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CASE REPORT SHAW ET AL PSEUDOCAVITATING BRONCHIOLOALVEOLAR CARCINOMA
AD, BAC, and AAH in the case patient might have occurred as a result of second-hit mutations L861Q and L858R in the setting of a germline V843I mutation. However, the effects of the EGFR V843I mutation on EGFR signaling and the molecular importance of the double mutation on EGFR exon 21 are unknown. The patient’s father and a brother had died of lung cancer. However, another brother and a sister, each of whom had germline EGFR V843I mutation, have not developed lung cancer despite being almost 70 years old. The role of germline EGFR V843I mutation in multifocal lung carcinogenesis and the familial occurrence of lung cancer in the case patient are still unclear. In vitro experiments are needed to clarify the effects of EGFR V843I mutation on EGFR signaling, as is accumulation of clinical cases to determine the role of germline EGFR mutation in lung carcinogenesis.
References
FEATURE ARTICLES
1. Zwirewich CV, Miller RR, Muller NL. Multicentric adenocarcinoma of the lung: CT-pathologic correlation. Radiology 1990;176:185–90. 2. Bell DW, Gore I, Okimoto RA, et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005;37:1315– 6. 3. Blons H, Côté JF, Le Corre D, et al. Epidermal growth factor receptor mutation in lung cancer is linked to bronchioloalveolar differentiation. Am J Surg Pathol 2006;30:1309 –15. 4. Tang X, Shigematsu H, Bekele N, et al. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res 2005;65:7568 –72. 5. Ji H, Li D, Chen L, et al. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cells 2006;9:485–95. 6. Shih J-Y, Gow C-H, Yu C-J, et al. Epidermal growth factor receptor mutation in needle biopsy/aspiration samples predicts response to gefitinib therapy and survival of patients with advanced non–small cell lung cancer. Int J Cancer 2006;118:963–9. 7. Leone F, Cavalloni G, Pignochino Y, et al. Somatic mutation of epidermal growth factor recepter in bile duct and gallbladder carcinoma. Clin Cancer Res 2006;12:1680 –5. 8. Knudson AG Jr. Overview: genes that predispose to cancer. Mutat Res 1991;247:185–90.
Pseudocavitating Bronchioloalveolar Carcinoma Followed Over a Decade Jason P. Shaw, MD, Pablo A. Bejarano, MD, and Richard J. Thurer, MD Department of Surgery, Division of Cardiothoracic Surgery, and Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida
A 38-year-old woman with bronchioloalveolar carcinoma (BAC) had a slow-growing cavitary nodule for nearly a Accepted for publication Oct 1, 2007. Address correspondence to Dr Shaw, Department of Surgery, Division of Cardiothoracic Surgery, University of Miami Miller School of Medicine, PO Box 016960 (R-114), Miami, FL 33010; e-mail:
[email protected].
© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
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decade. When she was hospitalized because of pneumonia 9 years earlier, a chest computed tomography scan showed a 1.5-cm cavitary right upper lobe nodule. At 1, 3, and 9 years computed tomography scans showed slow growth of the nodule to 2.4 cm, corresponding to a volume doubling time of 1494 days. Thoracoscopic biopsy and lobectomy were performed. Pathologic analysis revealed a well-differentiated mucinous BAC (T1N0M0). Pseudocavitation in solitary BAC is rare. A longer period of surveillance may be required to rule out malignancy in this setting. Surgical resection remains the mainstay of therapy. (Ann Thorac Surg 2008;85:1432– 4) © 2008 by The Society of Thoracic Surgeons
W
ith more widespread use of computed tomography (CT) of the lung, small bronchioloalveolar carcinomas (BACs) are being diagnosed with increasing frequency. Bronchioloalveolar carcinomas are generally thought to have a more indolent course than other subtypes of adenocarcinoma of the lung. While CT appearance varies, the presence of BAC as a solitary cavitary nodule is rare. We report the case of a slow-growing BAC in a young woman that highlights the importance of prolonged surveillance or resection when BAC is included in the differential diagnosis. A 38-year-old woman with nonpleuritic chest pain and a long-standing right upper lobe cavitary lesion, with a 3 pack-year smoking history, was referred for thoracic surgical evaluation. Nine years previously the patient had been hospitalized because of pneumonia involving the posterior segment of the right upper lobe. Results of tuberculin skin testing were negative. When a chest radiograph at 6-month follow-up showed a persistent mass, a CT scan of the chest was obtained, which revealed a 1.5-cm rounded lesion with central lucency (Fig 1A). Bronchoscopy performed 1 year after initial presentation was nondiagnostic. A chest CT scan obtained 9 years after initial presentation demonstrated the lesion in the right upper lobe measuring 2.4 cm. A fluorodeoxyglucose positron emission tomography scan demonstrated no uptake. Thoracoscopic biopsy followed by lobectomy with lymph node dissection was performed. Pathologic analysis revealed a 2.5-cm well-differentiated mucinous BAC (T1N0M0) (Figs 2, 3). The patient had an uneventful hospital course and was discharged on postoperative day 4. During nearly a decade, CT scans had been obtained at various institutions, at 6 months and at 1, 3, and 9 years after initial presentation (Figs 1A-D). Review of the scans revealed a largest tumor diameter of 1.5 cm, 1.5 cm, 1.6 cm, and 2.4 cm, respectively, suggesting tumor stability at 1 year. However, calculation of tumor volume from each CT scan (V ⫽ /6 ⫻ ab2, where a is the largest diameter and b is the largest diameter perpendicular to a) showed an increase in tumor volume at each interval, with volumes of 1.3 cm3, 1.4 cm3, 1.8 cm3, and 5.6 cm3, respectively. Tumor 0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2007.10.031
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CASE REPORT SHAW ET AL PSEUDOCAVITATING BRONCHIOLOALVEOLAR CARCINOMA
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volume doubling time (VDT) at each interval was calculated using the modified Schwartz equation (VDT ⫽ [t ⫻ log 2] ⫼ log[Vt/Vo]), where t is the interval in days between 2 scans, Vo is tumor volume on the initial CT scan, and Vt is tumor volume on subsequent CT scans) and revealed a VDT of 1,651, 2,643, and 1,261 days, respectively [1]. Tumor volume increased slowly over the first 3 years, with a subsequent increase in growth rate, although at all intervals the VDT was long. Overall VDT (calculated from the first and last scans) was 1,494 days.
Comment Bronchioalveolar carcinoma is an increasingly common primary lung neoplasm, although data about its incidence and prognosis are confounded by difficulties in case definition. A subtype of adenocarcinoma of the lung, BAC may have a more indolent course than other types of non–small cell lung cancers. It is classified pathologically as mucinous, nonmucinous, and mixed subtypes.
Fig 2. Lung specimen shows gelatinous tumor with a central hollow space.
Bronchioalveolar carcinoma seen as a solitary cavitary nodule is rare [2, 3]. Several mechanisms have been proposed to explain the cavitary appearance of a lesion on CT scans, that is, so-called pseudocavitation. One theory postulates that multiple oval areas of low attenuation mimic small cavities. Others suggest that the cavitary appearance results from a process analogous to that seen on an air bronchogram: proliferation of tumor cells along the alveolar walls without disruption of lung architecture and with maintenance of alveolar patency [4]. Given the mucinous histologic findings in this case, it is possible that the low attenuating, mucin-containing airspace within the tumor produced the appearance of a central cavity on CT scans and at gross pathologic examination.
Fig 3. At histologic analysis, tumor cells were noted growing along the alveolar septa in a lepidic pattern and the alveolar spaces were filled with mucin (hematoxylin-eosin stain, original magnification ⫻200).
FEATURE ARTICLES
Fig 1. (A-D) Computed tomography scans of the chest obtained at 6 months and at 1, 3, and 9 years, respectively, after initial presentation.
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CASE REPORT YAMADA ET AL BILATERAL PLEURAL COMMUNICATION
FEATURE ARTICLES
Differentiating pseudocavitary BAC from other causes of solitary cavitary nodules is challenging. The differential diagnosis includes tuberculosis, fungal infections, other lung cancers, metastases, necrotic rheumatoid nodules, Wegener granulomatosis, and eosinophilic granuloma. Although our patient’s age, sex, minimal smoking history, and presentation to several different institutions during nearly a decade likely all contributed to the delay in diagnosis, the initial lesion diameter of greater than 1 cm and the subsequent increase in size should have raised suspicion of malignancy. The lesion was followed up closely during the first 3 years, at which point it was thought to be benign. However, when BAC is included in the differential diagnosis, surveillance for as long as 5 years or longer may be required to rule out malignancy. Some studies suggest a worse prognosis for BAC of the mucinous subtype, with 5-year survival as low as 59% [5]. In addition, mucinous BAC cells may be more likely to detach from the underlying basement membrane and spread aerogenously [6]. In contrast, our calculated VDT of 1494 days, even longer than the mean of 851 days in women with BAC in one study [1], suggests an extremely indolent course. This VDT far exceeds the 400-day threshold used by some authors to define overdiagnosis in the context of lung cancer CT screening trials [7]. However, it is important to remember that these numbers may have a quite different meaning for the lifespan of a heavy smoker older than 60 years compared with our young, otherwise healthy patient. Until molecular diagnostic procedures enable more accurate prediction of prognosis, controversy about the clinical significance of small BACs and the extent of resection may continue, but surgery remains the mainstay of treatment.
Dr Caralee Caplan-Shaw provided editorial assistance.
References 1. Lindell RM, Hartman TE, Swensen SJ, et al. Five-year lung cancer screening experience: CT appearance, growth rate, location, and histologic features of 61 lung cancers. Radiology 2007;242:555– 62. 2. Weisbrod GL, Chamberlain D, Herman SJ. Cystic change (pseudocavitation) associated with bronchioloalveolar carcinoma: a report of four patients. J Thorac Imaging 1995;10:106 – 11. 3. Kuhlman JE, Fishman EK, Kuhajda FP, et al. Solitary bronchioloalveolar carcinoma: CT criteria. Radiology 1988; 167:379 – 82. 4. Shapiro R, Wilson GL, Yesner R, Shuman H. A useful roentgen sign in the diagnosis of localized bronchioloalveolar carcinoma. Am J Roentgenol Radium Ther Nucl Med 1972; 114:516 –24. 5. Furak J, Trojan I, Szoke T, et al. Bronchioloalveolar lung cancer: occurrence, surgical treatment and survival. Eur J Cardiothorac Surg 2003;23:818 –23. 6. Gaeta M, Blandino A, Pergolizzi S, et al. Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical resection: a radiological, histological, and immunohistochemical study. Lung Cancer 2003;42:319 –26. © 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
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7. Yankelevitz DF, Kostis WJ, Henschke CI, et al. Overdiagnosis in chest radiographic screening for lung carcinoma: frequency. Cancer 2003;97:1271–5.
Simultaneous Bilateral Spontaneous Pneumothorax With Pleural Window Communicating With Bilateral Pleural Spaces Shunsuke Yamada, MD, Kazuho Yoshino, MD, and Hiroshi Inoue, MD Department of Thoracic Surgery, Tokai University Hachioji Hospital and Tokai University School of Medicine, Hachioji, Tokyo, Japan
A pleural window communicating between bilateral pleural cavities is a serious condition in patients with pneumothorax, allowing air to leak from the affected lung into the contralateral pleural cavity and resulting in bilateral spontaneous pneumothorax. We treated a patient with a history of right-sided bullectomy for simultaneous bilateral spontaneous pneumothorax that subsequently recurred. A pleural window (1 cm long) was detected in the mid-mediastinum, and direct suture closure with localized pleural abrasion using argon beam coagulation on the circumference of the lesion was performed at video-assisted thoracoscopic surgery. (Ann Thorac Surg 2008;85:1434 – 6) © 2008 by The Society of Thoracic Surgeons
S
imultaneous bilateral spontaneous pneumothorax (SBSP) is rare but can be a critical clinical event. Almost all reported cases have involved underlying pulmonary disease such as chronic obstructive pulmonary disease, malignant neoplasm, or tuberculosis. In the present case, a congenital pleural window communicating between bilateral pleural cavities allowed air to leak from the affected lung into the contralateral pleural cavity, causing SBSP. Reports of surgical SBSP associated with congenital pleural communication are extremely rare. We report the case of a patient with SBSP associated with a congenital pleural window that was treated using video-assisted thoracoscopic surgery. A 21-year-old man was transferred to our hospital for surgical treatment of recurrent SBSP. Two months earlier he had been transferred to the emergency department of another hospital because of clinically critical complete collapse of both lungs and had undergone urgent bilateral tube thoracostomy. He subsequently underwent right-sided bullectomy with pleural abrasion using dry gauze in a right-sided axial thoracotomy as a procedure Accepted for publication Oct 8, 2007. Address correspondence to Dr Yamada, Department of Thoracic Surgery, Tokai University Hachioji Hospital, 1838 Isikawa, Hachioji, Tokyo, 1920032, Japan; e-mail:
[email protected].
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