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Bronchioloalveolar carcinoma, including adenocarcinoma in situ

Howard J West, MD
Section Editors
Rogerio C Lilenbaum, MD, FACP
James R Jett, MD
Deputy Editor
Sadhna R Vora, MD


The term bronchioloalveolar carcinoma (BAC) was originally applied to a subtype of adenocarcinoma of the lung that is distinguished by its peripheral location, well-differentiated cytology, growth along intact alveolar septa (the so-called "lepidic" growth pattern), and tendency for both aerogenous and lymphatic spread.

In the 2004 World Health Organization (WHO) classification of lung tumors, BAC was considered a subset of adenocarcinoma and is divided into mucinous, nonmucinous, and mixed subtypes [1]. This distinction is based upon histologic criteria, and is supported by immunohistochemical and molecular biology differences. Distinguishing mucinous from nonmucinous subtypes of BAC has significant therapeutic and prognostic implications [2].

In 2011, a multidisciplinary expert panel representing the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) proposed a major revision of the classification of adenocarcinomas that reclassified what had been called BAC into newly defined histologic subgroups and recommended discontinuation of the term BAC [3]. The proposed revisions are briefly presented in the relevant sections below and discussed in detail elsewhere. (See "Pathology of lung malignancies", section on 'Comparison of the 2015 and 2004 WHO classification of adenocarcinoma'.)

Currently, the term BAC continues to be used operationally by some pathologists and many clinicians to describe not only the noninvasive “pure” form but also some cases of mixed adenocarcinoma with a BAC component that share clinical characteristics. As the new classification of lung adenocarcinoma becomes variably applied, the term “lepidic predominant adenocarcinoma” is followed in many cases by the clarification, “the entity formerly known as BAC,” or similar duplication of terminology during this transitional period.

The treatment of other forms of non-small cell lung cancer (NSCLC) is discussed elsewhere. (See "Overview of the treatment of advanced non-small cell lung cancer" and "Overview of the initial evaluation, treatment and prognosis of lung cancer".)


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Literature review current through: Dec 2016. | This topic last updated: Tue Sep 16 00:00:00 GMT+00:00 2014.
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  1. Travis WD. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart, World Health Organization, International Agency for Research on Cancer, International Association for the Study of Lung Cancer, International Academy of Pathology (Eds), IARC Press, Oxford University Press, Lyon Oxford 2004.
  2. West HL, Garfield DH. Bronchioloalveolar carcinoma: not as easy as "BAC". J Thorac Oncol 2009; 4:1047.
  3. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6:244.
  4. Ebright MI, Zakowski MF, Martin J, et al. Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma. Ann Thorac Surg 2002; 74:1640.
  5. Lin DM, Ma Y, Zheng S, et al. Prognostic value of bronchioloalveolar carcinoma component in lung adenocarcinoma. Histol Histopathol 2006; 21:627.
  6. Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol 2013; 31:992.
  7. Watanabe S, Watanabe T, Arai K, et al. Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography. Ann Thorac Surg 2002; 73:1071.
  8. Sakurai H, Dobashi Y, Mizutani E, et al. Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diameter: a prognostic assessment. Ann Thorac Surg 2004; 78:1728.
  9. Yoshida J, Nagai K, Yokose T, et al. Limited resection trial for pulmonary ground-glass opacity nodules: fifty-case experience. J Thorac Cardiovasc Surg 2005; 129:991.
  10. Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer 1995; 75:2844.
  11. Borczuk AC, Qian F, Kazeros A, et al. Invasive size is an independent predictor of survival in pulmonary adenocarcinoma. Am J Surg Pathol 2009; 33:462.
  12. Yim J, Zhu LC, Chiriboga L, et al. Histologic features are important prognostic indicators in early stages lung adenocarcinomas. Mod Pathol 2007; 20:233.
  13. Shah RN, Badve S, Papreddy K, et al. Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma. Hum Pathol 2002; 33:915.
  14. Saad RS, Cho P, Silverman JF, Liu Y. Usefulness of Cdx2 in separating mucinous bronchioloalveolar adenocarcinoma of the lung from metastatic mucinous colorectal adenocarcinoma. Am J Clin Pathol 2004; 122:421.
  15. Simsir A, Wei XJ, Yee H, et al. Differential expression of cytokeratins 7 and 20 and thyroid transcription factor-1 in bronchioloalveolar carcinoma: an immunohistochemical study in fine-needle aspiration biopsy specimens. Am J Clin Pathol 2004; 121:350.
  16. Lau SK, Desrochers MJ, Luthringer DJ. Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases. Mod Pathol 2002; 15:538.
  17. Jerome Marson V, Mazieres J, Groussard O, et al. Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade. Histopathology 2004; 45:125.
  18. Goldstein NS, Thomas M. Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies. Am J Clin Pathol 2001; 116:319.
  19. Barsky SH, Cameron R, Osann KE, et al. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer 1994; 73:1163.
  20. Dumont P, Gasser B, Rougé C, et al. Bronchoalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically treated patients. Chest 1998; 113:391.
  21. Tao LC, Delarue NC, Sanders D, Weisbrod G. Bronchiolo-alveolar carcinoma: a correlative clinical and cytologic study. Cancer 1978; 42:2759.
  22. Kris MG, Giaccone G, Davies A, et al. Systemic therapy of bronchioloalveolar carcinoma: results of the first IASLC/ASCO consensus conference on bronchioloalveolar carcinoma. J Thorac Oncol 2006; 1:S32.
  23. Spitz MR, Hsu TC, Wu X, et al. Mutagen sensitivity as a biological marker of lung cancer risk in African Americans. Cancer Epidemiol Biomarkers Prev 1995; 4:99.
  24. Garfield DH, Cadranel J, West HL. Bronchioloalveolar carcinoma: the case for two diseases. Clin Lung Cancer 2008; 9:24.
  25. Wislez M, Antoine M, Baudrin L, et al. Non-mucinous and mucinous subtypes of adenocarcinoma with bronchioloalveolar carcinoma features differ by biomarker expression and in the response to gefitinib. Lung Cancer 2010; 68:185.
  26. Hata A, Katakami N, Fujita S, et al. Frequency of EGFR and KRAS mutations in Japanese patients with lung adenocarcinoma with features of the mucinous subtype of bronchioloalveolar carcinoma. J Thorac Oncol 2010; 5:1197.
  27. Sakuma Y, Matsukuma S, Yoshihara M, et al. Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations. Am J Clin Pathol 2007; 128:100.
  28. Finberg KE, Sequist LV, Joshi VA, et al. Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. J Mol Diagn 2007; 9:320.
  29. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol 2008; 3:13.
  30. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 2010; 46:1773.
  31. Read WL, Page NC, Tierney RM, et al. The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database. Lung Cancer 2004; 45:137.
  32. Falk RT, Pickle LW, Fontham ET, et al. Epidemiology of bronchioloalveolar carcinoma. Cancer Epidemiol Biomarkers Prev 1992; 1:339.
  33. Morabia A, Wynder EL. Relation of bronchioloalveolar carcinoma to tobacco. BMJ 1992; 304:541.
  34. Rolen, KA, Fulton, JP, Tamura, DJ, Strauss GM. Bronchioloalveolar carcinoma (BAC) of the lung is related to cigarette smoking: A case-control study from Rhode Island (RI). Proc Am Soc Clin Oncol 2003; 22:674.
  35. Morton WE, Treyve EL. Histologic differences in occupational risks of lung cancer incidence. Am J Ind Med 1982; 3:441.
  36. Rothschild H, Mulvey JJ. An increased risk for lung cancer mortality associated with sugarcane farming. J Natl Cancer Inst 1982; 68:755.
  37. García-Goti M, González L, Cousens C, et al. Sheep pulmonary adenomatosis: characterization of two pathological forms associated with jaagsiekte retrovirus. J Comp Pathol 2000; 122:55.
  38. Palmarini M, Fan H. Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. J Natl Cancer Inst 2001; 93:1603.
  39. Leroux C, Girard N, Cottin V, et al. Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep. Vet Res 2007; 38:211.
  40. SIGURDSSON B. Adenomatosis of sheep's lungs; experimental transmission. Arch Gesamte Virusforsch 1958; 8:51.
  41. Palmarini M, Sharp JM, de las Heras M, Fan H. Jaagsiekte sheep retrovirus is necessary and sufficient to induce a contagious lung cancer in sheep. J Virol 1999; 73:6964.
  42. Akira M, Atagi S, Kawahara M, et al. High-resolution CT findings of diffuse bronchioloalveolar carcinoma in 38 patients. AJR Am J Roentgenol 1999; 173:1623.
  43. Thompson WH. Bronchioloalveolar carcinoma masquerading as pneumonia. Respir Care 2004; 49:1349.
  44. Trigaux JP, Gevenois PA, Goncette L, et al. Bronchioloalveolar carcinoma: computed tomography findings. Eur Respir J 1996; 9:11.
  45. Aoki T, Tomoda Y, Watanabe H, et al. Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival. Radiology 2001; 220:803.
  46. Yang ZG, Sone S, Takashima S, et al. High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT. AJR Am J Roentgenol 2001; 176:1399.
  47. Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2:706.
  48. Greco RJ, Steiner RM, Goldman S, et al. Bronchoalveolar cell carcinoma of the lung. Ann Thorac Surg 1986; 41:652.
  49. Lee KS, Kim Y, Han J, et al. Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings. Radiographics 1997; 17:1345.
  50. Breathnach OS, Ishibe N, Williams J, et al. Clinical features of patients with stage IIIB and IV bronchioloalveolar carcinoma of the lung. Cancer 1999; 86:1165.
  51. Aquino SL, Halpern EF, Kuester LB, Fischman AJ. FDG-PET and CT features of non-small cell lung cancer based on tumor type. Int J Mol Med 2007; 19:495.
  52. Huang TW, Lin LF, Hsieh CM, et al. Positron emission tomography in bronchioloalveolar carcinoma of the lung. Eur J Surg Oncol 2012; 38:1156.
  53. Higashi K, Ueda Y, Seki H, et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998; 39:1016.
  54. Heyneman LE, Patz EF. PET imaging in patients with bronchioloalveolar cell carcinoma. Lung Cancer 2002; 38:261.
  55. Tsunezuka Y, Shimizu Y, Tanaka N, et al. Positron emission tomography in relation to Noguchi's classification for diagnosis of peripheral non-small-cell lung cancer 2 cm or less in size. World J Surg 2007; 31:314.
  56. Raz DJ, Odisho AY, Franc BL, Jablons DM. Tumor fluoro-2-deoxy-D-glucose avidity on positron emission tomographic scan predicts mortality in patients with early-stage pure and mixed bronchioloalveolar carcinoma. J Thorac Cardiovasc Surg 2006; 132:1189.
  57. Detterbeck FC, Lewis SZ, Diekemper R, et al. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:7S.
  58. Zell JA, Ignatius Ou SH, Ziogas A, Anton-Culver H. Validation of the proposed International Association for the Study of Lung Cancer non-small cell lung cancer staging system revisions for advanced bronchioloalveolar carcinoma using data from the California Cancer Registry. J Thorac Oncol 2007; 2:1078.
  59. Breathnach OS, Kwiatkowski DJ, Finkelstein DM, et al. Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease. J Thorac Cardiovasc Surg 2001; 121:42.
  60. Harpole DH, Bigelow C, Young WG Jr, et al. Alveolar cell carcinoma of the lung: a retrospective analysis of 205 patients. Ann Thorac Surg 1988; 46:502.
  61. Yamato Y, Tsuchida M, Watanabe T, et al. Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung. Ann Thorac Surg 2001; 71:971.
  62. Battafarano RJ, Meyers BF, Guthrie TJ, et al. Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival. Ann Thorac Surg 2002; 74:988.
  63. Roberts PF, Straznicka M, Lara PN, et al. Resection of multifocal non-small cell lung cancer when the bronchioloalveolar subtype is involved. J Thorac Cardiovasc Surg 2003; 126:1597.
  64. Hidaka N, Nagao K. Bronchioloalveolar carcinoma accompanied by severe bronchorrhea. Chest 1996; 110:281.
  65. Dwek JH, Charytan C, Stachura I, Kaganowicz A. Salt-wasting bronchorrhea and its mechanisms. Arch Intern Med 1977; 137:791.
  66. Kitazaki T, Fukuda M, Soda H, Kohno S. Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports. Lung Cancer 2005; 49:125.
  67. Milton DT, Kris MG, Gomez JE, Feinstein MB. Prompt control of bronchorrhea in patients with bronchioloalveolar carcinoma treated with gefitinib (Iressa). Support Care Cancer 2005; 13:70.
  68. Yano S, Kanematsu T, Miki T, et al. A report of two bronchioloalveolar carcinoma cases which were rapidly improved by treatment with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 ("Iressa"). Cancer Sci 2003; 94:453.
  69. Thotathil Z, Long J. Erlotinib effective against refractory bronchorrhea from advanced non-small cell lung cancer. J Thorac Oncol 2007; 2:881.
  70. Popat N, Raghavan N, McIvor RA. Severe bronchorrhea in a patient with bronchioloalveolar carcinoma. Chest 2012; 141:513.
  71. Hiratsuka T, Mukae H, Ihiboshi H, et al. [Severe bronchorrhea accompanying alveolar cell carcinoma: treatment with clarithromycin and inhaled beclomethasone]. Nihon Kokyuki Gakkai Zasshi 1998; 36:482.
  72. Marom ZM, Goswami SK. Respiratory mucus hypersecretion (bronchorrhea): a case discussion--possible mechanisms(s) and treatment. J Allergy Clin Immunol 1991; 87:1050.
  73. Nakajima T, Terashima T, Nishida J, et al. Treatment of bronchorrhea by corticosteroids in a case of bronchioloalveolar carcinoma producing CA19-9. Intern Med 2002; 41:225.
  74. Tamaoki J, Kohri K, Isono K, Nagai A. Inhaled indomethacin in bronchorrhea in bronchioloalveolar carcinoma: role of cyclooxygenase. Chest 2000; 117:1213.
  75. Homma S, Kawabata M, Kishi K, et al. Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma. Chest 1999; 115:1465.
  76. Hudson E, Lester JF, Attanoos RL, et al. Successful treatment of bronchorrhea with octreotide in a patient with adenocarcinoma of the lung. J Pain Symptom Manage 2006; 32:200.
  77. Falcoz PE, Hoan NT, Le Pimpec-Barthes F, Riquet M. Severe hypoxemia due to intrapulmonary shunting requiring surgery for bronchioloalveolar carcinoma. Ann Thorac Surg 2009; 88:287.
  78. Gu B, Burt BM, Merritt RE, et al. A dominant adenocarcinoma with multifocal ground glass lesions does not behave as advanced disease. Ann Thorac Surg 2013; 96:411.
  79. Cadranel J, Gervais M, Wislez P, et al. IFCT-0504 trial: Mucinous and nonmucinous cytologic subtypes interaction effect in first-line treatment of advanced broncioloalveolar carcinoma by erlotinib or carboplatin/paclitaxel (abstract 7521). J Clin Oncol 2011; 29:481s.
  80. West HL, Crowley JJ, Vance RB, et al. Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour infusion (SWOG 9714): a Southwest Oncology Group study. Ann Oncol 2005; 16:1076.
  81. Scagliotti GV, Smit E, Bosquee L, et al. A phase II study of paclitaxel in advanced bronchioloalveolar carcinoma (EORTC trial 08956). Lung Cancer 2005; 50:91.
  82. Marchetti A, Martella C, Felicioni L, et al. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 2005; 23:857.
  83. Miller VA, Riely GJ, Zakowski MF, et al. Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol 2008; 26:1472.
  84. West HL, Franklin WA, McCoy J, et al. Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest Oncology Group Study S0126. J Clin Oncol 2006; 24:1807.
  85. Cadranel J, Quoix E, Baudrin L, et al. IFCT-0401 Trial: a phase II study of gefitinib administered as first-line treatment in advanced adenocarcinoma with bronchioloalveolar carcinoma subtype. J Thorac Oncol 2009; 4:1126.
  86. Franklin WA, Chansky K, Gumerlock PH, et al. Association between activation of ErbB pathway genes and survival following gefitinib treatment in advanced BAC (SWOG 0126). Journal of Clinical Oncology 2004 (abstract #7015).