HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andrea, S. Articles by Enzo, P. Search for Related Content PubMed PubMed Citation Articles by Andrea, S. Articles by Enzo, P.

Eur J Cardiothorac Surg 2001;20:1101-1105
© 2001 Elsevier Science NL

Significance of a single pulmonary nodule in patients with previous history of malignancy

Department of Surgical, Anesthesiological and Radiological Sciences, University of Ferrara, Corso Giovecca 203, 44100 Ferrara, Italy

Received 23 April 2001; received in revised form 20 July 2001; accepted 3 September 2001.

Corresponding author. Tel.: +39-532-236385; fax: +39-532-207653
e-mail: srn{at}unife.it

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
Objectives: To determine the diagnosis, treatment and follow-up in patients with a solitary lung nodule and a previous primary extrapulmonary neoplasm. Methods: The authors evaluated the charts of 45 patients with an extrapulmonary malignant neoplasm and a solitary pulmonary nodule. The histologic characteristics of the nodule were correlated with those of the extrapulmonary neoplasm. Results: The histology of the nodule was not known preoperatively in 43 cases (93.5%); in the remaining three cases cytologic examination had shown the presence of atypical cells. The majority of pulmonary lesions (73.9%) were found during the follow-up of the previous tumour, but a significant percentage of nodules (17.4%) were found incidentally. Pre- or intraoperative localisation of the nodule was done in 19 cases (41.3%), and was successful in nine cases (47.4%). Thoracoscopy was performed in 44 patients (95.6%). The coincidence between the pathology of the previous tumour and that of the nodule was 41.3% (19/46). The coincidence rate was 100% for the tumours of ovary, prostate, and sarcomas. Conclusions: The advent of minimally invasive surgical techniques has made a definitive diagnosis likely, providing also therapy with a less painful engagement for the patient and a less cost for the community.

Key Words: Single pulmonary nodule • Thoracoscopic surgery • Extrapulmonary neoplasms

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
The solitary pulmonary nodule (SPN), a single intrapulmonary spherical lesion that is fairly well circumscribed, is a common clinical problem. Typically, the most relevant question is whether the lesion is malignant. The differential diagnosis includes infectious, inflammatory, and other benign etiologies. About half of the SPNs seen in clinical practice are malignant. Some nodules are primary tumours of other kinds or metastatic. The finding of SPN in a chest radiograph in patients with positive oncological anamnesis is more frequent than we suspect: most studies have shown that about 30% of malignant tumours give pulmonary metastasis [1,2].

The workup of these lesions has evolved, to some extent, over time [3–5]. Accuracy of radiologic assessment in diagnosing SPNs has not appreciably changed in over 30 years. Bayesian analysis using different criteria has been used to assess odds ratios for malignant diagnoses, improving the accuracy of radiologic interpretation [6].

Improvements in the technology of computerised tomography (CT) scanning have allowed for the ability to detect subcentimetre nodules that are more difficult to diagnose as benign or malignant [7]. The application of biological radioactive markers in positron emission tomography (PET) scanning with 18-fluorodeoxyglucose has allowed an accuracy varying between 77 and 100%, even if expense and availability have limited the application of PET technology to a few centres [8].

The exact pre- or intraoperative localisation and characterisation of the nodule is crucial for deciding the surgical strategy. Multiple techniques have been described that aid in the identification of the nodules, from preoperative needle or dye localisation to intraoperative ultrasound and utilisation of gamma-detection probes [9–15].

Minimally invasive thoracoscopic techniques are now widely used to diagnose indeterminate SPNs in the outer third of the lung field. These lesions can be removed easily for diagnosis and, if it is indicated, a definitive cancer operation can be performed. Thoracoscopy biopsy carries a significantly decreased risk of morbidity and mortality compared with open thoracotomy for wedge resection [5,9,16–18].

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
From November 1970 to December 2000, 611 procedures of pulmonary resection have been performed in our Surgical Department of the University of Ferrara. Of these, 85 cases (13.5%) were performed in patients with positive oncological anamnesis.

We reviewed the cases operated on from January 1990 to December 2000, because during this time patients have been submitted to a homogeneous diagnostic and therapeutic workup. During this time, 46 operations have been performed in 45 patients. They were 25 men and 20 women of mean age 64.5 years (range: 41–80 years).

The diagnosis of SPN has been done with a standard chest X-ray carried out for different reasons (oncological follow-up, preoperative exams, insurance reasons, forensic medicine, work screening for some jobs like butcher, etc.).

When present, symptoms complained by patients were cough, blood expectorate, dyspnea, and fever.

All patients have subsequently undergone chest CT with or without a biopsy, CT-guided, of the pulmonary nodule.

Only ten patients have been submitted to bronchoscopy with brushing or biopsy, since we believe that this method does not add more information, because of the periferic localisation and the extrabronchial growth of the metastatic nodule.

Surgery was indicated to make a definitive diagnosis and to provide therapy.

For a relatively small, peripherally located nodule a thoracoscopic technique was planned.

Very small lesions were difficult to localise using a thoracoscopic technique. In a few patients, dye localisation, use of a wired needle, intraoperative ultrasound, or radio-guided surgery were employed to aid in the identification of the nodules pre- and intraoperatively. In most settings, an examination of the chest CT scan was all that was necessary to aid in planning port placement and intraoperative finger palpation.

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
The histology of the nodule was not known preoperatively in 43 cases (93.5%); in the remaining three cases cytologic examination (obtained in one case through a CT-guided fine-needle biopsy, and through bronchoscopy with brushing in the other two cases) had shown the presence of atypical cells, so we always used the frozen section histology intraoperatively.

The majority of pulmonary lesions (73.9%) were found during the follow-up of the previous tumour, but a significant percentage of nodules (17.4%) were found incidentally, these patients had a chest X-ray not for oncological reasons but for others reasons (forensic scientist, insurance, preoperative for others type of pathology), because they go out of follow-up or they never come in.

Modalities of diagnosis are shown in Table 1.

The localisation and pathology of the previous tumour, and the interval between the diagnosis of the primary tumour and of the pulmonary nodule are shown in Table 2.

In 16 cases (34.7%) the nodules were located in the left lung: nine nodules (19.5%) in the superior lobe and seven (15.2%) in the inferior one.

The size of the nodule was <1 cm in seven cases, between 1 and 2.5 cm in 28 cases, and >2.5 cm but <3 cm in 11 cases.

Pre- or intraoperative localisation of the nodule was done in 19 cases (41.3%). Using the blue dye in six patients we have found the nodule in only one case (16%). Wired needle localisation was successful in 1/3 cases (33%), intrathoracoscopic ultrasound was successful in 4/5 cases (80%), and the radio-guided localisation was successful in 3/5 cases (66%).

Surgery was performed in all cases: the thoracoscopic technique was performed in 44 patients (95.6%). In 16 cases (34.7%) the procedure was converted. The traditional thoracotomic approach was employed in two patients (4.4%). The causes of conversion were difficulties in localising the nodule in nine patients, pleuric adhesions in four cases, technical problems in two cases, and centrally located lesion with associated mediastinic lymphadenopathy in one case. All patients with primary lung cancers had conversion for oncological reasons; in fact, we performed thoracotomic lobectomy.

We performed 34 atypical lung resections (73.9%) and 11 lobectomies (23.9%), and only one biopsy (2.2%). We evaluated the 11 lobectomies for primary lung cancers and for the recovery of previous malignancy, and how diffuse the neoplastic disease was. The pathological results of the SPNs are illustrated in Table 3.

We observed only one serious postoperative complication, which was hemothorax due to haemorrhage of an intercostal artery that required an emergency thoracotomy.

Data concerning the follow-up are shown in Table 4.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

In the management of SPN we have tried to always answer all these questions, for every patient.

The presumed diagnosis of the SPN is based on several factors: the age of the patient, associated symptoms, appearance of the lesion on the radiograph, the length of time lesion has been present.

A single pulmonary nodule is more likely to be malignant in patients with known cancer.

It is therefore important to obtain a precise history, in particular the presence of previous malignancy. Because of the presence of a ‘free interval’ between the diagnosis of the pulmonary nodule and the onset of the previous tumour, considering also the paucity of symptoms complained by patients with pulmonary metastasis, it is evident that the discovery of pulmonary metastasis is possible only with a correct oncological follow-up.

The longer the free interval, the lower is the aggressiveness of the metastasis and better is the prognosis, especially for surgically treated pulmonary lesions. The mean interval for prognosis inversion is about 18–24 months [4].

We have found the majority of pulmonary lesions (73.9%) during the follow-up of the previous tumour, but a significant percentage of nodules (17.4%) was found incidentally. Most of the patients in fact had no symptoms (73.9%). Blood expectorate, the only specific symptom, was present in four patients.

The mean interval between the diagnosis of the primary tumour and that of the pulmonary nodule was of 38.7 months, ranging from a minimum of 2 months (malignant melanoma of the back) to a maximum of 132 months (breast cancer).

The tumours that give most frequently pulmonary metastasis are sarcomas of whatever primitive localisation, and those neoplasms that give blood metastasis through the cava circle, such as those arising from kidney, prostate, male genital apparatus, breast, skin and annex (for example malignant melanoma), head and neck region, ovary, uterus, salivary gland, and from the other lung. Colorectal cancer frequently gives pulmonary metastasis without liver metastasis [1,2].

In our case study, the nodules were benign in 27% (12 cases), they were metastasis of previous malignant tumour in 41% (19 cases), and were primary pulmonary nodules (‘second tumours’) in 32% (15 cases). Their histology was: seven adeno carcinomas, five squamous carcinomas, two big cell carcinomas and one small cell carcinoma. The surgical approach was: 11 lobectomies, three atypical resections for the nodule less than 1 cm in diameter, and one biopsy. TNM were 14 T1 N0 M0 and one T1 N2 M0.

Despite the epidemiologic data of the literature, we have observed only two patients affected by metastatic nodules from sarcomas. The majority of SPNs were present in patients affected previously by colorectal or breast cancer (24 cases), probably because these patients have preferred to return to the same institute for the treatment of SPN.

The size of the nodule was <1 cm in seven cases, between 1 and 2.5 cm in 28 cases, and >2.5 cm but <3 cm in 11 cases.

As demonstrated by other authors, we have observed that nodules larger than 1.5 cm and smaller than 3 cm were more likely to be malignant. The seven nodules less than 1 cm were all benign. Moreover, the likelihood of a primary lung cancer versus a metastasis seems to depend on the histologic characteristics of the extrapulmonary neoplasm and on the patient's smoking history [2].

The exact pre- or intraoperative localisation and characterisation of the nodule is crucial for deciding the surgical strategy. Multiple techniques have been described that aid in the identification of the nodules: preoperative needle or dye localisation, intraoperative reperage on sight, digital palpation, fluoroscopy with use of contrast medium, intraoperative ultrasound and utilisation of gamma-detection probes [9–15].

Pre- or intraoperative localisation of the nodule was done only in 19 cases (41.3%).

We preferred to not perform CT-guided needle biopsy because most of the nodules appeared subpleuric at CT imaging, we could not have an onsite cytopathologist, and our experience in CT-guided needle biopsy was poor. Moreover, it has been demonstrated in 22% of false-negative results of biopsies, while inadequate sample of diagnostic material occur up to 18% of the time [7,10]. The best reported results came from studies that utilised onsite cytopathologists to immediately examine aspirates for diagnostic tissue. These authors claimed a 99% accuracy rate in 110 consecutive patients [19]. These results await confirmation, and with increasing experience with PET scanning and minimally invasive surgical techniques the utility of fine-needle aspiration biopsy might be limited further.

On the other hand, we had successful results with the intraoperative use of wired needle localisation associated with intrathoracoscopic ultrasound (80%).

In our experience only ten patients have been submitted to bronchoscopy with brushing or biopsy. Bronchoscopy with brushing or transbronchial biopsy does not seem to provide more information, because of the periferic localisation and the extrabronchial growth of the metastatic nodule. However, transbronchial biopsy and percutaneous needle aspiration, when used in combination, have reported sensitivity rates of 95% for detecting malignancy and of 60% in diagnosing benign lesions [20].

Localisation of pulmonary nodules with methylene blue injections for thoracoscopic resections was deluding in our experience: using the blue dye in six patients we have found the nodule in only one case (16%).

Intraoperative intrathoracoscopic ultrasound and utilisation of gamma-detection probes are very recent techniques and we are at the beginning of the ‘learning curve’ of these techniques [14,15]. However, intrathoracoscopic ultrasound was successful in 5/8 cases (80%) and radio-guided localisation was successful in 3/5 cases (66%).

The advent of minimally invasive surgical techniques has made a definitive diagnosis likely when the pulmonary nodules are quite small. These lesions can be removed easily for diagnosis and, if it is indicated, a definitive cancer operation can be performed. Thoracoscopy biopsy carries a significantly decreased risk of morbidity and mortality compared with open thoracotomy for wedge resection [5,9,16–18].

The thoracoscopic technique was performed in 44 patients (95.6%). In 16 cases (34.7%) the procedure was converted. The traditional thoracotomic approach was employed ‘d'emblée’ in two patients (4.4%).

In thoracoscopy the same criteria of surgical radicality are valuable. The entity of excision of the lesion and the extension of lymphadenectomy are related to histology, size, and localisation of the nodule and to the presence of satellites nodules [21,22]. Atypical resection is indicated in the case of small and periferic benign nodules. In the case of primitive malignant cancer an anatomic resection (lobectomy, bilobectomy, or pneumonectomy) is mandatory. In the case of metastatic lesion an extended atypical resection including the whole nodule is indicated, depending on the size and localisation of the nodule, the distance of healthy tissue being at least 1 cm from the nodule.

The extension of lymphadenectomy is related exclusively to the histology of the nodule, and it is essential for stadiation and prognosis, in the case of primitive and metastatic malignant nodule.

Our data concerning the follow-up document the importance to operate a metacronous SPN in patients with positive oncological anamnesis. In fact, after a mean follow-up of 28 months 62% of patients were still alive, ‘free from disease’, 14 (31%) are dead, seven from the previous malignant tumour, five from the primary pulmonary tumour, and two from other causes.

	5. Conclusions

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
The SPN is not an infrequent clinical problem in patients previously affected by a primary extrapulmonary neoplasm. The exact pre- or intraoperative localisation and characterisation of the nodule is crucial for deciding the surgical strategy, but in most cases the histology of the nodule is unknown preoperatively; therefore, surgeons have to excise the lesion without guaranteeing to the patients a diagnostic, therapeutic, and prognostic certainty.

However, multiple techniques are used to aid in the identification of the nodules: preoperative needle or dye localisation, intraoperative reperage on sight, digital palpation, fluoroscopy with the use of contrast medium, intraoperative ultrasound, and utilisation of gamma-detection probes [9–15].

The advent of minimally invasive surgical techniques has made a definitive diagnosis likely, with a less painful engagement for the patient and less cost for the community [16–18].

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 

1. Marchevsky A.M. Metastatic tumors of the lung. Lung Biol Health Dis 1990;44:231-245.
2. Quint L.E., Park C.H., Iannettoni M.D. Solitary pulmonary nodules in patients with extrapulmonary neoplasms. Radiology 2000;217(1):257-261.[Abstract/Free Full Text]
3. Viggiano R.W., Swensen S.J., Rosenow E.C. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 1992;13:83-95.[Medline]
4. Midthun D.E., Swensen S.J., Jett J.R. Approach to the solitary pulmonary nodule. Mayo Clin Proc 1993;68:378-385.[Medline]
5. Swanson S.J., Jaklitsch M.T., Mentzer S.J., Bueno R., Lukanich J.M., Sugarbaker D.J. Management of the solitary pulmonary nodule role of thoracoscopy in diagnosis and therapy. Chest 1999;116:523S-524S.[Abstract/Free Full Text]
6. Gurney J.W., Lyddon D.M., McKay J.A. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part I: theory. Radiology 1993;186:405-413.[Abstract/Free Full Text]
7. Munden R.F., Pugatch R.F., Liptay M.J. Small pulmonary nodules detected at CT: clinical importance. Radiology 1997;202:105-110.[Abstract/Free Full Text]
8. Gupta N.C., Maloof J. Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. Chest 1996;112:943-948.
9. Schwarz C.D., Lenglinger F., Eckmayr J., Schauer N., Hartl P., Mayer K.H. VATS (video-assisted thoracic surgery) of undefined pulmonary nodules. Preoperative evaluation of videoendoscopic resectability. Chest 1994;106(5):1570-1574.[Abstract/Free Full Text]
10. Van Sonnenberg E., Casola G., Ho M. Difficult thoracic lesions: CT-guided biopsy experience in 150 cases. Radiology 1988;167:457-461.[Abstract/Free Full Text]
11. Wicky S., Mayor B., Cuttat J.F., Schnyder P. CT-guided localization of pulmonary nodules with methylene blue injections for thoracoscopic resections. Chest 1994;106:1326-1328.[Abstract/Free Full Text]
12. Tsuchida M., Yamato Y., Aoki T., Watanabe T., Koizumi N., Emura I., Hayashi J. CT-guided agar marking for localization of nonpalpable peripheral pulmonary lesions. Chest 1999;116:139-143.[Abstract/Free Full Text]
13. Templeton P.A., Krasna M. Needle/wire lung nodule localization for thoracoscopic resection. Chest 1993;104(3):953-954.[Abstract/Free Full Text]
14. Santambrogio R., Montorsi M., Bianchi P., Mantovani A., Ghelma F., Mezzetti M. Intraoperative ultrasound during thoracoscopic surgery for solitary pulmonary nodules. Ann Thorac Surg 1999;68(1):218-222.[Abstract/Free Full Text]
15. Scheebaum S., Even-Sapir E., Cohen M., Shacham-Lehrman H., Gat A., Brazovsky E., Livehitz G., Stadler J., Skornick Y. Clinical application of gamma-detection probes – radioguided surgery. Eur J Nucl Med 1999;25(Suppl. 4):626-635.
16. Mack M.J., Hazelrigg S.R., Landreneau R.J., et al. Thoracoscopy for the diagnosis of the indeterminate solitary pulmonary nodule. Ann Thorac Surg 1993;56:825-832.[Abstract]
17. DeCamp M.M., Jr., Jaklitsch M.T., Mentzer S.J., et al. The safety and versatility of video-thoracoscopy: a prospective analysis of 895 consecutive cases. J Am Coll Surg 1995;181:113-120.[Medline]
18. Sortini A., Santini M., Navarra G., Sartori A., Donini I. Thoracoscopy and videoassisted thoracic surgery. Analysis on 248 cases. Surg Endosc 1998;12(5):529-530.
19. Santambrogio L., Nosotti M., Bellaviti N., et al. CT-guided fine-needle aspiration cytology of solitary pulmonary nodules: a prospective randomized study of immediate cytologic evaluation. Chest 1997;112:423-425.[Abstract/Free Full Text]
20. Gasparini S., Ferretti M., Secchi E.B., et al. Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses: experience with 1027 consecutive cases. Chest 1995;108:131-137.[Abstract/Free Full Text]
21. Kaseda S., Hangai N., Yamamoto S. Lobectomy with extended lymph node dissection by video-assisted thoracic surgery for lung cancer. Surg Endosc 1997;11(7):703-706.[Medline]
22. Liptay M.J. Solitary pulmonary nodule: treatment options. Chest 1999;116(Suppl. 6):517S-518S.[Abstract/Free Full Text]

This article has been cited by other articles:

				J. Herbst, R. Jenders, R. McKenna, and A. Marchevsky Evidence-Based Criteria to Help Distinguish Metastatic Breast Cancer From Primary Lung Adenocarcinoma on Thoracic Frozen Section Am J Clin Pathol, January 1, 2009; 131(1): 122 - 128. [Abstract] [Full Text] [PDF]

				A O Soubani The evaluation and management of the solitary pulmonary nodule Postgrad. Med. J., September 1, 2008; 84(995): 459 - 466. [Abstract] [Full Text] [PDF]

				D. Sortini, C. V. Feo, P. Carcoforo, G. Carrella, E. Pozza, and A. Sortini Should Lobectomy Ever Be the First Choice for Patients With Small Pulmonary Lesions? Ann. Thorac. Surg., November 1, 2004; 78(5): 1887 - 1888. [Full Text] [PDF]

				D. Sortini, C. V. Feo, G. Carrella, P. Carcoforo, E. Pozza, and A. Sortini Drawbacks to videothoracoscopic management of solitary pulmonary nodules Ann. Thorac. Surg., August 1, 2004; 78(2): 752 - 752. [Full Text] [PDF]

				P. Carcoforo, C. Feo, D. Sortini, E. Pozza, G. Carrella, A. Sortini, and K. Sugi Localization of Pulmonary Nodules Chest, February 1, 2004; 125(2): 796 - 797. [Full Text] [PDF]

				A. Sortini, D. Sortini, and G. Carrella Negative aspects of preoperative delay in early stage non-small cell lung cancer J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 609 - 610. [Full Text] [PDF]

				A. Sortini, G. Carrella, D. Sortini, and E. Pozza Single pulmonary nodules: localization with intrathoracoscopic ultrasound -- a prospective study Eur. J. Cardiothorac. Surg., September 1, 2002; 22(3): 440 - 442. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andrea, S. Articles by Enzo, P. Search for Related Content PubMed PubMed Citation Articles by Andrea, S. Articles by Enzo, P.