Pulmonary Neoplasia

Written By: Sam Savage

Published Date: July 16, 2008 Last Edited: July 16, 2008

By Allen, Timothy Craig

The diagnosis of pulmonary malignant neoplasia generally portends a poor prognosis. The facts are stark. Worldwide, lung cancer is expected to increase in prevalence during the 21st century.1 Lung cancer is the leading cause of cancer death in both men and women in the United States. One in 10 cigarette smokers will develop lung cancer during his or her lifetime, with a decades-static overall 5- year survival rate for lung cancer in the United States of approximately 15%.1-3 More people die of lung cancer than prostate, colon, and breast cancers combined. 4,5 Earlier detection of lung cancer is being promoted, and therapeutic response to epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib has been identified in a limited number of adenocarcinomas, generally in nonsmoking Asian women.6-9 However, although molecular therapies show promise for the future, presently molecular therapy does not affect overall lung cancer prognosis.10- 12 Although rare, pleural diffuse malignant mesothelioma has increased in incidence worldwide during the last several decades and is rapidly increasing in incidence throughout Western Europe.13-15 It is generally refractory to treatment, and overall survival is dismal, with a median of less than 12 months postdiagnosis.13,16

Differentiating benign and malignant pulmonary neoplasms, preneoplastic lesions, and tumor mimics, with their often markedly different therapies and prognoses, remains of the utmost importance. The surgical pathologist’s task of diagnosing malignant and benign pulmonary neoplasms, and their mimics, is not going to get easier in the near future. Indeed, to apply various molecular diagnostic and therapeutic tumor regimens that are anticipated to be available in the future, accurate histologic diagnosis is imperative. An understanding of the pathology of the common as well as uncommon malignant and benign lung and pleural neoplasms, tumor mimics, and preneoplastic lesions is necessary for accurate diagnosis of pulmonary tumors, and the goal of this special issue on pulmonary neoplasia is to assist the practicing pathologist in that endeavor.

In the 9 articles within this special issue, the authors cover a broad spectrum of topics relevant to the accurate diagnosis of pulmonary neoplasms. Radiologic correlation is an important adjunct to proper diagnosis in pulmonary disease, and the concept of neuroendocrine neoplasia in the lung is evolving. Drs Teri Franks and Jeff Galvin examine the radiologic-pathologic correlation of neuroendocrine lung neoplasms. Dr Mary Beth Beasley discusses the current state of immunohistochemistry as it relates to pulmonary neoplasia. Dr Sanja Dacic reviews the increasingly important subject of pulmonary preneoplasia. Drs Megan Dishop and Supriya Kuruvilla present a thorough and valuable examination of pediatric neoplasms and pseudotumors. Dr Leslie Litzky discusses the often-confusing sarcomatous pulmonary neoplasms. Dr Kelly Butnor presents a constructive article on avoiding overdiagnosis, underdiagnosis, and misdiagnosis in pulmonary neoplasia. Dr Alain Borczuk reviews a variety of benign lung neoplasms and pseudotumors. The literature contains many useful articles regarding the histologic and immunohistochemical features of pleural diffuse malignant mesothelioma (a few are referenced)17-24 so Dr Don Guinee and I offer a review of the pathology of primary pleural neoplasms other than diffuse malignant mesothelioma. Finally, because pulmonary histiocytic lesions, especially pulmonary Langerhans cell histiocytosis, may occasionally mimic neoplasms, a review of pulmonary histiocytoses is presented.

It is my privilege to present these articles written by a number of experts rich in experience in the pathology of pulmonary neoplasia. It is our hope that these articles will assist the general pathologist in making accurate diagnoses of lung and pleural neoplasms, premalignant lesions, and tumor mimics, whether they occur commonly or uncommonly. In closing, I offer my sincere appreciation and thanks to Dr Philip T. Cagle for the opportunity to put forth this special issue.

References

1. Siegfried JM. Lung cancer screening in high-risk populations. Clin Lung Cancer. 1999;1:100-106.

2. Franklin WA. Pathology of lung cancer. J Thorac Imaging. 2000;15:3-12.

3. Hirsch FR, Brambilla E, Gray N, et al. Prevention and early detection of lung cancer-clinical aspects. Lung Cancer. 1977;17:163- 174.

4. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. Ca Cancer J Clin. 2004;54:8-29.

5. McWilliams A, Lam S. Lung cancer screening. Curr Opin Pulm Med. 2005; 11:272-277.

6. Tsao AS, Tang XM, Sabloff B, et al. Clinicopathologic characteristics of the EGFR gene mutation in non-small cell lung cancer. J Thorac Oncol. 2006;1:231-239.

7. Kimura H, Suminoe M, Kasahara K, et al. Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer. 2007;97:778-784.

8. Pugh TJ, Bebb G, Barclay L, et al. Correlations of EGFR mutations and increases in EGFR and HER2 copy number to gefitinib response in a retrospective analysis of lung cancer patients. BMC Cancer. 2007;7:128.

9. Field JK, Brambilla C, Caporaso N, et al. Consensus statements from the Second International Lung Cancer Molecular Biomarkers Workshop: a European strategy for developing lung cancer molecular diagnostics in high risk populations. Int J Oncol. 2002;21:369-373.

10. Rosell R, Cobo M, Isla D, et al. Applications of genomics in NSCLC. Lung Cancer. 2005;50(suppl):S33-S40.

11. Alvarez M, Roman E, Santos ES, Raez LE. New targets for non- small-cell lung cancer therapy. Expert Rev Anticancer Ther. 2007;7:1423-1437.

12. Felip E, Santarpia M, Rosell R. Emerging drugs for on-small- cell lung cancer. Expert Opin Emerg Drugs. 2007;12:449-460.

13. Borasio P, Berruti A, Bille A, et al. Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients. Eur J Cardiothorac Surg. 2008;33:307-313.

14. Pelucchi C, Malvezzi M, La Vecchia C, et al. The mesothelioma epidemic in Western Europe: an update. Br J Cancer. 2004;90:1022- 1024.

15. Chapman A, Mulrennan S, Ladd B, Muers MF. Population-based epidemiology and prognosis of mesothelioma in Leeds, United Kingdom [published online ahead of print January 17, 2008]. Thorax. doi:10.1136/thx.2007.081430.

16. Baas P. Optimizing survival in malignant mesothelioma. Lung Cancer. 2007;57(suppl):S24-S29.

17. Wick MR, Moran CA, Mills SE, Suster S. Immunohistochemical differential diagnosis of pleural effusions, with emphasis on malignant mesothelioma. Curr Opin Pulm Med. 2001;7:187-192.

18. Attanoos RL, Gibbs AR. Pathology of malignant mesothelioma. Histopathology. 1997;30:403-418.

19. Churg A, Colby TV, Cagle P, et al. The separation of benign and malignant mesothelial proliferations. Am J Surg Pathol. 2000;24:1183-1200.

20. Allen TC. Recognition of histopathologic patterns of diffuse malignant mesothelioma in differential diagnosis of pleural biopsies. Arch Pathol Lab Med. 2005;129:1415-1420.

21. Cagle PT, Churg A. Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies. Arch Pathol Lab Med. 2005;1421-1427.

22. Hammar SP. Macroscopic, histologic, histochemical, immunohistochemical, and ultrastructural features of mesothelioma. Ultrastruc Pathol. 2006;30:3-17.

23. English JC, Leslie KO. Pathology of the pleura. Clin Chest Med. 2006;27: 157-180.

24. Mark EJ, Kradin RL. Pathological recognition of diffuse malignant mesothelioma of the pleura: the significance of the historical perspective as regards this signal tumor. Semin Diagn Pathol. 2006;23:25-34.

Timothy Craig Allen, MD, JD

Accepted for publication February 14, 2008.

From the Department of Pathology, The University of Texas Health Science Center at Tyler.

The author has no relevant financial interest in the products or companies described in this article.

Reprints: Timothy Craig Allen, MD, JD, Department of Pathology, The University of Texas Health Science Center at Tyler, 11937 US Hwy 271, Tyler, TX 75708 (e-mail: [email protected]).

Timothy Craig Allen, MD, JD, obtained his medical degree from Baylor College of Medicine in 1984. He completed his residency in anatomic pathology and clinical pathology and subsequently served on the faculty of Baylor College of Medicine until 1995. He then attended the University of Chicago Law School where he obtained the degree of Doctor of Law with honors in 1998. He subsequently practiced litigation and health care law. Dr Allen completed a 2- year fellowship in pulmonary pathology under the direction of Philip T. Cagle, MD, at the Texas Medical Center in Houston in 2004. He is currently chair of the Department of Pathology at the University of Texas Health Science Center at Tyler. Dr Allen is certified by the American Board of Pathology in anatomic and clinical pathology, with added qualification in cytopathology. He was a contributing editor to the 2000 edition of Product Liability Desk Reference, a book summarizing United States product liability laws. He has authored and coauthored a variety of articles and book chapters on lung and pleural pathology. Dr Allen was an associate editor of the first and second editions of Color Atlas and Text of Pulmonary Pathology, coeditor of the second edition of Diagnostic Pulmonary Pathology, and coeditor-in-chief of Transbronchial and Endobronchial Biopsies. Dr Allen is the current chair of the Program Committee of the Pulmonary Pathology Society. He is an associate editor of the Archives of Pathology & Laboratory Medicine.

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