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Bronchioloalveolar Carcinoma

Terminal Bronchiolar Carcinoma

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].

Fever
  • We present the case of a 61-year-old patient with fever, dry cough, bilateral patchy consolidation and high erythrocyte sedimentation rate. Open lung biopsy shows coexistence of BOOP and bronchioloalveolar carcinoma.[ncbi.nlm.nih.gov]
  • Her clinical history was remarkable for an intermittent dry cough since the age of 2, with recurrent episodes of purulent sputum and fever.[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.[radiographics.rsnajnls.org]
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]
  • […] congenital pulmonary airway malformation cystic adenomatoid malformation CASE HISTORY A 6-yr-old male presented in 1988 with recurrent episodes of fever, left-sided pleuritic chest pain, cough with significant bronchorrhea, intermittent haemoptysis, fatigue[erj.ersjournals.com]
  • Early symptoms may include: lingering or worsening cough coughing up phlegm or blood chest pain that worsens when you breathe deeply, laugh, or cough hoarseness shortness of breath wheezing weakness and fatigue loss of appetite and weight loss You might[healthline.com]
Painter
  • The present patient had been painter, and metals of carcinogens were proven in both tissue of COP and BAC. Here, we reported a painter with COP and new-onset BAC who had been exposed to particles proven by elemental analysis.[ncbi.nlm.nih.gov]
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]
  • We present the case of a 61-year-old patient with fever, dry cough, bilateral patchy consolidation and high erythrocyte sedimentation rate. Open lung biopsy shows coexistence of BOOP and bronchioloalveolar carcinoma.[ncbi.nlm.nih.gov]
  • Her clinical history was remarkable for an intermittent dry cough since the age of 2, with recurrent episodes of purulent sputum and fever.[ncbi.nlm.nih.gov]
  • 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.[radiographics.rsnajnls.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]
  • Prevalence and incidence of benign asbestos pleural effusion in a working population. JAMA 1982;247:617-622. ‎[books.google.it]
  • 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]
  • It is often a parenchymal peripheral lesion, occasionally involving the pleura, with or without an associated pleural effusion.[erj.ersjournals.com]
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]
  • Despite the administration of a macrolide and corticosteroid, sputum volume increased to 700 mL/d in case 1 and to 200 mL/d in case 2 and hypoxemia and dyspnea deteriorated.[ncbi.nlm.nih.gov]
  • Prompt resolution of these patients' bronchorrhea, dyspnea, and supplemental oxygen requirements are detailed.[ncbi.nlm.nih.gov]
  • The reduction in the sputum volume was associated with alleviation of dyspnea and hypoxemia.[ncbi.nlm.nih.gov]
  • CASE: A 35-year-old male with a 12-year history of PSS presented with exertional dyspnea and pain in the left side of the chest.[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]
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]
Urticaria
  • We report here a unique and initial urticaria on a patient, lasting for 6 months, who finally was diagnosed as early stage bronchioloalveolar carcinoma (T1aN0M0). After treatment of surgery, the symptom of urticaria disappeared and did not recur.[ncbi.nlm.nih.gov]
Vaginal Bleeding
  • 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]
Forgetful
  • In conclusion, to investigate the primary site of a metastatic ovarian cancer, clinicians should not forget the lungs since the incidence of lung cancer in females is increasing.[ncbi.nlm.nih.gov]
Ataxia
  • Genes overexpressed in adenocarcinoma with bronchioloalveolar features included fibroblast growth factor receptor 1, and CLDN18 (claudin 18), whereas those overexpressed in BAC included ataxia telangiectasia and Rad3 related (ataxia telangiectasia mutated[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 Abnormal
  • Case report This was a case report of a 53-year-old woman who admitted in Al-Zahra Hospital due to chest X-ray abnormality founded during evaluation of weight loss and headache [Figure 1]. There was no history of dyspnea, chills or fever.[advbiores.net]
Chest X-Ray Abnormal
  • Case report This was a case report of a 53-year-old woman who admitted in Al-Zahra Hospital due to chest X-ray abnormality founded during evaluation of weight loss and headache [Figure 1]. There was no history of dyspnea, chills or fever.[advbiores.net]
Bilateral 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]
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 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]
Anisocytosis
  • Positive likelihood ratios allowed for identification of the 5 most useful pathologic features for the diagnosis of AC: multiple growth patterns, anisocytosis, atypia more than 75%, macronucleoli, and atypical mitoses.[ncbi.nlm.nih.gov]
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]
  • Prevalence and incidence of benign asbestos pleural effusion in a working population. JAMA 1982;247:617-622. ‎[books.google.it]
  • 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]
  • It is often a parenchymal peripheral lesion, occasionally involving the pleura, with or without an associated pleural effusion.[erj.ersjournals.com]

Treatment

  • Surgery and surveillance were reasonable treatment options for selected patients. The precise roles of the various treatment strategies for multifocal BAC require further evaluation.[ncbi.nlm.nih.gov]
  • 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]
  • Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies.[ncbi.nlm.nih.gov]
  • No tumor marker has been validated in the diagnosis and follow-up of lung cancer, in particular to predict the outcome of treatment with EGFR inhibitors.[ncbi.nlm.nih.gov]
  • Following more than 8 months of treatment, no evidence of recurrence or severe adverse events has been observed.[ncbi.nlm.nih.gov]

Prognosis

  • Methylation of the MDR1 promoter may be mediated through pathways other than DNMT1 in BAC and does not appear to be associated with disease progression or patient prognosis.[ncbi.nlm.nih.gov]
  • Small ( 0.5 cm) invasive foci have little impact on the good prognosis associated with low-stage tumors.[ncbi.nlm.nih.gov]
  • 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]
  • […] the maximum standard uptake value of positron emission tomography-computed tomography in patients of pulmonary adenocarcinoma with bronchioloalveolar carcinoma features and whether SUVmax correlates with pathological status, lymph node metastasis, and prognosis[ncbi.nlm.nih.gov]
  • There are three subtypes of BAC and the symptoms and prognosis of the disease depend on the subtype and extent of disease, but are generally similar to other histologic types of NSCLC.[doi.org]

Etiology

  • The etiology of this disease is unclear, but multiple environmental insults have been implicated.[doi.org]
  • A lengthy infectious disease and autoimmune workup failed to reveal the etiology or produce benefit. Expert pathology review raised the possibility of pure bronchioloalveolar carcinoma.[ncbi.nlm.nih.gov]
  • Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches.[ncbi.nlm.nih.gov]

Epidemiology

  • This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC.[ncbi.nlm.nih.gov]
  • The impact of the 1999 WHO classification on the epidemiology of BAC has been investigated by others.[doi.org]
  • BAC is a form of adenocarcinoma with unique clinical, radiological, and epidemiological features.[ncbi.nlm.nih.gov]
  • Some epidemiologic studies report a significant increase in the incidence of BAC.[ncbi.nlm.nih.gov]
  • Further epidemiologic investigation is needed to elucidate the etiology and pathogenesis of this unique disease.[doi.org]
Sex distribution
Age distribution

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]
  • […] 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]
  • Smoking is known to cause an up-regulation of oncogenes and a down-regulation of tumor suppressor genes, and this may play a part in the pathophysiologic mechanisms.[web.archive.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]
  • Emphasis is also given to early detection, screening, prevention, and new imaging techniques.[books.google.es]
  • , 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]
  • Central to this approach that are essential for normal and aberrant cell is the endocrine control of breast development, the growth, have been major contributors to the therapy relationship of cell proliferation with the presence of and prevention of[books.google.es]

References

Article

  1. Thompson WH. Bronchioloalveolar carcinoma masquerading as pneumonia. Respir Care. 2004 Nov;49(11):1349-53.
  2. 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.
  3. Gardiner N, Jogai S, Wallis A. The revised lung adenocarcinoma classification—an imaging guide. J Thorac Dis. 2014;6(Suppl 5):S537-S546.
  4. Yatabe Y, Borczuk AC, Powell CA. Do all lung adenocarcinomas follow a stepwise progression? Lung cancer. 2011;74(1):7-11.
  5. 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.
  6. Sardenberg RAS, Mello ES, Younes RN. The lung adenocarcinoma guidelines: what to be considered by surgeons. J Thorac Dis. 2014;6(5):S561-S567.
  7. 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.

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Last updated: 2019-07-11 20:18