Portal de Periódicos da CAPES

Bronchioloalveolar Carcinoma

1998; Elsevier BV; Volume: 114; Issue: 1 Linguagem: Inglês

10.1378/chest.114.1.5

1931-3543

John P. Griffin,

Mycobacterium research and diagnosis

Bronchioloalveolar carcinoma (BAC) is a type of adenocarcinoma of the lung that remains controversial, with varying histological categorization, clinical and roentgenologic presentation, natural history, and approach to treatment. Although previous cases were reported, it was Liebow1Liebow A. Bronchiolo-alveolar carcinoma.Adv Intern Med. 1960; 10: 329-358PubMed Google Scholar in 1960 who characterized this tumor as a “well-differentiated adenocarcinoma primarily in the periphery of the lung beyond a grossly recognizable bronchus, with a tendency to spread chiefly within the confines of the lung by aerogenous and lymphatic routes, the walls of the distal air spaces often acting as supporting stroma for the neoplastic cells.” BAC is listed as a subtype of adenocarcinoma according to the World Health Organization histologic classification of bronchogenic carcinoma. Microscopically, it may consist of any admixture of mucin-secreting bronchiolar cells, Clara cells, and type II pneumonocytes.2Yesner R Carter D. Pathology of carcinoma of the lung: changing patterns.Clin Chest Med. 1982; 3: 257-289PubMed Google Scholar Individual cells may be columnar, cuboidal, or “hob nail,” with tuftlike proliferations into the airspaces. The multicentric forms resemble the viral sheep disease Jaagsiekte, but BAC has not been proven to be of viral origin.3Yesner R. Lung cancer: pathogenesis and pathology.Clin Chest Med. 1993; 14: 17-30PubMed Google Scholar Barsky and associates,4Barsky SH Cameron R Osann KE et al.Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features.Cancer. 1994; 73: 1163-1170Crossref PubMed Scopus (262) Google Scholar in reviewing a 35-year experience of 187 patients with BAC, concluded that there was a rising prevalence of this tumor and noted an increase from 5 to 24% of total lung cancer cases over that period. They considered that the clinicopathologic features of this tumor were unique and that prior distinction of a “sclerotic” variant was arbitrary in that many of the more common nonmucinous BAC variety were also associated with evidence of desmoplasia.4Barsky SH Cameron R Osann KE et al.Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features.Cancer. 1994; 73: 1163-1170Crossref PubMed Scopus (262) Google Scholar In a further work, Barsky and colleagues5Barsky SH Grossman DA Ho J et al.The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin.Mod Pathol. 1994; 7: 633-640PubMed Google Scholar questioned the traditional explanation of multifocality in BAC as due to intrapulmonary metastases, since the lymphatic-intra-alveolar spread-aerosol-aspiration hypothesis had never been proven experimentally, and they presented evidence that the synchronous multifocality could be better explained by multiclonality. Investigators at the Montreal Chest Hospital matched 43 consecutive BAC cases with a similar number of randomly selected patients with usual adenocarcinoma of the lung, as well as those with squamous and oat cell carcinomas.6Schraufnagel D Peloquin A Pare JA et al.Differentiating bronchioloalveolar carcinoma from adenocarcinoma.Am Rev Respir Dis. 1982; 125: 74-79PubMed Google Scholar They noted the strong female predominance and increased presence of scarring in the BAC group and found multiple differentiating epidemiologic features from other major cell types but not from other adenocarcinomas. Harpole and Bigelow7Harpole DH Bigelow C Young Jr, WG et al.Alveolar cell carcinoma of the lung: retrospective analysis of 205 patients.Ann Thorac Surg. 1988; 46: 502-507Abstract Full Text PDF PubMed Scopus (43) Google Scholar found BAC in only 3% of 7,406 patients with lung cancer over a 15-year period, noting the usual absence of symptoms in those with TNM stages I and II. Multivariate logistic regression identified weight loss and dyspnea as independent prognostic factors for predicting advanced disease, which correlated with poor survival irrespective of treatment utilized. Rapid onset of dyspnea with recent weight loss and copious sputum production correlated with the infiltrative form of BAC and its poor prognosis. Roentgenographic manifestations of BAC include: localized single or multiple nodules or an infiltrate, rarely with cavitation but confined to one segment; and diffuse lobar or bilateral infiltrates, often with consolidation but without volume loss. Trigaux and associates8Trigaux JP Gevenois PA Goncette L et al.Bronchioloalveolar carcinoma: computed tomography findings.Eur Respir J. 1996; 9: 9-11Crossref Scopus (39) Google Scholar investigated the CT patterns of 42 pathologically proven BAC cases and found only 38% with a solitary nodule or mass, 24% with lobar and 31% with multilobar consolidations, and 7% with diffuse nodules. Grover and Piantadosi,9Grover FL Piantadosi S. Recurrence and survival following resection of bronchioloalveolar carcinoma of lung—the Lung Cancer Study Group experience.Ann Surg. 1989; 209: 779-790Crossref PubMed Scopus (80) Google Scholar of the Lung Cancer Study Group, published the largest series of 235 successfully resected cases with uniform operative staging, which allowed accurate delineation of TNM status, and the authors concluded that surgically treatable BAC presents at an earlier stage than other adenocarcinomas, with a better survival and longer recurrence-free interval; this demonstrates the importance of diagnosis and resection while still in an early stage. With stage I extent of disease, the Duke University study reported no advantage in survival or recurrence rate at 3 years for wedge resection vs lobectomy.7Harpole DH Bigelow C Young Jr, WG et al.Alveolar cell carcinoma of the lung: retrospective analysis of 205 patients.Ann Thorac Surg. 1988; 46: 502-507Abstract Full Text PDF PubMed Scopus (43) Google Scholar In this issue of CHEST (see page 45), Regnard and colleagues report a large consecutive series of BAC cases referred to their facility for surgical treatment. Although accumulated over a 20-year period but managed in a similar fashion, the reexamination of all specimens in accordance with the currently accepted standard for definitive pathological diagnosis and the elimination of cases with admixture of other cell types makes this collection of 70 patients with this unusual tumor particularly informative. Their criteria were the following: intraparenchymal localization independent of bronchi, cellular proliferation that replaced epithelial cells, and conservation of the interstitial framework of the lung. This series, skewed toward potential resection, comprises these different clinicoradiologic patterns: 42 nodular, 21 “pneumonitic,” and 7 diffuse presentations. In 87% of the patients, complete surgical resection was possible with a 34% 5-year survival; the authors consider this outcome similar to that of other completely resected non-small cell lung cancers of similar extent. The pattern of recurrences was especially interesting with 26 instances in ipsilateral or contralateral lung, but with spread to mediastinal nodes in only 4 cases and metastatic to extrathoracic sites in only 9 patients. In a multivariate analysis, favorable prognostic factors were limited to (1) asymptomatic presentation, (2) low TNM stage, and (3) completeness of resection. In contrast to previous reports, patient age,9Grover FL Piantadosi S. Recurrence and survival following resection of bronchioloalveolar carcinoma of lung—the Lung Cancer Study Group experience.Ann Surg. 1989; 209: 779-790Crossref PubMed Scopus (80) Google Scholar mucin production by the tumor,10Daly RC Trastek VF Pairolero PC et al.Bronchoalveolar carcinoma: factors affecting survival.Ann Thorac Surg. 1991; 51: 368-376Abstract Full Text PDF PubMed Scopus (93) Google Scholar and survival in comparison with other lung adenocarcinomas9Grover FL Piantadosi S. Recurrence and survival following resection of bronchioloalveolar carcinoma of lung—the Lung Cancer Study Group experience.Ann Surg. 1989; 209: 779-790Crossref PubMed Scopus (80) Google Scholar, 10Daly RC Trastek VF Pairolero PC et al.Bronchoalveolar carcinoma: factors affecting survival.Ann Thorac Surg. 1991; 51: 368-376Abstract Full Text PDF PubMed Scopus (93) Google Scholar, 11Greco RJ Steiner RM Goldman S et al.Bronchoalveolar cell carcinoma of the lung.Ann Thorac Surg. 1986; 41: 652-656Abstract Full Text PDF PubMed Scopus (84) Google Scholar were not considered differentiating characteristics by Regnard and his coworkers. Additional features of interest in this article are the usually negative history of cigarette smoking and the failure to establish the pathologic diagnosis before resectional surgery. At a time of disagreement in the medical community about the efficacy of screening for lung cancer by standard radiologic examination of the chest,12Strauss GM Gleason RE Sugarbaker DJ. Screening for lung cancer: another look; a different view.Chest. 1997; 111: 754-768Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar,13Davis MP. There and back again: lung cancer screening.Chest. 1997; 111: 532-534Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar it is unfortunate that BAC, which has the best prognosis of all lung cancers if surgically removed at an early stage, will not be reliably detected in the high-risk smoking patient or in those with symptoms of intrathoracic neoplasia. As with other adenocarcinoma subtypes, abnormality will be routinely present on chest roentgenograms, and although cost-benefit analysts decry its use, there appears to be no alternative, at this time, to routine chest x-ray studies for finding “curable” stage I BAC. Since by definition these tumors do not involve the major airways, bronchofiberscopy can only be helpful if fluoroscopically directed transbronchial lung biopsy specimens are obtained. Most tumors are sufficient in size to be approached by transthoracic needle procedures, and Tao and his associates14Tao LC Weisbrod GL Pearson FG et al.Cytologic diagnosis of bronchioloalveolar carcinoma by fine-needle aspiration biopsy.Cancer. 1986; 57: 1565-1570Crossref PubMed Scopus (40) Google Scholar at Toronto General Hospital have reported on the cytologic diagnosis of BAC in 181 patients by aspiration biopsy. An excellent MEDLINE review by Barkley and Green15Barkley JE Green MR. Bronchioloalveolar carcinoma.J Clin Oncol. 1996; 14: 2377-2386Crossref PubMed Scopus (130) Google Scholar of English-language articles on BAC from 1966 to 1995 concludes that incidence appears to be increasing, particularly in young nonsmoking females and that further epidemiologic investigation of this unique disease is needed. Current pathologic investigations have described differentiating cytologic features of BAC from other adenocarcinomas of the lung in fine-needle aspirations16Auger M Katz RL Johnston DA. Differentiating cytological features of bronchioloalveolar carcinoma from adenocarcinoma of the lung in fine-needle aspirations: a statistical analysis of 27 cases.Diagn Cytopathol. 1997; 16: 253-257Crossref PubMed Scopus (29) Google Scholar and from other reactive pulmonary processes characterized by hyperplastic pulmonary proliferations.17Zaman SS van Hoeven KH Slott S et al.Distinction between bronchioloalveolar carcinoma and hyperplastic pulmonary proliferations: a cytologic and morphometric analysis.Diagn Cytopathol. 1997; 16: 396-401Crossref PubMed Scopus (32) Google Scholar Recent genetic studies have documented constant K-ras mutations in the mucinous type of BAC, representing it as a biological entity separate from conventional lung adenocarcinoma,18Marchetti A Buttitta F Pellegrini S et al.Bronchioloalveolar lung carcinomas: K-ras mutations are constant events in the mucinous subtype.J Pathol. 1996; 179: 254-259Crossref PubMed Scopus (107) Google Scholar whereas Nuorva and coworkers19Nuorva K Soini Y Kamel D et al.p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis.Int J Cancer. 1995; 64: 424-429Crossref PubMed Scopus (40) Google Scholar have identified the presence of human papillomavirus DNA and p53 protein accumulation in about one third of BAC patients, as predictive of a poor prognosis.