Bronchioloalveolar carcinoma

This review focuses on aspects of bronchioloalveolar carcinoma (BAC) in which it differs importantly from other forms of non-small-cell lung cancer. BAC is a form of adenocarcinoma with unique clinical, radiological, and epidemiological features. With the notable exception of a lower likelihood of a positive positron-emission tomographic (PET) scan in BAC, staging, diagnosis, and treatment are largely the same as for other histological subtypes of lung cancer. However, additional treatment options exist that are equivalent, if not more effective, for many patients with BAC. The diagnosis of BAC should be reserved for those tumors meeting the 1999/2004 criteria set forth by the World Health Organization. Revised nomenclature proposed by an expert consensus panel may change how this disease is viewed. Additional clinical trials are needed on patients with BAC, employing strict definitions and enrollment criteria to allow the results to be applied to appropriate patient populations.     

自然生长十年的细支气管肺泡细胞癌一例并文献复习

目的 提高对细支气管肺泡细胞癌(BAC)临床及影像学特点的认识.方法 分析2009年7月收治的1例BAC患者的临床资料及诊治经过,并结合相关文献进行复习.截至2010年6月,以bronchioloalveolar carcinoma、ground glass opacity、high resolution computed tomography为检索词,在PubMed检索系统进行检索,在万方数据库以细支气管肺泡细胞癌、磨玻璃影为检索词进行检索.结果 患者男,76岁,常规体检时胸部CT示左肺上叶小片状高密度影,但无特殊临床表现.随访10年,至2009年复查胸部CT示左肺上叶病灶密度稍有增加.考虑恶性肿瘤不能除外,在全身麻醉下行左上肺叶切除术加纵隔淋巴结清扫术,术后病理报告:左上肺BAC.在PubMed检索系统检索到35篇文献.共报道664例磨玻璃影表现的BAC,其中4篇为综述,24篇为回顾性分析,7篇为个案报道;在万方数据库检索到1篇回顾性分析,报道24例以磨玻璃影为表现的BAC.结论 影像学表现为磨玻璃影的BAC,其临床表现缺乏特异性,仅胸部CT表现为小片状高密度影.对于此类患者应定期随访,如提示恶变的可能,应及时进行手术治疗.     

Seeking a home for a PET, part 1: Defining the appropriate place for positron emission tomography imaging in the diagnosis of pulmonary nodules or masses

There is a growing experience with positron emission tomography (PET) in patients with pulmonary nodules or masses. As PET imaging becomes more widely available, it is important to thoughtfully define when application of this technology is warranted. Review of the literature to date suggests that PET imaging for diagnosis of pulmonary lesions is most useful in patients who have a low or intermediate risk of lung cancer as determined by an evaluation of symptoms, risk factors, and radiographic appearance. There is little role for PET in diagnosis in patients with a very low or a high risk of lung cancer, and there is little role in patients with lesions < 1 cm in diameter, or lesions suspected to be an infection, a bronchioloalveolar carcinoma, or a typical carcinoid tumor.     

Differentiating bronchioloalveolar carcinoma from adenocarcinoma

The recognition of bronchioloalveolar carcinoma (BAC) as distinct from adenocarcinoma of the lung, is controversial. Using strict pathologic criteria, 43 consecutive patients with BAC were matched by year of diagnosis and compared with a similar number of patients with adenocarcinoma, and for contrast, with those with squamous and oat cell carcinoma of the lung. We demonstrated that BAC is not sex related, and is not as smoking related as the other neoplasms. Unlike epidermoid carcinoma, BAC does not show a predilection for those occupations requiring manual labor. Also, BAC is frequently distinguishable radiologically from the other three by being smaller and peripheral. A pleural tag and an air bronchogram in a mass are rather specific, and BAC is less likely to have large airway involvement and adenopathy. The percentage of patients who were free of tumor after 2 yr was greater in the BAC group than in the others, but the overall survival rate between the BAC group and the adenocarcinoma group was not. Based on inter-observer variability, there is some overlap pathologically between these 2 groups. However, when the overlap between the adenocarcinoma and the BAC groups is compared with that between the adenocarcinoma and the squamous cell carcinoma groups, the difference is not significant. We conclude that BAC should be considered a distinct clinical entity.     

Ground-glass opacity nodules: histopathology, imaging evaluation, and clinical implications

Ground-glass opacity (GGO) nodules noted at thin-section computed tomography (CT) scan have been shown to have a histopathologic relationship with atypical adenomatous hyperplasia, bronchioloalveolar carcinoma (BAC, or adenocarcinoma in situ), and adenocarcinoma with a predominant BAC component (minimally invasive adenocarcinoma). Patients harboring GGO nodules of BAC or adenocarcinoma with a predominant BAC component demonstrate negative results for malignancy at positron emission tomography. In peripheral adenocarcinoma of a part-solid (mixed GGO and solid attenuation) nodular nature, both the degree of disappearance of GGO area, when the lung window is changed to a mediastinal window image at CT scanning, and the maximum standardized uptake value at positron emission tomography correlate well with histopathologic BAC and non-BAC ratios. However, a high non-BAC ratio appears to be the only independent prognosis-determining factor. Epidermal growth factor receptor mutations are positively correlated with the GGO ratio at a thin-section CT scan in lung adenocarcinomas. As patients with a GGO nodule of BAC or adenocarcinoma with a predominant BAC component have a good prognosis, a wedge resection is recommended as a treatment option, in preference to lobectomy. Even for multiple malignant pure GGO nodules, minimally invasive surgery (including multiple resections) with the preservation of lung volume and adequate imaging follow-up studies are the recommended diagnostic and therapeutic measures.     

Occurrence of bronchioloalveolar cell carcinoma in two brothers: comparison of clinical features and immunohistochemical findings

It has been suggested that lung cancer sometimes aggregates in families. However, the familial occurrence of bronchioloalveolar carcinoma (BAC) is extremely rare. We present a family in which two brothers had BAC. The clinical features and immunohistochemical findings of BAC in the two brothers were compared. Immunohistochemical findings revealed that both cases of BAC had very similar immunopathological features in epithelial marker expression. A review of the literature revealed that this is the third case of BACs in a single family.     

Bronchioloalveolar carcinoma arising in congenital cystic adenomatoid malformation in a child: A case report and review on malignancies originating in congenital cystic adenomatoid malformation

A type I congenital cystic adenomatoid malformation (CCAM) in the left lower lobe was removed from a 11-year-old boy with a 3-month history of recurrent pneumonia. As incidental finding, a bronchioloalveolar carcinoma (BAC) was found in the lung parenchyma adjacent to the cyst. A left lower lobectomy was performed. At 18 months after surgery the patient is well and free of neoplastic disease. To the best of our knowledge, this association has not been reported previously in a pediatric patient. Malignancies complicating CCAM are rarely seen, but have been reported in adults. Including our case, eight cases of BAC and five cases of rhabdomyosarcoma (RMS) in association with CCAM have been reported so far. As CCAM can host metaplastic mucous cells, primitive mesenchymal cells and differentiated but poorly organized striated muscle fibers, it has been proposed that CCAM may act as a predisposing condition for oncogenesis. Our experience adds further support that CCAM can act as a premalignant lesion. Previous reports of both BAC and RMS in asymptomatic CCAM suggest prompt resection shortly after diagnosis. Pediatr. Pulmonol. 1998; 25:62–66. © 1998 Wiley-Liss, Inc.     

Accuracy of F-18 fluorodeoxyglucose positron emission tomography for the evaluation of malignancy in patients presenting with new lung abnormalities: a retrospective review.

STUDY OBJECTIVE: To evaluate the accuracy of positron emission tomography (PET) in determining the presence of malignancy in patients presenting with new lung findings, either as an incidental finding or after treatment of a primary carcinoma. DESIGN: A retrospective review of the PET database of our hospital from April 29, 1997, to March 20, 1999, identified 196 patients referred for the evaluation of new lung findings, either as an incidental finding or following definitive treatment of a primary carcinoma. The diagnosis of either malignancy or a benign condition was established in 71 patients. This was determined by either histopathology from biopsy, or by subsequent imaging demonstrating disease progression, resolution, or stability of the initial lung findings. RESULTS: In patients presenting with new lung findings without a history of carcinoma (n = 37), the sensitivity and specificity of PET was 95% and 82%, respectively. In this population, the negative predictive value was 93% and the positive predictive value was 86%. PET was less sensitive and specific for evaluating metastatic or recurrent disease in patients previously treated for carcinoma. In patients presenting with a previously treated primary lung cancer (n = 13), the sensitivity of PET was 70%, with a specificity of 67%. The negative predictive value was only 40% and the positive predictive value was 88% in this subset of patients. In patients with an extrapulmonary primary carcinoma presenting with new lung nodules (n = 21), the sensitivity and specificity of PET was 92% and 63%, respectively. In this population, the negative predictive value was 83% while the positive predictive value was 80%. Of the 71 total cases for which follow-up data were available, there were 5 false-negative cases and 7 false-positive cases, for an overall sensitivity of 88%, specificity of 75%, negative predictive value of 81%, and positive predictive value of 84%. CONCLUSIONS: The sensitivity of PET is highest for the evaluation of new malignancy in patients without a known primary carcinoma. PET is less sensitive for evaluating metastatic or recurrent disease.     

From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung.

Bronchioloalveolar carcinoma (BAC) of the lungs is a known morphological subtype of nonsmall cell cancer. The current study presents several carcinogenetic theories of BAC and the possible relationship with atypical adenomatous hyperplasia and congenital pulmonary airway malformation (CPAM). The authors present an unusual case of BAC developed in an area of CPAM, with subsequent progression to metastatic adenocarcinoma (AC). The case is unique due to the combination of: early age of presentation; neoplastic transformation of a CPAM; unaltered course over 15 yrs; and its particular pattern of slow morphogenesis and degeneration into an invasive AC of the lung. The case also presents the unique features of a long-standing, unaltered natural course of paediatric BAC towards invasive and metastatic AC, illustrating that lack of growth over many years cannot be entirely trusted as a criterion of benignity. In conclusion, clinicians and pathologists need to be aware of the fact that congenital pulmonary airway malformation so far represents the only known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.     

细支气管肺泡癌的研究进展

肺癌在全球范围内呈上升状态，仅2005年在美国新发病者就有172000例之多。非小细胞肺癌（non-small cell lung cancer，NSCLC）占肺癌的80．0％以上。其中细支气管肺泡癌（bronchioloalveolar carcinoma，BAC）是肺腺癌的一个重要亚型，近年来BAC的发病率呈逐年上升趋势，治疗方面也取得了新的进展，是一值得重视的问题。本文就该病的流行病学、危险因子、病理学、临床表现和治疗，尤其表皮生长因子-酪氨酸激酶抑制物（epidermalgrowthfactorreceptors—tyrosinekinaseinhibitor，EGFR—TKIs）在BAC治疗方面作一综述。     

Localized bronchioloalveolar carcinoma with small foci of active fibroblastic proliferation. A report of 2 cases

Localized bronchioloalveolar carcinoma (LBAC) without foci of active fibroblastic proliferation has been reported to be a pN0 disease. Predominantly, these tumors have not been associated with cancer relapse or death subsequent to surgery. Based on these observations, LBAC cases have been considered candidates for limited lung resection without lymph node dissection. However, this surgical option requires careful validation, and an accurate diagnosis is indispensable. The absence of foci of active fibroblastic proliferation must be confirmed by a thorough investigation. Nonetheless, these foci may escape detection, and even currently accepted diagnostic modalities may not be sufficient to accurately determine their absence. We illustrate this point by reporting 2 cases of LBAC with small but distinct foci of active fibroblastic proliferation.     

Diagnosis and treatment of bronchioloalveolar carcinoma

PURPOSE OF REVIEW: Bronchioloalveolar carcinoma accounts for 5% of lung cancers, although histologically mixed bronchioloalveolar carcinoma and adenocarcinoma account for up to 20%. Bronchioloalveolar carcinoma histology is present in a majority of tumors found on lung-cancer screening by computed tomography. We review issues surrounding the diagnosis and treatment of bronchioloalveolar carcinoma, which often differs from other types of lung cancer. RECENT FINDINGS: A spectrum of disease from histologically pure bronchioloalveolar carcinoma to adenocarcinoma exists. The approach to treatment of diseases within this spectrum is still evolving. Evidence on the role of sub-lobar resection, resection of multifocal disease, and pulmonary transplantation is reviewed. We also discuss epidermal growth factor receptor tyrosine kinase inhibitors, and their role in patients with bronchioloalveolar carcinoma. SUMMARY: An understanding of recent developments in the diagnosis and treatment of patients with bronchioloalveolar carcinoma histology is important as early detection of lung cancer becomes more common. Ongoing clinical trials will provide important information on the role of limited resection. The use of epidermal growth factor receptor tyrosine kinase inhibitors should currently be limited to patients with advanced or recurrent disease who have failed cytotoxic chemotherapy. New targeted therapies are emerging for patients with bronchioloalveolar carcinoma histology.     

肺炎型细支气管肺泡癌6例临床分析

目的提高对肺炎型细支气管肺泡细胞癌(bronchioloalveolar carcinoma,BAC)的临床及影像学特点的认识。方法对2006年1月至2011年7月在巢湖市第一人民医院确诊的6例肺炎型BAC患者的临床症状、影像学特点、误诊情况等资料进行分析。结果 6例BAC患者男女各3例,年龄为47～78岁。6例中5例以咳嗽、咳痰为首发表现,其中咳大量泡沫痰2例,合并咯血1例,合并胸闷、呼吸困难2例。影像学检查主要表现为肺部实变及磨玻璃样影,位于周边部。2例经手术后标本病理确诊,4例经皮肺穿刺活检病理确诊。结论肺炎型BAC易误诊,咳嗽、咳痰为其主要症状,影像学检查以肺部实变影为主。经皮肺穿刺活检对肺炎型BAC诊断帮助较大。     

Uninodular bronchiolo-alveolar cancer. Apropos of 5 cases with a prolonged course

Five cases of uninodular bronchioloalveolar cell (BAC) carcinoma are reported. These 5 cases were characterized by the protracted course of the disease: 14.5 and 11.5 years respectively in the 2 patients who died; 7.5, 12 and 12.5 years respectively in the 3 patients who are still alive. Prior to being diagnosed at excision, the tumours had been followed up for an unusual 2 to 10 years period, with phases of radiological stability and phases of very slow growth. This very slow course is exceptional in lung cancer. It differs not only from the course of diffuse BAC carcinoma, but also from the habitual course of uninodular BAC carcinoma and from that of peripheral adenocarcinoma. Similar cases could be found in the literature, and a comparative study has been conducted between these slow-course carcinomas and normal-course carcinomas. Whatever their outcome, slow-course carcinomas are asymptomatic tumours which present at radiography of the chest as a peripheral round or oval opacity devoid of pathognomonic features. The post-operative prognosis of slow-course tumours seems to be more favourable than that of the other lung cancers. At histology, carcinomas with a protracted course usually show a pattern similar to that of lesions called by some authors "benign adenomatosis"; however, some of these tumours exhibit fairly distinct signs of malignancy, and electron microscopic images also are far from being uniform.     

Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours.

Human bronchioloalveolar carcinoma (BAC) is a lung cancer, morphologically similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary adenomatosis (SPA) or jaagsiekte. SPA is caused by an exogenous type B/D retrovirus (jaagsiekte sheep retrovirus (JSRV)), which prompted the present study to obtain evidence of a retrovirus in BAC. A panel of 249 human lung tumours, 21 nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other organs and a cell line expressing a human endogenous retrovirus protein was examined immunohistochemically using a rabbit antiserum directed against the JSRV capsid protein. Specific staining was detected only in the cytoplasm of recognizably neoplastic cells in the pulmonary alveoli of 39 of 129 (30%) BACs, 17 of 65 (26%) lung adenocarcinomas and two of seven large cell carcinomas. The remaining samples were negative. These results support the hypothesis that some human pulmonary tumours may be associated with a jaagsiekte sheep retrovirus-related retrovirus, warranting further studies.     

Seeking a home for a PET, part 2: Defining the appropriate place for positron emission tomography imaging in the staging of patients with suspected lung cancer

In patients who have a high likelihood of having lung cancer, there is little role for positron emission tomography (PET) imaging for diagnosis of the primary lesion. The primary impact of PET imaging is in extrathoracic staging, but it should not replace a clinical evaluation by a physician experienced in lung cancer. PET imaging is most useful for confirmation of the presumed extrathoracic stage in patients with intermediate stages of lung cancer. The role of PET imaging is limited in patients with strong clinical signs of metastatic disease, or in patients with a clinical stage I lung cancer and a negative clinical evaluation. With regard to intrathoracic staging, PET imaging has a definite role in communities in which mediastinoscopy is not available, whereas the impact is limited in institutions in which invasive mediastinal staging is available. The data suggest that a positive PET result in the mediastinum should be confirmed by biopsy. A mediastinoscopy is also reasonable in patients with clinical stage III lung cancer who have no mediastinal PET uptake. It is unclear and controversial whether a biopsy is needed in patients with clinical stage II lung cancer who have no PET uptake in the mediastinum.     

The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review

Background: Early detection trials with chest radiography and sputum cytology were ineffective in decreasing lung cancer mortality. The advent of low‐dose spiral chest computed tomography (LDCT) provided clinicians with a new tool that could be with early diagnosis; however, this also raised significant concerns regarding the systematic use of LDCT with its high false‐positive rate for benign nodules. At this time, there is limited information about the true role of PET (positron emission tomography) for early detection of lung cancer. Methods: We used systematic methods, including Preferred Reporting Items for Systematic reviews and Meta‐Analyses statement, to identify relevant studies, assess study eligibility, evaluate study methodological quality, and summarize findings regarding diagnostic accuracy and outcome. Results: In total, only seven eligible studies were selected from 82 potentially relevant studies. The sensitivity of 18F‐FDG‐PET for the detection of T1 lung cancers ranged between 68% and 95%. The rate of detection tended to be lower for carcinoid tumors, adenocarcinoma and bronchoalveolar cell carcinomas. FDG‐PET using SUV (standardized uptake value) level can predict the outcome of the screening detected lung cancer. A combination of FDG‐PET and LDCT may improve screening for lung cancer in high‐risk patients. Conclusions: PET or PET/CT may be used as a useful tool for early detection of lung cancer in high‐risk population based on the existing information. However, there is still limited information with regards to evidence of survival benefits from PET screening in high‐risk patients. Please cite this paper as: Chang C‐Y, Chang S‐J, Chang S‐C and Yuan M‐K. The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review. Clin Respir J 2013; 7: 1–6.     

A case of suspected lung metastasis of pancreatic carcinoma with bronchorrhea similar to bronchioloalveolar carcinoma]

There have been only a few reports of bronchorrhea in patients with metastatic pulmonary carcinoma. We report a case of suspected lung metastasis of pancreatic carcinoma with bronchorrhea, which was radiologically similar to bronchioloalveolar carcinoma. A 67-year-old man who had previously undergone surgical resection of pancreatic carcinoma was admitted because of a progressive cough producing copious amounts of serous sputum. A chest radiograph on admission revealed an infiltrative shadow with air bronchograms and ground glass opacities in the left middle and lower lung fields. A chest CT scan revealed a consolidative shadow with air bronchograms and bubble-like lucencies similar to bronchioloalveolar carcinoma in the left lower lobe. The histopathological features of the specimen obtained by transbronchial biopsy revealed adenocarcinoma with a pattern identical to that of the pancreatic carcinoma. Immunohistochemical staining with anti-SP-A antibody was entirely negative but those with anti-CA 19-9, Dupan 2 and CA 50 were positive in both lung and pancreatic tumors. These results strongly suggest that the pulmonary carcinoma was a metastasis of cystic adenocarcinoma of the pancreas. In summary, for a definitive diagnosis of bronchioloalveolar carcinoma, extrapulmonary adenocarcinoma as a primary site should first be ruled out.     

细支气管肺泡癌75例临床分析

目的 总结经病理证实的75例细支气管肺泡癌（BAC）的临床特征和诊断方法.方法 对我院2001年1月～2010年6月收治的75例BAC进行回顾性分析.结果 75例BAC患者男女比例为1∶1.34,平均年龄56.9岁,吸烟者占12％; CT检查58例表现为孤立结节型,8例为弥漫结节型,9例为炎症浸润型;26例患者行CT或超声引导下经皮肺穿刺活检,22例获得确诊,9例行支气管镜检查,仅1例确诊,52例为手术后组织活检确诊.结论 BAC的临床特征不同于其他类型肺癌,CT检查有助于BAC的诊断,而经皮肺穿刺活检则能提高BAC诊断的正确率.     

Bronchioloalveolar carcinoma masked by gravity-dependent gradient on computed tomography

A 78-year-old woman was found to have a small bronchioloalveolar carcinoma with ground-glass attenuation in the gravity-dependent gradient in the left lower lobe during a preoperative chest computed tomography (CT) evaluation, which was performed for previously-diagnosed adenocarcinoma of the right upper lobe. To remove the gravitational effect of the CT, the patient underwent a thin section CT in the prone position. Then, a ground-glass attenuation was revealed clearly in the left lower lobe. Postoperative pathological diagnosis was synchronous multiple bronchioloalveolar carcinomas, stage IA. This case suggests that focal areas of ground-glass attenuations on a thin-section CT in patients with BAC would be considered to be multicentric development of BAC. CT with the patient in the prone position helps to exclude the gravitational effect and narrow the differential diagnosis of ground-glass opacity, including localized forms of BAC.