Bronchioloalveolar carcinoma: A Review of the Epidemiology, Pathology, and Treatment

ABSTRACT

Bronchioloalveolar carcinoma (BAC) is an important subtype of pulmonary adenocarcinoma. It has received increasing attention in recent years, due to its increasing incidence and its rate of sensitivity to epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs). This article reviews the epidemiology, risk factors, pathology, clinical presentation, and treatment of this disease. Special focus is paid to the emerging role of oral EGFR-TKIs in Bronchioloalveolar cell carcinoma.

Adenocarcinoma - Bronchioloalveolar - carcinoma - non-small cell lung - receptor - epidermal growth factor - smoking

REFERENCES

• 1 Liebow A A. Bronchiolo-alveolar carcinoma.  Adv Intern Med. 1960;  10 329-358
• 2 Travis W D. World Health Organization, International Agency for Research on Cancer, International Association for the Study of Lung Cancer, International Academy of Pathology. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart Lyon Oxford; IARC Press, Oxford University Press (distributor) 2004
• 3 Jemal A, Murray T, Ward E et al.. Cancer statistics, 2005.  CA Cancer J Clin. 2005;  55 10-30
• 4 Brambilla E, Travis W D, Colby T V, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours.  Eur Respir J. 2001;  18 1059-1068
• 5 Barsky S H, Cameron R, Osann K E, Tomita D, Holmes E C. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features.  Cancer. 1994;  73 1163-1170
• 6 Auerbach O, Garfinkel L. The changing pattern of lung carcinoma.  Cancer. 1991;  68 1973-1977
• 7 Hsu C P, Chen C Y, Hsu N Y. Bronchioloalveolar carcinoma.  J Thorac Cardiovasc Surg. 1995;  110 374-381
• 8 Harpole D H, Bigelow C, Young Jr W G, Wolfe W G, Sabiston Jr D C. Alveolar cell carcinoma of the lung: a retrospective analysis of 205 patients.  Ann Thorac Surg. 1988;  46 502-507
• 9 Travis W D, Travis L B, Devesa S S. Lung cancer.  Cancer. 1995;  75(1 Suppl) 191-202
• 10 Read W L, Page N C, Tierney R M, Piccirillo J F, Govindan R. The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database.  Lung Cancer. 2004;  45 137-142
• 11 Falk R T, Pickle L W, Fontham E T et al.. Epidemiology of bronchioloalveolar carcinoma.  Cancer Epidemiol Biomarkers Prev. 1992;  1 339-344
• 12 Rolen K A, Fulton J P, Tamura D J, Strauss G M. Bronchioloalveolar carcinoma (BAC) of the lung is related to cigarette smoking: A case-control study from Rhode Island (RI) [abstract 2711].  Proc Am Soc Clin Oncol. 2003;  22 674
• 13 Morabia A, Wynder E L. Relation of bronchioloalveolar carcinoma to tobacco.  BMJ. 1992;  304 541-543
• 14 Morton W E, Treyve E L. Histologic differences in occupational risks of lung cancer incidence.  Am J Ind Med. 1982;  3 441-457
• 15 Rothschild H, Mulvey J J. An increased risk for lung cancer mortality associated with sugarcane farming.  J Natl Cancer Inst. 1982;  68 755-760
• 16 Palmarini M, Fan H. Retrovirus-induced ovine pulmonary adenocarcinoma: an animal model for lung cancer.  J Natl Cancer Inst. 2001;  93 1603-1614
• 17 Sharp J M. Sheep pulmonary adenomatosis: a contagious tumour and its cause.  Cancer Surv. 1987;  6 73-83
• 18 Sigurdsson B. Adenomatosis of sheep's lungs: experimental transmission.  Arch Gesamte Virusforsch. 1958;  8 51-58
• 19 Palmarini M, Sharp J M, 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 6964-6972
• 20 Garcia-Goti M, Gonzalez L, Cousens C et al.. Sheep pulmonary adenomatosis: characterization of two pathological forms associated with jaagsiekte retrovirus.  J Comp Pathol. 2000;  122 55-65
• 21 De las Heras M, Barsky S H, Hasleton P et al.. Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours.  Eur Respir J. 2000;  16 330-332
• 22 Travis W, Colby T, Corrin B et al.. The World Health Organization Histological Typing of Lung and Pleural Tumors. 3rd ed. Berlin; Springer Verlag 1999
• 23 Clayton F. Bronchioloalveolar carcinomas: cell types, patterns of growth, and prognostic correlates.  Cancer. 1986;  57 1555-1564
• 24 Daly R C, Trastek V F, Pairolero P C et al.. Bronchioloalveolar carcinoma: factors affecting survival.  Ann Thorac Surg. 1991;  51 368-376 discussion 376-377
• 25 Greco R J, Steiner R M, Goldman S, Cotler H, Patchefsky A, Cohn H E. Bronchioloalveolar cell carcinoma of the lung.  Ann Thorac Surg. 1986;  41 652-656
• 26 Manning Jr J T, Spjut H J, Tschen J A. Bronchioloalveolar carcinoma: the significance of two histopathologic types.  Cancer. 1984;  54 525-534
• 27 Matthews M J, Mackay B, Lukeman J. The pathology of non-small cell carcinoma of the lung.  Semin Oncol. 1983;  10 34-55
• 28 Travis W D. Pathology of lung cancer.  Clin Chest Med. 2002;  23 65-81
• 29 Singh G, Katyal S L. Clara Cell Proteins.  Ann N Y Acad Sci. 2000;  923 43-58
• 30 Singh G, Katyal S L, Torikata C. Carcinoma of type II pneumocytes: PAS staining as a screening test for nuclear inclusions of surfactant specific apoprotein.  Cancer. 1982;  50 946-948
• 31 Sidhu G S, Wieczorek R, Cassai N D, Zhu C C. The concept of bronchioloalveolar cell adenocarcinoma: redefinition, a critique of the 1999 WHO classification, and an ultrastructural analysis of 155 cases.  Int J Surg Pathol. 2003;  11 89-99
• 32 Bennett D E, Sasser W F. Bronchiolar carcinoma: a valid clinicopathologic entity? A study of 30 cases.  Cancer. 1969;  24 876-887
• 33 Greenberg S D, Smith M N, Spjut H J. Bronchiolo-alveolar carcinoma: cell of origin.  Am J Clin Pathol. 1975;  63 153-167
• 34 Copin M C, Buisine M P, Leteurtre E et al.. Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas.  Hum Pathol. 2001;  32 274-281
• 35 Lau S K, Luthringer D J, Eisen R N. Thyroid transcription factor-1: a review.  Appl Immunohistochem Mol Morphol. 2002;  10 97-102
• 36 Shah R N, Badve S, Papreddy K, Schindler S, Laskin W B, Yeldandi A V. Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma.  Hum Pathol. 2002;  33 915-920
• 37 Saad R S, Cho P, Silverman J F, Liu Y. Usefulness of Cdx2 in separating mucinous bronchioloalveolar adenocarcinoma of the lung from metastatic mucinous colorectal adenocarcinoma.  Am J Clin Pathol. 2004;  122 421-427
• 38 Saad R S, Liu Y L, Han H, Landreneau R J, Silverman J F. Prognostic significance of thyroid transcription factor-1 expression in both early-stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung.  Hum Pathol. 2004;  35 3-7
• 39 Simsir A, Wei X J, Yee H, Moreira A, Cangiarella J. 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;  121 350-357
• 40 Lau S K, Desrochers M J, Luthringer D J. Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases.  Mod Pathol. 2002;  15 538-542
• 41 Goldstein N S, Thomas M. Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies.  Am J Clin Pathol. 2001;  116 319-325
• 42 Johansson L. Histopathologic classification of lung cancer: relevance of cytokeratin and TTF-1 immunophenotyping.  Ann Diagn Pathol. 2004;  8 259-267
• 43 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;  45 125-134
• 44 Awaya H, Takeshima Y, Yamasaki M, Inai K. Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung.  Am J Clin Pathol. 2004;  121 644-653
• 45 Westra W H. Early glandular neoplasia of the lung.  Respir Res. 2000;  1 163-169
• 46 Lee K S, Kim Y, Han J, Ko E J, Park C K, Primack S L. Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings.  Radiographics. 1997;  17 1345-1357
• 47 Breathnach O S, Ishibe N, Williams J, Linnoila R I, Caporaso N, Johnson B E. Clinical features of patients with stage IIIB and IV bronchioloalveolar carcinoma of the lung.  Cancer. 1999;  86 1165-1173
• 48 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;  36 482-487
• 49 Hidaka N, Nagao K. Bronchioloalveolar carcinoma accompanied by severe bronchorrhea.  Chest. 1996;  110 281-282
• 50 Dwek J H, Charytan C, Stachura I, Kaganowicz A. Salt-wasting bronchorrhea and its mechanisms.  Arch Intern Med. 1977;  137 791-794
• 51 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 1465-1468
• 52 Marom Z M, Goswami S K. Respiratory mucus hypersecretion (bronchorrhea): a case discussion-possible mechanisms(s) and treatment.  J Allergy Clin Immunol. 1991;  87 1050-1055
• 53 Chang G C, Yang T Y, Wang N S, Huang C M, Chiang C D. Successful treatment of multifocal bronchioloalveolar cell carcinoma with ZD1839 (Iressa) in two patients.  J Formos Med Assoc. 2003;  102 407-411
• 54 Milton D T, Kris M G, Gomez J E, Feinstein M B. Prompt control of bronchorrhea in patients with bronchioloalveolar carcinoma treated with gefitinib (Iressa).  Support Care Cancer. 2005;  13 70-72
• 55 Takao M, Inoue K, Watanabe F et al.. Successful treatment of persistent bronchorrhea by gefitinib in a case with recurrent bronchioloalveolar carcinoma: a case report.  World J Surg Oncol. 2003;  1 8
• 56 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;  94 453-458
• 57 Chetty K G, Dick C, McGovern J, Conroy R M, Mahutte C K. Refractory hypoxemia due to intrapulmonary shunting associated with bronchioloalveolar carcinoma.  Chest. 1997;  111 1120-1121
• 58 Barlesi F, Doddoli C, Thomas P, Kleisbauer J P, Giudicelli R, Fuentes P. Bilateral bronchioloalveolar lung carcinoma: is there a place for palliative pneumonectomy?.  Eur J Cardiothorac Surg. 2001;  20 1113-1116
• 59 Trigaux J P, Gevenois P A, Goncette L, Gouat F, Schumaker A, Weynants P. Bronchioloalveolar carcinoma: computed tomography findings.  Eur Respir J. 1996;  9 11-16
• 60 Regnard J F, Santelmo N, Romdhani N et al.. Bronchioloalveolar lung carcinoma: results of surgical treatment and prognostic factors.  Chest. 1998;  114 45-50
• 61 Breathnach O S, Kwiatkowski D J, Finkelstein D M et al.. Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease.  J Thorac Cardiovasc Surg. 2001;  121 42-47
• 62 Ebright M I, Zakowski M F, Martin J et al.. Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma.  Ann Thorac Surg. 2002;  74 1640-1646 discussion 1646-1647
• 63 Noguchi M, Morikawa A, Kawasaki M et al.. Small adenocarcinoma of the lung. Histologic characteristics and prognosis.  Cancer. 1995;  75 2844-2852
• 64 Rena O, Papalia E, Ruffini E et al.. Stage I pure bronchioloalveolar carcinoma: recurrences, survival and comparison with adenocarcinoma of the lung.  Eur J Cardiothorac Surg. 2003;  23 409-414
• 65 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;  71 971-974
• 66 Watanabe S, Watanabe T, Arai K, Kasai T, Haratake J, Urayama H. Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography.  Ann Thorac Surg. 2002;  73 1071-1075
• 67 Feldman E R, Eagan R T, Schaid D J. Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognosis.  Mayo Clin Proc. 1992;  67 27-32
• 68 Sorensen J B, Hirsch F R, Olsen J. The prognostic implication of histopathologic subtyping of pulmonary adenocarcinoma according to the classification of the World Health Organization: an analysis of 259 consecutive patients with advanced disease.  Cancer. 1988;  62 361-367
• 69 Miller V A, Kris M G, Shah N et al.. The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (OSI-774) shows promising activity in patients with bonchioalveolar cell carcinoma (BAC): preliminary results of a phase II trial [abstract 2491].  Proc Am Soc Clin Oncol. 2003;  22 619
• 70 Janne P A, Ostler P A, Lucca J et al.. ZD1839 (“Iressa”) shows antitumor activity in patients with recurrent non-small cell lung cancer treated on a compassionate use protocol.  Proc Am Soc Clin Oncol. 2002;  21 319
• 71 Fukuoka M, Yano S, Giaccone G et al.. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial). [corrected].  J Clin Oncol. 2003;  21 2237-2246
• 72 Miller V A, Kris M G, Shah N et al.. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer.  J Clin Oncol. 2004;  22 1103-1109
• 73 Kris M G, Natale R B, Herbst R S et al.. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial.  JAMA. 2003;  290 2149-2158
• 74 Paez J G, Janne P A, Lee J C et al.. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.  Science. 2004;  304 1497-1500
• 75 Lynch T J, Bell D W, Sordella R et al.. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.  N Engl J Med. 2004;  350 2129-2139
• 76 Natale R B, Shak S, Aronson N et al.. Quantitative gene expression in non-small cell lung cancer from paraffin-embedded tissue specimens: predicting response to gefitinib, an EGFR kinase inhibitor [abstract 763].  Proc Am Soc Clin Oncol. 2003;  22 190
• 77 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;  23 857-865
• 78 Shigematsu H, Lin L, Takahashi T et al.. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers.  J Natl Cancer Inst. 2005;  97 339-346
• 79 Kris M G, Sandler A, Miller V A et al.. Cigarette smoking history predicts sensitivity to erlotinib: results of a phase II trial in patients with bronchioloalveolar carcinoma (BAC) [abstract 7062].  Proc Am Soc Clin Oncol. 2004;  22 14S
• 80 West H, Franklin W A, Gumerlock P H et al.. Gefitinib (ZD1839) therapy for advanced bronchioloalveolar lung cancer (BAC): Southwest Oncology Group (SWOG) Study S0126 [abstract 7014].  Proc Am Soc Clin Oncol. 2004;  22 14S
• 81 Jackman D J, Lucca J, Fidias P et al.. Phase II study of the EGFR tyrosine kinase inhibitor erlotinib in patients ≥ 70 years of age with previously untreated advanced non-small cell lung carcinoma [abstract 7148].  Proc Am Soc Clin Oncol. 2005;