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Journal of Thoracic Oncology : Official... Feb 2011Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung... (Review)
Review
International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.
INTRODUCTION
Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies.
METHODS
An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized.
CONCLUSIONS
This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.
Topics: Adenocarcinoma; Humans; Lung Neoplasms; Neoplasm Staging; Societies, Medical
PubMed: 21252716
DOI: 10.1097/JTO.0b013e318206a221 -
World Journal of Surgical Oncology Feb 2024Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial studies. Hence, this study aimed to comprehensively identify and summarize the prognostic factors associated with IMA.
METHODS
A comprehensive search of relevant literature was conducted in the PubMed, Embase, Cochrane, and Web of Science databases from their inception until June 2023. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) of overall survival (OS) and/or disease-free survival (DFS) were obtained to evaluate potential prognostic factors.
RESULTS
A total of 1062 patients from 11 studies were included. In univariate analysis, we found that gender, age, TNM stage, smoking history, lymph node metastasis, pleural metastasis, spread through air spaces (STAS), tumor size, pathological grade, computed tomography (CT) findings of consolidative-type morphology, pneumonia type, and well-defined heterogeneous ground-glass opacity (GGO) were risk factors for IMA, and spiculated margin sign was a protective factor. In multivariate analysis, smoking history, lymph node metastasis, pathological grade, STAS, tumor size, and pneumonia type sign were found to be risk factors. There was not enough evidence that epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) mutations, CT signs of lobulated margin, and air bronchogram were related to the prognosis for IMA.
CONCLUSION
In this study, we comprehensively analyzed prognostic factors for invasive mucinous adenocarcinoma of the lung in univariate and multivariate analyses of OS and/or DFS. Finally, 12 risk factors and 1 protective factor were identified. These findings may help guide the clinical management of patients with invasive mucinous adenocarcinoma of the lung.
Topics: Humans; Adenocarcinoma of Lung; Adenocarcinoma, Mucinous; Lung; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Pneumonia; Prognosis; Retrospective Studies; Male; Female
PubMed: 38303008
DOI: 10.1186/s12957-024-03326-4 -
Journal of Clinical Medicine Dec 2023There is no clear evidence on the prevalence and clinical presentation of appendiceal mucinous neoplasm (AMN) among patients with inflammatory bowel disease (IBD), so a... (Review)
Review
There is no clear evidence on the prevalence and clinical presentation of appendiceal mucinous neoplasm (AMN) among patients with inflammatory bowel disease (IBD), so a systematic review was performed to investigate the diagnosis, management and treatment of AMN in these patients. PubMed, Medline, Scopus and the Cochrane Library were searched for articles published up to September 2023. Twenty-three studies reporting data about 34 AMN patients were included. UC patients had a median age of 52 years and a median length of disease of 10 years; CD patients had a median age of 40.5 years and a median length of disease of 5 years. A pre-operative diagnosis was achieved in 44% of patients. Most patients were symptomatic (82.6%) and showed moderate-severe disease activity (61%). Surgical procedures were performed: laparoscopic appendectomy, ileocecal resection, right hemicolectomy and colectomy/proctocolectomy. Of the patients, 73.5% were diagnosed with low-grade mucinous neoplasm (LAMN) and nine with adenocarcinoma. Synchronous colorectal dysplasia/carcinoma was present in 23.5% of patients. IBD patients with long-standing disease should be routinely screened, not only for colorectal cancer but also for AMN, during gastro-enterologic follow-up. Laparoscopic appendectomy of unruptured LAMN as well as right hemicolectomy of non-metastatic adenocarcinoma are safe procedures in IBD patients.
PubMed: 38202199
DOI: 10.3390/jcm13010191 -
Diseases of the Colon and Rectum Dec 2016Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following neoadjuvant chemoradiotherapy and curative resection for rectal cancer has not been reached.
OBJECTIVE
The aim of the current study is to use meta-analytical techniques to assess the association between mucinous histology and response to neoadjuvant chemoradiotherapy in rectal cancer.
DATA SOURCES
A comprehensive literature search of PubMed, Embase, and The Cochrane Library was performed.
STUDY SELECTION
All studies examining the effect of mucinous histology on chemotherapeutic response in rectal cancer were included.
INTERVENTIONS
No direct interventions were performed.
MAIN OUTCOME MEASURES
Outcomes of mucinous rectal adenocarcinoma were compared with nonmucinous tumors by using random-effects methods to analyze data. Data are presented as ORs with 95% CIs. The main outcomes measured were the rates of pathological complete response, tumor and nodal downstaging, positive resection margin rate, local recurrence, and overall mortality.
RESULTS
Eight comparative series describing outcomes in 1724 patients were identified, 241 had mucinous tumors (14%). Mucinous tumors had a reduced rate of pathological complete response (OR, 0.078; 95% CI, 0.015-0.397; p = 0.002) and tumor downstaging (OR, 0.318; 95% CI, 0.185-0.547; p < 0.001) following neoadjuvant chemoradiotherapy with an increased rate of positive resection margin (OR, 5.018; 95% CI, 3.224-7.810; p < 0.001) and poorer overall survival (OR, 1.526; 95% CI, 1.060-2.198; p = 0.023) following resection. Mucin expression did not significantly affect nodal downstaging (OR, 0.706; 95% CI, 0.295-1.693; p = 0.435) or local recurrence (OR, 1.856; 95% CI, 0.933-3.693; p = 0.078). There was no across-study heterogeneity for any end point.
LIMITATIONS
Most studies were retrospectively designed, and there were variations in patient populations and duration of follow-up.
CONCLUSIONS
Mucinous rectal adenocarcinoma represents a biomarker for poor response to preoperative chemoradiotherapy and is an adverse prognostic indicator.
Topics: Adenocarcinoma, Mucinous; Chemoradiotherapy; Humans; Neoadjuvant Therapy; Prognosis; Rectal Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 27824706
DOI: 10.1097/DCR.0000000000000635 -
International Journal of Surgery... Nov 2019Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection.
METHODS
Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model.
RESULTS
A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57).
CONCLUSION
Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.
Topics: Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Pancreatic Ductal; Female; Humans; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Survival Rate
PubMed: 31546033
DOI: 10.1016/j.ijsu.2019.09.014 -
Discover Oncology Feb 2021Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare... (Review)
Review
Clinicopathological factors and survival outcomes of signet-ring cell and mucinous carcinoma versus adenocarcinoma of the colon and rectum: a systematic review and meta-analysis.
BACKGROUND
Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare clinicopathological characteristics, recurrence and overall survival between colorectal signet-ring cell (SC) and mucinous carcinoma (MC) to conventional adenocarcinoma (AC).
METHODS
A literature search of MEDLINE, EMBASE, Ovid and Cochrane Library was performed for studies that reported data on clinicopathological and survival outcomes on SC and/or MC versus AC from January 1985 to May 2020. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed.
RESULTS
Thirty studies of 1,087,055 patients were included: 11,510 (1.06%) with SC, 110,179 (10.13%) with MC and 965,366 (88.81%) with AC. Patients with SC were younger than patients with AC (WMD - 0.47; 95% CI - 0.84 to -0.10; I 88.6%; p = 0.014) and more likely to have right-sided disease (OR 2.12; 95% CI 1.72-2.60; I 82.9%; p < 0.001). Locoregional recurrence at 5 years was more frequent in patients with SC (OR 2.81; 95% CI 1.40-5.65; I 0.0%; p = 0.004) and MC (OR 1.92; 95% CI 1.18-3.15; I 74.0%; p = 0.009). 5-year overall survival was significantly reduced when comparing SC and MC to AC (HR 2.54; 95% CI 1.98-3.27; I 99.1%; p < 0.001 and HR 1.38; 95% CI 1.19-1.61; I 98.6%; p < 0.001, respectively).
CONCLUSION
SC and MC are associated with right-sided lesions, advanced stage at presentation, higher rates of recurrence and poorer overall survival. This has strong implications towards surgical and oncological management and surveillance of colorectal cancer.
PubMed: 35201441
DOI: 10.1007/s12672-021-00398-6 -
European Journal of Surgical Oncology :... Oct 2022Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a... (Meta-Analysis)
Meta-Analysis Review
Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis.
PURPOSE
Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy.
METHODS
Studies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963-August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI).
RESULTS
This meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07-1.41, p < 0.01, I = 80%), and the DFS (HR, 2.95, 95% CI, 1.22-7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups.
CONCLUSION
MAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.
Topics: Humans; Colorectal Neoplasms; Adenocarcinoma; Chemotherapy, Adjuvant; Adenocarcinoma, Mucinous; Prognosis
PubMed: 35768312
DOI: 10.1016/j.ejso.2022.06.024 -
JAMA Dermatology Apr 2014Evidence-based treatment guidelines are not available for primary cutaneous mucinous carcinoma (PCMC). (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Evidence-based treatment guidelines are not available for primary cutaneous mucinous carcinoma (PCMC).
OBJECTIVE
To assess outcomes associated with surgical treatment of PCMC.
DATA SOURCES
MEDLINE, Cumulative Index to Nursing and Allied Health, and Embase from 1952 to 2010. Search terms were "primary cutaneous mucinous carcinoma," "primary mucinous adenocarcinoma of the skin," "primary mucinous sweat-gland carcinoma," and "endocrine mucin-producing sweat gland carcinoma."
STUDY SELECTION
Articles describing primary data on treatment (ie, case reports, case series, and cohort studies) of any patients with PCMC. A total of 116 articles were identified, with 90 of these assessed for eligibility and 87 used for final analysis.
DATA EXTRACTION AND SYNTHESIS
Each case was verified to be of primary cutaneous origin by 2 observers. Histopathologic descriptions were confirmed to be consistent with PCMC. Extracted fields included age, sex, race, lesion duration, tumor diameter, method of treatment, follow-up, and whether the lesion recurred or metastasized.
MAIN OUTCOMES AND MEASURES
Outcomes were dichotomized into good and bad depending on the presence of recurrence or metastasis during follow-up. Multivariate logistic regression analysis was performed to determine significant factors for predicting bad outcomes. RESULTS One hundred fifty-nine cases of PCMC, of whom 54.7% were male and 77.2% were white, with mean (SD) age 63.5 (13.2) years, were analyzed. Most had been treated with traditional surgical excision (85.5%), with only 9.4% of cases treated with Mohs surgery. Older (odds ratio [OR], 0.93; P = .04) and Asian (OR, 0.02; P = .01) patients had relatively better postsurgical outcomes. Larger tumors (OR, 6.71; P = .14), those persistent for longer prior to surgery (OR, 1.02; P = .11), and those located on the trunk (OR, 103.24; P = .005) also were associated with poorer outcomes. Limitations included reliance on case report data.
CONCLUSIONS AND RELEVANCE
Patient demographic characteristics and tumor-specific features may provide predictive information regarding the risk of postsurgical recurrence and metastasis after treatment of PCMC.
Topics: Adenocarcinoma, Mucinous; Age Factors; Humans; Mohs Surgery; Neoplasm Metastasis; Neoplasm Recurrence, Local; Skin Neoplasms; Treatment Outcome
PubMed: 24452370
DOI: 10.1001/jamadermatol.2013.6006 -
Journal of Clinical Pathology May 2012Mucinous adenocarcinoma (MAC) of the colorectum has been known and studied for many years. The prognostic significance of this histological subtype remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucinous adenocarcinoma (MAC) of the colorectum has been known and studied for many years. The prognostic significance of this histological subtype remains controversial. The authors reviewed the prognostic significance of mucinous differentiation in colorectal cancer.
MATERIALS AND METHODS
A systematic web-based search was performed using Web of Knowledge and Medline. Articles published in English, German or French which used the WHO definition of MAC and described cohort studies, case-control studies or cross-sectional studies comparing survival in patients with MAC and adenocarcinoma (AC) not otherwise specified were included. Data on first author, year of publication, country, number of patients included, prevalence of MAC, % stage IV disease, % disease located in the proximal colon, mean age at presentation, % male patients and 5-year overall survival were extracted from individual studies. A fixed-effects meta-analysis model was used for analysis. The primary outcome was survival, expressed as the HR. Differences between categorical outcome parameters were quantified using the RR and corresponding 95% CI.
RESULTS
44 studies and 222 256 patients were included. The RR for proximal disease versus distal disease was 1.55 (95% CI 1.53 to 1.58). Mucinous differentiation was less frequent in male subjects (RR 0.93 (95% CI 0.91 to 0.94)). Interestingly, the prevalence of stage IV disease was similar in MAC and AC (RR 0.99 (95% CI 0.96 to 1.02)). Thirty-five articles were included in the survival analysis. A worse survival in MAC versus AC was demonstrated (HR 1.05 (95% CI 1.02 to 1.08)). Conversely, three out of four studies reported a better survival in MAC with microsatellite instability (MSI). Due to heterogeneity a meta-analysis on the effect of MSI was not possible.
CONCLUSION
MAC more often originates from the right colon and is less frequent in male subjects. The authors did not identify a difference in the proportion of stage IV patients at presentation. Mucinous differentiation results in a 2-8% increased hazard of death, which persists after correction for stage. More research is needed to define the interaction between mucinous differentiation, MSI and outcome.
Topics: Adenocarcinoma, Mucinous; Age Factors; Biomarkers, Tumor; Colorectal Neoplasms; Female; Humans; Male; Mucins; Neoplasm Staging; Prognosis; Survival Rate
PubMed: 22259177
DOI: 10.1136/jclinpath-2011-200340 -
Annals of Surgical Oncology Jan 2020The role of somatic mutation profiling in the management of appendiceal mucinous tumors (AMTs) is evolving. Using a systematic review, we identified somatic alterations...
INTRODUCTION
The role of somatic mutation profiling in the management of appendiceal mucinous tumors (AMTs) is evolving. Using a systematic review, we identified somatic alterations (SAs) that comprise histopathologic types of AMTs and those associated with aggressive clinical phenotypes.
METHODS
MEDLINE/PubMed was searched for studies on AMTs including molecular markers or genomic alterations, published between 1990 and 2018. Studies were grouped under low- and high-grade histological type for primary and metastatic tumors.
RESULTS
Twenty-one studies involving 1099 tumors (primary/metastatic) were identified. Seven studies involving 101 primary low-grade AMTs identified KRAS (76.5%) as the predominant SA. Four studies noted GNAS in 45.2% of 42 low-grade appendiceal mucinous neoplasms, and KRAS was identified in 74.4% of 14 studies with 238 low-grade pseudomyxoma peritonei (PMP). GNAS was noted in 56% of 101 tumors and TP53 was noted in only 9.7% of 31 tumors. Primary high-grade tumors demonstrated lower SAs in KRAS (50.4% of 369 tumors) and GNAS (27.8% of 97 tumors), and higher SAs in TP53 (26.0% of 123 tumors). In high-grade PMP, SAs were noted in KRAS (55.0% of 200 tumors), GNAS (35.0% of 60 tumors), and TP53 (26.3% of 19 tumors). No clear association was noted between SAs and survival.
CONCLUSIONS
KRAS and GNAS are frequently altered in low-grade AMTs, while TP53 is frequently altered in high-grade AMTs, with no apparent change in expression between primary and metastatic tumors. Although SAs may provide valuable insights into variability in tumor biology, larger studies utilizing clinically annotated genomic databases from multi-institutional consortiums are needed to improve their identification and clinical applicability.
Topics: Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Biomarkers, Tumor; Genetic Markers; Humans; Mutation; Phenotype; Prognosis
PubMed: 31583543
DOI: 10.1245/s10434-019-07879-7