Mucinous Bronchioloalveolar Carcinoma Research Articles

Favorable response to pemetrexed, cisplatin and bevacizumab in invasive mucinous adenocarcinoma: A case report and literature review.

Invasive mucinous adenocarcinoma (IMA) was formerly referred to as mucinous bronchioloalveolar carcinoma. The lack of effective chemotherapy and comprehensive treatment for this type of tumor poses a great challenge in clinical practice. We herein report the case of a male patient with IMA who was treated with a combination of pemetrexed (500 mg/m2), cisplatin (75 mg/m2) and bevacizumab (15 mg/kg) as first-line chemotherapy. The patient achieved significant radiological improvement with 6 courses of this regimen. After the tumor progressed, the patient again achieved marked improvement with an additional 4 courses of the same regimen. The patient survived for a total of 30 months after the first chemotherapy. Therefore, bevacizumab in combination with pemetrexed/cisplatin may be an effective strategy for the treatment of IMA. The available literature on this chemotherapy regimen was also reviewed and discussed in the present study.

Invasive mucinous adenocarcinoma of the lung presenting as a large, thin-walled cyst: A case report and literature review.

Invasive mucinous adenocarcinoma (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare variant form of invasive adenocarcinoma and is radiologically characterized by dense pneumonic consolidation, ground-glass opacity and nodules. By contrast, large, thin-walled cysts are rare. We herein report the case of a 75-year-old man with IMA presenting as a large, irregularly shaped cystic lesion. The histological diagnosis was based on specimens obtained during a bronchoscopy. The patient underwent lobectomy followed by anticancer chemotherapy for residual intrapulmonary metastases. Of note, the small metastatic nodules transformed into cystic lesions with thin walls and fused, forming a large, multiloculated cystic lesion. Typical pneumonic consolidation appeared in the pericystic parenchyma later during the clinical course. The available literature on this rare radiological manifestation was also reviewed and discussed. Clinicians should be aware of thin-walled cystic lesions as they may be an unusual radiological finding in IMA.

Nouvelle classification OMS 2015 des adénocarcinomes pulmonaires et prénéoplasies

The 2015 WHO classification of tumors of the lung, pleura, thymus and heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes involve (1) use of immunohistochemistry throughout the classification, (2) integration of molecular testing for personalized strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology, (4) a new classification of lung adenocarcinoma as proposed by the 2011 IASLC/ATS/ERS, (5) restriction of the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation. Regarding adenocarcinoma, the terms bronchioloalveolar carcinoma (BAC) and mixed subtype adenocarcinoma have been suppressed and replaced for the former by the term adenocarcinoma in situ (AIS) as a preinvasive lesion to join atypical adenomatous hyperplasia (AAH). A new category has been defined, the minimally invasive adenocarcinoma (MIA), and invasive adenocarcinomas are now classified according to the predominant subtype after subtyping by semi-quantitatively percentage of various subtypes present in 5% increments. The term "lepidic" is restricted to a non-invasive component (previously classified as BAC) present as part of an invasive adenocarcinoma. "Invasive mucinous adenocarcinoma" is used for formerly adenocarcinomas classified as mucinous BAC, excluding tumors that meet criteria for AIS or MIA. The subtypes of clear cell and signet ring adenocarcinoma are discontinued, as well the term of mucinous cystadenocarcinoma, included in the category of colloid adenocarcinoma. Thus new classification of lung adenocarcinoma is sustained by genetics and has clinical impact for therapeutic strategies.

Video-assisted thoracic surgery diagnosis of mucinous (colloid) lung adenocarcinoma: Case report

Abstract Background Mucinous colloid lung adenocarcinoma is an uncommon variant of lung carcinomas with similar features to tumours seen in the gastrointestinal tract. To distinguish between these tumours and other mucinous lung tumours, such as mucinous bronchioloalveolar cell carcinomas and metastatic mucinous lesions could be difficult with small biopsy specimens from fine needle aspiration. Clinical case The case is described of a 49-year-old female with history of dyspnoea and cough with bloody sputum and weight lose. Thorax axial computed tomography demonstrated a right lower lobe spiculated mass with calcifications. Transthoracic computed tomography-guided fine needle biopsy reported negative results, and the biopsy obtained with video-assisted thoracic surgery was useful for an adequate cytology report of a colloid variant of mucinous lung adenocarcinoma. Conclusion Video-assisted thoracic surgery is an appropriate option for obtaining a larger specimen in those cases where small biopsies are inconclusive for the diagnosis of thoracic pathologies such as malignant tumours.

Relation Between Thin-Section Computed Tomography and Clinical Findings of Mucinous Adenocarcinoma

Detailed reports on mucinous adenocarcinoma (formerly "mucinous bronchioloalveolar carcinoma") have not been published. We evaluated the correlation between thin-section computed tomography findings and the clinicopathologic characteristics and prognosis of mucinous adenocarcinoma. From April 1997 to March 2008, 45 resected lung carcinomas were diagnosed as mucinous adenocarcinoma. Five cases of multiple lung cancers or ambiguous mucinous adenocarcinoma were excluded. Tumors were classified as "solitary-type" or "pneumonic-type" tumors according to the thin-section computed tomography findings. We evaluated the clinicopathologic characteristics and the epidermal growth factor receptor and KRAS gene mutation statuses and correlated the thin-section computed tomography findings with patient prognoses. Thirty patients had solitary-type and 10 had pneumonic-type tumors. The lesions in 23, 14, and 3 patients were classified as pathologic stage I, stage II, and stage III, respectively. Five patients had adenocarcinoma in situ, 9 had minimally invasive adenocarcinoma, and 26had invasive mucinous adenocarcinoma. Thirteen patients showed recurrences, which were classified as intrapulmonary metastases in all patients. The 5-year overall and relapse-free survival rates were 83.3% and 88.8%, respectively, in patients with solitary-type tumors and 20.0% and 0%, respectively, in patients with pneumonic-type tumors (p < 0.001). The median follow-up time for surviving patients was 81 months. KRAS mutations were detected in 30 patients, but epidermal growth factor receptor mutations were absent in all patients. Our results indicated that thin-section computed tomography findings for mucinous adenocarcinoma were useful in predicting prognosis before surgical resection. Further studies are required to improve the treatment strategy for mucinous adenocarcinoma.

Genotype–phenotype correlation in Chinese patients with pulmonary mixed type adenocarcinoma: Relationship between histologic subtypes, TITF-1/SP-A expressions and EGFR mutations

This study aimed to explore the association between adenocarcinoma-related morphological and molecular characteristics and EGFR mutations in Chinese lung adenocarcinomas. A total of 139 consecutively resected pulmonary adenocarcinoma patients were screened for EGFR mutations by the amplification refractory mutation system assay. For the resected specimens, histologic subtypes were sub-classified using either the 2004 WHO classification or the 2011 IASLC/ATS/ERS classification. Meanwhile, TITF-1 (thyroid transcription factor 1) and SP-A (surfactant-associated protein A) immunohistochemistry staining was also detected. The results were correlated with EGFR mutations and clinicopathological features mentioned above. Both sub-classification methods reflected differences in frequencies of EGFR mutations in lung adenocarcinoma subtypes. In summary, mixed non-mucinous bronchioloalveolar carcinoma (BAC) or papillary components and papillary predominant adenocarcinoma showed a higher frequency of EGFR mutations than mucinous BAC components; Also, EGFR mutations were significantly more common in tumors with TITF-1 or SP-A expressions than in those without (p=0.002, p=0.026), especially the sensitivity of TITF-1 (96.9%) and the negative predictive value of TITF-1 (88.2%). Our data further showed significant genotype–phenotype correlations between EGFR mutations and adenocarcinoma-related morphological and molecular characteristics, and patients with special histologic and IHC staining features might have higher EGFR mutation rates. In addition, this study, for the first time, indicated the significant relationship between SPA IHC and EGFR mutations, which needed confirmation by further research.

Case report: Positron emission tomography fails to detect pulmonary adenocarcinoma recurrence after radiofrequency ablation

We describe the case of late recurrence of a focus of invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma) following radiofrequency ablation, despite a negative positron emission tomography/computed tomography scan at 13 months following the ablation. A computed tomography scan performed at 24 months demonstrated unequivocal recurrence of the lesion. Combined positron emission tomography/computed tomography has been described as an adequate modality for the follow-up of thermally ablated pulmonary lesions. However, its utility in the follow-up of well-differentiated pulmonary adenocarcinoma may be limited. Lesion activity may be underestimated by an inherently low metabolic activity. Small lesions may also be susceptible to partial volume effect. Long-term imaging follow-up of well-differentiated pulmonary adenocarcinoma beyond two years after thermal ablation is prudent to avoid missing late recurrence.

Congenital Cystic Adenomatoid Malformation with Associated Mucinous Bronchioloalveolar Carcinoma in a Neonate

Congenital cystic adenomatoid malformation (CCAM) of lung is a rare hamartomatous disorder characterized by abnormal branching morphogenesis of the lung. We report an unusual case of a 2-day-old male newborn with a pulmonary cystic lesion and lobectomy revealed a CCAM of the lung that has overlapping features of type 1 and type 2, complicating with multifocal mucinous bronchioloalveolar carcinoma (BAC). The case indicates that malignant transformation can occur in very early stage of the infancy in the patients with CCAM of lung.

Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification.

A new lung adenocarcinoma classification has been published by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. This new classification is needed to provide uniform terminology and diagnostic criteria, most especially for bronchioloalveolar carcinoma. It was developed by an international core panel of experts representing all 3 societies with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons.This summary focuses on the aspects of this classification that address resection specimens. The terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced, such as adenocarcinoma in situ and minimally invasive adenocarcinoma for small solitary adenocarcinomas with either pure lepidic growth (adenocarcinoma in situ) and predominant lepidic growth with invasion of 5 mm or less (minimally invasive adenocarcinoma), to define the condition of patients who will have 100% or near 100% disease-specific survival, respectively, if they undergo complete lesion resection. Adenocarcinoma in situ and minimally invasive adenocarcinoma are usually nonmucinous, but rarely may be mucinous. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous bronchioloalveolar carcinoma), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid, fetal, and enteric adenocarcinoma.It is possible that this classification may impact the next revision of the TNM staging classification, with adjustment of the size T factor according to only the invasive component pathologically in adenocarcinomas with lepidic areas.

Gefitinib Improves Bronchorrhea from Mucinous Bronchioloalveolar Carcinoma and Serum Surfactant Protein-D Levels is a Novel Surrogate Predictor of Treatment Benefit

Gefitinib Improves Bronchorrhea from Mucinous Bronchioloalveolar Carcinoma and Serum Surfactant Protein-D Levels is a Novel Surrogate Predictor of Treatment Benefit

New Pathologic Classification of Lung Cancer: Relevance for Clinical Practice and Clinical Trials

We summarize significant changes in pathologic classification of lung cancer resulting from the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. The classification was developed by an international core panel of experts representing IASLC, ATS, and ERS with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. Because 70% of patients with lung cancer present with advanced stages, a new approach to small biopsies and cytology with specific terminology and criteria focused on the need for distinguishing squamous cell carcinoma from adenocarcinoma and on molecular testing for EGFR mutations and ALK rearrangement. Tumors previously classified as non-small-cell carcinoma, not otherwise specified, because of the lack of clear squamous or adenocarcinoma morphology should be classified further by using a limited immunohistochemical workup to preserve tissue for molecular testing. The terms "bronchioloalveolar carcinoma" and "mixed subtype adenocarcinoma" have been discontinued. For resected adenocarcinomas, new concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma define patients who, if they undergo complete resection, will have 100% disease-free survival. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype with poor prognosis. Former mucinous bronchioloalveolar carcinomas are now called "invasive mucinous adenocarcinoma." Because the lung cancer field is now rapidly evolving with new advances occurring on a frequent basis, particularly in the molecular arena, this classification provides a much needed standard for pathologic diagnosis not only for patient care but also for clinical trials and TNM classification.

Napsin A Expression in Primary Mucin-Producing Adenocarcinomas of the Lung

Immunohistochemical expression of napsin A in primary pulmonary mucinous tumors is not well established. Napsin A immunoreactivity was evaluated in 43 mucin-producing adenocarcinomas of the lung consisting of 18 tumors formerly classified as mucinous bronchioloalveolar carcinoma, 15 colloid adenocarcinomas, 5 solid predominant adenocarcinomas with mucin production, and 5 adenocarcinomas with signet ring cell features, as well as in 25 extrapulmonary mucinous adenocarcinomas of different anatomic sites. Immunohistochemical expression of thyroid transcription factor 1 (TTF-1) was also compared. Thirty-three percent of mucinous lung tumors exhibited positive immunoreactivity for napsin A, whereas 42% expressed TTF-1. All 25 extrapulmonary mucinous adenocarcinomas lacked expression of napsin A and TTF-1. Mucin-producing neoplasms of the lung infrequently express napsin A, suggesting that immunohistochemical assessment of napsin A may have limited diagnostic usefulness for distinguishing primary and metastatic mucinous adenocarcinomas involving the lung.

Micropapillary Mucinous Adenocarcinoma of the Lung: A Brief Case Report

In 2011, the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification added micropapillary predomi nant adenocarcinoma of the lung as a new histologic subtype and reclassified the former mucinous bronchioloalveolar carcino ma (BAC) as a variant of invasive mucinous adenocarcinoma. 1 Recent studies regarding epidermal growth factor receptor (EGFR) and K-ras mutations in lung cancer demonstrated that BAC with a lepidic or hobnail growth pattern is more typically associated with EGFR mutation, while mucinous differentiation is more common in cases with K-ras mutation. 2-4 However, these studies were based on the 2004 World Health Organization (WHO) classification, and there had been a few reports on the micropapillary pattern of this disease and its correlation with EGFR and K-ras mutations. 4,5 According to the report of the IASLC, 1 micropapillary predominant adenocarcinoma is known to be related to K-ras (33%), EGFR (20%), and BRAF (20%) mutations. Hypothesizing that micropapillary predominant adenocarcinoma with mucinous differentiation may be correlated with K-ras mutation, we performed a histological review of a case of micropapillary mucinous adenocarcinoma with associated K-ras mutation.

A Favorable Response to Cisplatin, Pemetrexed and Bevacizumab in Two Cases of Invasive Mucinous Adenocarcinoma Formerly Known as Pneumonic-type Mucinous Bronchioloalveolar Carcinoma

The leading subtype of lung cancer, adenocarcinoma, received a new classification in 2011 when multifocal, pneumonic-type mucinous tumors, formerly called mucinous bronchioloalveolar carcinomas, were reclassified as "invasive mucinous adenocarcinomas." These tumors appear to be less sensitive to chemotherapy than other non-small cell lung cancers. We herein report two cases of invasive mucinous adenocarcinoma that showed a dramatic radiologic response to combination therapy with cisplatin, pemetrexed and bevacizumab. Recent data suggest that the use of paclitaxel-based chemotherapy is an acceptable therapeutic strategy in cases of invasive mucinous adenocarcinoma. The cases reported here and preclinical findings suggest the therapeutic efficacy of cisplatin, pemetrexed and bevacizumab in treating such tumors.

Prognostic Patterns in the Histopathology of Pulmonary Adenocarcinoma

Prognostic Patterns in the Histopathology of Pulmonary Adenocarcinoma

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.

Rare subtypes of adenocarcinoma of the lung

The 1999 WHO classification of adenocarcinoma of the lung and pleural tumors listed five rare variants of adenocarcinoma of the lung: well-differentiated fetal adenocarcinoma, colloid ‘mucinous’ adenocarcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma and clear-cell adenocarcinoma. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society developed a multidisciplinary, international classification of lung adenocarcinoma that was published in the February 2011 issue of the journal of Thoracic Oncology. This most current classification lists four rare variants of invasive adenocarcinoma of the lung: invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid adenocarcinoma (retained and expanded), fetal adenocarcinoma (retained) and enteric adenocarcinoma (new). Signet ring adenocarcinoma and clear-cell adenocarcinoma were removed from the list of variants of adenocarcinoma of the lung. Mucinous cystadenocarcinoma was merged into colloid adenocarcinoma. The new 2011 classification also takes into consideration of the amount of tissue sample available according to the two major methods how the tumor is procured: resection specimens versus small biopsy/cytology. Rare variants of invasive adenocarcinoma of the lung will only now be classified from resection specimens where adequate architecture of tumor can be identified.

LKB1 Mutations Frequently Detected in Mucinous Bronchioloalveolar Carcinoma

LKB1 mutations are common in patients with Peutz-Jeghers syndrome, which is characterized by mucocutaneous pigmentation, intestinal polyps and a high incidence of cancers at variable sites. This study investigated the status of the LKB1 gene in mucinous bronchioloalveolar carcinoma with or without Peutz-Jeghers syndrome. Three mucinous bronchioloalveolar carcinoma tumors from two Peutz-Jeghers syndrome patients and seven tumors from sporadic mucinous bronchioloalveolar carcinoma patients were collected by surgery between 2002 and 2008, and high molecular weight genomic DNA was extracted from them. The nucleotide sequences in exons 1-9 of LKB1 were determined by genomic polymerase chain reaction-direct sequencing. The loss of heterozygosity was analyzed by high-resolution fluorescent microsatellite analysis using two microsatellite markers that encompass the LKB1 locus, D19S886 and D19S565. The mutations of KRAS, EGFR and p53 were also evaluated. The germline mutation of LKB1 in the Peutz-Jeghers syndrome patients was identified as G215D by analyzing genomic DNA from normal lung tissue specimens. Furthermore, two of the three mucinous bronchioloalveolar carcinomas from these Peutz-Jeghers syndrome patients exhibited additional somatic mutations. On the other hand, four of seven sporadic 'non-Peutz-Jeghers syndrome' mucinous bronchioloalveolar carcinomas had LKB1 mutations. Loss of heterozygosity analyses revealed allelic loss in two tumors with LKB1 mutations. As a result, 70% of the mucinous bronchioloalveolar carcinomas exhibited LKB1 mutations. KRAS, EGFR and p53 mutations were mutually exclusive and observed in four, two and one tumors, respectively. Among them, five mutations occurred concomitantly with LKB1 mutations. The relatively high frequency of LKB1 mutations in mucinous bronchioloalveolar carcinoma patients may therefore suggest its involvement in lung carcinogenesis, at least in mucinous bronchioloalveolar carcinoma.

The “drunken honeycomb” feature of pulmonary mucinous adenocarcinoma: A diagnostic pitfall of bronchial brushing cytology

Pulmonary mucinous adenocarcinoma (PMA) is the terminology recently proposed in the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines for most tumors previously classified as mucinous bronchioloalveolar carcinomas (mBACs). PMA is histologically characterized by lepidic growth and at least some degree of invasive growth of goblet or columnar neoplastic cells with abundant intracytoplasmic mucin. We report here the cytologic features of PMA in a bronchial brushing specimen. The patient is an 84-year-old woman with a persistent dense consolidation in the right middle lobe of the lung found on non-contrast computed tomography (CT) scan. Bronchial brushing smears showed a monotonous population of columnar neoplastic cells forming "drunken honeycomb"-like cell clusters. The neoplastic cells displayed inconspicuous cytologic atypia. The concurrent transbronchial tissue biopsy and the resection specimen confirmed the diagnosis of PMA. Due to the bland nuclear features, the neoplastic cells in the bronchial brushing specimen were interpreted as benign at the time of the initial diagnosis, demonstrating a diagnostic pitfall of bronchial brushing cytology. A high index of suspicion is recommended when a lung lesion with "drunken honeycomb"-like cell clusters is encountered in bronchial brushing specimens. The review of the literature regarding the recently designated PMA is presented.

Successful Treatment with Pemetrexed in a Patient with Mucinous Bronchioloalveolar Carcinoma: Long-Term Response Duration with Mild Toxicity

Successful Treatment with Pemetrexed in a Patient with Mucinous Bronchioloalveolar Carcinoma: Long-Term Response Duration with Mild Toxicity