| Original Article | A clinicopathologic analysis of 88 lung resections of suspected metastatic |
| carcinomas with proven primaries | |
| Kathuria K, Jambhekar NA, Pramesh CS1, George K1, Desai SS Departments of Pathology and 1Thoracic Services, Tata Memorial Hospital, 8th Floor Annexe Building, Parel, Mumbai, Maharashtra, India | |
| Correspondence to: Dr. Nirmala A. Jambhekar, E-mail: najambhekar@rediffmail.com |
Abstract
BACKGROUND: The lung is the most common site for metastatic carcinomas. Very few studies have comprehensively analyzed all pulmonary resections for metastatic carcinomas. AIMS AND OBJECTIVES: To analyze all lung resections for suspected metastatic carcinomas accrued over 10 years to evaluate:
i. The most frequent primary site,
ii. The interval between primary tumor diagnosis and lung metastases, and
iii. The proportion of inadvertently resected benign lesions, clinicoradiologically mistakenfor metastatic deposits.
MATERIALS AND METHODS: Between 2002 and 2011, 88 pulmonary metastasectomies were done for suspected metastatic carcinomas, which form the basis of this study. RESULTS: In 81 of 88 cases (92%) the diagnosis of metastatic carcinoma was histologically confirmed, whereas 7 cases (8%) were non-neoplastic. The mean interval between primary tumor and metastases was 2.5 years. The primary sites were colorectum (30; 37%), kidney and breast (14; 17.3% each), cervix (9; 10%), salivary gland carcinoma (3), thyroid carcinoma (2), squamous carcinoma (2, one each of mandible and larynx), papillary urothelial carcinoma (2), hepatocellular carcinoma (1), endometrioid adenocarcinoma (1), carcinosarcoma of endometrium (1), adrenocortical carcinoma (1), and neuroendocrine carcinoma (1). The 7 non-neoplastic lesions (8%) histologically revealed tuberculosis (4), bronchopneumonia (2), and aspergillosis (1). CONCLUSIONS: Almost three fourths (71.6%) of the metastatic pulmonary resections comprised primaries from colorectum, breast and kidney. The interval between primary tumor and metastases ranged from zero months to 10 years (mean 2.5 years). Tuberculosis was the most common histologic diagnosis among the 8% of the non-neoplastic lesions, which were mistaken for metastatic carcinoma on clinical evaluation.
Key words: Carcinoma, colorectum, histology, kidney, pulmonary metastasectomy, tuberculosis
Introduction
The presence of metastases in patients with malignant tumors is a sign of advanced systemic disease.[1] Over 20% of patients with solid tumors, including adenocarcinomas may develop metastases exclusively in the pulmonary parenchyma, with no detectable involvement of other organs.[2] For patients in whom the primary disease is controlled and no effective nonsurgical treatment modality is available for pulmonary metastases, pulmonary metastasectomy remains an option. In such patients, surgical resection of lung metastases is known to significantly improve the long-term survival.[3,4]
| Access this article online | |
| Quick Response Code: | Website: www.indianjcancer.com |
| DOI: 10.4103/0019-509X.123628 | |
Herein, the 10-year data on pulmonary resections of suspected metastatic carcinomas has been reviewed.
Materials and Methods
All cases of pulmonary resections of metastatic carcinomas accrued between 2002 and 2011 were retrieved. The clinical and radiologic data were abstracted from the charts. The pathology slides and blocks were retrieved. The cases were retrospectively analyzed for gender, age, primary site, radiologic details, and interval between primary tumor and pulmonary metastases. The number (solitary/multiple, unilateral/ bilateral) and size of the pulmonary metastases was noted. The histology slides were reviewed for type of tumor, lymph nodal metastases, and pleural involvement.
A total of 87 patients underwent 88 resections for metastatic carcinomas. Patients with nonepithelial metastases (ie., metastatic sarcomas, metastatic germ cell tumors, and melanomas) were excluded from this study. The selection criteria for pulmonary metastasectomies were standard and as shown in table 1.[5,6]
The histology of the resected metastatic tumor was compared with the primary tumor.
Results
The most common cancer in our institute is oral cancer, constituting approximately 28.5% cases, followed by primary lung carcinoma, with 1300 new cases annually. The number of pulmonary resections for primary lung carcinoma in our institute is approximately 90 per year in the last 5 years.
A total of 402 pulmonary resections for various metastatic tumors were done in a 10-year period and 88 (22%) of these pulmonary resections were for suspected metastatic carcinomas. The remaining cases comprised metastatic sarcomas (66%), germ cell tumors (9%), metastatic giant cell tumor (1.5%) and melanoma, 1.5%. The surgical procedures were either wedge resections (67 cases), or lobectomies (18 cases) or pneumonectomies (3 cases).
Demographic data
There were 45 males and 42 females between 28 and 73 years of age (median, 54 years), and 81.5% of the patients were in the 5th to 7th decade. The youngest patient was a 28 year-old female who had a metastatic breast carcinoma and the oldest was a 73 year-old male patient who had a metastatic colonic adenocarcinoma. The lung metastases were solitary in 58.4% and multiple in 41.6%. [Table 2]. The interval between diagnosis of
Table 1: Selection criteria for pulmonary metastasectomies
Primary disease is controlled and if present, is resectable Extra thoracic disease is absent and if present, is resectable Metastases are completely resectable (R) resection) Adequate cardiopulmonary reserve
| Pulmonary metastases | No. (%) |
|---|---|
| Solitary | 52 (59.1) |
| Multiple (>1) | 36 (40.9) |
| n=2-4 | 23 |
| n>4 | 13 |
| Laterality | |
| Right | 38.6 |
| Left | 45.5 |
| Bilateral | 14 (15.9) |
| Gross size of the largest resected nodule | |
| <3 cm | 65 (74) |
| >3 cm | 23 (26) |
the primary tumor and pulmonary metastases ranged from zero months (synchronous) to 10 years (carcinoma cervix) with a mean of 2.5 years [Table 2]. The synchronous pulmonary metastases comprised one case each from squamous carcinoma ma
ndible and carcinoma breast. Radiologic findings (computed tomography scan, X-rays) were available in 63 (72%) cases; the lesions were either homogenous lobulated or seen as ill-defined opacities. The size of metastases ranged from 0.5-6.8 cm, with a mean of 2.5 cm.
The gross size of the largest metastatic deposit was more than 3 cm in 26% of the lung resections [Table 2]. Histologically the preoperative diagnosis of suspected metastasis was confirmed in 81 cases (92%), whereas in 7 cases (8%) the final histology revealed non-neoplastic pathology [Table 3]. Pulmonary resection of metastatic colorectal adenocarcinoma [Figure 1] was the most frequent diagnosis followed by resection of metastatic renal cell carcinoma [Figure 2], breast carcinoma [Figure 3] and cervical carcinoma. The histology of the primary and metastatic lesions was identical in all cases.
Pleural involvement was observed in 11 cases. Mediastinal/hilar lymph node dissection was performed in only 23 patients, of these 3 cases (13%) revealed metastatic deposits, all from primaries in colorectum.
In 7 patients, the diagnosis of suspected metastatic disease was not sustained on histologic evaluation. These lesions were non-neoplastic [Figure 4] and infective in etiology as shown in table 4.
Discussion
It is well known that lung, liver and bone are the common sites of distant metastatic disease. About 30-40% of all extrathoracic carcinomas lead to secondary pulmonary lesions during the course of the disease.[7,8] Metastatic carcinomas confer a higher stage and this is associated with poor prognosis. The 5-year survival rates for stage IV metastatic colon, breast and renal cell carcinoma have been reported to be 8.1%,[9] 26%,[10] and less than 10%[11] respectively. In a large study from The International Registry of Lung Metastases comprising 5206 cases, (inclusive of all histologies) following metastasectomies, the 5-year survival rate has been reported ranging from 30% to 40%. [3] More specifically, recent studies have shown significant improvement in the 5-year survival rates, up to 61.3% in colonic adenocarcinoma, [12] 38% in breast carcinoma,[13] and 52% in renal cell carcinoma[14] following metastasectomy, as shown in table 5. This survival benefit has broadened the indications for resection of pulmonary metastases.
| Site of primary carcinoma | No. (%) | Histology of suspected metastases | Interval between primary tumor and lung metastases | |
|---|---|---|---|---|
| Carcinoma | Inflammatory | |||
| Colorectum | 32 (36.4) | 30 | 02 | 6 months to 8 years |
| Kidney | 16 (18.2) | 14 | 02 | 5 months to 5.5 years |
| Breast | 16 (18.2) | 14 | 02 | 0 months to 3 years |
| Cervix | 09 (10.3) | 09 | - | 3-10 years |
| Salivary gland | 03 (3.4) | 03 | - | 0.5-9.5 years |
| Urothelial ca | 02 (2.3) | 02 | - | 1-2.3 years |
| Thyroid | 02 (2.3) | 02 | - | 14-16 months |
| Endometrium | 02 (2.3) | 02 | - | 1-3 years |
| Mandible | 01 (1.1) | 01 | - | 0 months (synchronous) |
| Liver | 01 (1.1) | 01 | - | 7 years |
| Neuroendocrine | 01 (1.1) | 01 | - | 6 months |
| Adrenal | 01 (1.1) | 01 | - | 6 years |
| Larynx | 01 (1.1) | 01 | - | 2 years |
| Skin adnexal tumor | 01 (1.1) | - | 01 | 6 months |
| Total | 88 (100) | 81 | 07 | 0 months to 10 years |
| ca, Cancer. Final histology | No. (%) | Primary tumor: No. |
|---|---|---|
| Tuberculosis | 04 (57.1) | Breast ca: 1 Renal cell ca: 1 Colorectal ca: 1 Skin adnexal tumor: 1 |
| Pneumonia | 02 (28.6) | Breast ca: 1 Renal cell ca: 1 |
| Aspergillus | 01 (14.3) | Colorectal ca:1 |
| Author | Site of primary carcinoma | No. of pulmonary resections | % median survival (5 years) |
|---|---|---|---|
| Pfannschmidt et al.[12] | Colorectum | 1080 | 24-61.3 |
| Hoffmann et al.[13] | Kidney | 64 | 52 |
| Godehard et al.[14] | Breast | 467 | 38 |
The colorectum, constituted 37% of all resected pulmonary metastases, followed by breast and kidney together amounting to 34.6% of cases. Colon is the single most common primary site of carcinoma in patients undergoing pulmonary resections for metastatic disease; this is followed by carcinomas of breast and kidney [Table 6].
Although earlier literature seemed to indicate that the site of primary carcinoma was a determinant of long-term survival,[3,19] recent reports[14,15,17] incorporating multivariate analysis do not support this observation. The other factors that have been analyzed to predict survival following
| Author | No. of pulmonary resections | Primary sites n (%) | ||
|---|---|---|---|---|
| Colon | Breast | Kidney | ||
| Casiraghi et al.[15] | 372 | 210 (56.4) | 51 (13.7) | 86 (23.1) |
| Casali et al.[16] | 142 | 64 (45) | 23 (16.2) | 31 (21.8) |
| Monteiro et al.[17] | 78 | 35 (44.9) | 12 (15.4) | 06 (7.7) |
| McCormack et al.[18] | 188 | 40 (21.3) | 28 (14.9) | 16 (8.5) |
| Present study, 2011 | 81 | 30 (37) | 14 (17.3) | 14 (17.3) |
pulmonary metastasectomy include the number and size of the metastatic deposits, lymph node involvement (hilar/ mediastinal) and disease-free interval (DFI).
In the present study, solitary metastasis was present in 52 patients (59.1%), whereas metastases were multiple in 36 cases (40.9%). Several authors have documented that the number of metastases is the most potent indicator for recurrence.[12,17,20] Patients who have had 3 or more pulmonary metastases were twice as likely to experience a recurrence.[20] However in other studies, the number of metastases did not statistically influence the long-term survival.[15,16]
It has also been shown that the size of the largest metastatic nodule affects the long-term survival.[14,17,21]A size of less than 3 cm is associated with better 5-year survival rate as compared with a size more than 3 cm. One fourth of our patients had tumor size more than 3 cm.
The involvement of mediastinal lymph node in patients with pulmonary metastases is considered a rare event.[16] In
the present study, the incidence of mediastinal/hilar lymph node involvement was 13%, in those cases where lymph node dissection was done. In a large study, the incidence of lymph node metastases in adenocarcinomas was 6%.[3] More recent studies, however, have reported a 12-28% incidence of mediastinal/hilar lymph node metastases.[16,22]
Ercan et al.[22] have proposed that complete mediastinal lymph node dissection should be considered at the time of pulmonary metastasectomy of carcinomas to improve staging and guide further treatment. There are conflicting reports on the prognostic impact of lymph nodal metastases, whereas some studies have shown an adverse effect on prognosis[12,14,22] another study[17] failed to reveal any prognostic impact of the nodal status at the time of pulmonary metastasectomy. In our institute, lymph node dissection is restricted to cases where there is radiologic evidence of involvement or on the basis of clinical evaluation during surgery.
Several studies have observed that patients with a DFI of more than 36 months have improved 5-year survival
a
b
rates as opposed to those with a DFI of less than 36 months.[15,21]
Survival studies incorporating multiple variables, which includes DFI, number, and size of the metastatic nodules have been published.[14,17] Monteiro et al.[17] have observed a survival rate of 66.7% in patients with single metastasis and a DFI of more than 36 months as opposed to survival rate of 21.8% in patients with more than one metastasis and a DFI of less than 36 months. Another more recent study by Younes et al.[14] observed that patients with less than 3 pulmonary metastatic nodules, with a diameter <3 cm, and a DFI >36 months, reached a 5-year survival rate of 61.4%. In the present analysis, the followup information was inadequate and too short to analyze the impact on survival of the factors listed above.
The final histologic examination of 7 pulmonary resected specimens (8%) did not confirm the diagnosis of metastatic carcinoma and all 7 lesions were inflammatory in nature. Tuberculosis was the most common diagnosis (4 cases) followed by pneumonia (2 cases) and aspergillosis (1 case). Tuberculosis constituted 57% of the inflammatory lesions; perhaps these patients could have been treated with antituberculosis drugs.
Conclusions
Herein, 88 pulmonary resections for suspected metastatic carcinoma were analyzed. Primary carcinomas of colorectum, breast and kidney together constituted 71.6% of cases wherein pulmonary metastasectomy was performed. The interval between primary tumor and metastases ranged from zero months to 10 years. In all 8% of patients were mistakenly resected for a presumed preoperative diagnosis of pulmonary metastases, which proved to be inflammatory on final histology, two thirds of these mistaken lesions were tuberculous in etiology. Hence in areas where tuberculosis is endemic, a preoperative confirmation of a radiologically detected lesion, either by cytology or histology can help avoid surgical intervention.
References
1. Mountain CF, Khalil KG, Hermes KE, Frazier OH. The contribution of surgery to the management of carcinomatous pulmonary metastases. Cancer 1978;41:833-40.
2. Warwick R, Page R. Resection of pulmonary metastases from colorectal carcinoma. Eur J Surg Oncol 2007;33Suppl 2:S59-63.
3. Pastorino U, Buyse M, Friedel G, Ginsberg R, Girard P, Goldstraw P, et al. Long-term results of lung metastasectomy: Prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997; 113:37-49.
4. Girard P, Ducreux M, Baldeyrou P, Girard P, Rougier P, Le Chevalier T, et al. Surgery for lung metastases from colorectal cancer: analysis of prognostic factors. J Clin Oncol 1996; 14:2047-535.
5. fannschmidt J, Muley T, Hoffmann H, Dienemann H. Prognostic factors and survival after complete resection of pulmonary metastases from colorectal carcinoma: Experiences in 167 patients. J Thorac Cardiovasc Surg 2003; 126:732-9.
6. Greelish JP, Friedberg JS. Secondary pulmonary malignancy. Surg Clin North Am 2000;80:633-57.
7. Younes RN, Haddad F, Ferreira F, Gross JL. Surgical removal of pulmonary metastasis: Prospective study in 182 patients. Rev Assoc Med Bras 1998;44:218-25.
8. Pastorino U. Lung metastasectomy: Why, when, how. Crit Rev Oncol Hematol 1997;26: 137-45.
9. Connell JB, Maggard MA, Clifford YK. Colon cancer survival rates with the new american joint committee on cancer sixth edition staging. J Natl Cancer Inst 2004;96: 1420-4.
10. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66.
11. Motzer R, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999; 17:2530-40.
12. Pfannschmidt J, Dienemann H, Hoffmann H. Surgical resection of pulmonary metastases from colorectal cancer: A systematic review of published series. Ann Thorac Surg 2007;84:324-33.
13. Hofmann H, Heinz N, Katharina K, Petko A, Rolf-Edgar S. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol 2005;48:77-82.
14. Godehard F, Pastorino U, Robert J, Peter G, Micheal J. Results of lung metastasectomy from breast cancer: Prognostic criteria on the basis of 467 cases of international registry of lung metastases. Eur J Cardiothorac Surg 2002;22:335-44.
15. Casiraghi M, Pas T, Maisonneuve P, Brambilla D, Ciprandi B, Galetta D, et al. A 10-year single-center experience on 708 lung metastasectomies. The evidence of the “International Registry of Lung Metastases”. J Thorac Oncol 2011;6:1373-8,
16. Casali C, Stefani A, Storelli E, Morandi U. Prognostic factors and survival after resection of lung metastases from epithelial tumors. Interact Cardiovasc Thorac Surg 2006;5:317-21.
17. Monteiro A, Nuria A, João B, Luís E, Manuel J. Surgical resection of lung metastases from epithelial tumors. Ann Thorac Surg 2004;77:431-7.
18. McCormack P, Bains M, Beattie E Jr, Martini N. Pulmonary resection in metastatic carcinoma. Chest 1978;73:163-6.
19. Mountain CF, McMurtrey MJ, Hermes KE. Surgery for pulmonary metastases: A 20-year experience. Ann Thorac Surg 1984;38:323-30.
20. Onaitis M, Petersen R, Haney J, Saltz L, Park B, Flores R, et al. Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases. Ann Thorac Surg 2009;87: 1684-9.
21. Younes R, Fares A, Gross J. Pulmonary metastasectomy: A multivariate analysis of 440 patients undergoing complete resection. Interact Cardiovasc Thorac Surg 2012; 14: 156-61.
22. Ercan S, Nichols F, Trastek V, Deschamps C, Allen M, Mille D, et al. Prognostic significance of lymph node metastasis found during pulmonary metastasectomy for extrapulmonary carcinoma. Ann Thorac Surg 2004;77:1786-91.
How to site this article: Kathuria K, Jambhekar NA, Pramesh CS, George K, Desai SS. A clinicopathologic analysis of 88 lung resections of suspected metastatic carcinomas with proven primaries. Indian J Cancer 2013;50:356-60.
Source of Support: Nil,. Conflict of Interest: None declared.
Copyright of Indian Journal of Cancer is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use.