Case Study
Triple synchronous primary lung cancer Patrick Zardo1, Thomas Kru¨er2, Stefan Schiffmann2, Stefan Freermann1 and Stefan Fischer1
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(7) 865–868 ß The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313495550 aan.sagepub.com
Abstract Synchronous multiple primary lung cancer is rare and difficult to differentiate from metastatic disease. State-of-the-art diagnostic tools may contribute to discern synchronous multiple primary lung cancer from lung cancer or other primary tumors with pulmonary metastases, thus allowing implementation of curative strategies. We report the case of a 72-yearold woman with 3 synchronous primary lung cancers.
Keywords Carcinoma, non-small-cell lung, Carcinoma, squamous cell, Lung neoplasms, Neoplasms, multiple primary, Small cell lung carcinoma
Introduction Synchronous multiple primary lung cancer (SMPLC) is rare and generally difficult to differentiate from metastatic disease.1 Even though state-of-the-art diagnostic tools such as positron-emission tomography-computed tomography may contribute to discern SMPLC from lung cancer or other primary tumors with pulmonary metastases, the reported prevalence is still low and varies between 0.3% and 4.6%.2 Unfortunately, despite the first diagnostic criteria being proposed in the 1970s,2 no guidelines on optimal diagnosis and treatment of SMPLC exist at present. As relevant therapeutic and prognostic implications arise from correct histological staging and curative resection is feasible in SMPLC, surgical staging and/or therapy is generally encouraged.3,4
Case report A 72-year-old woman in reasonable overall health (Eastern Cooperative Oncology Group score 1–2) was referred to our institution for diagnostic resection of a growing pulmonary mass in her left lower lobe (Figure 1). In addition to this mass, which was first described more than 2 years earlier and considered secondary to rheumatoid arthritis, a previously unknown upper right lobe lesion was detected through positronemission tomography (Figure 2). She had a history of
heavy smoking (70 pack years), multiple allergies, and rheumatoid arthritis. Although cytological examination suggested left lower lobe small-cell lung cancer, lung cancer was deemed unlikely due to an atypical clinical course. After ascertaining full operability and resectability, we scheduled her for concomitant left-sided conventional anatomical segmentectomy with radical lymphadenectomy and right-sided wedge resection by video-assisted thoracoscopic surgery. Clear resection margins were confirmed intraoperatively by direct section and microscopic examination. After on-table extubation and transfer to our intensive care unit, postoperative recovery was uneventful with inflammatory markers reaching normal values on postoperative day 3. Histological analysis confirmed left-sided smallcell lung cancer (pT1b, pN0, cM0, pL0, pV0, R0; Figure 2) and right-sided non-small-cell lung cancer (adenocarcinoma, pT1a, pN0, cM0, pL0, pV0, R0; Figure 3) with additional squamous cell carcinoma of bronchiolar origin (pTis, pN0, cM0, pL0, pV0, 1 Division of Thoracic Surgery and Lung Support, Ibbenbu¨ren General Hospital, Ibbenbu¨ren, Germany 2 Pathology Medical Center Osnabru¨ck, Osnabru¨ck, Germany
Corresponding author: Patrick Zardo, MD, Division of Thoracic Surgery and Lung Support, Ibbenbu¨ren General Hospital, Grosse Strasse 41, 49477 Ibbenbu¨ren, Germany. Email: [email protected]
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
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Figure 1. Full-body positron-emission tomography-computed tomography scan on admission, showing lesions in the left lower and right upper lobes.
Figure 2. Small-cell lung cancer. (a) Hematoxylin and eosin stain, original magnification 20. (b) Synaptophysin immunostaining, original magnification 20. (c) Ki-67 immunostaining, original magnification 20. (d) CD56 immunostaining, original magnification 20.
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Figure 3. Non-small-cell lung cancer (adenocarcinoma). (a) Hematoxylin and eosin stain, original magnification 20. (b) Thyroid transcription factor-1 immunostaining, original magnification 20. (c) Ki-67 immunostaining, original magnification 20. (d) Cytokeratin 7 immunostaining, original magnification 20.
R0; Figure 4). Immunohistochemistry showed marked expression of Ki-67 (95%), cytokeratin 7, CD56, thyroid transcription factor 1 (80%), and synaptophysin, while it was negative for basal cell cytokeratin 5/6 in the left-sided small-cell lung cancer, which radically differed from the right-sided profile (Ki-67 15%, CD56negative, synaptophysin-negative). These findings prompted us to carefully reevaluate our surgical strategy and perform a second right-sided anatomical completion lobectomy through a posterolateral incision. The patient’s further recovery was uneventful, and histological examination confirmed a rheumatoid nodule. She was discharged on postoperative day 10, and scheduled for thorough short-term follow-up.
Discussion Synchronous multiple primary lung cancers are generally defined as ‘‘simultaneously diagnosed lung cancers, physically distinct and separate, and without involvement of common lymphatics’’.2 As state-of-the-art diagnostic tools such as multislice computed tomography, positron-emission tomography, endobronchial ultrasound, and fluorescence, allow detection of increasingly smaller nodules, differentiation between SMLPC and multifocal disease becomes more difficult. With the lung being a primary target for metastatic spread in a variety of oncologic diseases, and the possibility of hematogenous metastases from contralateral
lung cancer, clinical decision-making becomes arduous. As relevant therapeutic and prognostic implications arise from correct histological staging, with curative resection being feasible in SMPLC, a proactive surgical stance is encouraged.3–5 The generally low reported prevalence of SMPLC among lung cancers (0.3%– 4.6%) may be partly attributed to a selection bias,2 as most surgeons are still reluctant to offer surgical treatment to patients with bilateral lesions.5 Interestingly, a number of current reports indicate a rising number of SMPLC patients,5,6 which correlates with the introduction of the aforementioned diagnostic tools, suggesting a more aggressive surgical stance paired with improvements in noninvasive mediastinal staging, among others. Even though no clear-cut guidelines on optimal management of suspected SMPLC exist, conventional mediastinoscopic staging and a search for hematogenous spread are strongly advised.5,7 Furthermore, a number of technical aspects such as extensiveness and timing of surgery need to be addressed. While certain authors encourage concomitant bilateral procedures, others prefer a staged approach, and although some surgeons perform bilateral anatomical resection, others deem a large wedge resection sufficient.5,6 Personally, we lean towards anatomical resection because it is associated with lower local recurrence rates, even though overall morbidity might be slightly increased.8 At present, we suggest thorough initial
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
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Figure 4. Squamous cell carcinoma. (a) Hematoxylin and eosin stain, original magnification 20. (b) Ki-67 immunostaining, original magnification 20. (c) Hematoxylin and eosin stain, original magnification 10. (d) Cytokeratin 5/6 immunostaining, original magnification 20.
staging including a positron-emission tomographycomputed tomography scan and magnetic resonance imaging. Although positron-emission tomographycomputed tomography has a high specificity, we encourage further mediastinal staging either through endobronchial ultrasound-guided transbronchial needle aspiration or, preferably, via mediastinoscopy. As previously mentioned, we recommend a staged approach and bilateral anatomical resection because we deem the potentially increased morbidity as negligible. Most published series suggest that surgical treatment leads to an appreciable increase in overall survival, with 5-year rates as high as 38%.5 Therefore, we agree with de Leyn and colleagues5 that ‘‘a patient with a single contralateral lung lesion should have an extensive search for metastatic spread and thorough functional assessment. In appropriate cases, the clinician treating must then decide whether this patient is likely to have two primaries, and is a candidate for radical treatment with bilateral resection, rather than for an approach for disseminated stage IV disease’’. Only thorough and aggressive staging allows for timely detection of SMPLC and offers the possibility of implementing potentially curative strategies in patients conventionally considered as metastasized. Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
Conflict of interest statement None declared
References 1. Kontic M, Stevic R, Stojsic J, Jekic B and Bunjevacki V. Synchronous primary lung cancers: a multidisciplinary approach in diagnosis. Tumori 2011; 97: e16–e19. 2. Martini N and Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg 1975; 70: 606–612. 3. Xue X, Xue Q, Wang N, et al. Early clinical diagnosis of synchronous multiple primary lung cancer. Oncology Lett 2012; 3: 234–237. 4. van Rens MT, Zanen P, Brutel de La Rivie`re A, Elbers HR, van Swieten HA and van Den Bosch JM. Survival in synchronous versus single lung cancer: upstaging better reflects prognosis. Chest 2000; 118: 952–958. 5. De Leyn P, Moons J, Vansteenkiste J, et al. Survival after resection of synchronous bilateral lung cancer. Eur J Cardiothorac Surg 2008; 34: 1215–1222. 6. Trousse D, Barlesi F, Loundou A, et al. Synchronous multiple primary lung cancer: an increasing clinical occurrence requiring multidisciplinary management. J Thorac Cardiovasc Surg 2007; 133: 1193–1200. 7. De Leyn P, Lardinois D, Van Schil P, et al. ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer. Eur J Cardiothorac Surg 2007; 32: 1–8. 8. De Zoysa MK, Hamed D, Routledge T and Scarci M. Is limited pulmonary resection equivalent to lobectomy for surgical management of stage I non-small-cell lung cancer? Interact Cardiovasc Thorac Surg 2012; 14: 816–820.
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
Triple synchronous primary lung cancer Patrick Zardo1, Thomas Kru¨er2, Stefan Schiffmann2, Stefan Freermann1 and Stefan Fischer1
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(7) 865–868 ß The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313495550 aan.sagepub.com
Abstract Synchronous multiple primary lung cancer is rare and difficult to differentiate from metastatic disease. State-of-the-art diagnostic tools may contribute to discern synchronous multiple primary lung cancer from lung cancer or other primary tumors with pulmonary metastases, thus allowing implementation of curative strategies. We report the case of a 72-yearold woman with 3 synchronous primary lung cancers.
Keywords Carcinoma, non-small-cell lung, Carcinoma, squamous cell, Lung neoplasms, Neoplasms, multiple primary, Small cell lung carcinoma
Introduction Synchronous multiple primary lung cancer (SMPLC) is rare and generally difficult to differentiate from metastatic disease.1 Even though state-of-the-art diagnostic tools such as positron-emission tomography-computed tomography may contribute to discern SMPLC from lung cancer or other primary tumors with pulmonary metastases, the reported prevalence is still low and varies between 0.3% and 4.6%.2 Unfortunately, despite the first diagnostic criteria being proposed in the 1970s,2 no guidelines on optimal diagnosis and treatment of SMPLC exist at present. As relevant therapeutic and prognostic implications arise from correct histological staging and curative resection is feasible in SMPLC, surgical staging and/or therapy is generally encouraged.3,4
Case report A 72-year-old woman in reasonable overall health (Eastern Cooperative Oncology Group score 1–2) was referred to our institution for diagnostic resection of a growing pulmonary mass in her left lower lobe (Figure 1). In addition to this mass, which was first described more than 2 years earlier and considered secondary to rheumatoid arthritis, a previously unknown upper right lobe lesion was detected through positronemission tomography (Figure 2). She had a history of
heavy smoking (70 pack years), multiple allergies, and rheumatoid arthritis. Although cytological examination suggested left lower lobe small-cell lung cancer, lung cancer was deemed unlikely due to an atypical clinical course. After ascertaining full operability and resectability, we scheduled her for concomitant left-sided conventional anatomical segmentectomy with radical lymphadenectomy and right-sided wedge resection by video-assisted thoracoscopic surgery. Clear resection margins were confirmed intraoperatively by direct section and microscopic examination. After on-table extubation and transfer to our intensive care unit, postoperative recovery was uneventful with inflammatory markers reaching normal values on postoperative day 3. Histological analysis confirmed left-sided smallcell lung cancer (pT1b, pN0, cM0, pL0, pV0, R0; Figure 2) and right-sided non-small-cell lung cancer (adenocarcinoma, pT1a, pN0, cM0, pL0, pV0, R0; Figure 3) with additional squamous cell carcinoma of bronchiolar origin (pTis, pN0, cM0, pL0, pV0, 1 Division of Thoracic Surgery and Lung Support, Ibbenbu¨ren General Hospital, Ibbenbu¨ren, Germany 2 Pathology Medical Center Osnabru¨ck, Osnabru¨ck, Germany
Corresponding author: Patrick Zardo, MD, Division of Thoracic Surgery and Lung Support, Ibbenbu¨ren General Hospital, Grosse Strasse 41, 49477 Ibbenbu¨ren, Germany. Email: [email protected]
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
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Figure 1. Full-body positron-emission tomography-computed tomography scan on admission, showing lesions in the left lower and right upper lobes.
Figure 2. Small-cell lung cancer. (a) Hematoxylin and eosin stain, original magnification 20. (b) Synaptophysin immunostaining, original magnification 20. (c) Ki-67 immunostaining, original magnification 20. (d) CD56 immunostaining, original magnification 20.
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
Zardo et al.
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Figure 3. Non-small-cell lung cancer (adenocarcinoma). (a) Hematoxylin and eosin stain, original magnification 20. (b) Thyroid transcription factor-1 immunostaining, original magnification 20. (c) Ki-67 immunostaining, original magnification 20. (d) Cytokeratin 7 immunostaining, original magnification 20.
R0; Figure 4). Immunohistochemistry showed marked expression of Ki-67 (95%), cytokeratin 7, CD56, thyroid transcription factor 1 (80%), and synaptophysin, while it was negative for basal cell cytokeratin 5/6 in the left-sided small-cell lung cancer, which radically differed from the right-sided profile (Ki-67 15%, CD56negative, synaptophysin-negative). These findings prompted us to carefully reevaluate our surgical strategy and perform a second right-sided anatomical completion lobectomy through a posterolateral incision. The patient’s further recovery was uneventful, and histological examination confirmed a rheumatoid nodule. She was discharged on postoperative day 10, and scheduled for thorough short-term follow-up.
Discussion Synchronous multiple primary lung cancers are generally defined as ‘‘simultaneously diagnosed lung cancers, physically distinct and separate, and without involvement of common lymphatics’’.2 As state-of-the-art diagnostic tools such as multislice computed tomography, positron-emission tomography, endobronchial ultrasound, and fluorescence, allow detection of increasingly smaller nodules, differentiation between SMLPC and multifocal disease becomes more difficult. With the lung being a primary target for metastatic spread in a variety of oncologic diseases, and the possibility of hematogenous metastases from contralateral
lung cancer, clinical decision-making becomes arduous. As relevant therapeutic and prognostic implications arise from correct histological staging, with curative resection being feasible in SMPLC, a proactive surgical stance is encouraged.3–5 The generally low reported prevalence of SMPLC among lung cancers (0.3%– 4.6%) may be partly attributed to a selection bias,2 as most surgeons are still reluctant to offer surgical treatment to patients with bilateral lesions.5 Interestingly, a number of current reports indicate a rising number of SMPLC patients,5,6 which correlates with the introduction of the aforementioned diagnostic tools, suggesting a more aggressive surgical stance paired with improvements in noninvasive mediastinal staging, among others. Even though no clear-cut guidelines on optimal management of suspected SMPLC exist, conventional mediastinoscopic staging and a search for hematogenous spread are strongly advised.5,7 Furthermore, a number of technical aspects such as extensiveness and timing of surgery need to be addressed. While certain authors encourage concomitant bilateral procedures, others prefer a staged approach, and although some surgeons perform bilateral anatomical resection, others deem a large wedge resection sufficient.5,6 Personally, we lean towards anatomical resection because it is associated with lower local recurrence rates, even though overall morbidity might be slightly increased.8 At present, we suggest thorough initial
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
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Asian Cardiovascular & Thoracic Annals 22(7)
Figure 4. Squamous cell carcinoma. (a) Hematoxylin and eosin stain, original magnification 20. (b) Ki-67 immunostaining, original magnification 20. (c) Hematoxylin and eosin stain, original magnification 10. (d) Cytokeratin 5/6 immunostaining, original magnification 20.
staging including a positron-emission tomographycomputed tomography scan and magnetic resonance imaging. Although positron-emission tomographycomputed tomography has a high specificity, we encourage further mediastinal staging either through endobronchial ultrasound-guided transbronchial needle aspiration or, preferably, via mediastinoscopy. As previously mentioned, we recommend a staged approach and bilateral anatomical resection because we deem the potentially increased morbidity as negligible. Most published series suggest that surgical treatment leads to an appreciable increase in overall survival, with 5-year rates as high as 38%.5 Therefore, we agree with de Leyn and colleagues5 that ‘‘a patient with a single contralateral lung lesion should have an extensive search for metastatic spread and thorough functional assessment. In appropriate cases, the clinician treating must then decide whether this patient is likely to have two primaries, and is a candidate for radical treatment with bilateral resection, rather than for an approach for disseminated stage IV disease’’. Only thorough and aggressive staging allows for timely detection of SMPLC and offers the possibility of implementing potentially curative strategies in patients conventionally considered as metastasized. Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
Conflict of interest statement None declared
References 1. Kontic M, Stevic R, Stojsic J, Jekic B and Bunjevacki V. Synchronous primary lung cancers: a multidisciplinary approach in diagnosis. Tumori 2011; 97: e16–e19. 2. Martini N and Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg 1975; 70: 606–612. 3. Xue X, Xue Q, Wang N, et al. Early clinical diagnosis of synchronous multiple primary lung cancer. Oncology Lett 2012; 3: 234–237. 4. van Rens MT, Zanen P, Brutel de La Rivie`re A, Elbers HR, van Swieten HA and van Den Bosch JM. Survival in synchronous versus single lung cancer: upstaging better reflects prognosis. Chest 2000; 118: 952–958. 5. De Leyn P, Moons J, Vansteenkiste J, et al. Survival after resection of synchronous bilateral lung cancer. Eur J Cardiothorac Surg 2008; 34: 1215–1222. 6. Trousse D, Barlesi F, Loundou A, et al. Synchronous multiple primary lung cancer: an increasing clinical occurrence requiring multidisciplinary management. J Thorac Cardiovasc Surg 2007; 133: 1193–1200. 7. De Leyn P, Lardinois D, Van Schil P, et al. ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer. Eur J Cardiothorac Surg 2007; 32: 1–8. 8. De Zoysa MK, Hamed D, Routledge T and Scarci M. Is limited pulmonary resection equivalent to lobectomy for surgical management of stage I non-small-cell lung cancer? Interact Cardiovasc Thorac Surg 2012; 14: 816–820.
Downloaded from aan.sagepub.com at University of Central Florida Libraries on March 27, 2015
