Bronchioloalveolar cell carcinoma presenting as a "non-resolving consolidation" for two years.

Bronchioloalveolar carcinoma (BAC), a rare form of lung malignancy, is usually seen in non-smokers and women. Three distinct histological forms have been identified viz, mucinous, non-mucinous and mixed or indeterminate. The mucinous variety of BAC may present as a consolidation which is very difficult to differentiate from an infective pneumonia. We present a case of a middle aged female who was evaluated for a "non-resolving consolidation" for a period of two years. She had undergone an inconclusive bronchoscopy and had received several courses of antibiotics including anti-tuberculous therapy without relief. The size of the lesion had remained largely unchanged during this period and there was no significant clinical deterioration in the patient. Transbronchial biopsy done on presentation revealed BAC of the mucinous variety. BAC presenting as a large consolidation without significant change for a period of two years has rarely been documented in the literature.

[Difficulties in the radiodiagnosis of lung injuries in phthisiatric practice].

The paper describes clinical cases of concomitant lung and intrathoracic lymph node involvements as evidenced by conventional radiography and computed tomography (CT). It shows difficulties in the differential diagnosis of different nosological entities in pulmonary tuberculosis. The x-ray semiotics of concomitant lung injuries is also depicted.

The use of octreotide to manage symptoms of bronchorrhea: a case report.

Octreotide, a synthetic analogue of the hormone somatostatin, is primarily used in palliative medicine because of its antisecretory effect and has been shown to be effective in the management of bowel obstruction, nausea, and diarrhea. Octreotide also has been successfully used for the management of bronchorrhea in both inpatient and outpatient settings. We report the case of a 47-year-old female with a history of bronchioloalveolar cell carcinoma whose copious bronchial secretions were controlled with octreotide. Octreotide should be further evaluated as a first-line treatment for bronchorrhea.

Adenocarcinoma mucosecretor de pulmón con diseminación pleural que se manifiesta con neumotórax. Presentación de un caso clínico / Mucosecretor adenocarcinoma of the lung with pleural involvement presenting as a pneumothorax. Presentation of a clinical case

La asociación de un neumotórax y un carcinoma broncopulmonar es infrecuente y el diagnóstico es complicado. La sospecha clínica debe hacerse a partir de los hallazgos radiográficos y la existencia de factores de riesgo. Son discutidos los mecanismos implicados en la aparición del neumotórax en pacientes con neoplasias de pulmón, así como el significado clínico y la conducta diagnóstica y terapéutica recomendada en estos casos (AU)

The combination of a pneumothorax and lung cancer is rare and diagnosis is complex. Clinical suspicion of cancer must be based on radiological findings and the existence of risk factors. We discuss the mechanisms involved in the development of pneumothorax in patients with lung cancer, as well as the clinical significance, the recommended diagnostic approach, and therapeutic guidelines (AU)

A coupled discrete/continuum model for describing cancer-therapeutic transport in the lung.

We propose a computational simulation framework for describing cancer-therapeutic transport in the lung. A discrete vascular graph model (VGM) is coupled to a double-continuum model (DCM) to determine the amount of administered therapeutic agent that will reach the cancer cells. An alveolar cell carcinoma is considered. The processes in the bigger blood vessels (arteries, arterioles, venules and veins) are described by the VGM. The processes in the alveolar capillaries and the surrounding tissue are represented by a continuum approach for porous media. The system of equations of the coupled discrete/continuum model contains terms that account for degradation processes of the therapeutic agent, the reduction of the number of drug molecules by the lymphatic system and the interaction of the drug with the tissue cells. The functionality of the coupled discrete/continuum model is demonstrated in example simulations using simplified pulmonary vascular networks, which are designed to show-off the capabilities of the model rather than being physiologically accurate.

Severe bronchorrhea in a patient with bronchioloalveolar carcinoma.

Mucinous bronchioloalveolar carcinoma (BAC) can be associated with significant bronchorrhea. 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. We used azithromycin, scopolamine, and inhaled fluticasone with moderate success. The initiation of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, resulted in dramatic improvement in the volume of pulmonary secretions produced. The patient's EGFR mutation status was subsequently found to be negative, which supports the hypothesis that the mechanism of reduction of bronchorrhea is independent of the antiproliferative effect of the drug.

Prevalence and pattern of nodal metastasis in pT4 gingivobuccal cancers and its implications for treatment.

CONTEXT: The pattern of nodal spread in oral cancers is largely predictable and treatment of neck can be tailored with this knowledge. Most studies available on the pattern are from the western world and for early cancers of the tongue and floor of the mouth. AIMS: The present study was aimed to evaluate the prevalence and pattern of nodal metastasis in patients with pathologic T4 (pT4) buccal/alveolar cancers. SETTINGS AND DESIGN: Medical records of the patients with pT4 primary buccal and alveolar squamous cell carcinomas treated by single-stage resection of primary tumor and neck dissection at Gujarat Cancer and Research Institute (GCRI), Ahmedabad, a regional cancer center in India, during September 2004 to August 2006, were analyzed for nodal involvement. MATERIALS AND METHODS: The study included 127 patients with pT4 buccal/alveolar cancer. Data pertaining to clinical nodal status, histologic grade, pT and pN status (TNM classification of malignant tumors, UICC, 6th edition, 2002), total number of nodes removed, and those involved by tumor, and levels of nodal involvement were recorded. Statistical analysis was performed using the Chi-square test. RESULTS: Fifty percent of the patients did not have nodal metastasis on final histopathology. Occult metastasis rate was 23%. All of these occurred in levels I to III. Among those with clinically palpable nodes, level V involvement was seen only in 4% of the patients with pT4 buccal cancer and 3% of the patients with alveolar cancer. CONCLUSIONS: Elective treatment of the neck in the form of selective neck dissection of levels I to III is needed for T4 cancers of gingivobuccal complex due to a high rate of occult metastasis. Selected patients with clinically involved nodes could be well served by a selective neck dissection incorporating levels I to III or IV.

Non-mucinous and mucinous subtypes of adenocarcinoma with bronchioloalveolar carcinoma features differ by biomarker expression and in the response to gefitinib.

There is no optimal established therapy for treating advanced or recurrent adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC), and it remains unclear whether chemotherapy achieves therapeutic results comparable to those seen in the more common non-small lung carcinoma subtypes. In order to improve the decisions made during the treatment of advanced ADC-BAC, we attempted to better characterize the mucinous and non-mucinous ADC-BAC subtypes. Fifty pathological samples were obtained from 62 patients included in a multicenter prospective phase II trial (IFCT0401) conducted to evaluate gefitinib as a first-line therapy for non-resectable ADC-BAC. These samples were centrally reviewed and re-classified as non-mucinous (n=25) or mucinous (n=25) subtypes. We demonstrated that demographic data, clinical characteristics and stage at presentation (extrathoracic versus lung metastasis, as well as TNM staging) did not distinguish between the two subtypes. In contrast, three biological markers (PAS staining, TTF-1 expression and EGFR genomic gain combined with mutation analysis) enabled us to independently segregate all but 2 of the 50 patients into the mucinous and non-mucinous ADC-BAC subtypes. Finally, only mucinous tumors appeared to be resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Additional prospective studies are required to better approach therapeutic strategy in mucinous tumors, which are a distinct entity from non-mucinous tumors.

Major and prolonged response to pemetrexed in two cases of lung adenocarcinoma with bronchioloalveolar carcinoma features.

Bronchioloalveolar carcinoma (BAC) and adenocarcinoma mixed subtype with bronchioloalveolar features (ADC-WBF) represent a unique anatomo-clinical entity accounting for some 20% of non-small cell lung cancers (NSCLC). These tumors seem less sensitive to chemotherapy than other NSCLC. We report two cases of advanced ADC-WBF treated with second-line and fourth-line pemetrexed. Major and durable radiological response associated with clinical and functional improvement was achieved in both patients, without important drug toxicity. After treatment arrest, the two patients experienced progressive disease but responded to retreatment with pemetrexed. Recent data suggest that paclitaxel-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors could be an acceptable therapeutic strategy in unresectable CBA and ADC-WBF. The cases reported here and preclinical findings suggest a therapeutic efficacy of pemetrexed in these tumors. Prospective studies are required to evaluate this hypothesis.

Curative wedge resection for non-invasive bronchioloalveolar carcinoma.

Pure bronchioloalveolar carcinomas have no stromal, vascular or pleural invasion, and they are candidates for curative wedge resection, although standard operative procedure for lung cancer is a pulmonary lobectomy. Most lung cancers with ground glass opacity (GGO), namely faint homogeneous shadows with sharp margin, are pure bronchioloalveolar carcinomas. This report presents the results of a pilot study on wedge resection with candidate selection by high-resolution computed tomography and positron emission tomography with 18F-fluorodeoxyglucose (FDG). The criteria for wedge resection were; 1) clinically no nodal or distant metastasis, 2) the location of the tumor was peripheral enough to undergo wedge resection, 3) the diameter of the shadow was 8-20 mm, 4) GGO% (diameter of GGO area/diameter of whole tumor) was 80% or over, 5) FDG uptake of the tumor was less than that of the mediastinum, 6) the intraoperative pathological diagnosis was non-invasive bronchioloalveolar carcinoma, and 7) informed consent was obtained. Nine tumors from 8 patients were selected in the study. The maximum diameter of the tumors was 9-18 mm and GGO% was 82-100%. All of nine tumors were treated with a wedge resection under video-assisted thoracic surgery. The postoperative courses were uneventful and no recurrence has been detected after 19-50-month follow-up. The changes in pulmonary function before and after the surgery were minimal. In conclusion, wedge resections were safely performed without any recurrence, and the postoperative pulmonary function was well preserved, suggesting the advantage of wedge resections for non-invasive bronchioloalveolar carcinomas.

2007 Annual Meeting of the National Lung Cancer Partnership: a summary of meeting highlights.

This report presents highlights from The National Lung Cancer Partnership's Annual Meeting, held in June 2007 in Chicago. It discusses recent refinements in the histologic, genetic, and epigenetic subtyping of lung cancers and suggests reasons why certain therapies benefit only a subset of lung cancer patients. It also describes new molecular data about the subtype-specific differences in drug resistance among bronchioloalveolar-associated non-small cell lung cancers and discusses strategies to avoid or tackle specific drug-resistant tumors. Finally, it describes new findings about epigenetic differences-specifically in DNA hypermethylation-among lung tumors, including some male/female differences, which may prove useful as biomarkers for diagnosis, prognosis, and prediction of response to treatments.

BAC consensus conference, November 4-6, 2004: epidemiology, pathogenesis, and preclinical models.

INTRODUCTION: Human bronchioloalveolar carcinoma (BAC) is a disease with an evolving definition. "Pure" BAC, characterized by a bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion, represents only 2 to 6% of non-small cell lung cancer (NSCLC) cases, but up to 20% of NSCLC cases may contain elements of BAC. This imprecise definition makes it difficult to perform epidemiologic analyses or to generate accurate animal models. However, because BAC appears to behave clinically differently from adenocarcinoma, a better understanding of this disease entity is imperative. METHODS/RESULTS: At the BAC Consensus Conference in 2004, our committee discussed issues relevant to BAC epidemiology, pathogenesis, and preclinical models. CONCLUSIONS: Elucidation of molecular events involved in BAC tumorigenesis will allow for more precise epidemiologic studies and improved animal models, which will enable development of more effective treatments against the disease.

Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lung.

The authors investigated the protein expression of double-stranded RNA-activated protein kinase (PKR), which was identified by using a previous cDNA microarray study, to discover PKR's correlations with several pathological parameters and to elucidate its role in neoplastic transformation and progression of lung adenocarcinomas. Immunohistochemistry for PKR was performed and a semiquantitative scoring method was calculated based on staining intensity and percentage of immunoreactive tumor cells (high vs low) for one bronchioloalveolar carcinoma (BAC), 16 adenocarcinomas consisting of BAC and invasive carcinoma (mixed) and 21 invasive adenocarcinomas without BAC (invasive). The BAC had high-grade expression and the mixed type tended to more frequently show high-grade expression than the invasive type (P = 0.028). There were no significant associations with age, tumor size, lymph node metastasis, lymphovascular invasion or the pathological stage. The Kaplan-Meier survival curves demonstrated that the patients with high-grade PKR expression had significantly shorter survival periods than those patients with low-grade PKR expression (P = 0.018). These results do not support the concept of PKR as a tumor suppressor in small-size peripheral adenocarcinomas of the lung.

Sublobar resection for the subcentimeter pulmonary nodule.

Several studies have demonstrated an increased local recurrence rate with sublobar resection (SR) when compared with lobar resection for the treatment of non-small-cell lung cancer (NSCLC). Therefore, lobectomy has remained the gold standard therapy for NSCLC with lesser resection reserved as a compromise operation for high-risk patients. The increased identification of small NSCLC tumors by CT scan is leading many surgeons to question the appropriateness of lobectomy for these tumors. There has been increasing interest by many surgeons to use SR as intentional therapy for patients with small peripheral NSCLC. This article reviews the recent literature and evidence supporting intentional SR for NSCLC. Although lobectomy should continue to be regarded as the procedure of choice for NSCLC, we believe that a subset of patients with favorable characteristics may be appropriately treated with intentional SR as long as good assessment of nodal involvement is made. Future investigation is required to better define when SR is appropriate.

Mutations of the epidermal growth factor receptor gene in atypical adenomatous hyperplasia and bronchioloalveolar carcinoma of the lung.

A hypothesis of multistep carcinogenesis of lung adenocarcinoma from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma through bronchioloalveolar carcinoma (BAC) has been proposed. However, the genetic alterations that play a role during these processes are not yet clear. Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in lung adenocarcinoma. We examined the status of EGFR mutations in AAH and BAC to elucidate the role they play during multistage of lung adenocarcinoma. We found somatic EGFR mutations in 3% (1/35) of AAH, 10.8% (4/37) of BAC and 41.9% (13/31) of invasive adenocarcinoma. Sixteen of 18 EGFR mutations were found in exon 19 and two were in exon 21. Among the 16 EGFR mutations in exon 19, 13 were deletions of 15bp and one was an insertion/duplication of 18bp. Mutations of the K-ras gene were detected in 26.7% (8/30) of AAH, 16.7% (5/30) of BAC and 10% (3/30) of invasive adenocarcinoma. None of the tumors with EGFR mutations had K-ras mutation simultaneously. Patients who had invasive adenocarcinoma with EGFR mutations were younger than those without mutations (60.6 versus 67.4 years, p=0.03). These results suggest that tumors with EGFR mutations may progress more rapidly and develop into invasive cancer faster than those without mutations. Alternatively it is also possible that some invasive adenocarcinomas with EGFR mutations may not follow the AAH-adenocarcinoma sequence. We analyzed 24 patients with multiple lung lesions and 13 patients had at least one lesion that had either an EGFR or K-ras mutation. In all cases each lesion had a different mutation status. This finding suggests that the genetic alterations responsible for the development of lung adenocarcinoma occur randomly even under exposure to the same carcinogen.

Epidermal growth factor receptor, HER-2/neu and related pathways in lung adenocarcinomas with bronchioloalveolar features.

Lung adenocarcinomas with bronchioalveolar features (ABAF), formerly called bronchioloalveolar cancers (BAC), constitute a distinct clinical, radiological and pathological entity among lung malignancies. Epidermal growth factor receptor (EGFR) and to a less extent, HER-2/neu, are known to be overexpressed in non-small lung cancers, but their exact status in ABAF is not well-documented. Stimulation of these two receptors results in the initiation of two major cascades, namely phosphatidylinositol 3-kinase (PI-3K) and Ras-dependent pathways. We have therefore studied the expressions of EGFR, HER-2/neu as well as phosphorylated AKT (pAKT) and phosphorylated extracellular-signal regulated kinase (ERK), which are key molecules in these two pathways, in 15 ABAF patients. EGFR was found to be overexpressed in 9 of 15 patients (60%). HER-2/neu overexpression was detected in 6 of the 14 tumors tested (43%). pAKT and pERK were both found to be positive in 13 of 15 patients (87%). Six of the seven tumors with mucinous pattern were negative for EGFR, while all of the other eight cases were positive (P=0.001). Mucinous tumors were also less likely than non-mucinous tumors to overexpress HER-2/neu (17% versus 63%, respectively). These findings suggest that ABAF, particularly those with non-mucinous histology, commonly harbors EGFR and HER-2/neu overexpression. PI-3K and Ras-dependant pathways that lie downstream are generally activated, even in the absence of EGFR and/or HER-2/neu overexpression. ABAF may be a particularly promising candidate for EGFR-targeted strategies and this possibility merits extensive evaluation in clinical trials.

Prompt control of bronchorrhea in patients with bronchioloalveolar carcinoma treated with gefitinib (Iressa).

Bronchorrhea is a condition in which voluminous sputum is produced daily, typically seen with bronchioloalveolar cell carcinoma (BAC). Unless the underlying cancer can be controlled, bronchorrhea causes substantial symptomatic distress. We report two cases of bronchorrhea associated with advanced BAC successfully treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib. Prompt resolution of these patients' bronchorrhea, dyspnea, and supplemental oxygen requirements are detailed. Given the limited success of alternative interventions, a trial of gefitinib should be considered for patients with bronchorrhea secondary to BAC.