Summary Screening for lung cancer produces two groups of lung cancers. Baseline cases include all prevalent cases with the expectation that slower-growing cancers and those that have achieved higher ...stage will be found in greater frequency. Repeat examination is expected to detect those cancers which have crossed the threshold for detection during the screening interval – 1 year in this study – and these are typically more rapidly growing cancers. The two groups encompass the full spectrum of lung cancers. Comparison of the baseline and annual repeat cases revealed differences in types of lung cancer. There were 202 baseline-detected cancers spanning the spectrum of pulmonary neoplasms with some slowly growing, some rapidly progressive and some at high stage; the 48 annual repeat cancers also included a spectrum of lung cancers but with more of the rapidly growing types, and more closely approximated the clinical spectrum of lung cancers. The NE carcinomas showed this trend best; small-cell carcinomas were under-represented and typical carcinoids were only found in the baseline group. Repeat cancers were found to grow rapidly, were typically smaller, less often multiple and the adenocarcinomas were less often pure BAC and less frequently contained a BAC component when invasive. The baseline adenocarcinomas included most of the BAC's, which is a diagnosis that requires special attention to its WHO definition. AAH was found to be frequently associated with adenocarcinoma, particularly BAC. Both baseline and annual repeat cases had a high percentage of invasive carcinomas with comparably high rates of resectability, high rates of node negativity and consequently a high proportion of cases in low stage.
Lung cancer is the leading cause of cancer mortality worldwide. Despite technological, therapeutic, and scientific advances, most patients present with incurable disease and a poor chance of ...long-term survival. For those with potentially curable disease, lung cancer staging greatly influences therapeutic decisions. Therefore, surgical pathologists determine many facets of lung cancer patient care.
To present the current lung cancer staging system and examine the importance of mediastinal lymph node sampling, and also to discuss particularly confusing and/or challenging areas in lung cancer staging, including assessment of visceral pleura invasion, bronchial and carinal involvement, and the staging of synchronous carcinomas.
Published current and prior staging manuals from the American Joint Committee on Cancer and the International Union Against Cancer as well as selected articles pertaining to lung cancer staging and diagnosis accessible through PubMed (National Library of Medicine) form the basis of this review.
Proper lung cancer staging requires more than a superficial appreciation of the staging system. Clinically relevant specimen gross examination and histologic review depend on a thorough understanding of the staging guidelines. Common sense is also required when one is confronted with a tumor specimen that defies easy assignment to the TNM staging system.
Multimodality treatment of squamous cell carcinoma of the head and neck (SCCHN) often involves radiotherapy and cisplatin-based therapy. Elevated activity of DNA repair mechanisms, such as the ...nucleotide excision repair (NER) pathway, of which ERCC1 is a rate-limiting element, are associated with cisplatin and possibly RT resistance. We have determined excision repair cross-complementing group 1 (ERCC1) expression in human papillomavirus (HPV)-negative SCCHN treated with surgery ± adjuvant radiotherapy/chemoradiation (CRT).
We assessed ERCC1 protein expression in archival tumors using immunofluorescence staining and automatic quantitative analysis (AQUA) with three antibodies to ERCC1 (8F1, FL297, and HPA029773). Analysis with Classification and Regression Tree (CART) methods ascertained the cutoff points between high/low ERCC1 expression. Multivariable analysis adjusted for age, T, and N stage. Kaplan-Meier curves determined median survival. ERCC1 expression at initial tumor presentation and in recurrent disease were compared. Performance characteristics of antibodies were assessed.
ERCC1 low/high groups were defined on the basis of AQUA analysis with 8F1/2009, FL297, and HPA029773. Among patients treated with surgery plus adjuvant radiotherapy/CRT, longer median survival was observed in ERCC1-low versus ERCC1-high tumors (64 vs. 29 months; P = 0.02; HPA029773). Data obtained with HPA029773 indicated no survival difference among patients treated only with surgery. Recurrent cancers had lower ERCC1 AQUA scores than tumors from initial presentation. Extensive characterization indicated optimal specificity and performance by the HPA029773 antibody.
Using AQUA, with the specific ERCC1 antibody HPA029773, we found a statistical difference in survival among high/low-ERCC1 tumors from patients treated with surgery and adjuvant radiotherapy.
Surgical removal and pathologic handling of lung tissue has a compressive effect upon its architecture. The effect of surgical atelectasis on morphology has not been examined in depth, especially ...with respect to lung adenocarcinomas.
To examine the influence of surgical atelectasis on morphologic lepidic growth pattern, mimicking papillary adenocarcinoma pattern.
In 2 cases serial sections of resected pulmonary adenocarcinoma were used, as was a 3-dimensional reconstruction. Elastin stains were performed on primary and metastatic adenocarcinomas.
Perfusion fixation of another case showed marked morphologic differences of less compressed peripheral lung tissue, emphasizing the preexisting alveolar structure. An elastic stain may help identify true lesional architecture.
We demonstrate that microscopic sections of adenocarcinoma in situ in compressed/collapsed tissue may give rise to a pseudopapillary pattern mimicking invasive adenocarcinoma. Accurate appreciation of different tumor architecture in lung adenocarcinoma has important biologic and clinical implications. Pathologists should be aware of the possibility of misclassification of adenocarcinoma pattern due to tissue artifacts caused by lung tissue handling.
Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15-20% of smokers develop this disorder. Because oxidants are the major mechanism of smoking-induced airway ...damage, we hypothesized that smoking is associated with upregulation of various antioxidant-related genes in the airway epithelium, but the magnitude of the response shows high inter-individual variability. Microarray analysis was used to assess levels of expression of 44 antioxidant-related genes in four categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance; and pentose phosphate cycle) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 nonsmokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right versus left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared with nonsmokers. Subgroups of smokers were identified with clusters of expression levels of antioxidant-related genes. We propose that the antioxidant-related genes demonstrating the most variability in the level of expression in smokers may be useful genetic markers in epidemiologic studies assessing susceptibility to smoking-induced chronic bronchitis.
Advances in the pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) have demonstrated important new prognostic features that have led to changes in ...classification and diagnostic criteria.
The literature and a set of cases were reviewed by a pathology/CT review panel of pathologists and radiologists who met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The group addressed the question of whether sufficient data exist to modify the 2004 World Health Organization (WHO) classification of adenocarcinoma and BAC to define a “minimally invasive” adenocarcinoma with BAC. The problems of diffuse and/or multicentric BAC and adenocarcinoma were evaluated.
The clinical concept of BAC needs to be reevaluated with careful attention to the new 2004 WHO criteria because of the major clinical implications. Existing data indicate that patients with solitary, small, peripheral BAC have a 100% 5-year survival rate. The favorable prognostic impact of the restrictive criteria for BAC is already being detected in major epidemiologic data sets such as the Surveillance Epidemiology and End-Results registry. Most lung adenocarcinomas, including those with a BAC component, are invasive and consist of a mixture of histologic patterns. Therefore, they are best classified as adenocarcinoma, mixed subtype. This applies not only to adenocarcinomas with a solitary nodule presentation but also to tumors with a diffuse/multinodular pattern. The percentage of BAC versus invasive components in lung adenocarcinomas seems to be prognostically important. However, at the present time, a consensus definition of “minimally invasive” BAC with a favorable prognosis was not recommended by the panel, so the 1999/2004 WHO criteria for BAC remain unchanged. In small biopsy specimens or cytology specimens, recognition of a BAC component is possible. However, it is not possible to exclude an invasive component. The diagnosis of BAC requires thorough histologic sampling of the tumor.
Advances in understanding of the pathology and CT features of BAC and adenocarcinoma have led to important changes in diagnostic criteria and classification of BAC and adenocarcinoma. These criteria need to be uniformly applied by pathologists, radiologists, clinicians, and researchers. The 2004 WHO classification of adenocarcinoma is readily applicable to research studies, but attention needs to be placed on the relative proportion of the adenocarcinoma subtypes. Other recently recognized prognostic features such as size of scar, size of invasive component, or pattern of invasion also seem to be important. More work is needed to determine the most important prognostic pathologic features in lung adenocarcinoma.
Despite renewed interest in early detection of lung cancer, the relationship between tumor size and survival remains controversial. The objective of this study was to evaluate the relationship ...between size and stage in patients with T1 (≤ 3.0 cm) non-small cell lung cancer (NSCLC).
A retrospective review of a lung cancer database from 1995 to 2003 identified 503 patients with completely resected invasive NSCLC with tumors ≤ 3 cm. All clinical and pathologic characteristics were recorded. Univariate associations between nodal status and other prognostic factors were explored by χ2 and t tests. The independent effect of tumor size > 2 cm vs ≤ 2 cm on the risk of nodal disease was analyzed using a logistic regression model.
Of the 503 patients, 324 patients (64.4%) had stage IA disease, 52 patients (10.3%) had stage IB disease, 37 patients (7.4%) had stage IIA disease, 15 patients (3%) had stage IIB disease, 43 patients (8.6%) had stage IIIA disease, 24 patients (4.8%) had stage IIIB disease, and 8 patients (1.6%) had stage IV disease. One hundred patients (19.9%) had nodal metastases. The mean (± SD) tumor size of cases without nodal disease was 1.90 ± 0.67 cm, compared to 2.18 ± 0.69 cm for node-positive tumors (p = 0.0003; 95% confidence interval CI for mean difference, 0.13 to 0.43). Forty-eight of 308 patients (15.6%) with smaller carcinomas (≤ 2.0 cm) compared to 52 of 195 patients (26.7%) with carcinomas > 2.0 cm had nodal metastases (p = 0.002). Exploratory multivariate analysis revealed that only tumor size (≤ 2.0 cm referent vs > 2.0 cm) affected nodal status and thus stage (adjusted odds ratio, 2.0; 95% CI, 1.3 to 3.1; p = 0.002).
Primary invasive NSCLC > 2.0 cm was twice as likely to have nodal metastases than carcinomas ≤ 2.0 cm. Our results suggest that in lung cancer smaller lesions may represent earlier stage disease. These results also suggest the need for further subclassification by tumor size within the current International Union Against Cancer/American Joint Committee on Cancer stage I, with tumors < 2 cm in size contained in a separate substage. This refinement may help to better clarify which patients might benefit from novel adjuvant or neoadjuvant therapeutic interventions.
Sixty-five people had a resection of their baseline screen-diagnosed lung cancers in the Early Lung Cancer Action Program. Forty-nine of the carcinomas were solitary, and 42 of these were ...adenocarcinomas. More than 1 carcinoma was found in 16 patients after pathologic examination of the lobectomy specimen; 15 of the 16 second carcinomas were adenocarcinomas, mixed subtype. Eighteen cases were submitted by local pathologists as Bronchioloalveolar carcinomas but were found to be invasive adenocarcinomas according to the World Health Organization classification by the Pathology Review Panel. Of the 65 resected cases, 57 were N0, 7 were N1, and 1 was N2. Upon careful review of the lobectomy specimens, 49 cases had solitary malignancies, 30 were Stage IA, 13 Stage IB, 3 Stage IIA, 2 Stage IIB, and 1 Stage IIIA on the basis of the American Joint Committee on Cancer/International Union for Cancer Control criteria. In the 16 cases found to have multiple malignancies, 6 had histologically different carcinomas and the remaining 10 had histologically identical malignancies. Eighty-three percent (76/92) of the carcinomas invaded the stroma with destruction of normal lung, and 21% (19/92) also showed either pleural or angiolymphatic invasion, even though 88% (57/65) of the carcinomas were free of lymph node metastases. This report describes the pathologic findings of the resected cases. Histopathologic distinctions among atypical adenomatous hyperplasia, bronchioloalveolar carcinomas, and invasive adenocarcinoma are described in detail.
Six hundred ninety-five mice received adeno-associated virus (AAV) vectors, mostly via portal vein injection. At necropsy, the livers were inspected for tumors, and tissue sections were prepared for ...histology. We observed only one tumor, a lipoma, resulting in a tumor frequency of 0.14%. This tumor contained fewer vector genomes per total DNA than the surrounding liver tissue, as shown by quantitative PCR. In another mouse we found a macroscopically visible nodule containing lymphocytes. Immunohistochemistry revealed cells not of monoclonal origin, and they contained fewer AAV genomes than the surrounding hepatocytes. There were no macroscopic tumors in 226 control mice. Upon microscopic examination, lymphocytic infiltrates were found in 5% of livers of both control and vector-treated mice; no transgene expression was seen in those infiltrates in AAV-injected animals. Compared to an average frequency of spontaneous liver tumors in C57BL/6 mice (0-10%), and given the absence of high levels of vector DNA in the observed tumor, we conclude that AAV vectors do not predispose these target animals to the formation of liver tumors.
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