Intrapulmonary Spread Research Articles

ASO Visual Abstract: Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

ASO Visual Abstract: Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

Invasive mucinous adenocarcinoma (IMA) is distinct from non-mucinous adenocarcinoma, but studies on recurrent IMA are scarce. Thus, this study aimed to evaluate the recurrence patterns of IMA and the role of pulmonary local therapy (LT) in resectable pulmonary recurrence of IMA. The study reviewed 403 patients with surgically resected IMA between 1998 and 2018. The recurrence patterns were categorized as solitary pulmonary recurrence (SPR), multiple pulmonary recurrence (MPR), and extra-pulmonary recurrence (EPR). The clinicopathologic characteristics, overall survival (OS), and post-recurrence survival (PRS) were analyzed according to the recurrence pattern and LT administration. Recurrences were found in 91 (22.6%) patients, including 18 patients with SPR, 37 patients with MPR, and 36 patients with EPR. Compared with the MPR and EPR groups, the SPR group had a longer disease-free interval (32.5 vs. 9.6 vs. 10.1 months, respectively; p < 0.01) and a better OS (5-year OS: 88.5%, 41.5%, and 22.9%, respectively; p < 0.01). In case of resectable pulmonary recurrence, pulmonary LT was administered to 15 patients with SPR and 3 patients with MPR. These patients showed a better 5-year PRS than the other patients with pulmonary recurrence (86.3% vs. 30.4%; p < 0.01). Notably, long-term survival was observed for one patient with MPR undergoing LT and two patients with SPR undergoing a second LT for a second pulmonary recurrence. In this series, the patients with recurrent IMA showed different prognoses according to the recurrence pattern. The patients with pulmonary recurrence of IMA undergoing LT showed a favorable prognosis, suggesting the potential role of LT for resectable pulmonary recurrence of IMA.

Genomic characteristics of invasive mucinous adenocarcinoma of the lung with multiple pulmonary sites of involvement

Invasive mucinous adenocarcinoma (IMA) of the lung frequently presents with diffuse pneumonic-type features or multifocal lesions, which are regarded as a pattern of intrapulmonary metastases. However, the genomics of multifocal IMAs have not been well studied. We performed whole exome sequencing on samples taken from 2 to 5 regions in seven patients with synchronous multifocal IMAs of the lung (24 regions total). Early initiating driver events, such as KRAS, NKX2-1, TP53, or ARID1A mutations, are clonal mutations and were present in all multifocal IMAs in each patient. The tumor mutational burden of multifocal IMAs was low (mean: 1.13/mega base), but further analyses suggested intra-tumor heterogeneity. The mutational signature analysis found that IMAs were predominantly associated with endogenous mutational process (signature 1), APOBEC activity (signatures 2 and 13), and defective DNA mismatch repair (signature 6), but not related to smoking signature. IMAs synchronously located in the bilateral lower lobes of two patients with background usual interstitial pneumonia had different mutation types, suggesting that they were double primaries. In conclusion, genomic evidence found in this study indicated the clonal intrapulmonary spread of diffuse pneumonic-type or multifocal IMAs, although they can occur in multicentric origins in the background of usual interstitial pneumonia. IMAs exhibited a heterogeneous genomic landscape despite the low somatic mutation burden. Further studies are warranted to determine the clinical significance of the genomic characteristics of IMAs in expanded cohorts.

Invasive Mucinous Adenocarcinomas With Spatially Separate Lung Lesions: Analysis of Clonal Relationship by Comparative Molecular Profiling

IntroductionPulmonary invasive mucinous adenocarcinomas (IMAs) often present with spatially separate lung lesions. Clonal relationship between such lesions, particularly those involving contralateral lobes, is not well established. Here, we used comparative genomic profiling to address this question. MethodsPatients with genomic analysis performed on two IMAs located in different lung regions were identified. Molecular assays included DNA-based next-generation sequencing (NGS) for 410 to 468 genes (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets), RNA-based NGS for 62 genes (Memorial Sloan Kettering-Fusion), or non-NGS assays. ResultsComparative genomic profiling was performed on two separate IMAs in 24 patients, of whom 19 had contralateral lesions. Tumors from all but one patient shared matching driver alterations, including KRAS (n = 19), NRG1 (n = 2), ERBB2 (n = 1) or BRAF (n = 1). In addition, in patients with paired tumors profiled by NGS (n = 12), shared driver alterations were accompanied by up to 4 (average 2.6) other identical mutations, further supporting the clonal relationship between the tumors. Only in a single patient separate IMAs harbored entirely nonoverlapping mutation profiles, supporting clonally unrelated, distinct primary tumors. Notably, in a subset of patients (n = 3), molecular testing confirmed a clonal relationship between the original resected IMAs and subsequent contralateral IMA presenting after an extremely long latency (8.1–11.7 y). ConclusionsComparative molecular profiling supports that nearly all separate pulmonary IMA lesions represent intrapulmonary spread arising from a single tumor and documents a subset with a remarkably protracted course of intrapulmonary progression. This study reinforces the unique biology and clinical behavior of IMAs while further highlighting the value of genomic testing for clarifying the clonal relationship between multiple lung carcinomas.

FROM BAD TO WORSE: A CASE OF MALIGNANT TRANSFORMATION OF RESPIRATORY PAPILLOMATOSIS TO SQUAMOUS CELL CANCER OF THE LUNG IN AN HIV-POSITIVE PATIENT

SESSION TITLE: Lung Pathology 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a rare disease manifested by the presence of numerous papillomas within the larynx and tracheobronchial tree. Etiologically derived from human papilloma virus (HPV), primarily from serotypes 6 and 11, RRP has a course with a wide spectrum of possibilities including spontaneous regression to malignant transformation. CASE PRESENTATION: A 57-year-old African American male with a 30 pack-year smoking history and medical history of HIV (on ARVs) and tracheobronchial papillomatosis presented as a walk-in to the pulmonary clinic for complaints of hemoptysis, weight loss and fatigue. The physical exam was significant for coarse breath sounds and inspiratory crackles over the right middle and lower lobe. He was not in respiratory distress. He did not have any evidence of oral, sinonasal, laryngeal, anal, or genital papillomatosis. Bronchoscopic tissue sampling 3 months previously confirmed benign papillomatosis. The chest X-ray demonstrated new confluent mass-like consolidation in the right lower lobe and a new medial left lower lobe consolidation. A previous CT of the chest demonstrated collapse of the bilateral lower lobe bronchioles, numerous scattered nodules, and increased consolidative nodularity in the right greater than left lower lobe. He underwent bronchoscopy with biopsy, which demonstrated squamous papilloma with high-grade dysplasia and small cell carcinoma without definite invasion. A PET CT scan demonstrated multiple bilateral nodular densities with intense FDG uptake and no evidence of metastasis. He was referred to oncology and is currently receiving chemotherapy with Carboplatin and Paclitaxel. DISCUSSION: Adult-onset RRP is rare, most commonly occurring in the juvenile age group. Rarer is extension into the lung parenchyma, occurring in less than 1% of patients. Malignant transformation is most rare in this usually benign disease, though active smoking and HIV infection increases the risk of this occurring. In fact, it is known that malignant transformation to squamous cell carcinoma of the anus, also associated with HPV-related papillomatosis, is one of the most frequent non-AIDS defining illnesses in HIV patients. It is thus reasonable to extrapolate from this information that an increased risk for malignant transformation from HPV-related papillomatosis occurs in the lungs as well. To our knowledge, this is the first report of malignant transformation to squamous cell carcinoma of the lung in an HIV-infected individual with adult-onset RRP. CONCLUSIONS: RRP ranges from benign disease to risk for malignant transformation. Behavior modification with smoking cessation and close follow-up are strongly encouraged. Hammoud D, Haddad BE. Squamous cell carcinoma of the lungs arising in recurrent respiratory papillomatosis. Respiratory Medicine CME. 2010;3(4):270-272. https://doi.org/10.1016/j.rmedc.2009.09.021. Reference #1: Xiao Y, Wang J, Han D, Ma L. A Case of the Intrapulmonary Spread of Recurrent Respiratory Papillomatosis With Malignant Transformation. Lopez FA, ed. The American Journal of the Medical Sciences. 2015;350(1):55-57. https://doi.org/10.1097/MAJ.0000000000000370. Reference #2: Moanna A, Flenaugh EL, Lennox JL, Moss M, Vuchetich A. Severe Recurrent Respiratory Papillomatosis in an HIV-infected Adult on Highly Active Antiretroviral Therapy. Journal of Bronchology. 2005;12(4):210-213. https://doi.org/10.1097/01.lab.0000174647.08643.cc.Hidalgo-Tenorio Reference #3: C, Gil-Anguita C, Ramírez-Taboada J, et al. Risk factors for infection by oncogenic human papillomaviruses in HIV-positive MSM patients in the ART era (2010–2016). Maatouk. I, ed. Medicine. 2017;96(39):e8109. https://doi.org/10.1097/MD.0000000000008109. DISCLOSURES: No relevant relationships by Aarti Duggal, source=Web Response No relevant relationships by Eric Flenaugh, source=Web Response No relevant relationships by Marilyn Foreman, source=Web Response No relevant relationships by Marina Mosunjac, source=Web Response No relevant relationships by Snigdha Nutalapati, source=Web Response No relevant relationships by Dana Thomas, source=Web Response

A retrospective analysis of CO(2) laser and microdebrider for the treatment of severe juvenile on-set recurrent respiratory papillomatosis

Objective: Juvenile on-set recurrent respiratory papillomatosis (JORRP) can be an aggressive and potentially life-threatening disease. To emphasize the importance of complication prevention in local excision surgery, the single-center experience of RRP treatment in a group of patients with relatively short recurrence-free-interval (>4 times/yrs) was reported. Methods: Data of 49 patients underwent papilloma resection during 2002-2013 were retrospectively analyzed. Combined techniques of laser microsurgery and microdebriders were used to remove papillomas, prevent the formation of scar tissue and improve respiratory distress. Forty-nine cases were followed up for 99.0[74.5; 121.0]months, ranging from 39 to 185 months. The age of disease onset was 2[1; 3] years old. Most of the patients had difficulty in breathing(42 of 49 cases). Seven patients had hoarseness.53.0% patients had subglottic or trachea papillomatosis spreading. The rate of complications, synechia formation, tracheal stenosis, needing for tracheostomy, mortality was recorded. Patients were followed up for at least three years. The characteristics of the patients, improvement in symptoms, recurrence-free interval, and the rate of tracheal extubation were evaluated. Wilcoxon signed ranks test and chi-square test were used for data comparation. Results: Long-term relieve in disease(≤2 surgeries were needed/year) were achieved in 29(59.1%) subjects, in which 8(16.3%) of the subjects did not need surgical treatment for at least 3 years. Long-term relieve had been achieved in 25 of subjects who did not accept tracheostomy. Seven subjects did not need surgical treatment for at least 3 years. The rate of successful tracheal extubation was 53.8% in 13 patients who had undergone tracheostomy. Three cases dead of intrapulmonary spread. Conclusions: Combined techniques of laser microsurgery and microdebriders are effective in improvement in both respiratory distress and voice quality. The combined technique are helpful to avoid inevitable long-term stenotic complications, ultimately affecting the quality of life.

Association between interleukin-27 polymorphisms and pulmonary tuberculosis.

To investigate the effect of interleukin (IL) 27 -964A/G, 2095T/G, 4603G/A and 4730T/C gene polymorphisms on the development of pulmonary tuberculosis (PTB), radiographic characteristics and severity. Differences in the allele and genotype distributions of the -964A/G, 2095T/G, 4603G/A and 4730T/C polymorphisms between 224 PTB patients and 233 healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavitation, were investigated. Serum IL-27 concentration was measured using an enzyme-linked immunosorbent assay. There were no significant differences in the allele or genotype distributions between PTB patients and healthy controls. However, the -964A/A genotype was more prevalent in patients with single-lobe involvement than the -964A/G or -964G/G genotype in patients with multi-lobe involvement (50.0% vs. 31.3%, P = 0.01). There was no difference between patients with and without cavitation (P > 0.05). Serum median IL-27 concentration was significantly higher in patients with single-lobe involvement than in those with multi-lobe involvement (P = 0.03) and in those with -964A/A genotypes than in those with -964A/G or -964G/G genotypes (P = 0.02). In terms of serum IL-27 levels, the -964 A/A genotype may be associated with a protective role that prevents the intrapulmonary spread of PTB rather than its development.

Pattern of Metastasis Outside Tumor-Bearing Segments in Primary Lung Cancer: Rationale for Segmentectomy

Patterns of intrapulmonary metastasis, particularly metastasis outside tumor-bearing segments, were investigated in lung cancer patients to address the rationale for segmentectomy. In a consecutive series of patients who underwent resection of two or more pulmonary segments for primary lung cancer, intrapulmonary spread patterns, such as segmental/intersegmental node metastasis and pulmonary parenchymal metastasis, were pathologically examined. Eligible 244 lesions included 167 adenocarcinomas, 66 squamous cell carcinomas, and 11 large cell carcinomas. Pathologic stages included 0 to IA (n=111), IB (n=56), IIA (n=31), IIB (n=20), IIIA (n=23), and IIIB to IV (n=3); and N1 (n=26) and N2 (n=22). Intrapulmonary spread was observed in 24 cases (9.8%). Of these, metastasis outside tumor-bearing segments was only observed in 4 cases (1.6%), and such cancer spread was more frequently seen in cases with extrapulmonary (hilar to mediastinal) nodal metastasis (7.9%) than in cases without extrapulmonary metastasis (0.5%; p=0.01). Metastasis outside tumor-bearing segments was not observed in 64 tumors with pure or mixed ground glass opacity features on computed tomography. Although tumor location (peripheral or central/intermediate) was not related to the incidence of metastasis outside tumor-bearing segments, intrapulmonary spread was observed in only 1 of 52 peripheral small (≤20 mm) tumors. Metastasis outside tumor-bearing segments is rarely observed in cases with tumors (1) without extrapulmonary nodal metastasis and (2) with ground glass opacity or peripheral small (≤20 mm) features.

The Adult Cystic Fibrosis Airway Microbiota Is Stable over Time and Infection Type, and Highly Resilient to Antibiotic Treatment of Exacerbations

Cystic fibrosis (CF) is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function. Taken together, these results indicate that the adult CF lung microbiome is largely stable through periods of exacerbation and antibiotic treatment and that short-term compositional changes in the airway microbiota do not account for CF pulmonary exacerbations.

Evaluation of intrapulmonary nodules by thoracoscopic ultrasonography

We evaluated the usefulness of thoracoscopic ultrasonography for diagnosing intrapulmonary nodules. We studied 7 patients undergoing thoracoscopic operations. Three had benign lung tumors, one had metastatic lung tumors from a renal cell cancer, and three had primary lung cancers. During thoracoscopy three benign tumors were seen as masses protruding from the visceral pleura in to the pleural space, and two primary lung cancers were seen as pleural indentations. However, the presence of one metastatic lung tumor and one primary lung cancer could not be confirmed by thoracoscopy because of the lack of pleural changes. Furthermore, intrapulmonary spread of malignant tumors in four cases could not be seen by thoracoscopy. All tumors were seen clearly and their characteristics were identified by thoracoscopic ultrasonography. Partial lung resection during thoracoscopy was successful in all patients. We found thoracoscopic ultrasonography to be useful for confirming the presence of peripheral solid nodules, and for deciding where to make incisions for partial lung resection.

Epidermal Growth Factor Receptor Mutation and Pathologic-Radiologic Correlation Between Multiple Lung Nodules with Ground-Glass Opacity Differentiates Multicentric Origin from Intrapulmonary Spread

No standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread. Twenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18-21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients. High frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change. This study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO.

Effect of matrix metalloproteinase-9 −1562C/T gene polymorphism on manifestations of pulmonary tuberculosis

Increased levels of matrix metalloproteinase-9 (MMP-9) in patients with tuberculous meningitis, tuberculous pleuritis, and advanced pulmonary tuberculosis (TB) suggest a pivotal role for MMP-9 in the development of pulmonary TB and its clinical manifestations. The present study was performed to evaluate the role of the -1562C/T single nucleotide polymorphism (SNP) in the promoter region of the human MMP-9 gene in development of pulmonary TB and its radiographic characteristics. A case-control study was performed with a study population of 205 patients with pulmonary TB and 223 healthy controls. Differences were explored in the allele and genotype distributions of the -1562C/T polymorphism between patients with pulmonary TB and healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavities. The -1562C/C genotype was more common in patients with multi-lobe involvement than in those with single-lobe involvement (81.8 vs. 67.6%, P=0.03). However, there were no significant differences in the distribution between patients with pulmonary TB and healthy controls (P=0.40) or between patients with and without cavities (P=0.18). These results suggest that the -1562C/C genotype is associated with the intrapulmonary spread of TB rather than its development.

Pulmonary lymphangitic sarcomatosis and a review of the literature

Intrapulmonary spread of a sarcoma via lymphatics is a rare cause of death in a young adult. A 31-year old man was admitted to our hospital complaining of dyspnea and malaise of 2 months' duration. A chest radiography revealed bilateral hilar enlargement, and reticulonodular infiltrations. Thoracic CT-scans demonstrated mediastinal lymphadenopathy, thickening of interlobular septa, polygonal lines, and thickening of bronchovascular bundles. The diagnosis was made by open-lung biopsy. The patient died within 3 months after diagnosis. Pulmonary lymphangitic sarcomatosis is a rare but important manifestation of an angiosarcoma. Optimal treatment of these patients is not well defined, but a trial of chemotherapy may be warranted.

Neutrophils Promote Aerogenous Spread of Lung Adenocarcinoma with Bronchioloalveolar Carcinoma Features

Adenocarcinoma with bronchioloalveolar carcinoma (BAC) features is a subtype of non-small cell lung cancers characterized by an intense inflammatory reaction composed of macrophages and neutrophils and by a distinct natural history with intrapulmonary spread leading to death due to respiratory failure. We hypothesized that neutrophils could promote aerogenous spread of lung adenocarcinoma with BAC features. We examined the effect of neutrophils on A549 cell line detachment in vitro and we quantified desquamation of tumor cells on tumor tissue (n = 25) and on matched bronchioloalveolar lavage (n = 17) in vivo in a series of patients with adenocarcinoma with BAC features. Neutrophils induced A549 detachment mediated by signals through cell-to-cell contact. Detached A549 cells were still viable and able to proliferate in vitro. Neutralization studies identified several membrane-bound molecules involved in detachment (i.e., intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, tumor necrosis factor alpha/tumor necrosis factor alpha receptor inhibitor, interleukin-1alpha /interleukin-1alpha receptor, and neutrophil elastase). In tumor tissue, shedding was detected in all samples, with a median shedding score of 42% (range, 4-95%). Micropapillary clusters were detected in 23 of the 25 tumor tissue samples, with a median micropapillary score of 1.40 (range, 0-2.1), and tumor cells were detected in 7 of 17 lavages. The micropapillary score was associated with a high neutrophil count in bronchioloalveolar lavage (P = 0.051). The shedding cell percentage was a significant factor in shorter survival (P = 0.034, univariate Cox analysis). Tumor shedding is induced by neutrophils. It is a significant factor of shorter survival and may be an important event in adenocarcinoma progression.

Long-term survival differences for bronchioloalveolar carcinoma (BAC) patients with ipsilateral intrapulmonary metastasis at diagnosis

7207 Background: It has been suggested that survival for BAC patients with stage IIIB disease due to multiple lesions in the same lobe is improved over other stage IIIB patients, and that patients with multicentric BAC have improved survival over BAC patients with distant metastasis. To determine the prognostic implications of these various subsets of advanced stage BAC patients, we compared survival rates using a large population-based cohort. Methods: A case-only analysis of data from the U.S. SEER database during 1998–2002 was conducted. The primary outcome measured was overall survival (OS). OS and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method; multivariate survival analyses were performed using Cox proportional hazards ratios. Results: 2653 incident cases of BAC were analyzed with a 5-year follow-up duration, including 831 patients with advanced (i.e. stage IIIB or IV) BAC. Patients with stage IIIB BAC due to multiple lesions in the same lobe (n = 96) had significantly improved median OS (46 months) and LCSS (not reached at &gt;58 months) compared to other stage IIIB BAC patients on univariate analysis (n = 133; OS = 8 months, LCSS = 9 months) (P &lt; 0.0001). Stage IV BAC patients with intrapulmonary metastasis (n = 320) had significantly improved median OS (13 months) and LCSS (15 months) compared to those with stage IV BAC due to distant spread on univariate analysis (n = 282; OS = 7 months, LCSS = 7 months) (P &lt; 0.0001). These observed survival differences remained after adjustment for age, gender, ethnicity, and surgical treatment status (Table). Conclusions: Patients with stage IIIB BAC due to tumors in the same lobe have significantly better outcomes than other stage IIIB BAC patients. Stage IV BAC patients due to intrapulmonary spread have significantly improved outcomes over stage IV BAC patients with distant metastasis. These results add further support for modification to the current NSCLC staging system. [Table: see text] No significant financial relationships to disclose.

Remote intrapulmonary spread of recurrent respiratory papillomatosis with malignant transformation

Recurrent respiratory papillomatosis is the most common neoplasm of the larynx in childhood. Extension into lung parenchyma occurs in less than 1% of patients and has a low risk of malignant transformation. Treatment options for intrapulmonary spread have shown limited success. We describe a case of recurrent respiratory papillomatosis with extensive parenchymal involvement and adenosquamous carcinoma in a 14-year-old girl.

Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical resection: a radiological, histological, and immunohistochemical study

Purpose: Bronchioloalveolar carcinoma (BAC) is a subtype of lung adenocarcinoma whose incidence is raising. Bronchioloalveolar carcinoma has a tendency to involve diffusely the lung. No agreement exists about whether diffuse bronchioloalveolar carcinoma has a multicentric or unicentric origin. The purpose of this work is to evaluate the correlation between intrapulmonary spread of bronchioloalveolar carcinoma and its histologic and immunohistochemical characteristics. Design: Surgical specimens of 20 bronchioloalveolar carcinomas with radiologically proved evolution from focal to diffuse disease were retrieved and reviewed. Patterns of pulmonary spread were defined on the basis of CT and MR imaging examinations. Immunohistochemical studies were performed to investigate the expression of gelatinase A and α2-integrin. Correlation between immunohistochemical results and patterns of pulmonary spread was evaluated. Statistical evaluation was performed by using Fisher Exact Test. Results: Three histological subtypes of bronchioloalveolar carcinoma were found: mucinous (11 cases), non-mucinous (3 cases), and mixed adenocarcinoma with prominent bronchioloalveolar pattern (6 cases). Three patterns of pulmonary spread were depicted radiologically: parenchymal opacification (11 cases), multiple nodules (7 cases) and mixed pattern (2 cases). Eleven out of 12 mucin-producing versus none out of 8 non-mucin producing cancers developed parenchymal opacification. The difference was statistically significant ( P<0.028). A statistically significant difference was also found between the development of parenchymal opacification and the level of α2-integrin: 11 out of 13 tumors with negative α2-integrin versus none out of 7 with positive α2-integrin immunoreactivity ( P>0.033). Conclusions: Diffuse bronchioloalveolar carcinoma may develop from a prior focal cancer. Mucinous subtype is the most prone to develop diffuse disease with parenchymal opacification, probably representing aerogenous spread. Low levels of α2-integrin receptors were found in bronchioloalveolar carcinoma which developed parenchymal opacification.