction demarcated the last mentioned contour draining into the IVC, consistent with scimitar syndrome (Figure 3). The patient was treated conservatively due to age, optimizing therapy for obstructive lung and cardiovascular disease.
Discussion
Partial anomalous pulmonary venous return is a relatively uncommon congenital anomaly, accounting for 0.5% to 1% of congenital heart disease.4,5 The characteristic abnormality is PAPVR of part of or the entire right lung to the IVC, either below the diaphragm or at the junction of the IVC and the right atrium. The rare combination (3%-5%) of an association of PAPVR, right lung hypoplasia, and dextroposition of the heart is designated scimitar syndrome. The scimitar vein sign is a characteristic chest roentgenographic finding of a crescentlike shadow in the right lower lung field where the curvilinear dimension gives the appearance of a scimitar sword.
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Normally, the pulmonary veins from the right and left lung carry oxygenated blood into the left atrium, then to the left ventricle, and then flowing out systemically. The SCV and IVC return the deoxygenated blood from the body system to the right atrium. From the right atrium, blood flows into the right ventricle, and then through pulmonary arteries, reaching the lungs where oxygenation occurs. In this syndrome, a left-to-right shunt is established when the anomalous pulmonary vein drains blood from the right lung into the IVC, resulting in an increased risk of developing right ventricular failure due to long-standing right ventricular volume overload.
Presentation and Diagnosis
There are two clinical presentations of scimitar syndrome: infantile and pediatric/adult. Infantile scimitar syndrome has a clinical presentation of tachypnea and heart failure within the first 2 months of life, with a high mortality rate. The pediatric/adult type is milder and frequently asymptomatic, and the diagnosis is usually incidental after performing an imaging study. Scimitar vein sign appears in 70% of the noninfantile cases, and lung hypoplasia is less severe. A spirometry may reveal mild deficits in vital capacity and FEV1. An electrocardiogram may show right ventricular hypertrophy.
Cardiac catheterization is required to confirm the diagnosis. Additionally, this procedure can help in the assessment of the pulmonary venous drainage course, pulmonary artery anatomy and pressure, scimitar vein stenosis, and presence of left-to-right shunt or other cardiac anomalies, if present. Other modalities have been suggested as alternative methods for diagnosing this condition, including the use of coronary CT and 3D echocardiography.6,7 However, these diagnostic tests are not available in all facilities and are very costly.
Treatment and Prognosis
Vida and colleagues conducted a multicentric study for the European Congenital Heart Surgeons Association on scimitar syndrome.8 Data were collected from 1997 to 2007 for 68 patients who underwent a surgical procedure. A total of 11 patients were categorized as late onset, and when compared with the infantile category, they had fewer postoperatory complications, hospital mortality, late mortality, and were less likely to develop pulmonary hypertension. Both pulmonary stenosis and pulmonary hypertension were linked with poor outcomes. It seems the younger the patient (infantile), the higher the possibility of complications and mortality. Adults who are incidentally diagnosed have a better outcome if asymptomatic. Findings such as hypoplastic lungs may predispose these patients to developing recurrent pneumonias.8,9
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Dusenbery and colleagues documented in a cohort study the relationship between poor survival and other variables. Significant variables included age at presentation, nonatrial septal defect (non-ASD) congenital heart disease, left pulmonary vein stenosis, and pulmonary artery pressure (PAP) at the time of presentation. Predictors of survival for nonsurgical patients were directly related to PAP at presentation and absence of non-ASD congenital heart disease. If the patient’s PAP is less than half of the systemic pressure, the survival is near 100% at 5 years from initial presentation.9
Surgery is the definitive treatment for PAPVR. However, asymptomatic patients with PAPVR with small left-to-right shunt do not require intervention, as the defect has no significant clinical impact, and patients have a normal life expectancy without correction.10
Surgical treatment may be considered in the following circumstances:
- A hemodynamically significant left-to-right shunt (a ratio of pulmonary to systemic blood flow is greater than 2:1), often manifested as right ventricular volume overload
- Recurrent pulmonary infections
- Compression or obstruction of surrounding structures caused by the anomalous vein
- During surgical repair of other major cardiac lesions, depending on the surgical risk of a repair and level and degree of shunting
Surgical options include redirecting the venous drainage to the left atria, ligation/embolization of vascular supply to the sequestered lobe, and pneumonectomy. The procedure complications may include thrombosis of the scimitar vein, lung infarct, hemoptysis, and pulmonary hypertension, which may lead to resection of the lung.11,12 Surgical procedures are recommended in cases where the patient has had recurrent lung infections or a significant degree of shunting. Studies have compared both approaches, demonstrating a better outcome after 10 years for those patients who were medically treated considering the aforementioned surgical indications.
Conclusion
Scimitar syndrome is a rare but welldescribed constellation of cardiopulmonary anomalies, accounting for 0.5% to 1% of congenital heart disease. It is a variant of PAPVR, in which part of or even the entire right lung is drained by right pulmonary veins that connect anomalously to the IVC. Although a diagnosis can be made by chest radiograph, further imaging is needed to corroborate the diagnosis and demonstrate other associated abnormalities.
Additional tests have been described in the literature, but these procedures are not available in all facilities and may incur a higher cost. Therefore, CT angiographic reconstruction is an alternative, noninvasive procedure. Surgery is the definitive treatment; however, asymptomatic patients with PAPVR and small left-to-right shunt do not require intervention.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
1. Cooper G. Case of malformation of the thoracic viscera: consisting of imperfect development of the right lung, and transposition of the heart. London Med Gaz. 1836;18:600-602.
2. Spentzouris G, Zandian A, Cesmebasi A, et al. The clinical anatomy of the inferior vena cava: a review of common congenital anomalies and the considerations for clinicians. Clin Anat. 2014;27(8):1234-1243.
3. Neill CA, Ferencz C, Sabiston DC, Sheldon H. The familial occurrence of hypoplastic right lung with systemic arterial supply and venous drainage “scimitar syndrome.” Bull Johns Hopkins Hosp. 1960;107:1-21.
4. Ward KE, Mullins CE. Anomalous pulmonary venous connections, pulmonary vein stenosis, and atresia of the common pulmonary vein. In: Garson A, Bricker JT, Fisher DJ, Neish SR, eds. The Science and Practice of Pediatric Cardiology. 2nd ed. Baltimore, MD: Williams and Wilkins; 1998:1431-1461.
5. Garcia-Barreto L, Vega W, Deliz R, Rodriguez W. Right hilar abnormality in a young man. Respiration. 1996;63(4):246-250.
6. Simmons DB, Menon RS, Pomeroy WL, Batts TC, Slim AM. An unusual presentation of scimitar syndrome in a military service member. Case Rep Vasc Med. 2013;2013:632402.
7. Palios J, Pernetz MA, Clements S Jr, Lerakis S. Three-dimensional echocardiography images showing anomalous pulmonary venous return in an adult with scimitar syndrome. Echocardiography. 2014;31(3):E103.
8. Vida VL, Padalino MA, Boccuzzo G, et al. Scimitar syndrome: a European Congenital Heart Surgeons Association (ECHSA) multicentric study. Circulation. 2010;122(12):1159-1166.
9. Dusenbery SM, Geva T, Seale A, et al. Outcome predictors and implications for management of scimitar syndrome. Am Heart J. 2013;165(5):770-777.
10. Sehgal A, Loughran-Fowlds A. Scimitar syndrome. Indian J Pediatr. 2005;72(3):249-251.
11. Najm HK, Williams WG, Coles JG, Rebeyka IM, Freedom RM. Scimitar syndrome: twenty years’ experience and results of repair. J Thorac Cardiovasc Surg. 1996;112(5):1161-1169.
12. Dupuis C, Charaf LA, Brevière GM, Abou P, Rémy-Jardin M, Helmius G. The “adult” form of the scimitar syndrome. Am J Cardiol. 1992;70(4):502-507.
Anatomic variations may result in abnormal return from the pulmonary veins to the right side of the heart. This group of congenital anomalies, also known as partial anomalous pulmonary venous return (PAPVR), may connect oxygenated blood from the pulmonary vein to a systemic vein before reaching the right atrium. The most common PAPVR is derived from the left upper pulmonary vein, which then connects to the left innominate vein and drains into the superior vena cava (SVC).
Scimitar syndrome is a rare PAPVR variant in which part of or the entire right lung is drained by the pulmonary vein into the inferior vena cava (IVC), giving the curvilinear dimension the appearance of a Middle Eastern sword (scimitar). The syndrome is frequently associated with other abnormalities, such as right lung hypoplasia and abnormal right lung lobation, dextroposition of the heart, right pulmonary artery hypoplasia, systemic arterial blood supply to the right lower lung from the infradiaphragmatic aorta, atrial septal defects of the secundum type, right-sided diaphragmatic hernia, and horseshoe lung.1,2 The syndrome was first described in 1836 by Cooper during an autopsy of an infant, and Dotter diagnosed the first symptomatic patient in 1949.3,4
Case Report
A 62-year-old man, former smoker (40 pack-year), with a past medical history of arterial hypertension and asthma visited the clinic, reporting exertional dyspnea. He also reported oppressive, retrosternally located exertional chest pain, 6/10 in intensity, of 3 minutes’ duration that radiated to the right chest and ameliorated with rest. Symptoms had occurred every other day for the past year. His physical exam was remarkable for central obesity. Lung auscultation was essentially clear. There was no jugular vein distention. The patient’s heart showed a regular rate and rhythm without evidence of murmurs or gallops. There was no evidence of leg edema or cyanosis. The patient’s resting oxygen saturation of 98% remained unchanged after exercise.
Related: Venous Thromboembolism Prophylaxis in Acutely Ill Veterans With Respiratory Disease
An electrocardiogram showed normal sinus rhythm with no ischemic changes. A pulmonary function test showed a forced expiratory volume (FEV1) of 1.44 L (61% of predicted), forced vital capacity (FVC) of 1.99 L (68% of predicted), and slow vital capacity (SVC) of 2.09 L (60% of predicted), with an FEV1/SVC ratio of 68% of predicted. These results suggested moderate-to-severe obstructive ventilatory impairment.
There was no response to bronchodilator therapy. Lung volumes were measured by plethysmography. The residual volume (RV), total lung capacity (TLC), and RV/TLC ratio were 2.57 L (147% of predicted), 4.66 L (88% of predicted), and 55%, respectively, suggesting severe air trapping. Diffusion lung capacity (DLCO) testing revealed 16.95 mL/min/mm Hg (73% of predicted) when corrected by hemoglobin and DLCO/alveolar volume of 4.97 mL/min/mm Hg/L (114% of predicted). This result was consistent with a mild reduction of gas transfer, which normalized when corrected by alveolar volume.
A posteroanterior chest radiograph image was remarkable for mediastinal shifting toward the right side, volume loss of the right lung, and evidence of a previous gunshot on the right chest wall (Figure 1). Previous chest imaging done in October 2009 showed an opacification of the right lower lung with indistinctness of the right cardiac border and partial obliteration of the right hemidiaphragm. The patient was treated with inhaled steroids and long- acting bronchodilators with partial improvement in dyspnea symptoms.
Myocardial perfusion imaging revealed scintigraphic evidence of heart rate-induced ischemia on the inferior and apical wall segments of the left ventricular myocardium. A transthoracic echocardiogram showed a very poor echocardiographic window. Left ventricular function seemed preserved. Transesophageal echocardiography was scheduled, but the patient missed the appointment.
Cardiac catheterization was only remarkable for 40% to 50% obstruction of the mid-left anterior descending artery, which did not explain the patient’s dyspnea or chest pain. Right side pressures were described as follows: right atrial mean, 10 mm Hg; right ventricle, 36/8 mm Hg; pulmonary artery, 33/16 mm Hg; pulmonary artery mean, 23 mm Hg; pulmonary capillary wedge pressure, 12 mm Hg; and a mean arterial pressure of 100 mm Hg. He had a left ventricle ejection fraction of 60%.
Because images suggested dextroposition of the heart and right lung hypoplasia, a chest computed tomography (CT) and angiography were done (Figure 2). The images showed hypoplasia of the right lung field with an anomalous venous return from the right midlung, having a vertical contour that drained into the supradiaphragmatic IVC. In addition, CT reconstruction demarcated the last mentioned contour draining into the IVC, consistent with scimitar syndrome (Figure 3). The patient was treated conservatively due to age, optimizing therapy for obstructive lung and cardiovascular disease.
Discussion
Partial anomalous pulmonary venous return is a relatively uncommon congenital anomaly, accounting for 0.5% to 1% of congenital heart disease.4,5 The characteristic abnormality is PAPVR of part of or the entire right lung to the IVC, either below the diaphragm or at the junction of the IVC and the right atrium. The rare combination (3%-5%) of an association of PAPVR, right lung hypoplasia, and dextroposition of the heart is designated scimitar syndrome. The scimitar vein sign is a characteristic chest roentgenographic finding of a crescentlike shadow in the right lower lung field where the curvilinear dimension gives the appearance of a scimitar sword.
Related: Another Reason Not to Smoke: Acute Eosinophilic Pneunomia
Normally, the pulmonary veins from the right and left lung carry oxygenated blood into the left atrium, then to the left ventricle, and then flowing out systemically. The SCV and IVC return the deoxygenated blood from the body system to the right atrium. From the right atrium, blood flows into the right ventricle, and then through pulmonary arteries, reaching the lungs where oxygenation occurs. In this syndrome, a left-to-right shunt is established when the anomalous pulmonary vein drains blood from the right lung into the IVC, resulting in an increased risk of developing right ventricular failure due to long-standing right ventricular volume overload.
Presentation and Diagnosis
There are two clinical presentations of scimitar syndrome: infantile and pediatric/adult. Infantile scimitar syndrome has a clinical presentation of tachypnea and heart failure within the first 2 months of life, with a high mortality rate. The pediatric/adult type is milder and frequently asymptomatic, and the diagnosis is usually incidental after performing an imaging study. Scimitar vein sign appears in 70% of the noninfantile cases, and lung hypoplasia is less severe. A spirometry may reveal mild deficits in vital capacity and FEV1. An electrocardiogram may show right ventricular hypertrophy.
Cardiac catheterization is required to confirm the diagnosis. Additionally, this procedure can help in the assessment of the pulmonary venous drainage course, pulmonary artery anatomy and pressure, scimitar vein stenosis, and presence of left-to-right shunt or other cardiac anomalies, if present. Other modalities have been suggested as alternative methods for diagnosing this condition, including the use of coronary CT and 3D echocardiography.6,7 However, these diagnostic tests are not available in all facilities and are very costly.
Treatment and Prognosis
Vida and colleagues conducted a multicentric study for the European Congenital Heart Surgeons Association on scimitar syndrome.8 Data were collected from 1997 to 2007 for 68 patients who underwent a surgical procedure. A total of 11 patients were categorized as late onset, and when compared with the infantile category, they had fewer postoperatory complications, hospital mortality, late mortality, and were less likely to develop pulmonary hypertension. Both pulmonary stenosis and pulmonary hypertension were linked with poor outcomes. It seems the younger the patient (infantile), the higher the possibility of complications and mortality. Adults who are incidentally diagnosed have a better outcome if asymptomatic. Findings such as hypoplastic lungs may predispose these patients to developing recurrent pneumonias.8,9
Related: Prevention of Venous Thromboembolism After Total Joint Replacement: A Rivaroxaban Update
Dusenbery and colleagues documented in a cohort study the relationship between poor survival and other variables. Significant variables included age at presentation, nonatrial septal defect (non-ASD) congenital heart disease, left pulmonary vein stenosis, and pulmonary artery pressure (PAP) at the time of presentation. Predictors of survival for nonsurgical patients were directly related to PAP at presentation and absence of non-ASD congenital heart disease. If the patient’s PAP is less than half of the systemic pressure, the survival is near 100% at 5 years from initial presentation.9
Surgery is the definitive treatment for PAPVR. However, asymptomatic patients with PAPVR with small left-to-right shunt do not require intervention, as the defect has no significant clinical impact, and patients have a normal life expectancy without correction.10
Surgical treatment may be considered in the following circumstances:
- A hemodynamically significant left-to-right shunt (a ratio of pulmonary to systemic blood flow is greater than 2:1), often manifested as right ventricular volume overload
- Recurrent pulmonary infections
- Compression or obstruction of surrounding structures caused by the anomalous vein
- During surgical repair of other major cardiac lesions, depending on the surgical risk of a repair and level and degree of shunting
Surgical options include redirecting the venous drainage to the left atria, ligation/embolization of vascular supply to the sequestered lobe, and pneumonectomy. The procedure complications may include thrombosis of the scimitar vein, lung infarct, hemoptysis, and pulmonary hypertension, which may lead to resection of the lung.11,12 Surgical procedures are recommended in cases where the patient has had recurrent lung infections or a significant degree of shunting. Studies have compared both approaches, demonstrating a better outcome after 10 years for those patients who were medically treated considering the aforementioned surgical indications.
Conclusion
Scimitar syndrome is a rare but welldescribed constellation of cardiopulmonary anomalies, accounting for 0.5% to 1% of congenital heart disease. It is a variant of PAPVR, in which part of or even the entire right lung is drained by right pulmonary veins that connect anomalously to the IVC. Although a diagnosis can be made by chest radiograph, further imaging is needed to corroborate the diagnosis and demonstrate other associated abnormalities.
Additional tests have been described in the literature, but these procedures are not available in all facilities and may incur a higher cost. Therefore, CT angiographic reconstruction is an alternative, noninvasive procedure. Surgery is the definitive treatment; however, asymptomatic patients with PAPVR and small left-to-right shunt do not require intervention.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Anatomic variations may result in abnormal return from the pulmonary veins to the right side of the heart. This group of congenital anomalies, also known as partial anomalous pulmonary venous return (PAPVR), may connect oxygenated blood from the pulmonary vein to a systemic vein before reaching the right atrium. The most common PAPVR is derived from the left upper pulmonary vein, which then connects to the left innominate vein and drains into the superior vena cava (SVC).
Scimitar syndrome is a rare PAPVR variant in which part of or the entire right lung is drained by the pulmonary vein into the inferior vena cava (IVC), giving the curvilinear dimension the appearance of a Middle Eastern sword (scimitar). The syndrome is frequently associated with other abnormalities, such as right lung hypoplasia and abnormal right lung lobation, dextroposition of the heart, right pulmonary artery hypoplasia, systemic arterial blood supply to the right lower lung from the infradiaphragmatic aorta, atrial septal defects of the secundum type, right-sided diaphragmatic hernia, and horseshoe lung.1,2 The syndrome was first described in 1836 by Cooper during an autopsy of an infant, and Dotter diagnosed the first symptomatic patient in 1949.3,4
Case Report
A 62-year-old man, former smoker (40 pack-year), with a past medical history of arterial hypertension and asthma visited the clinic, reporting exertional dyspnea. He also reported oppressive, retrosternally located exertional chest pain, 6/10 in intensity, of 3 minutes’ duration that radiated to the right chest and ameliorated with rest. Symptoms had occurred every other day for the past year. His physical exam was remarkable for central obesity. Lung auscultation was essentially clear. There was no jugular vein distention. The patient’s heart showed a regular rate and rhythm without evidence of murmurs or gallops. There was no evidence of leg edema or cyanosis. The patient’s resting oxygen saturation of 98% remained unchanged after exercise.
Related: Venous Thromboembolism Prophylaxis in Acutely Ill Veterans With Respiratory Disease
An electrocardiogram showed normal sinus rhythm with no ischemic changes. A pulmonary function test showed a forced expiratory volume (FEV1) of 1.44 L (61% of predicted), forced vital capacity (FVC) of 1.99 L (68% of predicted), and slow vital capacity (SVC) of 2.09 L (60% of predicted), with an FEV1/SVC ratio of 68% of predicted. These results suggested moderate-to-severe obstructive ventilatory impairment.
There was no response to bronchodilator therapy. Lung volumes were measured by plethysmography. The residual volume (RV), total lung capacity (TLC), and RV/TLC ratio were 2.57 L (147% of predicted), 4.66 L (88% of predicted), and 55%, respectively, suggesting severe air trapping. Diffusion lung capacity (DLCO) testing revealed 16.95 mL/min/mm Hg (73% of predicted) when corrected by hemoglobin and DLCO/alveolar volume of 4.97 mL/min/mm Hg/L (114% of predicted). This result was consistent with a mild reduction of gas transfer, which normalized when corrected by alveolar volume.
A posteroanterior chest radiograph image was remarkable for mediastinal shifting toward the right side, volume loss of the right lung, and evidence of a previous gunshot on the right chest wall (Figure 1). Previous chest imaging done in October 2009 showed an opacification of the right lower lung with indistinctness of the right cardiac border and partial obliteration of the right hemidiaphragm. The patient was treated with inhaled steroids and long- acting bronchodilators with partial improvement in dyspnea symptoms.
Myocardial perfusion imaging revealed scintigraphic evidence of heart rate-induced ischemia on the inferior and apical wall segments of the left ventricular myocardium. A transthoracic echocardiogram showed a very poor echocardiographic window. Left ventricular function seemed preserved. Transesophageal echocardiography was scheduled, but the patient missed the appointment.
Cardiac catheterization was only remarkable for 40% to 50% obstruction of the mid-left anterior descending artery, which did not explain the patient’s dyspnea or chest pain. Right side pressures were described as follows: right atrial mean, 10 mm Hg; right ventricle, 36/8 mm Hg; pulmonary artery, 33/16 mm Hg; pulmonary artery mean, 23 mm Hg; pulmonary capillary wedge pressure, 12 mm Hg; and a mean arterial pressure of 100 mm Hg. He had a left ventricle ejection fraction of 60%.
Because images suggested dextroposition of the heart and right lung hypoplasia, a chest computed tomography (CT) and angiography were done (Figure 2). The images showed hypoplasia of the right lung field with an anomalous venous return from the right midlung, having a vertical contour that drained into the supradiaphragmatic IVC. In addition, CT reconstruction demarcated the last mentioned contour draining into the IVC, consistent with scimitar syndrome (Figure 3). The patient was treated conservatively due to age, optimizing therapy for obstructive lung and cardiovascular disease.
Discussion
Partial anomalous pulmonary venous return is a relatively uncommon congenital anomaly, accounting for 0.5% to 1% of congenital heart disease.4,5 The characteristic abnormality is PAPVR of part of or the entire right lung to the IVC, either below the diaphragm or at the junction of the IVC and the right atrium. The rare combination (3%-5%) of an association of PAPVR, right lung hypoplasia, and dextroposition of the heart is designated scimitar syndrome. The scimitar vein sign is a characteristic chest roentgenographic finding of a crescentlike shadow in the right lower lung field where the curvilinear dimension gives the appearance of a scimitar sword.
Related: Another Reason Not to Smoke: Acute Eosinophilic Pneunomia
Normally, the pulmonary veins from the right and left lung carry oxygenated blood into the left atrium, then to the left ventricle, and then flowing out systemically. The SCV and IVC return the deoxygenated blood from the body system to the right atrium. From the right atrium, blood flows into the right ventricle, and then through pulmonary arteries, reaching the lungs where oxygenation occurs. In this syndrome, a left-to-right shunt is established when the anomalous pulmonary vein drains blood from the right lung into the IVC, resulting in an increased risk of developing right ventricular failure due to long-standing right ventricular volume overload.
Presentation and Diagnosis
There are two clinical presentations of scimitar syndrome: infantile and pediatric/adult. Infantile scimitar syndrome has a clinical presentation of tachypnea and heart failure within the first 2 months of life, with a high mortality rate. The pediatric/adult type is milder and frequently asymptomatic, and the diagnosis is usually incidental after performing an imaging study. Scimitar vein sign appears in 70% of the noninfantile cases, and lung hypoplasia is less severe. A spirometry may reveal mild deficits in vital capacity and FEV1. An electrocardiogram may show right ventricular hypertrophy.
Cardiac catheterization is required to confirm the diagnosis. Additionally, this procedure can help in the assessment of the pulmonary venous drainage course, pulmonary artery anatomy and pressure, scimitar vein stenosis, and presence of left-to-right shunt or other cardiac anomalies, if present. Other modalities have been suggested as alternative methods for diagnosing this condition, including the use of coronary CT and 3D echocardiography.6,7 However, these diagnostic tests are not available in all facilities and are very costly.
Treatment and Prognosis
Vida and colleagues conducted a multicentric study for the European Congenital Heart Surgeons Association on scimitar syndrome.8 Data were collected from 1997 to 2007 for 68 patients who underwent a surgical procedure. A total of 11 patients were categorized as late onset, and when compared with the infantile category, they had fewer postoperatory complications, hospital mortality, late mortality, and were less likely to develop pulmonary hypertension. Both pulmonary stenosis and pulmonary hypertension were linked with poor outcomes. It seems the younger the patient (infantile), the higher the possibility of complications and mortality. Adults who are incidentally diagnosed have a better outcome if asymptomatic. Findings such as hypoplastic lungs may predispose these patients to developing recurrent pneumonias.8,9
Related: Prevention of Venous Thromboembolism After Total Joint Replacement: A Rivaroxaban Update
Dusenbery and colleagues documented in a cohort study the relationship between poor survival and other variables. Significant variables included age at presentation, nonatrial septal defect (non-ASD) congenital heart disease, left pulmonary vein stenosis, and pulmonary artery pressure (PAP) at the time of presentation. Predictors of survival for nonsurgical patients were directly related to PAP at presentation and absence of non-ASD congenital heart disease. If the patient’s PAP is less than half of the systemic pressure, the survival is near 100% at 5 years from initial presentation.9
Surgery is the definitive treatment for PAPVR. However, asymptomatic patients with PAPVR with small left-to-right shunt do not require intervention, as the defect has no significant clinical impact, and patients have a normal life expectancy without correction.10
Surgical treatment may be considered in the following circumstances:
- A hemodynamically significant left-to-right shunt (a ratio of pulmonary to systemic blood flow is greater than 2:1), often manifested as right ventricular volume overload
- Recurrent pulmonary infections
- Compression or obstruction of surrounding structures caused by the anomalous vein
- During surgical repair of other major cardiac lesions, depending on the surgical risk of a repair and level and degree of shunting
Surgical options include redirecting the venous drainage to the left atria, ligation/embolization of vascular supply to the sequestered lobe, and pneumonectomy. The procedure complications may include thrombosis of the scimitar vein, lung infarct, hemoptysis, and pulmonary hypertension, which may lead to resection of the lung.11,12 Surgical procedures are recommended in cases where the patient has had recurrent lung infections or a significant degree of shunting. Studies have compared both approaches, demonstrating a better outcome after 10 years for those patients who were medically treated considering the aforementioned surgical indications.
Conclusion
Scimitar syndrome is a rare but welldescribed constellation of cardiopulmonary anomalies, accounting for 0.5% to 1% of congenital heart disease. It is a variant of PAPVR, in which part of or even the entire right lung is drained by right pulmonary veins that connect anomalously to the IVC. Although a diagnosis can be made by chest radiograph, further imaging is needed to corroborate the diagnosis and demonstrate other associated abnormalities.
Additional tests have been described in the literature, but these procedures are not available in all facilities and may incur a higher cost. Therefore, CT angiographic reconstruction is an alternative, noninvasive procedure. Surgery is the definitive treatment; however, asymptomatic patients with PAPVR and small left-to-right shunt do not require intervention.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
1. Cooper G. Case of malformation of the thoracic viscera: consisting of imperfect development of the right lung, and transposition of the heart. London Med Gaz. 1836;18:600-602.
2. Spentzouris G, Zandian A, Cesmebasi A, et al. The clinical anatomy of the inferior vena cava: a review of common congenital anomalies and the considerations for clinicians. Clin Anat. 2014;27(8):1234-1243.
3. Neill CA, Ferencz C, Sabiston DC, Sheldon H. The familial occurrence of hypoplastic right lung with systemic arterial supply and venous drainage “scimitar syndrome.” Bull Johns Hopkins Hosp. 1960;107:1-21.
4. Ward KE, Mullins CE. Anomalous pulmonary venous connections, pulmonary vein stenosis, and atresia of the common pulmonary vein. In: Garson A, Bricker JT, Fisher DJ, Neish SR, eds. The Science and Practice of Pediatric Cardiology. 2nd ed. Baltimore, MD: Williams and Wilkins; 1998:1431-1461.
5. Garcia-Barreto L, Vega W, Deliz R, Rodriguez W. Right hilar abnormality in a young man. Respiration. 1996;63(4):246-250.
6. Simmons DB, Menon RS, Pomeroy WL, Batts TC, Slim AM. An unusual presentation of scimitar syndrome in a military service member. Case Rep Vasc Med. 2013;2013:632402.
7. Palios J, Pernetz MA, Clements S Jr, Lerakis S. Three-dimensional echocardiography images showing anomalous pulmonary venous return in an adult with scimitar syndrome. Echocardiography. 2014;31(3):E103.
8. Vida VL, Padalino MA, Boccuzzo G, et al. Scimitar syndrome: a European Congenital Heart Surgeons Association (ECHSA) multicentric study. Circulation. 2010;122(12):1159-1166.
9. Dusenbery SM, Geva T, Seale A, et al. Outcome predictors and implications for management of scimitar syndrome. Am Heart J. 2013;165(5):770-777.
10. Sehgal A, Loughran-Fowlds A. Scimitar syndrome. Indian J Pediatr. 2005;72(3):249-251.
11. Najm HK, Williams WG, Coles JG, Rebeyka IM, Freedom RM. Scimitar syndrome: twenty years’ experience and results of repair. J Thorac Cardiovasc Surg. 1996;112(5):1161-1169.
12. Dupuis C, Charaf LA, Brevière GM, Abou P, Rémy-Jardin M, Helmius G. The “adult” form of the scimitar syndrome. Am J Cardiol. 1992;70(4):502-507.
1. Cooper G. Case of malformation of the thoracic viscera: consisting of imperfect development of the right lung, and transposition of the heart. London Med Gaz. 1836;18:600-602.
2. Spentzouris G, Zandian A, Cesmebasi A, et al. The clinical anatomy of the inferior vena cava: a review of common congenital anomalies and the considerations for clinicians. Clin Anat. 2014;27(8):1234-1243.
3. Neill CA, Ferencz C, Sabiston DC, Sheldon H. The familial occurrence of hypoplastic right lung with systemic arterial supply and venous drainage “scimitar syndrome.” Bull Johns Hopkins Hosp. 1960;107:1-21.
4. Ward KE, Mullins CE. Anomalous pulmonary venous connections, pulmonary vein stenosis, and atresia of the common pulmonary vein. In: Garson A, Bricker JT, Fisher DJ, Neish SR, eds. The Science and Practice of Pediatric Cardiology. 2nd ed. Baltimore, MD: Williams and Wilkins; 1998:1431-1461.
5. Garcia-Barreto L, Vega W, Deliz R, Rodriguez W. Right hilar abnormality in a young man. Respiration. 1996;63(4):246-250.
6. Simmons DB, Menon RS, Pomeroy WL, Batts TC, Slim AM. An unusual presentation of scimitar syndrome in a military service member. Case Rep Vasc Med. 2013;2013:632402.
7. Palios J, Pernetz MA, Clements S Jr, Lerakis S. Three-dimensional echocardiography images showing anomalous pulmonary venous return in an adult with scimitar syndrome. Echocardiography. 2014;31(3):E103.
8. Vida VL, Padalino MA, Boccuzzo G, et al. Scimitar syndrome: a European Congenital Heart Surgeons Association (ECHSA) multicentric study. Circulation. 2010;122(12):1159-1166.
9. Dusenbery SM, Geva T, Seale A, et al. Outcome predictors and implications for management of scimitar syndrome. Am Heart J. 2013;165(5):770-777.
10. Sehgal A, Loughran-Fowlds A. Scimitar syndrome. Indian J Pediatr. 2005;72(3):249-251.
11. Najm HK, Williams WG, Coles JG, Rebeyka IM, Freedom RM. Scimitar syndrome: twenty years’ experience and results of repair. J Thorac Cardiovasc Surg. 1996;112(5):1161-1169.
12. Dupuis C, Charaf LA, Brevière GM, Abou P, Rémy-Jardin M, Helmius G. The “adult” form of the scimitar syndrome. Am J Cardiol. 1992;70(4):502-507.