Bronchioalveolar carcinoma, recently replaced by the terms pulmonary adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), is considered a premalignant lesion. The clinical presentation is nonspecific, with organ-related symptoms of chest pain and cough. Both laboratory and radiographic findings may point toward the diagnosis. A biopsy is usually needed to make a definite confirmation.
Presentation
Until recently, bronchioalveolar carcinoma (BAC) encompassed various premalignant lesions of pulmonary adenocarcinoma that develops from the epithelium of the terminal bronchioles and their acini at the peripheries of the lung and was distinguished by the absence of blood vessel or pleural involvement (also known as lepidic growth) [1] [2]. Because of its poor histological and radiographic specificity, bronchioalveolar carcinoma was recently replaced with the terms pulmonary adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), with mucinous, non-mucinous and mixed forms as subtypes of both lesions [2] [3] [4] [5] [6]. In addition, subtypes of invasive adenocarcinoma (lepidic predominant adenocarcinoma - LPA, and invasive mucinous adenocarcinoma) are also terms that have arisen from BAC [3]. One of the most important features of BAC is that its clinical presentation, comprised of a cough, chest pain and the production of sputum, can have a broad differential diagnosis (infections, hypersensitivity pneumonitis, etc.) [1]. The absence of fever, however, which is never seen in BAC, should point toward a noninfectious etiology [1]. Unfortunately, more than 60% of patients have no apparent symptoms, thus the diagnosis might be difficult to make [1]. But because BAC is a premalignant lesion and because 5-year survival rates are 100% if appropriate therapy is implemented early on, usually in the form of surgical resection, recognition of these lesions is vital in limiting its progression to a malignant tumor, which then carries a significantly poor prognosis regardless of the stage [6] [7].
Entire Body System
- Fever
The most frequent symptoms and signs are cough, sputum, shortness of breath, weight loss, hemoptysis, and fever. Bronchorrhea is unusual and a late manifestation. [ncbi.nlm.nih.gov]
- Fatigue
Grade 3 diarrhea and fatigue were noted in three and five patients, respectively. [ncbi.nlm.nih.gov]
Paraschiv and partners published a case in the Letters to the Editor section. 1 These authors describe a case of a male, 35-year smoker with a 35 pack-year history, consulting with symptoms of fatigue, cough and chest pain of 2-week duration. [archbronconeumol.org]
Since they are located in the outer regions of the lungs away from the airways, however, these "typical symptoms" may be less common, and symptoms such as shortness of breath with exertion or profound fatigue may first be noted. [verywellhealth.com]
Respiratoric
- Cough
The clinical presentation is nonspecific, with organ-related symptoms of chest pain and cough. Both laboratory and radiographic findings may point toward the diagnosis. A biopsy is usually needed to make a definite confirmation. [symptoma.com]
Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. [ncbi.nlm.nih.gov]
The most frequent symptoms and signs are cough, sputum, shortness of breath, weight loss, hemoptysis, and fever. Bronchorrhea is unusual and a late manifestation. [doi.org]
- Pleural Effusion
PATIENTS AND METHODS: Patients with histologically confirmed stage IIIB (with malignant pleural effusion) or stage IV adenocarcinoma with BAC features or pure BAC were eligible. [ncbi.nlm.nih.gov]
No pleural effusions or evidence of mediastinal adenopathy. Sputum, right and left main bronchus lavage were positive for malignant cells consistent with carcinoma. [radiopaedia.org]
Thoracocentesis and pleural fluid cytology are indicated in patients with pleural effusions. [lungindia.com]
effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor], any N, M0) Stage IV disease (any T, any N, M1 [distant metastases present]) Recurrent disease in a separate lobe after prior resection within the past [clinicaltrials.gov]
Prevalence and incidence of benign asbestos pleural effusion in a working population. JAMA 1982;247:617-622. [books.google.it]
- Dyspnea
A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. [ncbi.nlm.nih.gov]
- Productive Cough
She just mentioned productive cough since about 6 months ago. History taking revealed neither inhalation exposure nor hemoptysis. Weight loss was about 15 kg during recent 3 months. [advbiores.net]
She gradually developed productive cough and dyspnea since July 2001. Chest CT on June 25, 2002 revealed multiple pneumonia-like consolidations on each lobe of the right lung (Fig. 1 ). [wjso.biomedcentral.com]
cough with bronchorrhea and/or dyspnea caused by “shunting” of blood. [hematologyandoncology.net]
- Rales
On referral to our hospital, he was cachectic, with scleral icterus, asterixis, fetor hepaticus, and rales in the base of the right lung. He had ascites without abdominal organomegaly or masses. His palms and soles had hyperkeratotic [jamanetwork.com]
Gastrointestinal
- Pelvic Mass
Four years later, she complained of vaginal bleeding, and a pelvic mass was discovered by an abdominal computerized tomography scan. Tumor debulking and total hysterectomy with bilateral salpingo-oopherectomy were performed. [ncbi.nlm.nih.gov]
Workup
Premalignant lesions of the lungs can only be detected with a comprehensive approach, starting with a detailed patient history and a complete physical examination that could possibly identify an ongoing pathological process in the lungs. As signs and symptoms are often lacking, however, imaging studies, a full laboratory workup, and pathohistological evaluation are necessary steps. The absence of leukocytosis in the presence of respiratory symptoms can often exclude pneumonia and other infectious processes [1]. Conversely, the use of imaging procedures provides essential clues in making a presumptive diagnosis [1]. Recent reports have established that BAC (or all of its newly described variants) appears as a solitary nodule ranging from 5-30 mm in diameter, although lobar, multilobar or even patchy infiltrates may be seen on plain radiography or computed tomography (CT), suggesting its multicentric development in some patients [1] [3] [5] [6]. CT is often preferred to chest X-rays, as it provides a better view of the lung parenchyma, but a biopsy of the lesion is often necessary, especially when inconclusive findings are seen on CT [5]. Thus, the diagnosis of BAC (now called AIS or MIA) now rests on radiographic criteria, but more importantly, on a proper histopathological examination [5] [6].
X-Ray
- Pulmonary Infiltrate
A 52-year-old woman with human immunodeficiency virus (HIV) developed weight loss, cough, and breathing difficulties, accompanied by extensive bilateral pulmonary infiltrates. [ncbi.nlm.nih.gov]
- Bilateral Pulmonary Infiltrates
A 52-year-old woman with human immunodeficiency virus (HIV) developed weight loss, cough, and breathing difficulties, accompanied by extensive bilateral pulmonary infiltrates. [ncbi.nlm.nih.gov]
- X-Ray Abnormal
According to chest X-ray finding a lung scan computed tomography (CT) was done [Figure 2] and [Figure 3]. [advbiores.net]
- Chest X-Ray Abnormal
According to chest X-ray finding a lung scan computed tomography (CT) was done [Figure 2] and [Figure 3]. [advbiores.net]
- Bilateral Pulmonary Opacities
In 7 patients the chest radiography revealed multiple bilateral pulmonary opacities, with air bronchogram and tendency to necrosis at 1. One patient had 2 pulmonary nodules. [erj.ersjournals.com]
Pleura
- Pleural Effusion
PATIENTS AND METHODS: Patients with histologically confirmed stage IIIB (with malignant pleural effusion) or stage IV adenocarcinoma with BAC features or pure BAC were eligible. [ncbi.nlm.nih.gov]
No pleural effusions or evidence of mediastinal adenopathy. Sputum, right and left main bronchus lavage were positive for malignant cells consistent with carcinoma. [radiopaedia.org]
Thoracocentesis and pleural fluid cytology are indicated in patients with pleural effusions. [lungindia.com]
effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor], any N, M0) Stage IV disease (any T, any N, M1 [distant metastases present]) Recurrent disease in a separate lobe after prior resection within the past [clinicaltrials.gov]
Prevalence and incidence of benign asbestos pleural effusion in a working population. JAMA 1982;247:617-622. [books.google.it]
Treatment
Surgical treatment is the best option for selected BAC patients. Survival is associated with the treatment modality. Larger scale studies are necessary to confirm these findings. [ncbi.nlm.nih.gov]
Prognosis
The prognosis and staging of multifocal disease remain unresolved, as does the question of whether a small amount of invasion adversely affects prognosis. [ncbi.nlm.nih.gov]
They believed that, with early diagnosis and treatment, the prognosis was at least as good as for other forms of bronchogenic carcinoma. [pubs.rsna.org]
Etiology
The etiology of this disease is unclear, but multiple environmental insults have been implicated. [ncbi.nlm.nih.gov]
Epidemiology
The impact of the 1999 WHO classification on the epidemiology of BAC has been investigated by others. [doi.org]
Department of Epidemiology UCLA School of Public Health Los Angeles USA 9. Cancer Research Center of Hawaii University of Hawaii Honolulu USA 10. Department of Epidemiology University of Michigan Ann Arbor USA 11. [link.springer.com]
This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC. [ncbi.nlm.nih.gov]
Pathophysiology
[…] atypical alveolar cell hyperplasia, alveolar intraepithelial neoplasia, well differentiated bronchioloalveolar carcinoma of Clara cell type / type II pneumocyte type Adenocarcinoma in situ: preinvasive lesion > 0.5 cm Sites Peripheral lung parenchyma Pathophysiology [pathologyoutlines.com]
[…] associated with a K-Ras mutation Non-Mucinous BAC: More common More often seen in smokers Originate from the terminal respiratory cells, type II pneumocytes, and Clara cells Presents usually as a ground glass opacity Frequently associated with EFGR mutations Pathophysiology [wikidoc.org]
Pathophysiology Both exposure (environmental or occupational) to particular agents and an individual’s susceptibility to these agents are thought to contribute to one’s risk of developing lung cancer. [emedicine.medscape.com]
Prevention
A 46-year-old man presented with BAC with 2,000 mL of sputum production on a daily basis, which prevented him from being extubated. As this condition is rare, there are only case reports outlining the therapy for the associated bronchorrhea. [ncbi.nlm.nih.gov]
Also discussed are the cancer-preventive effects of vitamins, lipids, carotenoids, flavonoids, and other components of diet. [books.google.es]
Reconstitution Instructions These slides are paraffin coated to prevent sample oxidization, it is recommended that slides are first de-paraffinized by baking at 62 degrees C for 1 hour in a vertical orientation prior to performing antigen retrieval procedures [novusbio.com]
Sunghun Na, +9 authors Seok-Ho Hong Published 2017 in The Korean journal of physiology & pharmacology… DOI: 10.4196/kjpp.2017.21.2.161 Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing [semanticscholar.org]
References
- Thompson WH. Bronchioloalveolar carcinoma masquerading as pneumonia. Respir Care. 2004 Nov;49(11):1349-53.
- Garfield DH, Cadranel JL, Wislez M, Franklin WA, Hirsch FR. The bronchioloalveolar carcinoma and peripheral adenocarcinoma spectrum of diseases. J Thorac Oncol. 2006;1(4):344-359.
- Gardiner N, Jogai S, Wallis A. The revised lung adenocarcinoma classification—an imaging guide. J Thorac Dis. 2014;6(Suppl 5):S537-S546.
- Yatabe Y, Borczuk AC, Powell CA. Do all lung adenocarcinomas follow a stepwise progression? Lung cancer. 2011;74(1):7-11.
- Tang ER, Schreiner AM, Pua BB. Advances in lung adenocarcinoma classification: a summary of the new international multidisciplinary classification system (IASLC/ATS/ERS). J Thorac Dis. 2014;6(5):S489-S501.
- Sardenberg RAS, Mello ES, Younes RN. The lung adenocarcinoma guidelines: what to be considered by surgeons. J Thorac Dis. 2014;6(5):S561-S567.
- Jiang L, Yin W, Peng G, et al. Prognosis and status of lymph node involvement in patients with adenocarcinoma in situ and minimally invasive adenocarcinoma—a systematic literature review and pooled-data analysis. J Thorac Dis. 2015;7(11):2003-2009.