Imprint cytologic features of pulmonary sclerosing hemangioma: comparison with well-differentiated papillary adenocarcinoma

BACKGROUND: Sclerosing hemangiomas (SH) of the lung are uncommon tumors and are thought to be benign. However, histogenesis of these tumors has not yet been characterized adequately. Moreover, there are few reports dealing with their cytologic features, and it is generally considered difficult to make accurate diagnoses of sclerosing hemangiomas that have a predominantly papillary pattern.METHODS: Cytologic features were analyzed for 15 sclerosing hemangiomas, and cytologic features of sclerosing hemangioma were compared with features of 22 cases of well-differentiated papillary adenocarcinoma classified as pathologic Stage 1A.RESULTS: Blood and round cells were observed more frequently in SH than in adenocarcinomas (P < 0.05), whereas necrosis was seen more frequently in adenocarcinomas than in SH (P < 0.05). The presence of nucleoli, nuclear indentations, irregularities of nuclear margins, nuclear polymorphisms, and high nuclear-cytoplasmic (NC) ratios of tumor cells were observed less frequently in SH. Polynuclear (having three or more nuclei) tumor cells were observed only in adenocarcinoma cases. In morphometric studies, the nuclear areas, cytoplasmic areas, NC ratios, long axes of nuclei, short axes of nuclei, and nuclear rotundity ratios were significantly higher in adenocarcinoma cells than in SH cells (P < 0.05).CONCLUSIONS:The presence of polymorphous cells and tumor cells with bland nuclei are characteristic cytologic findings associated with sclerosing hemangioma. It is possible to make accurate diagnoses for SH cases preoperatively by careful cytologic characterization.     

Cytopathologic factors can predict invasion in small-sized peripheral lung adenocarcinoma with a bronchioloalveolar carcinoma component

BACKGROUND: Patients with noninvasive, small-sized primary adenocarcinomas of the lung have excellent prognosis after lobectomy. Several researchers have suggested that limited resection could be an acceptable alternative for these patients. Therefore, a preoperative or intraoperative judgment of invasiveness would be one of the critical determinants of the surgical procedure in each case. Cytopathologic findings that can distinguish invasive from noninvasive adenocarcinomas remain to be elucidated. METHODS: Imprint smears were obtained from 60 resected adenocarcinomas with nonmucinous bronchioloalveolar features. Thirteen cytologic factors were evaluated: the presence of necrosis, fibrovascular tissue, proportion of macrophages, the presence of large tumor cell clusters, nuclear grooves, nuclear overlapping, variation in nuclear size, chromatin pattern, presence of a nucleolus, intranuclear inclusions, multinucleated cells, spindle cells, and mitosis. Each factor was examined by univariate analysis for correlation with the presence of histopathologic invasion. RESULTS: In the univariate analysis, 5 cytologic factors--presence of tumor cell clusters consisting of more than 50 tumor cells (P < .001), nuclear overlapping in more than 3 layers (P < .001), presence of nuclear grooves (P = .007), more than 3-fold variation in nuclear size (P < .001), and 1 mitotic cell per 1000 tumor cells (P = .035)--were associated significantly with invasion. Among these, nuclear overlapping in more than 3 layers (P = .003) and more than 3-fold variation in nuclear size (P = .005) were found to be independent predictive factors for invasion by multivariate analysis. CONCLUSIONS: Using imprint smears, the presence of invasion in small-sized primary adenocarcinomas of the lung is predictable by the 2 above-mentioned cytologic findings. Imprint smear cytology may effectively aid intraoperative judgement of invasion in cases where frozen section histology is difficult to interpret.     

Cytologic factors associated with prognosis in patients with peripheral adenocarcinoma of the lung measuring 3 cm or less in greatest dimension

BACKGROUND: Recently, peripheral lung adenocarcinomas (PLA) measuring < or = 3 cm in greatest dimension often have been diagnosed using diagnostic radiology. The objective of the current study was to determine which cytologic factors are associated with a favorable outcome and an unfavorable outcome in patients with PLA. METHODS: Imprint smears from 134 patients with PLA were examined. Sixteen cytologic factors, including necrosis, cellular distribution, overlapping of cell clusters, cluster aggregation, cluster size, cluster thickness, nuclear irregularity, nuclear size, variation in nuclear size, multinucleated cells, intranuclear inclusions, type of intranuclear inclusions, appearance of nucleoli, eosinophilic nucleoli, multinucleoli, and mitosis, were evaluated using univariate and multivariate analyses. A counting method was used to determine the prognosis for individual patients. RESULTS: In the univariate analysis, a cluster size that measured > or = 831 microm in short dimension (P = 0.0011), moderate or severe nuclear irregularity (P = 0.0030), > or = 5 multinucleated cells per 100 tumor cells (P = 0.0047), moderate or severe variation in nuclear size (P = 0.0061), medium or large nuclear size (P = 0.0169), and > or = 1 mitotic cell per 100 tumor cells (P = 0.0412) were associated significantly with a poor outcome. In the multivariate analysis, cluster size in short dimension (P = 0.0018), multinucleated cells (P = 0.0066), and nuclear irregularity (P = 0.0310) were found to be independent prognostic factors. CONCLUSIONS: The combination of cytologic features using intraoperative imprint smears, namely, cluster sizes < or = 830 microm in short dimension, < or = 4 multinucleated cells per 100 tumor cells, and mild nuclear irregularity, may provide favorable predictive information in patients with PLA.     

Fine-needle aspiration biopsy of bronchioloalveolar carcinoma

BACKGROUND: The purpose of the current study was to determine the accuracy of the cytologic diagnosis of bronchioloalveolar carcinoma (BAC) by fine-needle aspiration biopsy (FNAB). METHODS: During a 4-year period (1994-1998), 1664 lung FNABs were performed. Forty-nine patients with BAC diagnosed by FNAB and/or surgical biopsy formed the basis of this study. RESULTS: Twenty-four patients diagnosed with BAC by FNAB had histologic confirmation. Surgical pathology revealed BAC in 15 patients with a cytologic diagnosis of large cell carcinoma (LCA) or adenocarcinoma (ACA). Nine patients diagnosed with BAC by FNAB were found to have ACA histologically. One unsatisfactory aspirate was diagnosed as BAC by surgical pathology. Review of 15 FNAB specimens with a diagnosis of LCA or ACA revealed cytologic features typical of BAC. In six aspirates, additional features such as pronounced nuclear crowding and overlapping, variation in nuclear size, and increased number of pleomorphic cells interfered with the FNAB diagnosis of BAC. Nine FNABs with a diagnosis of BAC were found histologically to have ACA with a focal BAC growth pattern. One unsatisfactory FNAB aspirate diagnosed as BAC histologically was due to sampling error. CONCLUSIONS: A diagnosis of BAC by FNAB is possible using conventional cytologic criteria. Some BACs show pronounced nuclear crowding and overlapping, variation in nuclear size, and an increased number of pleomorphic cells cytologically, which may interfere with an FNAB diagnosis of BAC. FNABs from ACA cases with a focal BAC pattern remain a diagnostic dilemma due to the nature of the lesion. In addition, sampling error by FNAB can be a diagnostic pitfall. Cancer (Cancer Cytopathol) Copyright 2001 American Cancer Society.     

The cytologic basis for classification of lung tumors

Nuclear changes in cells of bronchial biopsies and surgical specimens were studied in relation to nuclear structures of cells at various mitotic phases. Cell structures comparable to early and late G1 and G2 phases were correlated with histologic types of lung tumors according to the 1981 WHO classification. The evolved cellular classification added another parameter for diagnosis of histologic alterations and for interpretation of cellular changes in cytologic specimens. Benign histological alterations contained cells in either early or late G1 phase. Well-differentiated adenocarcinomas, bronchiolo-alveolar cell carcinomas, and carcinoid tumors had cells with structure of the late G1 phase. These were distinguished from benign cells with similar structures by their increased nuclear size, their increased amount of nuclear chromatin, hyperchromasia, and increased nuclear cytoplasmic ratio. Well-differentiated acinar adenocarcinomas, papillary adenocarcinomas, clear cell carcinomas, and large cell carcinomas had cribriform nuclear structures with prominent nucleoli related to early G2 phase. Squamous cell carcinomas, poorly differentiated adenocarcinomas, giant cell carcinomas, and solid carcinomas with mucus formation had usually prominent nucleoli with nuclear structures of the late G2 phase. Small cell carcinomas were the only malignant tumors of the lung that had cells with the malignant cribriform nuclear structure of the early G2 phase without a nucleolus. Cellular markers of malignant neoplasms had also the nuclear structure of early G2 without a nucleolus but differed from small cell carcinoma by their differentiated state with presence of cilia. The cytologic diagnosis of 506 malignant tumors of 1031 cases examined resulted in a sensitivity of 86.6%. The correct diagnosis of 244 of 247 cases without tumor resulted in a diagnostic specificity of 98.8%.     

Diagnostic dilemmas in pulmonary cytology.

BACKGROUND: Diagnostic difficulties in pulmonary cytology may be compounded by other medical problems, lack of pertinent information, and the presence of rare tumors. In the current study, the authors describe six cases of lower respiratory tract cytology that presented particular diagnostic challenges or pitfalls. METHODS: Three lung fine-needle aspiration biopsies (FNAB) from three patients, four bronchoalveolar lavages from two patients, and one bronchial washing from one patient, each with histologic confirmation, were reviewed. Cytologic material included direct smears, ThinPrep slides, and cell blocks. Cytologic findings were compared with established cytologic criteria for each final diagnosis. RESULTS: Two cases with Aspergillus infection that demonstrated reactive atypical cells were misinterpreted as squamous cell carcinoma and nonsmall cell carcinoma. Two cases diagnosed as significant atypia and negative, respectively, subsequently were found to show bronchioloalveolar carcinoma (as well as lymphangioleiomyomatosis, which was suspected clinically) and bronchogenic adenocarcinoma, respectively. One lung FNAB from a patient subsequently confirmed to have bronchiolitis obliterans-organizing pneumonia (BOOP) showed reactive pneumocytes that initially were misinterpreted as being suspicious for carcinoid. These reactive pneumocytes were identified histologically in the area of BOOP. The last case was an FNAB of a well differentiated fetal-type adenocarcinoma, an unusual variant of adenocarcinoma that to the authors' knowledge rarely is described in the cytology literature. CONCLUSIONS: Cytomorphologic features of lower respiratory tract pathology combined with appropriate clinical information and diagnostic discretion usually allow accurate diagnoses and should decrease both false-positive and false-negative result rates. Clinical information and radiologic findings may be invaluable, but may not always parallel the cytologic diagnosis.     

Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung

Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.     

Immunocytochemical study of RAS oncoprotein in cytologic specimens of primary lung tumours

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).     

A molecular diagnostic test for distinguishing lung adenocarcinoma from malignant mesothelioma using cells collected from pleural effusions.

PURPOSE: Patients with malignant mesothelioma or adenocarcinoma of the lung often present with respiratory complications associated with a malignant pleural effusion. Distinguishing between these malignancies is frequently problematic, as many of the clinical, cytologic, and histologic features of the diseases overlap. Following cytologic analysis of pleural effusions, subsequent confirmatory tissue biopsies involve increased patient morbidity and expense. We have therefore designed a gene expression-based test to classify the primary tumor causing a malignant pleural effusion, using cells collected from the effusion itself. EXPERIMENTAL DESIGN: We have used microarray data for 190 lung adenocarcinomas and 33 malignant mesotheliomas to identify genes differentially expressed between the two diseases. Genes expressed in normal mesothelial cells were removed, allowing the development of a PCR-based test to measure the expression of genes that discriminate between mesothelioma and lung adenocarcinoma from cytology specimens. RESULTS: Applying an real-time PCR-based assay involving 17 genes to 13 independent samples from biopsy-proven malignant mesothelioma and lung adenocarcinomas resulted in the correct identification of all samples. CONCLUSIONS: We have developed a test that is able to distinguish between lung adenocarcinoma and mesothelioma in cells collected from pleural effusions.     

Micropapillary clusters in early-stage lung adenocarcinomas: a distinct cytologic sign of significantly poor prognosis

BACKGROUND: It is known that patients who have pulmonary adenocarcinomas with a pathologic micropapillary pattern (pMPP) featuring small papillary tufts that lack a central fibrovascular core have a poor prognosis. Although the pMPP initially was identified in surgical material, preoperative detection is desirable from the standpoint of making treatment decisions. Therefore, the authors focused on cytologic features resembling the pMPP in lung adenocarcinomas, with particular reference to the survival of patients with pathologic Stage I disease. METHODS: The authors reviewed clinical course data, preoperative cytologic specimens, and histologic materials from 110 patients with Stage I adenocarcinoma of the lung who presented between 1986 and 1995. Cytology of micropapillary clusters (MPCs) was characterized by round, 3-dimensional, cohesive clusters of neoplastic cells (consisting of > 3 cells and < 20 cells) with a pseudopapillary configuration. Total counts of cohesive clusters that consisted of more than three neoplastic cells on slides and frequencies of MPCs were investigated. RESULTS: All patients (54 females and 56 males) had a preoperative diagnosis of malignancy and underwent complete surgical resection. The patients with Stage I disease were subclassified into an MPC-positive group (n = 41) and an MPC-negative group (n = 69). The 5-year survival rate was 91.3% for patients in the MPC-negative group and 75.6% for patients in the MPC-positive group; this difference was statistically significant. CONCLUSIONS: MPC cytology is a distinct prognostic marker for early-stage lung adenocarcinoma with poor prognosis. The presence of this component, therefore, should alert the clinician to the need for close follow-up.     

Prognostic significance of grading in lung adenocarcinoma

BACKGROUND:

Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that the authors found to have prognostic significance in patients with lung adenocarcinoma.

METHODS:

The authors studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count.

RESULTS:

In univariate analysis, overall survival was associated significantly with sex (P = .045), age (P = .0008), tumor status (P < .0001), lymph node status (P = .02), solid pattern (P = .046), and cytologic atypia (P = .01), but not with mitotic count (P = .26). On the basis of optimal cutoff values, the authors found that a solid pattern ≥90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2 = well differentiated, 3 = moderately differentiated, 4 = poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times, 72.4, 39.5, and 8.7 months for well, moderately, and poorly differentiated adenocarcinoma, respectively; P = .0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P = .002).

CONCLUSIONS:

The authors describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma. Cancer 2010. © 2009 American Cancer Society.     

Sputum cytologic atypia predicts incident lung cancer: defining latency and histologic specificity.

BACKGROUND: There is a need for early detection methods for lung cancer. Radiologic imaging may be more sensitive for peripheral cancers than for cancers arising in the central airways, from which bronchial epithelial cells are exfoliated into the sputum. METHODS: Sputum samples were collected at baseline and periodically thereafter in a cohort of smokers and former smokers with chronic obstructive lung disease. The association between cytologic atypia and incident lung cancer was assessed by hazard ratios (HR; 95% confidence intervals) using Cox regression and by odds ratios (95% confidence intervals) using logistic regression, adjusting for potential confounding factors. RESULTS: We observed 174 incident lung cancers in a cohort of 2,521 people over 9,869 person-years of observation. Risk for incident lung cancer was increased among those with cytologic atypia graded as moderate or worse (adjusted HR, 2.37; 1.68-3.34). The association between sputum atypia and lung cancer incidence was greatest for those sputum samples collected 5 months or less before the diagnosis of lung cancer (odds ratio, 10.32; 5.34-19.97). The association was substantially stronger for squamous cell lung cancers (HR, 5.13; 2.89-9.10) than for adenocarcinomas (HR, 1.85; 0.94-3.65). CONCLUSION: Cytologic atypia is a marker for increased lung cancer risk. These cytologic changes seem to arise from late events that are most apparent for cancers arising in the central respiratory airways. Whether cytologic atypia might complement radiologic imaging in a combined approach to lung cancer, early detection requires additional evaluation of those two methods used together.     

Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis

To reveal useful prognostic factors in cases of small-sized pulmonary adenocarcinoma, we conducted a histological and karyometric analysis of 116 small-sized pulmonary adenocarcinomas measuring less than 2 cm in maximum diameter and four specimens of atypical adenomatous hyperplasia (AAH). The small-sized pulmonary adenocarcinomas were classified by using criteria described previously [Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Lung Cancer 1995:75;2844-52]. There were 99 tumors of replacement-type adenocarcinoma, comprising 11 type A, localized bronchioloalveolar adenocarcinoma (LBAC); 6 type B, LBAC with alveolar collapse; and 82 type C, LBAC with foci of fibroblastic proliferation. The 17 remaining tumors were non-replacement-type adenocarcinomas. Among the potential prognostic factors examined, histological subtype was the most closely correlated with 5-year relapse-free survival rate. Furthermore, in patients with type C adenocarcinomas, a small fibroblastic proliferation (F) to fibrosis area (f) ratio (F-f ratio) (<10%) of the tumor and a small maximum nuclear diameter (Max ND; <13.50 microm) of tumor cells were closely associated with an excellent prognosis. Histological subtypes of type A and B adenocarcinomas, a small F-f ratio, and a small Max ND of type C adenocarcinomas were closely correlated with an excellent prognosis in small-sized adenocarcinoma.     

The differential effects of mutant p53 alleles on advanced murine lung cancer

We report a direct comparison of the differential effects of individual p53 mutations on lung tumor growth and progression, and the creation of a murine model of spontaneous advanced lung adenocarcinoma that closely recapitulates several aspects of advanced human pulmonary adenocarcinoma. We generated compound conditional knock-in mice with mutations in K-ras combined with one of three p53 alleles: a contact mutant, a structural mutant, or a null allele. p53 loss strongly promoted the progression of K-ras-induced lung adenocarcinomas, yielding a mouse model that is strikingly reminiscent of advanced human lung adenocarcinoma. The influence of p53 loss on malignant progression was observed as early as 6 weeks after tumor initiation. Furthermore, we found that the contact mutant p53R270H, but not the structural mutant p53R172H, acted in a partially dominant-negative fashion to promote K-ras-initiated lung adenocarcinomas. However, for both mutants, loss-of-heterozygosity occurred uniformly in advanced tumors, highlighting a residual tumor-suppressive function conferred by the remaining wild-type allele of p53. Finally, a subset of mice also developed sinonasal adenocarcinomas. In contrast to the lung tumors, expression of the point-mutant p53 alleles strongly promoted the development of sinonasal adenocarcinomas compared with simple loss-of-function, suggesting a tissue-specific gain-of-function.     

Severe cervical glandular cell lesions with coexisting squamous cell lesions

BACKGROUND: In the current report, the authors present the results of a reevaluation of cytologic smears and histologic specimens obtained from patients with severe cervical glandular cell lesions (adenocarcinoma in situ [AIS] or adenocarcinoma [ADCA] of the cervix) and coexisting Grade 1, Grade 2, or Grade 3 cervical intraepithelial neoplasia or squamous cell carcinoma. The goal of the current study was to assess whether knowledge of the specific cytologic characteristics of the cervical glandular cell lesions could have made the cytologic diagnosis of these combined neoplasms more accurate. METHODS: Cytologic smears and histologic specimens obtained from 36 patients with combined severe cervical lesions were evaluated for the presence of a range of microscopic cytologic and histologic features that were considered indicative of glandular cell changes. RESULTS: The findings of the current study suggest that the proper identification of characteristic cytomorphologic features of cervical glandular lesions would have resulted in more accurate diagnoses of combined severe cervical lesions. In the set of samples reevaluated by the authors, consideration of these features would have increased the accuracy of cytologic diagnosis from 55.6% to 75.0%. The presence of AIS was predicted in the majority of cytologic specimens, and in most cases, the identity of the predominant subtype of AIS could also be predicted. CONCLUSIONS: The current analysis revealed that consideration of specific cytomorphologic features of glandular lesions of the cervix increased the authors' accuracy in diagnosing combined severe lesions of the cervix. More accurate identification of intraepithelial glandular cell lesions may eventually lead to decreases in cervical adenocarcinoma incidence, just as increases in diagnostic accuracy have led to decreases in the incidence of squamous intraepithelial lesions and invasive squamous carcinoma of the cervix.     

Calretinin staining pattern aids in the differentiation of mesothelioma from adenocarcinoma in serous effusions

BACKGROUND: The differentiation between malignant mesothelioma and adenocarcinoma based on morphology alone can be a diagnostic challenge. The majority of the available antibodies recognize molecules expressed by adenocarcinoma whereas to the authors' knowledge specific markers for mesothelial cells are lacking. Calretinin, a calcium-binding protein, has been reported to be a selective marker for mesothelioma and largely is absent from adenocarcinoma on histologic material. The results with cytologic preparations have been inconsistent. METHODS: To evaluate the specificity of calretinin in differentiating mesothelioma from adenocarcinoma in cytologic preparations, 21 paraffin embedded cells blocks of serous effusions from 15 patients with metastatic adenocarcinoma and 16 cell blocks from 9 patients with malignant mesothelioma were stained with a monoclonal antibody against calretinin. The immunoreactivity was evaluated blindly by two observers. Positive staining was defined as nuclear and cytoplasmic staining with or without intense membranous decoration. The former resulted in a characteristic "fried egg" appearance. RESULTS: Calretinin staining was positive in all but 2 cases of mesothelioma (14 of 16 cases; 87.5%). The latter contained predominantly spindle-shaped neoplastic mesothelial cells in the cell block preparations. All adenocarcinoma specimens were classified as negative for calretinin staining; 9 (42.9%) lacked any immunoreactivity and 12 (57.1%) showed weak, sparse, coarse, granular cytoplasmic staining without nuclear or membranous staining. Benign reactive mesothelial cells, when observed in association with adenocarcinoma, also showed the characteristic "fried egg" appearance. The difference in the staining pattern of calretinin between cells of mesothelial origin and adenocarcinoma cells was statistically significant. CONCLUSIONS: Calretinin is a useful marker in differentiating mesothelioma of the epithelial type from adenocarcinoma in serous effusions. The "fried-egg" appearance or cytoplasmic and nuclear staining pattern is characteristic of cells of mesothelial origin.     

ECT2 amplification and overexpression as a new prognostic biomarker for early‐stage lung adenocarcinoma

Genetic abnormality in early‐stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array‐comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real‐time genomic PCR and immunohistochemistry. The results were then verified using another set of early‐stage adenocarcinomas. Array‐comparative genomic hybridization indicated frequent amplification at chromosome 3q26. Of the seven genes located in this region, we focused on the epithelial cell transforming sequence 2 (ECT2) oncogene, as ECT2 amplification was detected only in invasive adenocarcinoma, and not in in situ carcinoma. Quantitative PCR and immunohistochemistry analyses also detected overexpression of ECT2 in invasive adenocarcinoma, and this was correlated with both the Ki‐67 labeling index and mitotic index. In addition, it was associated with disease‐free survival and overall survival of patients with lung adenocarcinoma. These results were verified using another set of early‐stage adenocarcinomas resected at another hospital. Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma.     

Small lung tumors with the size of 1cm or less in diameter: clinical, radiological, and histopathological characteristics

BACKGROUND: The detection rate of small nodules in the peripheral lung area is increasing due to the widespread use of CT scanning. However, the radiological and pathological characteristics of very small tumors have not been fully investigated. METHODS: We evaluated 44 lung tumors with the size of 1cm or less in diameter resected from 38 patients (19 men and 19 women, with an average of 62 years) from 1997 through 2001. The clinical records, the findings of high-resolution CT (HRCT) and histopathological features of resected specimens were analyzed. Adenocarcinoma was histologically further subclassified into types A to F according to the Noguchi's classification. RESULTS: Lobectomy was performed in 20 patients, wedge resection in 15 and segmentectomy in 3, respectively. Thirty-two tumors were adenocarcinomas, 4 were squamous cell carcinomas, and eight were atypical adenomatous hyperplasia (AAH), respectively. All carcinoma cases were proved to be stage IA. In adenocarcinoma, type A was detected in 12 tumors, type B in 13, type C in 1, type D in 2, type E in 1, and type F in 3, respectively. Most of AAH and type A showed pure ground-glass attenuation on HRCT scan, whereas types B to F as well as squamous cell carcinoma frequently had malignant CT signs such as lobulation and convergence of peripheral vessels. Lymphatic or vascular invasion was observed in two adenocarcinomas (types D and F) and two squamous cell carcinomas, and HRCT scan of these four tumors showed soft-tissue attenuation occupying more than two-thirds of each nodule. All patients are currently alive without signs of recurrence after a mean follow-up period of 35.5 months. CONCLUSION: Types A and B of adenocarcinoma were the most common histologic types among lung tumors with the size of 1cm or less in diameter. Limited lung resection appears to be an adequate for such small lung tumors in which soft-tissue attenuation consists of less than two-thirds of the nodule on HRCT.     

Histologic types of lung carcinoma and age at onset

BACKGROUND: Previous research has demonstrated that adenocarcinoma is the leading cell type among patients with early age onset lung carcinoma. An increase in adenocarcinoma at the expense of squamous cell carcinoma in general was observed in recent years and may be due to the smoking of filtered cigarettes. METHODS: To rule out whether shifts in smoking patterns or other etiologic factors are responsible for the high rates of adenocarcinoma in young patients, personal interviews regarding smoking, occupation, and family history of cancer were conducted in 251 young patients (age < or =45 years) and 2009 older patients (ages 55-69 years) with histologically confirmed lung carcinoma from selected study clinics in Germany between 1990 and 1996. RESULTS: Young male patients were found to have significantly more adenocarcinomas (41%) than older male patients (28%), whereas adenocarcinomas were dominant in young and older women (43% and 47%, respectively). Because smoking patterns were different between young and older patients, the authors stratified for comparable levels of smoking exposure. Histology did not differ in never smokers (dominance of adenocarcinomas in both age groups) and in male heavy smokers (dominance of squamous cell carcinomas in both age groups), whereas young male low dose smokers showed significantly more cases of adenocarcinoma than older low dose smokers. A family history of lung carcinoma was significantly higher in young patients compared with older patients, but no association with histologic type was observed. CONCLUSIONS: The results of the current study show that differences in the histologic type of lung carcinoma based on age at onset can be explained in part by differences in smoking patterns. However, there still are unknown factors that appear to favor the development of adenocarcinoma in the young.     

Glandular neoplasia of the lung. A proposed analogy to colonic tumors

In 62 consecutive resections for adenocarcinoma of the lung, 50 cases (81%) had single adenocarcinomas and 12 (19%) had multiple adenocarcinomas. In seven of these 12 patients, two adenocarcinomas were found. In the other five patients, the specimen contained a dominant adenocarcinoma and several 0.1- to 1-cm nodules of similar histologic appearance. In four of the 50 single tumor patients and one of seven double tumor patients, 1- to 2-mm nodules were found along with adenocarcinomas that we interpreted as being bronchioloalveolar tumors of uncertain malignant potential. An analogy is drawn between these four types of findings and single tumors of the colon, double tumors of the colon, polyposis syndromes, and tubular adenomas of the colon, respectively.